Leptin-induced basal Akt phosphorylation and its implication in exercise-mediated improvement of insulin sensitivity.

PubMed

Zheng, Xianjie; Niu, Sen

2018-01-29

Physical exercise is an efficient therapeutical tool in the management of insulin resistance (IR) and related metabolic diseases. Leptin, the well-known obesity hormone and the absence of which leads to IR, showed controversial effects on IR as research continues. Thus, in this study, a detailed investigation of the effect of leptin on exercise-mediated improvement of insulin sensitivity and its underlying mechanism was carried out. Using a rat model of chronic or acute swimming exercise training, we found that serum leptin increased 1 h after either acute exercise or the last session of chronic exercise, when impaired insulin action was observed in previous reports. However, chronic exercise reducd basal serum leptin levels and promoted insulin sensitivity compared with sedentary controls or rats subjected to one bout of aerobic exercise. Our animal results indicated the potential linkage between leptin and insulin sensitivity, which is further investigated in the skeletal muscle L6 cells. Leptin treatment in L6 cells promoted the basal levels of insulin signaling as well as glucose uptake, while blocking JAK2 signaling with either pharmacological intervention (JAK2 inhibitor AG490) or genetic manipulation (siRNA knockdown) decreased the basal levels of insulin signaling. Furthermore, leptin treatment inhibited insulin-stimulated insulin signaling and glucose uptake, while blocking JAK2 signaling restored leptin-attenuated insulin sensitivity. Taken together, our results demonstrated that reduced serum leptin, at least in part, contributes to exercise-mediated improvement of insulin sensitivity, indicating JAK2 as a potent therapeutical target of insulin resistance. Copyright © 2018 Elsevier Inc. All rights reserved.

Insulin sensitivity and metabolic flexibility following exercise training among different obese insulin-resistant phenotypes.

PubMed

Malin, Steven K; Haus, Jacob M; Solomon, Thomas P J; Blaszczak, Alecia; Kashyap, Sangeeta R; Kirwan, John P

2013-11-15

Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P < 0.05). Exercise reduced glucose iAUCOGTT in IGT only (P < 0.05), and the decrease in glucose iAUCOGTT was inversely correlated with the increase in peripheral but not hepatic insulin sensitivity (P < 0.01). Increased clamp-derived peripheral insulin sensitivity was also correlated with enhanced metabolic flexibility, reduced fasting RQ, and higher nonoxidative glucose disposal (P < 0.05). Adults with IFG + IGT had smaller gains in clamp-derived peripheral insulin sensitivity and metabolic flexibility, which was related to blunted improvements in postprandial glucose. Additional work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects

PubMed Central

Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T.; Molina-Carrion, Marjorie; DeFronzo, Ralph A.; Sakamoto, Kei

2012-01-01

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of V̇o2max). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS Km for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50–70% (Ser641, Ser645, and Ser645,649,653,657), and phosphorylation of these sites remained decreased after 3.5 h; Ser7 phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased Km for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects. PMID:22510711

Effect of acute exercise on glycogen synthase in muscle from obese and diabetic subjects.

PubMed

Jensen, Jørgen; Tantiwong, Puntip; Stuenæs, Jorid T; Molina-Carrion, Marjorie; DeFronzo, Ralph A; Sakamoto, Kei; Musi, Nicolas

2012-07-01

Insulin stimulates glycogen synthase (GS) through dephosphorylation of serine residues, and this effect is impaired in skeletal muscle from insulin-resistant [obese and type 2 diabetic (T2DM)] subjects. Exercise also increases GS activity, yet it is not known whether the ability of exercise to affect GS is impaired in insulin-resistant subjects. The objective of this study was to examine the effect of acute exercise on GS phosphorylation and enzyme kinetic properties in muscle from insulin-resistant individuals. Lean normal glucose-tolerant (NGT), obese NGT, and obese T2DM subjects performed 40 min of moderate-intensity cycle exercise (70% of Vo(2max)). GS kinetic properties and phosphorylation were measured in vastus lateralis muscle before exercise, immediately after exercise, and 3.5 h postexercise. In lean subjects, GS fractional activity increased twofold after 40 min of exercise, and it remained elevated after the 3.5-h rest period. Importantly, exercise also decreased GS K(m) for UDP-glucose from ≈0.5 to ≈0.2 mM. In lean subjects, exercise caused significant dephosphorylation of GS by 50-70% (Ser(641), Ser(645), and Ser(645,649,653,657)), and phosphorylation of these sites remained decreased after 3.5 h; Ser⁷ phosphorylation was not regulated by exercise. In obese NGT and T2DM subjects, exercise increased GS fractional activity, decreased K(m) for UDP-glucose, and decreased GS phosphorylation as effectively as in lean NGT subjects. We conclude that the molecular regulatory process by which exercise promotes glycogen synthesis in muscle is preserved in insulin-resistant subjects.

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness.

PubMed

Stuart, Charles A; Lee, Michelle L; South, Mark A; Howell, Mary E A; Cartwright, Brian M; Ramsey, Michael W; Stone, Michael H

2017-03-01

Stuart, CA, Lee, ML, South, MA, Howell, MEA, Cartwright, BM, Ramsey, MW, and Stone, MH. Pre-training muscle characteristics of subjects who are obese determine how well exercise training will improve their insulin responsiveness. J Strength Cond Res 31(3): 798-808, 2017-Only half of prediabetic subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pretraining characteristics favoring a positive response to exercise training. Thirty nondiabetic subjects who were obese volunteered for 8 weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition, and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow-twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and glucose transporter type 4 (GLUT4) expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole-body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pretraining baseline.

Pre-Training Muscle Characteristics of Subjects Who Are Obese Determine How Well Exercise Training Will Improve Their Insulin Responsiveness

PubMed Central

Stuart, Charles A.; Lee, Michelle L.; South, Mark A.; Howell, Mary E.A.; Cartwright, Brian M.; Ramsey, Michael W.; Stone, Michael H.

2016-01-01

Only half of pre-diabetic, subjects who are obese who underwent exercise training without weight loss increased their insulin responsiveness. We hypothesized that those who improved their insulin responsiveness might have pre-training characteristics favoring a positive response to exercise training. Thirty non-diabetic, subjects who are obese volunteered for eight weeks of either strength training or endurance training. During training, subjects increased their caloric intake to prevent weight loss. Insulin responsiveness by euglycemic clamps and muscle fiber composition and expression of muscle key biochemical pathways were quantified. Positive responders initially had 52% higher intermediate muscle fibers (fiber type IIa) with 27% lower slow twitch fibers (type I) and 23% lower expression of muscle insulin receptors. Whether after weight training or stationary bike training, positive responders' fiber type shifted away from type I and type IIa fibers to an increased proportion of type IIx fibers (fast twitch). Muscle insulin receptor expression and GLUT4 expression increased in all trained subjects, but these moderate changes did not consistently translate to improvement in whole body insulin responsiveness. Exercise training of previously sedentary subjects who are obese can result in muscle remodeling and increased expression of key elements of the insulin pathway, but in the absence of weight loss, insulin sensitivity improvement was modest and limited to about half of the participants. Our data suggest rather than responders being more fit, they may have been less fit, only catching up to the other half of subjects who are obese whose insulin responsiveness did not increase beyond their pre-training baseline. PMID:27379957

Mechanisms for greater insulin-stimulated glucose uptake in normal and insulin-resistant skeletal muscle after acute exercise

PubMed Central

2015-01-01

Enhanced skeletal muscle and whole body insulin sensitivity can persist for up to 24–48 h after one exercise session. This review focuses on potential mechanisms for greater postexercise and insulin-stimulated glucose uptake (ISGU) by muscle in individuals with normal or reduced insulin sensitivity. A model is proposed for the processes underlying this improvement; i.e., triggers initiate events that activate subsequent memory elements, which store information that is relayed to mediators, which translate memory into action by controlling an end effector that directly executes increased insulin-stimulated glucose transport. Several candidates are potential triggers or memory elements, but none have been conclusively verified. Regarding potential mediators in both normal and insulin-resistant individuals, elevated postexercise ISGU with a physiological insulin dose coincides with greater Akt substrate of 160 kDa (AS160) phosphorylation without improved proximal insulin signaling at steps from insulin receptor binding to Akt activity. Causality remains to be established between greater AS160 phosphorylation and improved ISGU. The end effector for normal individuals is increased GLUT4 translocation, but this remains untested for insulin-resistant individuals postexercise. Following exercise, insulin-resistant individuals can attain ISGU values similar to nonexercising healthy controls, but after a comparable exercise protocol performed by both groups, ISGU for the insulin-resistant group has been consistently reported to be below postexercise values for the healthy group. Further research is required to fully understand the mechanisms underlying the improved postexercise ISGU in individuals with normal or subnormal insulin sensitivity and to explain the disparity between these groups after similar exercise. PMID:26487009

Improvement of insulin sensitivity in response to exercise training in type 2 diabetes mellitus is associated with vascular endothelial growth factor A expression.

PubMed

Wagner, Henrik; Fischer, Helene; Degerblad, Marie; Alvarsson, Michael; Gustafsson, Thomas

2016-09-01

Insulin sensitivity changes in response to exercise training demonstrate a large variation. Vascular endothelial growth factor A could promote increased insulin sensitivity through angiogenesis. We investigated associations between changes in expression of key genes and insulin sensitivity, aerobic capacity and glycaemic control following exercise training in diabetes mellitus type 2. Subjects with diabetes mellitus type 2 underwent 12 weeks of structured exercise. Euglycaemic clamp, exercise test and HbA1c were performed. Muscle biopsies were obtained for mRNA expression. A total of 16 subjects completed the study. Change in vascular endothelial growth factor A expression was positively associated with an increase in insulin sensitivity (p = 0.004) and with a decrease in HbA1c (p = 0.034). Vascular endothelial growth factor A receptor-1 expression showed similar associations. The variation in physical adaptation to exercise training in diabetes mellitus type 2 was associated with changes in expression of vascular endothelial growth factor A in muscle. This difference in induced gene expression could contribute to the variation in exercise training effects on insulin sensitivity. Measures of capillary blood flow need to be assessed in future studies. © The Author(s) 2016.

Effect of body weight gain on insulin sensitivity after retirement from exercise training

NASA Technical Reports Server (NTRS)

Dolkas, Constantine B.; Rodnick, Kenneth J.; Mondon, Carl E.

1990-01-01

The effect of the body-weight gain after retirement from an exercise-training program on the retained increase in insulin sensitivity elicited by the training was investigated in exercise-trained (ET) rats. Insulin sensitivity was assessed by oral glucose tolerance and insulin suppression tests immediately after training and during retirement. Results show that, compared with sedentary controls, exercise training enhanced insulin-induced glucose uptake, but the enhanced sensitivity was gradually lost with the end of running activity until after seven days of retirement, when it became equal to that of controls. This loss of enhanced sensitivity to insulin was associated with an accelerated gain in body weight beginning one day after the start of retirement. However, those animals that gained weight only at rates similar to those of control rats, retained their enhanced sensitivity to insulin.

The effect of insulin resistance and exercise on the percentage of CD16(+) monocyte subset in obese individuals.

PubMed

de Matos, Mariana A; Duarte, Tamiris C; Ottone, Vinícius de O; Sampaio, Pâmela F da M; Costa, Karine B; de Oliveira, Marcos F Andrade; Moseley, Pope L; Schneider, Suzanne M; Coimbra, Cândido C; Brito-Melo, Gustavo E A; Magalhães, Flávio de C; Amorim, Fabiano T; Rocha-Vieira, Etel

2016-06-01

Obesity is a low-grade chronic inflammation condition, and macrophages, and possibly monocytes, are involved in the pathological outcomes of obesity. Physical exercise is a low-cost strategy to prevent and treat obesity, probably because of its anti-inflammatory action. We evaluated the percentage of CD16(-) and CD16(+) monocyte subsets in obese insulin-resistant individuals and the effect of an exercise bout on the percentage of these cells. Twenty-seven volunteers were divided into three experimental groups: lean insulin sensitive, obese insulin sensitive and obese insulin resistant. Venous blood samples collected before and 1 h after an aerobic exercise session on a cycle ergometer were used for determination of monocyte subsets by flow cytometry. Insulin-resistant obese individuals have a higher percentage of CD16(+) monocytes (14.8 ± 2.4%) than the lean group (10.0 ± 1.3%). A positive correlation of the percentage of CD16(+) monocytes with body mass index and fasting plasma insulin levels was found. One bout of moderate exercise reduced the percentage of CD16(+) monocytes by 10% in all the groups evaluated. Also, the absolute monocyte count, as well as all other leukocyte populations, in lean and obese individuals, increased after exercise. This fact may partially account for the observed reduction in the percentage of CD16(+) cells in response to exercise. Insulin-resistant, but not insulin-sensitive obese individuals, have an increased percentage of CD16(+) monocytes that can be slightly modulated by a single bout of moderate aerobic exercise. These findings may be clinically relevant to the population studied, considering the involvement of CD16(+) monocytes in the pathophysiology of obesity. Copyright © 2016 John Wiley & Sons, Ltd. Obesity is now considered to be an inflammatory condition associated with many pathological consequences, including insulin resistance. It is proposed that insulin resistance contributes to the aggravation of the inflammatory dysfunction in obesity. The effect of obesity on the percentage of monocytes was previously observed in class II and III obese individuals who presented other alterations in addition to insulin resistance. In this study we observed that insulin-resistant obese individuals, but not insulin-sensitive ones, had an increased percentage of CD14(+) CD16(+) monocytes. This fact shows that a dysfunction of the monocyte percentage in class I obese individuals is only seen when this condition is associated with insulin resistance. Copyright © 2016 John Wiley & Sons, Ltd.

Hyperinsulinemia prevents prolonged hyperglycemia after intense exercise in insulin-dependent diabetic subjects.

PubMed

Sigal, R J; Purdon, C; Fisher, S J; Halter, J B; Vranic, M; Marliss, E B

1994-10-01

Hyperglycemia with accompanying hyperinsulinemia occurs after brief, greater than 85% maximum oxygen consumption exercise to exhaustion in normal subjects and persists up to 60 min of recovery. To determine the importance of endogenous insulin secretion during and after intense exercise, responses to exercise of lean fit male post-absorptive insulin-dependent diabetes mellitus (IDDM) subjects, aged 18-34 yr, were compared with those of control subjects (C; n = 6). Three iv insulin protocols were employed: hyperglycemic (HG; n = 7) and euglycemic (EG1; n = 6) with constant insulin infusion, and euglycemic with doubled insulin infusion during recovery (EG2; n = 6). Overnight iv insulin was adjusted to achieve prolonged euglycemia (5.4 +/- 0.3 mmol/L) or hyperglycemia (8.6 +/- 0.3 mmol/L) before exercise. This allowed for comparisons between HG and EG1 (constant infusion) and between C and EG2 (to approximate physiological hyperinsulinemia by doubling the infusion rates at exhaustion for 56 +/- 7 min during recovery). Subjects exercised to 89-98% of their individual maximum oxygen consumption for 12.8 +/- 0.3 min. Glycemia increased to maximum values at 6 min of recovery (9.8 +/- 0.5 in HG, 6.9 +/- 0.4 in EG1, 7.3 +/- 0.3 in EG2, and 6.9 +/- 0.4 mmol/L in C). Whereas in EG2 and C, glucose returned to resting values in 50-80 min, it remained elevated at 120 min recovery in HG and EG1. During exercise, [3-3H]-glucose-determined glucose production increased markedly and exceeded disappearance in all groups, but less so in the HG subjects than in the other groups. An early recovery decline in glucose production did not differ among groups, but MCR (rate of glucose disappearance/glycemia) were markedly lower in HG and EG1, in whom plasma free insulin remained unchanged from 15 min of recovery onward (MCR, 1.6-1.9 vs. 2.3-2.8 mL/kg.min in C). Doubling the insulin infusion rate in EG2 restored the MCR response to that of C subjects. In summary, constant insulin infusion is insufficient to prevent prolonged postexercise hyperglycemia in IDDM subjects, even when provided at a rate sufficient to maintain normal resting glycemia and glucose turnover. The finding that increasing the rate of insulin infusion restored plasma glucose to normal in IDDM subjects suggests that the postexercise increase in insulin levels observed in normal subjects is essential to return plasma glucose to resting levels. Therefore, special strategies, differing from those for less strenuous exercise, are required for the management of insulin therapy in IDDM during and after intense exercise.

Effect of home-based exercise intervention on fasting insulin and Adipocytokines in colorectal cancer survivors: a randomized controlled trial.

PubMed

Lee, Mi Kyung; Kim, Ji-Young; Kim, Dong-Il; Kang, Dong-Woo; Park, Ji-Hye; Ahn, Ki-Yong; In Yang, Hyuk; Lee, Dong Hoon; Roh, Yun Ho; Lee, Ji-Won; Chu, Sang-Hui; Meyerhardt, Jeffrey A; Jones, Lee W; Kim, Nam-Kyu; Jeon, Justin Y

2017-11-01

Elevated circulating insulin is associated with increased risk of recurrence and cancer mortality in early-stage colorectal cancer (CRC). We conducted a randomized controlled trial to determine the effect of a 12-week home-based exercise program on fasting insulin, adipocytokines, and physical function in CRC survivors. One hundred and twenty-three stage II-III CRC patients were randomly assigned to either a home-based exercise (n=62) or standard care control group (n=61) for 12weeks. Home-based exercise consisted of aerobic and resistance training, with a goal of obtaining ≥18 metabolic equivalent task (MET)-h/wk. Participants in the exercise group were instructed to participate in >18MET-h/wk. of aerobic and resistance exercise while the participants in the control group were asked to maintain their usual daily activity. The primary outcome was fasting insulin levels. Secondary outcomes were adiponectin, TNF-α levels and 6min walk distance from baseline to post-intervention. After the 12-weeks, moderate-vigorous physical activity participation increased from 9.1±14.7MET-h/wk. to 26.6±21.7MET-h/wk. in the exercise group, with no change in the control group (p<0.01 for group and time interaction). Circulating insulin level decreased by 1μU/ml (6.0±3.9 vs. 5.0±3.5, p=0.009) in the exercise group with no change in the control group (p=0.022 for group and time interaction). A similar trend was observed in TNF-α (p=0.030 for group and time interaction). Six minute walk distance increased by 25.2m in the exercise group with no change in the control group (p=0.061 for group and time interaction). The 12week home-based exercise program increased level of physical activity and decreased circulating insulin levels in CRC survivors. Copyright © 2017 Elsevier Inc. All rights reserved.

Predicting Insulin Absorption and Glucose Uptake during Exercise in Type 1 Diabetes

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Szeri, Andrew; Basu, Ananda

2017-11-01

A dose of insulin infused into subcutaneous tissue has been shown to absorb more quickly during exercise, potentially causing hypoglycemia in persons with type 1 diabetes. We develop a model that relates exercise-induced physiological changes to enhanced insulin-absorption (k) and glucose uptake (GU). Drawing on concepts of the microcirculation we derive a relationship that reveals that k and GU are mainly determined by two physiological parameters that characterize the tissue: the tissue perfusion rate (Q) and the capillary permeability surface area (PS). Independently measured values of Q and PS from the literature are used in the model to make predictions of k and GU. We compare these predictions to experimental observations of healthy and diabetic patients that are given a meal followed by rest or exercise. The experiments show that during exercise insulin concentrations significantly increase and that glucose levels fall rapidly. The model predictions are consistent with the experiments and show that increases in Q and PS directly increase k and GU. This mechanistic understanding provides a basis for handling exercise in control algorithms for an artificial pancreas. Now at University of British Columbia.

Acute exercise alters skeletal muscle mitochondrial respiration and H2O2 emission in response to hyperinsulinemic-euglycemic clamp in middle-aged obese men

PubMed Central

Trewin, Adam J.; Levinger, Itamar; Parker, Lewan; Shaw, Christopher S.; Serpiello, Fabio R.; Anderson, Mitchell J.; McConell, Glenn K.; Hare, David L.

2017-01-01

Obesity, sedentary lifestyle and aging are associated with mitochondrial dysfunction and impaired insulin sensitivity. Acute exercise increases insulin sensitivity in skeletal muscle; however, whether mitochondria are involved in these processes remains unclear. The aim of this study was to investigate the effects of insulin stimulation at rest and after acute exercise on skeletal muscle mitochondrial respiratory function (JO2) and hydrogen peroxide emission (JH2O2), and the associations with insulin sensitivity in obese, sedentary men. Nine men (means ± SD: 57 ± 6 years; BMI 33 ± 5 kg.m2) underwent hyperinsulinemic-euglycemic clamps in two separate trials 1–3 weeks apart: one under resting conditions, and another 1 hour after high-intensity exercise (4x4 min cycling at 95% HRpeak). Muscle biopsies were obtained at baseline, and pre/post clamp to measure JO2 with high-resolution respirometry and JH2O2 via Amplex UltraRed from permeabilized fibers. Post-exercise, both JO2 and JH2O2 during ADP stimulated state-3/OXPHOS respiration were lower compared to baseline (P<0.05), but not after subsequent insulin stimulation. JH2O2 was lower post-exercise and after subsequent insulin stimulation compared to insulin stimulation in the rest trial during succinate supported state-4/leak respiration (P<0.05). In contrast, JH2O2 increased during complex-I supported leak respiration with insulin after exercise compared with resting conditions (P<0.05). Resting insulin sensitivity and JH2O2 during complex-I leak respiration were positively correlated (r = 0.77, P<0.05). We conclude that in obese, older and sedentary men, acute exercise modifies skeletal muscle mitochondrial respiration and H2O2 emission responses to hyperinsulinemia in a respiratory state-specific manner, which may have implications for metabolic diseases involving insulin resistance. PMID:29161316

Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance.

PubMed

Lin, Po-Ju; Borer, Katarina T

2016-01-01

Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states. Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR). The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia. Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to 30% compared to no such changes after three 60%-carbohydrate meals, an effect that was independent of pre-meal exercise. The parallel timing and magnitude of postprandial insulin and GIP changes suggest their dependence on a delayed intestinal adaptation to a low-carbohydrate diet. Pre-meal exercise exacerbated glucose intolerance with both diets most likely due to impairment of insulin signaling by pre-meal elevation of FFAs.

Post-Exercise Carbohydrate-Energy Replacement Attenuates Insulin Sensitivity and Glucose Tolerance the Following Morning in Healthy Adults

PubMed Central

Taylor, Harry L.; Wu, Ching-Lin; Chen, Yung-Chih; Wang, Pin-Ging; Betts, James A.

2018-01-01

The carbohydrate deficit induced by exercise is thought to play a key role in increased post-exercise insulin action. However, the effects of replacing carbohydrate utilized during exercise on postprandial glycaemia and insulin sensitivity are yet to be determined. This study therefore isolated the extent to which the insulin-sensitizing effects of exercise are dependent on the carbohydrate deficit induced by exercise, relative to other exercise-mediated mechanisms. Fourteen healthy adults performed a 90-min run at 70% V˙O2max starting at 1600–1700 h before ingesting either a non-caloric artificially-sweetened placebo solution (CHO-DEFICIT) or a 15% carbohydrate solution (CHO-REPLACE; 221.4 ± 59.3 g maltodextrin) to precisely replace the measured quantity of carbohydrate oxidized during exercise. The alternate treatment was then applied one week later in a randomized, placebo-controlled, and double-blinded crossover design. A standardized low-carbohydrate evening meal was consumed in both trials before overnight recovery ahead of a two-hour oral glucose tolerance test (OGTT) the following morning to assess glycemic and insulinemic responses to feeding. Compared to the CHO-DEFICIT condition, CHO-REPLACE increased the incremental area under the plasma glucose curve by a mean difference of 68 mmol·L−1 (95% CI: 4 to 132 mmol·L−1; p = 0.040) and decreased the Matsuda insulin sensitivity index by a mean difference of −2 au (95% CI: −1 to −3 au; p = 0.001). This is the first study to demonstrate that post-exercise feeding to replaceme the carbohydrate expended during exercise can attenuate glucose tolerance and insulin sensitivity the following morning. The mechanism through which exercise improves insulin sensitivity is therefore (at least in part) dependent on carbohydrate availability and so the day-to-day metabolic health benefits of exercise might be best attained by maintaining a carbohydrate deficit overnight. PMID:29370143

Effect of an acute bout of aerobic exercise on chemerin levels in obese adults

PubMed Central

Lloyd, Jesse W.; Evans, Kristin A.; Zerfass, Kristy M.; Holmstrup, Michael E.; Kanaley, Jill A.; Keslacy, Stefan

2015-01-01

AIMS Serum chemerin concentrations are elevated in obese individuals and may play a role in type 2 diabetes. Exercise improves insulin sensitivity, which may be related to changes in chemerin. This study explored how an acute bout of aerobic exercise affected chemerin levels in non-diabetic obese adults. METHODS Blood samples from 11 obese adults were obtained during two separate conditions: sedentary (SED) and exercise (EX; 60-65% VO2peak). Samples were drawn at baseline, immediately following exercise and hourly for an additional 2 hours. ANOVA was used to test for differences in chemerin between conditions. RESULTS Unadjusted analysis showed no difference in overall change (baseline to 2 hrs post) in chemerin between conditions. During the 2-hr post-exercise period, chemerin decreased to 12% below baseline, compared to a 2.5% increase above baseline during that time period on the sedentary day (p=0.06, difference in post-to-2hr change between conditions). Controlling for homeostatic model assessment of insulin resistance (HOMA-IR), a significant difference existed between EX and SED in the change in chemerin from baseline to 2-hr post (p=0.02). Stratified analyses showed a consistent exercise-induced decrease in chemerin among non-insulin resistant subjects, while chemerin increased during exercise among insulin resistant subjects, and then decreased post-exercise. CONCLUSION An acute bout of exercise in obese individuals may elicit a drop in chemerin levels during the post-exercise period, and this response may vary based on insulin resistance. PMID:26008676

Exercise and insulin resistance in youth: a meta-analysis.

PubMed

Fedewa, Michael V; Gist, Nicholas H; Evans, Ellen M; Dishman, Rod K

2014-01-01

The prevalence of obesity and diabetes is increasing among children, adolescents, and adults. Although estimates of the efficacy of exercise training on fasting insulin and insulin resistance have been provided, for adults similar estimates have not been provided for youth. This systematic review and meta-analysis provides a quantitative estimate of the effectiveness of exercise training on fasting insulin and insulin resistance in children and adolescents. Potential sources were limited to peer-reviewed articles published before June 25, 2013, and gathered from the PubMed, SPORTDiscus, Physical Education Index, and Web of Science online databases. Analysis was limited to randomized controlled trials by using combinations of the terms adolescent, child, pediatric, youth, exercise training, physical activity, diabetes, insulin, randomized trial, and randomized controlled trial. The authors assessed 546 sources, of which 4.4% (24 studies) were eligible for inclusion. Thirty-two effects were used to estimate the effect of exercise training on fasting insulin, with 15 effects measuring the effect on insulin resistance. Estimated effects were independently calculated by multiple authors, and conflicts were resolved before calculating the overall effect. Based on the cumulative results from these studies, a small to moderate effect was found for exercise training on fasting insulin and improving insulin resistance in youth (Hedges' d effect size = 0.48 [95% confidence interval: 0.22-0.74], P < .001 and 0.31 [95% confidence interval: 0.06-0.56], P < .05, respectively). These results support the use of exercise training in the prevention and treatment of type 2 diabetes.

Additive insulinogenic action of Opuntia ficus-indica cladode and fruit skin extract and leucine after exercise in healthy males

PubMed Central

2013-01-01

Background Oral intake of a specific extract of Opuntia ficus-indica cladode and fruit skin (OpunDia™) (OFI) has been shown to increase serum insulin concentration while reducing blood glucose level for a given amount of glucose ingestion after an endurance exercise bout in healthy young volunteers. However, it is unknown whether OFI-induced insulin stimulation after exercise is of the same magnitude than the stimulation by other insulinogenic agents like leucine as well as whether OFI can interact with those agents. Therefore, the aims of the present study were: 1) to compare the degree of insulin stimulation by OFI with the effect of leucine administration; 2) to determine whether OFI and leucine have an additive action on insulin stimulation post-exercise. Methods Eleven subjects participated in a randomized double-blind cross-over study involving four experimental sessions. In each session the subjects successively underwent a 2-h oral glucose tolerance test (OGTT) after a 30-min cycling bout at ~70% VO2max. At t0 and t60 during the OGTT, subjects ingested 75 g glucose and capsules containing either 1) a placebo; 2) 1000 mg OFI; 3) 3 g leucine; 4) 1000 mg OFI + 3 g leucine. Blood samples were collected before and at 30-min intervals during the OGTT for determination of blood glucose and serum insulin. Results Whereas no effect of leucine was measured, OFI reduced blood glucose at t90 by ~7% and the area under the glucose curve by ~15% and increased serum insulin concentration at t90 by ~35% compared to placebo (P<0.05). From t60 to the end of the OGTT, serum insulin concentration was higher in OFI+leucine than in placebo which resulted in a higher area under the insulin curve (+40%, P<0.05). Conclusion Carbohydrate-induced insulin stimulation post-exercise can be further increased by the combination of OFI with leucine. OFI and leucine could be interesting ingredients to include together in recovery drinks to resynthesize muscle glycogen faster post-exercise. Still, it needs to be confirmed that such nutritional strategy effectively stimulates post-exercise muscle glycogen resynthesis. PMID:24144232

AMPK-α2 is involved in exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following high-fat diet.

PubMed

Abbott, Marcia J; Turcotte, Lorraine P

2014-10-15

AMP-activated protein kinase (AMPK) has been studied extensively and postulated to be a target for the treatment and/or prevention of metabolic disorders such as insulin resistance. Exercise training has been deemed a beneficial treatment for obesity and insulin resistance. Furthermore, exercise is a feasible method to combat high-fat diet (HFD)-induced alterations in insulin sensitivity. The purpose of this study was to determine whether AMPK-α2 activity is required to gain beneficial effects of exercise training with high-fat feeding. Wild-type (WT) and AMPK-α2 dominant-negative (DN) male mice were fed standard diet (SD), underwent voluntary wheel running (TR), fed HFD, or trained with HFD (TR + HFD). By week 6, TR, irrespective of genotype, decreased blood glucose and increased citrate synthase activity in both diet groups and decreased insulin levels in HFD groups. Hindlimb perfusions were performed, and, in WT mice with SD, TR increased insulin-mediated palmitate uptake (76.7%) and oxidation (>2-fold). These training-induced changes were not observed in the DN mice. With HFD, TR decreased palmitate oxidation (61-64%) in both WT and DN and increased palmitate uptake (112%) in the WT with no effects on palmitate uptake in the DN. With SD, TR increased ERK1/2 and JNK1/2 phosphorylation, regardless of genotype. With HFD, TR reduced JNK1/2 phosphorylation, regardless of genotype, carnitine palmitoyltransferase 1 expression in WT, and CD36 expression in both DN and WT. These data suggest that low AMPK-α2 signaling disrupts, in part, the exercise training-induced adaptations in insulin-stimulated metabolism in skeletal muscle following HFD. Copyright © 2014 the American Physiological Society.

Lower dipeptidyl peptidase-4 following exercise training plus weight loss is related to increased insulin sensitivity in adults with metabolic syndrome.

PubMed

Malin, Steven K; Huang, Hazel; Mulya, Anny; Kashyap, Sangeeta R; Kirwan, John P

2013-09-01

Dipeptidyl peptidase-4 (DPP-4) is a circulating glycoprotein that impairs insulin-stimulated glucose uptake and is linked to obesity and metabolic syndrome. However, the effect of exercise on plasma DPP-4 in adults with metabolic syndrome is unknown. Therefore, we determined the effect of exercise on DPP-4 and its role in explaining exercise-induced improvements in insulin sensitivity. Fourteen obese adults (67.9±1.2 years, BMI: 34.2±1.1kg/m(2)) with metabolic syndrome (ATP III criteria) underwent a 12-week supervised exercise intervention (60min/day for 5 days/week at ∼85% HRmax). Plasma DPP-4 was analyzed using an enzyme-linked immunosorbent assay. Insulin sensitivity was measured using the euglycemic-hyperinsulinemic clamp (40mU/m(2)/min) and estimated by HOMA-IR. Visceral fat (computerized tomography), 2-h glucose levels (75g oral glucose tolerance), and basal fat oxidation as well as aerobic fitness (indirect calorimetry) were also determined before and after exercise. The intervention reduced visceral fat, lowered blood pressure, glucose and lipids, and increased aerobic fitness (P<0.05). Exercise improved clamp-derived insulin sensitivity by 75% (P<0.001) and decreased HOMA-IR by 15% (P<0.05). Training decreased plasma DPP-4 by 10% (421.8±30.1 vs. 378.3±32.5ng/ml; P<0.04), and the decrease in DPP-4 was associated with clamp-derived insulin sensitivity (r=-0.59; P<0.04), HOMA-IR (r=0.59; P<0.04) and fat oxidation (r=-0.54; P<0.05). Increased fat oxidation also correlated with lower 2-h glucose levels (r=-0.64; P<0.02). Exercise training reduces plasma DPP-4, which may be linked to elevated insulin sensitivity and fat oxidation. Maintaining low plasma DPP-4 concentrations is a potential mechanism whereby exercise plus weight loss prevents/delays the onset of type 2 diabetes in adults with metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of prior exercise on the action of insulin-like growth factor I in skeletal muscle

NASA Technical Reports Server (NTRS)

Henriksen, E. J.; Louters, L. L.; Stump, C. S.; Tipton, C. M.

1992-01-01

Prior exercise increases insulin sensitivity for glucose and system A neutral amino acid transport activities in skeletal muscle. Insulin-like growth factor I (IGF-I) also activates these transport processes in resting muscle. It is not known, however, whether prior exercise increases IGF-I action in muscle. Therefore we determined the effect of a single exhausting bout of swim exercise on IGF-I-stimulated glucose transport activity [assessed by 2-deoxy-D-glucose (2-DG) uptake] and system A activity [assessed by alpha-(methylamino)isobutyric acid (MeAIB) uptake] in the isolated rat epitrochlearis muscle. When measured 3.5 h after exercise, the responses to a submaximal concentration (0.2 nM), but not a maximal concentration (13.3 nM), of insulin for activation of 2-DG uptake and MeAIB uptake were enhanced. In contrast, prior exercise increased markedly both the submaximal (5 nM) and maximal (20 nM) responses to IGF-I for activation of 2-DG uptake, whereas only the submaximal response to IGF-I (3 nM) for MeAIB uptake was enhanced after exercise. We conclude that 1) prior exercise significantly enhances the response to a submaximal concentration of IGF-I for activation of the glucose transport and system A neutral amino acid transport systems in skeletal muscle and 2) the enhanced maximal response for IGF-I action after exercise is restricted to the signaling pathway for activation of the glucose transport system.

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

NASA Astrophysics Data System (ADS)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults

PubMed Central

Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina

2017-01-01

Background Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. Methods One hundred seven frail, obese older adults were randomized into the control (N = 27), diet (N = 26), exercise (N = 26), and diet-exercise (N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). Results UcOC increased in the diet group (36 ± 11.6%) but not in the other groups (P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months (P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only (R2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆R2 = 0.140 and 0.107) and diet-exercise (∆R2 = 0.427 and 0.243) groups (P < 0.05 for all). Conclusions Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107. PMID:28951766

Effect of Weight Loss, Exercise, or Both on Undercarboxylated Osteocalcin and Insulin Secretion in Frail, Obese Older Adults.

PubMed

Colleluori, Georgia; Napoli, Nicola; Phadnis, Uma; Armamento-Villareal, Reina; Villareal, Dennis T

2017-01-01

Obesity exacerbates age-related decline in glucometabolic control. Undercarboxylated osteocalcin (UcOC) regulates pancreatic insulin secretion. The long-term effect of lifestyle interventions on UcOC and insulin secretion has not been investigated. One hundred seven frail, obese older adults were randomized into the control ( N = 27), diet ( N = 26), exercise ( N = 26), and diet-exercise ( N = 28) groups for 1 year. Main outcomes included changes in UcOC and disposition index (DI). UcOC increased in the diet group (36 ± 11.6%) but not in the other groups ( P < 0.05 between groups). Although similar increases in DI occurred in the diet-exercise and diet groups at 6 months, DI increased more in the diet-exercise group (92.4 ± 11.4%) than in the diet group (61.9 ± 15.3%) at 12 months ( P < 0.05). UcOC and body composition changes predicted DI variation in the diet group only ( R 2 = 0.712), while adipocytokines and physical function changes contributed to DI variation in both the diet (∆ R 2 = 0.140 and 0.107) and diet-exercise (∆ R 2 = 0.427 and 0.243) groups ( P < 0.05 for all). Diet, but not exercise or both, increases UcOC, whereas both diet and diet-exercise increase DI. UcOC accounts for DI variation only during active weight loss, while adipocytokines and physical function contribute to diet-exercise-induced DI variation, highlighting different mechanisms for lifestyle-induced improvements in insulin secretion. This trial was registered with ClinicalTrials.gov number NCT00146107.

Effects of resistance training on insulin sensitivity in overweight Latino adolescent males.

PubMed

Shaibi, Gabriel Q; Cruz, Martha L; Ball, Geoff D C; Weigensberg, Marc J; Salem, George J; Crespo, Noe C; Goran, Michael I

2006-07-01

Insulin resistance is thought to be a core defect in the pathophysiology of obesity-related comorbidities in children, such as type 2 diabetes. Exercise training is known to improve insulin resistance and reduce the risk of type 2 diabetes in adults. However, very little is known regarding the effects of exercise on insulin resistance in youth. Therefore, we examined the effects of a 16-wk resistance training exercise intervention on insulin sensitivity in youth at high risk for developing type 2 diabetes. Twenty-two overweight Latino adolescent males were randomly assigned to either a twice-per-week resistance training group (RT=11) or a nonexercising control group (C=11) for 16 wk. Strength was assessed by one-repetition maximum, body composition was quantified by dual-energy x-ray absorptiometry, and insulin sensitivity was determined by the frequently sampled intravenous glucose tolerance test with minimal modeling. Significant increases in upper- and lower-body strength were observed in the RT compared with the C group. The RT group significantly increased insulin sensitivity compared with the C group (P<0.05), and this increase remained significant after adjustment for changes in total fat mass and total lean tissue mass (P<0.05). Compared with baseline values, insulin sensitivity increased 45.1+/-7.3% in the RT group versus -0.9+/-12.9% in controls (P<0.01). A twice-per-week 16-wk resistance training program can significantly increase insulin sensitivity in overweight Latino adolescent males independent of changes in body composition.

Short-Term Exercise Training Does Not Stimulate Skeletal Muscle ATP Synthesis in Relatives of Humans With Type 2 Diabetes

PubMed Central

Kacerovsky-Bielesz, Gertrud; Chmelik, Marek; Ling, Charlotte; Pokan, Rochus; Szendroedi, Julia; Farukuoye, Michaela; Kacerovsky, Michaela; Schmid, Albrecht I.; Gruber, Stephan; Wolzt, Michael; Moser, Ewald; Pacini, Giovanni; Smekal, Gerhard; Groop, Leif; Roden, Michael

2009-01-01

OBJECTIVE We tested the hypothesis that short-term exercise training improves hereditary insulin resistance by stimulating ATP synthesis and investigated associations with gene polymorphisms. RESEARCH DESIGN AND METHODS We studied 24 nonobese first-degree relatives of type 2 diabetic patients and 12 control subjects at rest and 48 h after three bouts of exercise. In addition to measurements of oxygen uptake and insulin sensitivity (oral glucose tolerance test), ectopic lipids and mitochondrial ATP synthesis were assessed using1H and31P magnetic resonance spectroscopy, respectively. They were genotyped for polymorphisms in genes regulating mitochondrial function, PPARGC1A (rs8192678) and NDUFB6 (rs540467). RESULTS Relatives had slightly lower (P = 0.012) insulin sensitivity than control subjects. In control subjects, ATP synthase flux rose by 18% (P = 0.0001), being 23% higher (P = 0.002) than that in relatives after exercise training. Relatives responding to exercise training with increased ATP synthesis (+19%, P = 0.009) showed improved insulin sensitivity (P = 0.009) compared with those whose insulin sensitivity did not improve. A polymorphism in the NDUFB6 gene from respiratory chain complex I related to ATP synthesis (P = 0.02) and insulin sensitivity response to exercise training (P = 0.05). ATP synthase flux correlated with O2uptake and insulin sensitivity. CONCLUSIONS The ability of short-term exercise to stimulate ATP production distinguished individuals with improved insulin sensitivity from those whose insulin sensitivity did not improve. In addition, the NDUFB6 gene polymorphism appeared to modulate this adaptation. This finding suggests that genes involved in mitochondrial function contribute to the response of ATP synthesis to exercise training. PMID:19265027

Physical activity into the meal glucose-insulin model of type 1 diabetes: in silico studies.

PubMed

Man, Chiara Dalla; Breton, Marc D; Cobelli, Claudio

2009-01-01

A simulation model of a glucose-insulin system accounting for physical activity is needed to reliably simulate normal life conditions, thus accelerating the development of an artificial pancreas. In fact, exercise causes a transient increase of insulin action and may lead to hypoglycemia. However, physical activity is difficult to model. In the past, it was described indirectly as a rise in insulin. Recently, a new parsimonious model of exercise effect on glucose homeostasis has been proposed that links the change in insulin action and glucose effectiveness to heart rate (HR). The aim of this study was to plug this exercise model into our recently proposed large-scale simulation model of glucose metabolism in type 1 diabetes to better describe normal life conditions. The exercise model describes changes in glucose-insulin dynamics in two phases: a rapid on-and-off change in insulin-independent glucose clearance and a rapid-on/slow-off change in insulin sensitivity. Three candidate models of glucose effectiveness and insulin sensitivity as a function of HR have been considered, both during exercise and recovery after exercise. By incorporating these three models into the type 1 diabetes model, we simulated different levels (from mild to moderate) and duration of exercise (15 and 30 minutes), both in steady-state (e.g., during euglycemic-hyperinsulinemic clamp) and in nonsteady state (e.g., after a meal) conditions. One candidate exercise model was selected as the most reliable. A type 1 diabetes model also describing physical activity is proposed. The model represents a step forward to accurately describe glucose homeostasis in normal life conditions; however, further studies are needed to validate it against data. © Diabetes Technology Society

Changes in body composition, blood lipid profile, and growth factor hormone in a patient with Prader-willi syndrome during 24 weeks of complex exercise: a single case study.

PubMed

Joung, Hee Joung; Lim, In Soo

2018-03-30

Prader-Willi syndrome (PWS) is a genetic disorder characterized by excessive appetite with progressive obesity and growth hormone (GH) deficiency. Excessive eating causes progressive obesity with increased risk of morbidities and mortality. Although GH treatment has beneficial effects on patients with PWS, adverse events have occurred during GH treatment. Exercise potentially has a positive effect on obesity management. The purpose of this research was to examine the effects of 24-week complex exercise program on changes in body composition, blood lipid profiles, and growth factor hormone levels in a patient with PWS. The case study participant was a 23-year-old man with PWS who also had type II diabetes mellitus because of extreme obesity. Complex exercises, including strength and aerobic exercises, were conducted 5 times one week for 60 minutes per session, over 24 weeks. Blood sampling was conducted five times: before and at 8, 16, 20, and 24 weeks after commencement of the exercise program. Weight, fat mass, triglycerides/high-density lipoprotein (TG/HDL) ratio, mean blood glucose, and GH decreased after training. Blood insulin and insulin-like growth factor (IGF-1) levels increased after training. At 15 and 20 weeks, insulin injection was discontinued. Insulin levels increased and average blood glucose decreased to normal levels; IGF-1 increased continuously during the 24-week exercise program. Conclusion] Twenty-four weeks of complex exercises had a positive effect on obesity and diabetes in the patient with PWS. Therefore, long-period complex exercises might be an effective intervention for improvement of metabolic factors in PWS patients. ©2018 The Korean Society for Exercise Nutrition.

Effects of food pattern change and physical exercise on cafeteria diet-induced obesity in female rats.

PubMed

Goularte, Jéferson F; Ferreira, Maria B C; Sanvitto, Gilberto L

2012-10-28

Obesity affects a large number of people around the world and appears to be the result of changes in food intake, eating habits and physical activity levels. Changes in dietary patterns and physical exercise are therefore strongly recommended to treat obesity and its complications. The present study tested the hypothesis that obesity and metabolic changes produced by a cafeteria diet can be prevented with dietary changes and/or physical exercise. A total of fifty-six female Wistar rats underwent one of five treatments: chow diet; cafeteria diet; cafeteria diet followed by a chow diet; cafeteria diet plus exercise; cafeteria diet followed by a chow diet plus exercise. The duration of the experiment was 34 weeks. The cafeteria diet resulted in higher energy intake, weight gain, increased visceral adipose tissue and liver weight, and insulin resistance. The cafeteria diet followed by the chow diet resulted in energy intake, body weight, visceral adipose tissue and liver weight and insulin sensitivity equal to that of the controls. Exercise increased total energy intake at week 34, but produced no changes in the animals' body weight or adipose tissue mass. However, insulin sensitivity in animals subjected to exercise and the diet was similar to that of the controls. The present study found that exposure to palatable food caused obesity and insulin resistance and a diet change was sufficient to prevent cafeteria diet-induced obesity and to maintain insulin sensitivity at normal levels. In addition, exercise resulted in normal insulin sensitivity in obese rats. These results may help to develop new approaches for the treatment of obesity and type 2 diabetes mellitus.

Morphological assessment of pancreatic islet hormone content following aerobic exercise training in rats with poorly controlled Type 1 diabetes mellitus.

PubMed

McDonald, Matthew W; Murray, Michael R; Hall, Katharine E; Noble, Earl G; Melling, C W James

2014-01-01

Regular exercise has been shown to improve many complications of Type 1 diabetes mellitus (T1DM) including enhanced glucose tolerance and increased cardiac function. While exercise training has been shown to increase insulin content in pancreatic islets of rats with T1DM, experimental models were severely hyperglycemic and not undergoing insulin treatment. Further, research to date has yet to determine how exercise training alters glucagon content in pancreatic islets. The purpose of the present investigation was to determine the impact of a 10-week aerobic training program on pancreatic islet composition in insulin-treated rats with T1DM. Second, it was determined whether the acute, exercise-mediated reduction in blood glucose experienced in rats with T1DM would become larger in magnitude following aerobic exercise training. Diabetes was induced in male Sprague-Dawley rats by multiple low dose injections of streptozotocin (20mg/kg i.p.) and moderate intensity aerobic exercise training was performed on a motorized treadmill for one hour per day for a total of 10 weeks. Rats with T1DM demonstrated significantly less islet insulin, and significantly more islet glucagon hormone content compared with non-T1DM rats, which did not significantly change following aerobic training. The reduction in blood glucose in response to a single exercise bout was similar across 10 weeks of training. Results also support the view that different subpopulations of islets exist, as small islets (<50 μm diameter) had significantly more insulin and glucagon in rats with and without T1DM.

The role of resistance and aerobic exercise training on insulin sensitivity measures in STZ-induced Type 1 diabetic rodents.

PubMed

Hall, Katharine E; McDonald, Matthew W; Grisé, Kenneth N; Campos, Oscar A; Noble, Earl G; Melling, C W James

2013-10-01

Individuals with Type 1 Diabetes Mellitus (T1DM) can develop insulin resistance. Regular exercise may improve insulin resistance partially through increased expression of skeletal muscle GLUT4 content. To examine if different exercise training modalities can alter glucose tolerance through changes in skeletal muscle GLUT4 content in T1DM rats. Fifty rats were divided into 5 groups; control, diabetic control, diabetic resistance exercised, and diabetic high and low intensity treadmill exercised. Diabetes was induced using multiple low dose Streptozotocin (20 mg/kg/day) injections and blood glucose concentrations were maintained moderately hyperglycemic through subcutaneous insulin pellets. Resistance trained rats climbed a ladder with incremental loads, while treadmill trained rats ran on a treadmill at 27 or 15 m/min, respectively, all for 6 weeks. At weeks 3 and 6, area under the curve measurements following an intravenous glucose tolerance test (AUC-IVGTT) in all diabetic groups were higher than control rats (p<0.05). At 6 weeks, all exercise groups had significantly lower AUC-IVGTT values than diabetic control animals (p<0.05). Treadmill trained rats had the lowest insulin dose requirement of the T1DM rats and the greatest reduction in insulin dosage was evident in high intensity treadmill exercise. Concomitant with improvements in glucose handling improvements, tissue-specific elevations in GLUT4 content were demonstrated in both red and white portions of vastus lateralis and gastrocnemius muscles, suggesting that glucose handling capacity was altered in the skeletal muscle of exercised T1DM rats. These results suggest that, while all exercise modalities can improve glucose tolerance, each mode leads to differential improvements in insulin requirements and protein content alterations. Copyright © 2013 Elsevier Inc. All rights reserved.

Insulin Responsiveness in Metabolic Syndrome after Eight Weeks of Cycle Training

PubMed Central

Stuart, Charles A.; South, Mark A.; Lee, Michelle L.; McCurry, Melanie P.; Howell, Mary E. A.; Ramsey, Michael W.; Stone, Michael H.

2013-01-01

Introduction Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Methods Eighteen non-diabetic, sedentary subjects, eleven with the metabolic syndrome, participated in eight weeks of increasing intensity stationary cycle training. Results Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (VO2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. Activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of 2x fibers decreased with a concomitant increase in 2a mixed fibers in the control subjects, but in metabolic syndrome, 2x fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups and GLUT4 expression increased in the metabolic syndrome subjects. Excess phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. Conclusion In the absence of weight loss, cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis, and increased expression of insulin receptors and GLUT4 in muscle, but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337 and this is not ameliorated by eight weeks of endurance exercise training. PMID:23669880

Insulin responsiveness in metabolic syndrome after eight weeks of cycle training.

PubMed

Stuart, Charles A; South, Mark A; Lee, Michelle L; McCurry, Melanie P; Howell, Mary E A; Ramsey, Michael W; Stone, Michael H

2013-11-01

Insulin resistance in obesity is decreased after successful diet and exercise. Aerobic exercise training alone was evaluated as an intervention in subjects with the metabolic syndrome. Eighteen nondiabetic, sedentary subjects, 11 with the metabolic syndrome, participated in 8 wk of increasing intensity stationary cycle training. Cycle training without weight loss did not change insulin resistance in metabolic syndrome subjects or sedentary control subjects. Maximal oxygen consumption (V·O 2max), activated muscle AMP-dependent kinase, and muscle mitochondrial marker ATP synthase all increased. Strength, lean body mass, and fat mass did not change. The activated mammalian target of rapamycin was not different after training. Training induced a shift in muscle fiber composition in both groups but in opposite directions. The proportion of type 2× fibers decreased with a concomitant increase in type 2a mixed fibers in the control subjects, but in metabolic syndrome, type 2× fiber proportion increased and type 1 fibers decreased. Muscle fiber diameters increased in all three fiber types in metabolic syndrome subjects. Muscle insulin receptor expression increased in both groups, and GLUT4 expression increased in the metabolic syndrome subjects. The excess phosphorylation of insulin receptor substrate 1 (IRS-1) at Ser337 in metabolic syndrome muscle tended to increase further after training in spite of a decrease in total IRS-1. In the absence of weight loss, the cycle training of metabolic syndrome subjects resulted in enhanced mitochondrial biogenesis and increased the expression of insulin receptors and GLUT4 in muscle but did not decrease the insulin resistance. The failure for the insulin signal to proceed past IRS-1 tyrosine phosphorylation may be related to excess serine phosphorylation at IRS-1 Ser337, and this is not ameliorated by 8 wk of endurance exercise training.

Effects of Exercise on AMPK Signaling and Downstream Components to PI3K in Rat with Type 2 Diabetes

PubMed Central

Cao, Shicheng; Li, Bowen; Yi, Xuejie; Chang, Bo; Zhu, Beibei; Lian, Zhenzhen; Zhang, Zhaoran; Zhao, Gang; Liu, Huili; Zhang, He

2012-01-01

Exercise can increase skeletal muscle sensitivity to insulin, improve insulin resistance and regulate glucose homeostasis in rat models of type 2 diabetes. However, the potential mechanism remains poorly understood. In this study, we established a male Sprague–Dawley rat model of type 2 diabetes, with insulin resistance and β cell dysfunction, which was induced by a high-fat diet and low-dose streptozotocin to replicate the pathogenesis and metabolic characteristics of type 2 diabetes in humans. We also investigated the possible mechanism by which chronic and acute exercise improves metabolism, and the phosphorylation and expression of components of AMP-activated protein kinase (AMPK) and downstream components of phosphatidylinositol 3-kinase (PI3K) signaling pathways in the soleus. As a result, blood glucose, triglyceride, total cholesterol, and free fatty acid were significantly increased, whereas insulin level progressively declined in diabetic rats. Interestingly, chronic and acute exercise reduced blood glucose, increased phosphorylation and expression of AMPKα1/2 and the isoforms AMPKα1 and AMPKα2, and decreased phosphorylation and expression of AMPK substrate, acetyl CoA carboxylase (ACC). Chronic exercise upregulated phosphorylation and expression of AMPK upstream kinase, LKB1. But acute exercise only increased LKB1 expression. In particular, exercise reversed the changes in protein kinase C (PKC)ζ/λ phosphorylation, and PKCζ phosphorylation and expression. Additionally, exercise also increased protein kinase B (PKB)/Akt1, Akt2 and GLUT4 expression, but AS160 protein expression was unchanged. Chronic exercise elevated Akt (Thr308) and (Ser473) and AS160 phosphorylation. Finally, we found that exercise increased peroxisome proliferator-activated receptor-γ coactivator 1 (PGC1) mRNA expression in the soleus of diabetic rats. These results indicate that both chronic and acute exercise influence the phosphorylation and expression of components of the AMPK and downstream to PIK3 (aPKC, Akt), and improve GLUT4 trafficking in skeletal muscle. These data help explain the mechanism how exercise regulates glucose homeostasis in diabetic rats. PMID:23272147

Does a single bout of resistance or aerobic exercise after insulin dose reduction modulate glycaemic control in type 2 diabetes? A randomised cross-over trial.

PubMed

Gordon, Brett A; Bird, Stephen R; MacIsaac, Richard J; Benson, Amanda C

2016-10-01

Regular exercise is advocated for individuals with type 2 diabetes, without fully understanding the acute (0-72h post-exercise) glycaemic response. This study assessed post-exercise glycaemic profiles of non-exercising individuals with insulin treated type 2 diabetes, following resistance and aerobic exercise. Randomised cross-over trial. Fourteen individuals with insulin treated type 2 diabetes (9 males, 5 females) aged 58.1±7.1 years (HbA1c: 8.0±0.6%) were allocated to single sessions of resistance (six whole-body exercises, three sets, 8-10 repetitions, 70% 1RM) and aerobic (30min cycling, 60% VO2peak) exercise, 7-days apart, with the day prior to the first exercise day of each intervention being the control condition. Immediately prior to exercise, insulin dosage was halved and breakfast consumed. Continuous glucose monitoring was undertaken to determine area under the curve and glucose excursions. Blood glucose initially increased (0-2h) following both resistance and aerobic exercise (p<0.001), peaking at 12.3±3.4mmolL(-1) and 12.3±3.3mmolL(-1), respectively. Area under the glucose curve was not statistically different over any of the 24h periods (p=0.12), or different in response to resistance (222±41mmolL(-1)24h(-1)) or aerobic (211±40 mmolL(-1)24h(-1)) exercise (p=0.56). Incidence of hyperglycaemia did not differ between exercise modes (p=0.68). Hypoglycaemic events were identified in three and four participants following resistance and aerobic exercise respectively: these did not require treatment. Glycaemic response is not different between exercise modes, although 50% insulin dose reduction prior to exercise impairs the expected improvement. A common clinical recommendation of 50% insulin dose reduction does not appear to cause adverse glycaemic events. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Impaired muscle AMPK activation in the metabolic syndrome may attenuate improved insulin action after exercise training.

PubMed

Layne, Andrew S; Nasrallah, Sami; South, Mark A; Howell, Mary E A; McCurry, Melanie P; Ramsey, Michael W; Stone, Michael H; Stuart, Charles A

2011-06-01

Strength training induces muscle remodeling and may improve insulin responsiveness. This study will quantify the impact of resistance training on insulin sensitivity in subjects with the metabolic syndrome and correlate this with activation of intramuscular pathways mediating mitochondrial biogenesis and muscle fiber hypertrophy. Ten subjects with the metabolic syndrome (MS) and nine sedentary controls underwent 8 wk of supervised resistance exercise training with pre- and posttraining anthropometric and muscle biochemical assessments. Resistance exercise training took place in a sports laboratory on a college campus. Pre- and posttraining insulin responsiveness was quantified using a euglycemic clamp. Changes in expression of muscle 5-AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathways were quantified using immunoblots. Strength and stamina increased in both groups. Insulin sensitivity increased in controls (steady-state glucose infusion rate = 7.0 ± 2.0 mg/kg · min pretraining training vs. 8.7 ± 3.1 mg/kg · min posttraining; P < 0.01) but did not improve in MS subjects (3.3 ± 1.3 pre vs. 3.1 ± 1.0 post). Muscle glucose transporter 4 increased 67% in controls and 36% in the MS subjects. Control subjects increased muscle phospho-AMPK (43%), peroxisome proliferator-activated receptor γ coactivator 1α (57%), and ATP synthase (60%), more than MS subjects (8, 28, and 21%, respectively). In contrast, muscle phospho-mTOR increased most in the MS group (57 vs. 32%). Failure of resistance training to improve insulin responsiveness in MS subjects was coincident with diminished phosphorylation of muscle AMPK, but increased phosphorylation of mTOR, suggesting activation of the mTOR pathway could be involved in inhibition of exercise training-related increases in AMPK and its activation and downstream events.

Exercise as an intervention to improve metabolic outcomes after intrauterine growth restriction.

PubMed

Gatford, Kathryn L; Kaur, Gunveen; Falcão-Tebas, Filippe; Wadley, Glenn D; Wlodek, Mary E; Laker, Rhianna C; Ebeling, Peter R; McConell, Glenn K

2014-05-01

Individuals born after intrauterine growth restriction (IUGR) are at an increased risk of developing diabetes in their adult life. IUGR impairs β-cell function and reduces β-cell mass, thereby diminishing insulin secretion. IUGR also induces insulin resistance, with impaired insulin signaling in muscle in adult humans who were small for gestational age (SGA) and in rodent models of IUGR. There is epidemiological evidence in humans that exercise in adults can reduce the risk of metabolic disease following IUGR. However, it is not clear whether adult IUGR individuals benefit to the same extent from exercise as do normal-birth-weight individuals, as our rat studies suggest less of a benefit in those born IUGR. Importantly, however, there is some evidence from studies in rats that exercise in early life might be able to reverse or reprogram the long-term metabolic effects of IUGR. Studies are needed to address gaps in current knowledge, including determining the mechanisms involved in the reprogramming effects of early exercise in rats, whether exercise early in life or in adulthood has similar beneficial metabolic effects in larger animal models in which insulin resistance develops after IUGR. Human studies are also needed to determine whether exercise training improves insulin secretion and insulin sensitivity to the same extent in IUGR adults as in control populations. Such investigations will have implications for customizing the recommended level and timing of exercise to improve metabolic health after IUGR.

Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake.

PubMed

Cartee, Gregory D; Arias, Edward B; Yu, Carmen S; Pataky, Mark W

2016-11-01

One exercise session can induce subsequently elevated insulin sensitivity that is largely attributable to greater insulin-stimulated glucose uptake by skeletal muscle. Because skeletal muscle is a heterogeneous tissue comprised of diverse fiber types, our primary aim was to determine exercise effects on insulin-independent and insulin-dependent glucose uptake by single fibers of different fiber types. We hypothesized that each fiber type featuring elevated insulin-independent glucose uptake immediately postexercise (IPEX) would be characterized by increased insulin-dependent glucose uptake at 3.5 h postexercise (3.5hPEX). Rat epitrochlearis muscles were isolated and incubated with 2-[ 3 H]deoxyglucose. Muscles from IPEX and sedentary (SED) controls were incubated without insulin. Muscles from 3.5hPEX and SED controls were incubated ± insulin. Glucose uptake (2-[ 3 H]deoxyglucose accumulation) and fiber type (myosin heavy chain isoform expression) were determined for single fibers dissected from the muscles. Major new findings included the following: 1) insulin-independent glucose uptake was increased IPEX in single fibers of each fiber type (types I, IIA, IIB, IIBX, and IIX), 2) glucose uptake values from insulin-stimulated type I and IIA fibers exceeded the values for the other fiber types, 3) insulin-stimulated glucose uptake for type IIX exceeded IIB fibers, and 4) the 3.5hPEX group vs. SED had greater insulin-stimulated glucose uptake in type I, IIA, IIB, and IIBX but not type IIX fibers. Insulin-dependent glucose uptake was increased at 3.5hPEX in each fiber type except for IIX fibers, although insulin-independent glucose uptake was increased IPEX in all fiber types (including type IIX). Single fiber analysis enabled the discovery of this fiber type-related difference for postexercise, insulin-stimulated glucose uptake. Copyright © 2016 the American Physiological Society.

Influence of a mini-trampoline rebound exercise program on insulin resistance, lipid profile and central obesity in individuals with type 2 diabetes.

PubMed

Nuhu, Jibril M; Maharaj, Sonill S

2018-04-01

Exercises are important as an adjuvant for managing diabetes but due to fatigue and time constraints, individuals with diabetes may not engage in them. Jumping on a mini-trampoline referred to as rebound exercise is an aerobic activity used for exercise training benefits but only little research is available on its effects in diabetes. The purpose of this study was to determine the effect of mini-trampoline rebound exercise on insulin resistance, lipid profile and central obesity in type 2 diabetics. Sixty non-insulin dependent type 2 diabetics (median age: 39.0 years, median body mass index: 25.2 kg/m2) recruited using convenience sampling were randomized to a rebound exercise group (N.=30) or a control group (N.=30). The control group read health magazines or watched television while the rebound exercise group jumped on a mini-trampoline at moderate intensity for 30 minutes three times per week for 12 weeks. Postrebound exercise, significant improvements in insulin resistance, lipid profile and waist circumference were noted when compared to the control (P<0.05). The values for high density lipoprotein cholesterol increased with low density lipoprotein cholesterol, triglycerides, insulin resistance decreasing significantly from baseline (P<0.05). The findings suggest that mini-trampoline rebound exercise is beneficial for individuals with type 2 diabetes and can serve as a useful exercise approach in the management of cardiovascular risk in diabetes.

Effect of resistance exercise under conditions of reduced blood insulin on AMPKα Ser485/491 inhibitory phosphorylation and AMPK pathway activation.

PubMed

Kido, Kohei; Yokokawa, Takumi; Ato, Satoru; Sato, Koji; Fujita, Satoshi

2017-08-01

Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK α-subunit. Thus lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation. Based on previous findings, we hypothesized that the acute resistance exercise-induced AMPK pathway activation would be augmented by disruptions in insulin secretion through a decrease in AMPKα Ser485/491 inhibitory phosphorylation. To test the hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting β-cells. Three days postinjection, the right gastrocnemius muscle from STZ and control rats was subjected to resistance exercise by percutaneous electrical stimulation. Animals were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream pathways in the muscle tissue was analyzed by Western blotting and real-time PCR. Notably, STZ rats showed a significant decrease in basal Akt and AMPKα Ser485/491 phosphorylation, but substantial exercise-induced increases in both AMPKα Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were observed. Although no significant impact on resistance exercise-induced Akt pathway activation or glucose uptake was found, resistance exercise-induced peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 α (PGC-1α) gene expression was augmented by STZ treatment. Collectively, these data suggest that circulating insulin levels may regulate acute resistance exercise-induced AMPK pathway activation and AMPK-dependent gene expression relating to basal AMPKα Ser485/491 phosphorylation. Copyright © 2017 the American Physiological Society.

Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

PubMed

Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

2017-06-15

Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Is carbohydrate needed to further stimulate muscle protein synthesis/hypertrophy following resistance exercise?

PubMed Central

2013-01-01

It is now well established that protein supplementation after resistance exercise promotes increased muscle protein synthesis, which ultimately results in greater net muscle accretion, relative to exercise alone or exercise with supplementary carbohydrate ingestion. However, it is not known whether combining carbohydrate with protein produces a greater anabolic response than protein alone. Recent recommendations have been made that the composition of the ideal supplement post-exercise would be a combination of a protein source with a high glycemic index carbohydrate. This is based on the hypothesis that insulin promotes protein synthesis, thus maximising insulin secretion will maximally potentiate this action. However, it is still controversial as to whether raising insulin level, within the physiological range, has any effect to further stimulate muscle protein synthesis. The present commentary will review the evidence underpinning the recommendation to consume carbohydrates in addition to a protein supplementation after resistance exercise for the specific purpose of increasing muscle mass. The paucity of data will be discussed, thus our conclusions are that further studies are necessary prior to any conclusions that enable evidence-based recommendations to be made. PMID:24066806

Role of Exercise and Nutrition in the Prevention of Sarcopenia.

PubMed

Makanae, Yuhei; Fujita, Satoshi

2015-01-01

The age-associated loss of skeletal muscle mass and strength (sarcopenia) has been shown to increase the risk of injury due to falls and incidence of metabolic complications including insulin resistance and diabetes, which subsequently becomes a significant factor to disability among the elderly population. Nutrient intake is the most important anabolic stimulus for skeletal muscle. Specifically, the amino acid leucine and meal-induced insulin both independently stimulate muscle protein synthesis. However, age-specific changes in muscle anabolic responses to leucine become apparent when sub-maximal amounts of amino acids are administered in older subjects. Furthermore, insulin resistance of muscle protein metabolism with aging has been demonstrated in healthy non-diabetic older subjects. Resistance exercise is another anabolic stimulus which increases myofibrillar muscle protein synthesis in both young and older individuals. The increased muscle anabolism is apparent within 2-3 h after a single bout of heavy resistance exercise and remains elevated up to 2 d following the exercise. The mTOR signaling pathway in skeletal muscle is associated with an increased rate of muscle protein synthesis during the early recovery phase following a bout of resistance exercise. Finally, recent evidence on the cumulative effect of resistance exercise in combination with nutritional supplement on muscle protein metabolism will be discussed to propose a possible preventative measure against sarcopenia.

Effects of insulin and exercise training on FGF21, its receptors and target genes in obesity and type 2 diabetes.

PubMed

Kruse, Rikke; Vienberg, Sara G; Vind, Birgitte F; Andersen, Birgitte; Højlund, Kurt

2017-10-01

Pharmacological doses of FGF21 improve glucose tolerance, lipid metabolism and energy expenditure in rodents. Induced expression and secretion of FGF21 from muscle may increase browning of white adipose tissue (WAT) in a myokine-like manner. Recent studies have reported that insulin and exercise increase FGF21 in plasma. Obesity and type 2 diabetes are potentially FGF21-resistant states, but to what extent FGF21 responses to insulin and exercise training are preserved, and whether FGF21, its receptors and target genes are altered, remains to be established. The effects of insulin during euglycaemic-hyperinsulinaemic clamps and 10 week endurance training on serum FGF21 were examined in individuals with type 2 diabetes and in glucose tolerant overweight/obese and lean individuals. Gene expression of FGF21, its receptors and target genes in muscle and WAT biopsies was evaluated by quantitative real-time PCR (qPCR). Insulin increased serum and muscle FGF21 independent of overweight/obesity or type 2 diabetes, and there were no effects associated with exercise training. The insulin-induced increases in serum FGF21 and muscle FGF21 expression correlated tightly (p < 0.001). In WAT, overweight/obesity with and without type 2 diabetes led to reduced expression of KLB, but increased FGFR1c expression. However, the expression of most FGF21 target genes was unaltered except for reduced CIDEA expression in individuals with type 2 diabetes. Insulin-induced expression of muscle FGF21 correlates strongly with a rise in serum FGF21, and this response appears intact in overweight/obesity and type 2 diabetes. FGF21 resistance may involve reduced KLB expression in WAT. However, increased FGFR1c expression or other mechanisms seem to ensure adequate expression of most FGF21 target genes in WAT.

Impairments in Site-Specific AS160 Phosphorylation and Effects of Exercise Training

PubMed Central

Consitt, Leslie A.; Van Meter, Jessica; Newton, Christopher A.; Collier, David N.; Dar, Moahad S.; Wojtaszewski, Jørgen F.P.; Treebak, Jonas T.; Tanner, Charles J.; Houmard, Joseph A.

2013-01-01

The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18–84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation. A euglycemic-hyperinsulinemic clamp and skeletal muscle biopsies were performed in 73 individuals encompassing a wide age range (18–84 years of age), and insulin-stimulated AS160 phosphorylation was determined. Decrements in whole-body insulin action were associated with impairments in insulin-induced phosphorylation of skeletal muscle AS160 on sites Ser-588, Thr-642, Ser-666, and phospho-Akt substrate, but not Ser-318 or Ser-751. Twelve weeks of endurance- or strength-oriented exercise training increased whole-body insulin action and reversed impairments in AS160 phosphorylation evident in insulin-resistant aged individuals. These findings suggest that a dampening of insulin-induced phosphorylation of AS160 on specific sites in skeletal muscle contributes to the insulin resistance evident in a sedentary aging population and that exercise training is an effective intervention for treating these impairments. PMID:23801578

The impact of exercise training compared to caloric restriction on hepatic and peripheral insulin resistance in obesity.

PubMed

Coker, Robert H; Williams, Rick H; Yeo, Sophie E; Kortebein, Patrick M; Bodenner, Don L; Kern, Philip A; Evans, William J

2009-11-01

It has been difficult to distinguish the independent effects of caloric restriction versus exercise training on insulin resistance. Utilizing metabolic feeding and supervised exercise training, we examined the influence of caloric restriction vs. exercise training with and without weight loss on hepatic and peripheral insulin resistance. Thirty-four obese, older subjects were randomized to: caloric restriction with weight loss (CR), exercise training with weight loss (EWL), exercise training without weight loss (EX), or controls. Based on an equivalent caloric deficit in EWL and CR, we induced matched weight loss. Subjects in the EX group received caloric compensation. Combined with [6,6(2)H(2)]glucose, an octreotide, glucagon, multistage insulin infusion was performed to determine suppression of glucose production (SGP) and insulin-stimulated glucose disposal (ISGD). Computed tomography scans were performed to assess changes in fat distribution. Body weight decreased similarly in EWL and CR, and did not change in EX and controls. The reduction in visceral fat was significantly greater in EWL (-71 +/- 15 cm(2)) compared to CR and EX. The increase in SGP was also almost 3-fold greater (27 +/- 2%) in EWL. EWL and CR promoted similar improvements in ISGD [+2.5 +/- 0.4 and 2.4 +/- 0.9 mg x kg fat-free mass (FFM)(-1) x min(-1)], respectively. EWL promoted the most significant reduction in visceral fat and the greatest improvement in SGP. Equivalent increases in ISGD were noted in EWL and CR, whereas EX provided a modest improvement. Based on our results, EWL promoted the optimal intervention-based changes in body fat distribution and systemic insulin resistance.

Effects of aerobic exercise on ectopic lipids in patients with growth hormone deficiency before and after growth hormone replacement therapy.

PubMed

Christ, Emanuel R; Egger, Andrea; Allemann, Sabin; Buehler, Tania; Kreis, Roland; Boesch, Chris

2016-01-21

Growth hormone replacement therapy (GHRT) increases exercise capacity and insulin resistance while it decreases fat mass in growth hormone-deficient patients (GHD). Ectopic lipids (intramyocellular (IMCL) and intrahepatocellular lipids (IHCL) are related to insulin resistance. The effect of GHRT on ectopic lipids is unknown. It is hypothesized that exercise-induced utilization of ectopic lipids is significantly decreased in GHD patients and normalized by GHRT. GHD (4 females, 6 males) and age/gender/waist-matched control subjects (CS) were studied. VO2max was assessed on a treadmill and insulin sensitivity determined by a two-step hyperinsulinaemic-euglycaemic clamp. Visceral (VAT) and subcutaneous (SAT) fat were quantified by MR-imaging. IHCL and IMCL were measured before and after a 2 h exercise at 50-60% of VO2max using MR-spectroscopy (∆IMCL, ∆IHCL). Identical investigations were performed after 6 months of GHRT. VO2max was similar in GHD and CS and significantly increased after GHRT; GHRT significantly decreased SAT and VAT. 2 h-exercise resulted in a decrease in IMCL (significant in CS and GHRT) and a significant increase in IHCL in CS and GHD pre and post GHRT. GHRT didn't significantly impact on ∆IMCL and ∆IHCL. We conclude that aerobic exercise affects ectopic lipids in patients and controls. GHRT increases exercise capacity without influencing ectopic lipids.

Improved Insulin Sensitivity After Exercise Training is Linked to Reduced Plasma C14:0 Ceramide in Obesity and Type 2 Diabetes

PubMed Central

Kasumov, Takhar; Solomon, Thomas P.J.; Hwang, Calvin; Huang, Hazel; Haus, Jacob M.; Zhang, Renliang; Kirwan, John P.

2015-01-01

Objective To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Methods Twenty-four adults with obesity and normal glucose tolerance (NGT, n=14), or diabetes (n=10) were studied before and after a 12-week supervised exercise-training program (5 d/wk, 1 hr/d, 80–85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m2/min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0 and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Results Plasma ceramides were similar for the obese NGT and subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity, and increased peripheral insulin sensitivity in both groups (P<0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P<0.05). Decreases in total (r=-0.51, P=0.02) and C14:0 (r=-0.56, P=0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Conclusion Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. PMID:25966363

Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes.

PubMed

Kasumov, Takhar; Solomon, Thomas P J; Hwang, Calvin; Huang, Hazel; Haus, Jacob M; Zhang, Renliang; Kirwan, John P

2015-07-01

To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Twenty-four adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n = 10) were studied before and after a 12-week supervised exercise-training program (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups (P < 0.05). In addition, plasma C14:0, C16:0, C18:1, and C24:0 ceramide levels were reduced in all subjects following the intervention (P < 0.05). Decreases in total (r = -0.51, P = 0.02) and C14:0 (r = -0.56, P = 0.009) ceramide were negatively correlated with the increase in insulin sensitivity. Ceramides are linked to exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. © 2015 The Obesity Society.

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing

PubMed Central

Strauss, Juliette A.; Shepherd, Sam O.; Keske, Michelle A.; Cocks, Matthew

2015-01-01

Abstract This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF‐A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age‐related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF‐B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres. PMID:25627798

[Role of physical activity in the therapy and prevention of Type II diabetes mellitus].

PubMed

Lehmann, R; Spinas, G A

1996-12-01

Increased physical activity should be part of the treatment for non insulin-dependent diabetic patients. Increased physical activity delays the onset of non insulin-dependent diabetes mellitus (NIDDM) or even prevents the disease in about 50% of susceptible individuals (positive family history of NIDDM, body-mass index > 25, hypertension or gestational diabetes). Regular exercise has been shown to lower plasma triglyceride and to increase high-density lipoprotein cholesterol levels. Exercise has also beneficial effects on hypertension, body composition and fat distribution. Improved glucose tolerance has been achieved in type II diabetic patients in as little as one week with an exercise program. The beneficial effect of regular exercise on glucose control appears to reflect the cumulative effect of transient improvement in glucose tolerance following each individual bout of exercise. Increased insulin sensitivity is lost after as little as three days of inactivity. Most studies suggest that the maximum benefit from exercise is most likely to occur in patients with mild diabetes in whom insulin resistance and hyperinsulinemia are present (i.e. patients with fasting blood glucose of < 11 mM). The recommended frequency and duration of exercise is three times per week or every other day and, as adjunct for weight reduction, five to seven times per week for 30 to 45 min. at an intensity of 50 to 70% VO2max (or 60 to 80% of maximal the heart rate). Because of the high incidence of ischemic heart disease in type II diabetic patients, patients older than 35 years of age should undergo a graded exercise stress electrocardiogram. Attention should be paid to foot-care and the use of appropriate footwear and diabetic late complications, such as autonomic and peripheral neuropathy. Older obese NIDDM patients can achieve significant metabolic benefits from low-intensity programs, such as daily walking, which can be easily incorporated into daily living. Taking the necessary precautions, most patients with diabetes can take part in a monitored exercise program safely.

Differential Impact of Acute High-Intensity Exercise on Circulating Endothelial Microparticles and Insulin Resistance between Overweight/Obese Males and Females

PubMed Central

Durrer, Cody; Robinson, Emily; Wan, Zhongxiao; Martinez, Nic; Hummel, Michelle L.; Jenkins, Nathan T.; Kilpatrick, Marcus W.; Little, Jonathan P.

2015-01-01

Background An acute bout of exercise can improve endothelial function and insulin sensitivity when measured on the day following exercise. Our aim was to compare acute high-intensity continuous exercise (HICE) to high-intensity interval exercise (HIIE) on circulating endothelial microparticles (EMPs) and insulin sensitivity in overweight/obese men and women. Methods Inactive males (BMI = 30 ± 3, 25 ± 6 yr, n = 6) and females (BMI = 28 ± 2, 21 ± 3 yr, n = 7) participated in three experimental trials in a randomized counterbalanced crossover design: 1) No exercise control (Control); 2) HICE (20 min cycling @ just above ventilatory threshold); 3) HIIE (10 X 1-min @ ∼90% peak aerobic power). Exercise conditions were matched for external work and diet was controlled post-exercise. Fasting blood samples were obtained ∼18 hr after each condition. CD62E+ and CD31+/CD42b- EMPs were assessed by flow cytometry and insulin resistance (IR) was estimated by homeostasis model assessment (HOMA-IR). Results There was a significant sex X exercise interaction for CD62E+ EMPs, CD31+/CD42b- EMPs, and HOMA-IR (all P<0.05). In males, both HICE and HIIE reduced EMPs compared to Control (P≤0.05). In females, HICE increased CD62E+ EMPs (P<0.05 vs. Control) whereas CD31+/CD42b- EMPs were unaltered by either exercise type. There was a significant increase in HOMA-IR in males but a decrease in females following HIIE compared to Control (P<0.05). Conclusions Overweight/obese males and females appear to respond differently to acute bouts of high-intensity exercise. A single session of HICE and HIIE reduced circulating EMPs measured on the morning following exercise in males but in females CD62E+ EMPs were increased following HICE. Next day HOMA-IR paradoxically increased in males but was reduced in females following HIIE. Future research is needed to investigate mechanisms responsible for potential differential responses between males and females. PMID:25710559

Skeletal Muscle Sorbitol Levels in Diabetic Rats with and without Insulin Therapy and Endurance Exercise Training

PubMed Central

Sánchez, O. A.; Walseth, T. F.; Snow, L. M.; Serfass, R. C.; Thompson, L. V.

2009-01-01

Sorbitol accumulation is postulated to play a role in skeletal muscle dysfunction associated with diabetes. The purpose of this study was to determine the effects of insulin and of endurance exercise on skeletal muscle sorbitol levels in streptozotocin-induced diabetic rats. Rats were assigned to one experimental group (control sedentary, control exercise, diabetic sedentary, diabetic exercise, diabetic sedentary no-insulin). Diabetic rats received daily subcutaneous insulin. The exercise-trained rats ran on a treadmill (1 hour, 5X/wk, for 12 weeks). Skeletal muscle sorbitol levels were the highest in the diabetic sedentary no-insulin group. Diabetic sedentary rats receiving insulin had similar sorbitol levels to control sedentary rats. Endurance exercise did not significantly affect sorbitol levels. These results indicate that insulin treatment lowers sorbitol in skeletal muscle; therefore sorbitol accumulation is probably not related to muscle dysfunction in insulin-treated diabetic individuals. Endurance exercise did not influence intramuscular sorbitol values as strongly as insulin. PMID:20016800

A Comparison of the Effects of Aerobic and Intense Exercise on the Type 2 Diabetes Mellitus Risk Marker Adipokines, Adiponectin and Retinol Binding Protein-4

PubMed Central

Phillips, Amy

2014-01-01

With a more sedentary population comes growing rates of obesity and increased type 2 diabetes mellitus (T2DM) risk. Exercise generally induces positive changes in traditional T2DM risk markers such as lipids, glucose tolerance, and insulin sensitivity; however alterations in concentrations of many circulating cytokines and their respective receptors are also becoming apparent. These cytokines may be early-response health risk factors otherwise overlooked in traditional T2DM risk marker analysis. Plasma levels of two adipocyte-originating cytokines, adiponectin and retinol binding protein 4 (RBP-4), alter following exercise. Adiponectin has anti-inflammatory, anti-atherosclerotic, and anti-insulin resistance roles and its secretion increases with physical activity, whilst elevated RBP-4 leads to increased insulin resistance, and secretion decreases with increasing physical activity; thus these plasma adipokine levels alter favourably following exercise. Although current data are limited, they do suggest that the more intense the exercise, the greater the positive effect on plasma RBP-4 levels, whilst lower intensity aerobic exercise may positively improve adiponectin concentrations. Therefore short-duration, high intensity training may provide a time-efficient alternative to the recommended 150 min moderate aerobic exercise per week in providing positive changes in RBP-4 and other traditional T2DM risk markers and due to increased compliance give greater health benefits over the longer term. PMID:26464853

Closed-Loop Insulin Delivery for Adults with Type 1 Diabetes Undertaking High-Intensity Interval Exercise Versus Moderate-Intensity Exercise: A Randomized, Crossover Study.

PubMed

Jayawardene, Dilshani C; McAuley, Sybil A; Horsburgh, Jodie C; Gerche, André La; Jenkins, Alicia J; Ward, Glenn M; MacIsaac, Richard J; Roberts, Timothy J; Grosman, Benyamin; Kurtz, Natalie; Roy, Anirban; O'Neal, David N

2017-06-01

We aimed to compare closed-loop glucose control for people with type 1 diabetes undertaking high-intensity interval exercise (HIIE) versus moderate-intensity exercise (MIE). Adults with type 1 diabetes established on insulin pumps undertook HIIE and MIE stages in random order during automated insulin delivery via a closed-loop system (Medtronic). Frequent venous sampling for glucose, lactate, ketones, insulin, catecholamines, cortisol, growth hormone, and glucagon levels was performed. The primary outcome was plasma glucose <4.0 mmol/L for ≥15 min, from exercise commencement to 120 min postexercise. Secondary outcomes included continuous glucose monitoring and biochemical parameters. Twelve adults (age mean ± standard deviation 40 ± 13 years) were recruited; all completed the study. Plasma glucose of one participant fell to 3.4 mmol/L following MIE completion; no glucose levels were <4.0 mmol/L for HIIE (primary outcome). There were no glucose excursions >15.0 mmol/L for either stage. Mean (±standard error) plasma glucose did not differ between stages pre-exercise; was higher during exercise in HIIE than MIE (11.3 ± 0.5 mmol/L vs. 9.7 ± 0.6 mmol/L, respectively; P < 0.001); and remained higher until 60 min postexercise. There were no differences in circulating free insulin before, during, or postexercise. During HIIE compared with MIE, there were greater increases in lactate (P < 0.001), catecholamines (all P < 0.05), and cortisol (P < 0.001). Ketones increased more with HIIE than MIE postexercise (P = 0.031). Preliminary findings suggest that closed-loop glucose control is safe for people undertaking HIIE and MIE. However, the management of the postexercise rise in ketones secondary to counter-regulatory hormone-induced insulin resistance observed with HIIE may represent a challenge for closed-loop systems.

Exercise associated hormonal signals as powerful determinants of an effective fat mass loss.

PubMed

Bajer, B; Vlcek, M; Galusova, A; Imrich, R; Penesova, A

2015-07-01

Obesity management for achieving an effective weight loss includes dietary modification and exercise [resistance (strength), endurance (cardiovascular) or intervals training (high-intensity intermittent exercise)]. Regular exercise acutely increases fat oxidation, which induces loss of fat mass and increases energy expenditure. Moreover, it has a positive effect on the physical (improved insulin sensitivity, lipid profile, etc.) and mental health (mood, cognition, memory, sleep, etc.). Endocrine responses to muscle actions are affected by many factors, including the exercise muscle groups (lower and upper body), load/volume, time-under tension, and rest-period intervals between sets, training status, gender, and age. The aim of this review is to summarize, evaluate, and clarify the literature data focusing on the endocrine responses to different types of exercise, including the frequency, intensity, and type of movement with regard to the fat loss strategies. Many studies have investigated anabolic [growth hormone, insulin-like growth factor-1 (IGF-1), testosterone] and gluco- and appetite- regulatory (insulin, cortisol, ghrelin) hormone responses and adaptations of skeletal muscles to exercise. Muscle tissue is a critical endocrine organ, playing important role in the regulation of several physiological and metabolic events. Moreover, we are also describing the response of some other substances to exercise, such as myokines [irisin, apelin, brain-derived neurotrophic factor (BDNF), myostatin, and fibroblast growth factor 21 (FGF21)]. It is proposed that reducing intra-abdominal fat mass and increasing cardiorespiratory fitness through improving nutritional quality, reducing sedentary behavior, and increase the participation in physical activity/exercise, might be associated with clinical benefits, sometimes even in the absence of weight loss.

The effects of muscle contraction and recombinant osteocalcin on insulin sensitivity ex vivo.

PubMed

Levinger, I; Lin, X; Zhang, X; Brennan-Speranza, T C; Volpato, B; Hayes, A; Jerums, G; Seeman, E; McConell, G

2016-02-01

We tested whether GPRC6A, the putative receptor of undercarboxylated osteocalcin (ucOC), is present in mouse muscle and whether ucOC increases insulin sensitivity following ex vivo muscle contraction. GPPRC6A is expressed in mouse muscle and in the mouse myotubes from a cell line. ucOC potentiated the effect of ex vivo contraction on insulin sensitivity. Acute exercise increases skeletal muscle insulin sensitivity. In humans, exercise increases circulating ucOC, a hormone that increases insulin sensitivity in rodents. We tested whether GPRC6A, the putative receptor of ucOC, is present in mouse muscle and whether recombinant ucOC increases insulin sensitivity in both C2C12 myotubes and whole mouse muscle following ex vivo muscle contraction. Glucose uptake was examined in C2C12 myotubes that express GPRC6A following treatment with insulin alone or with insulin and increasing ucOC concentrations (0.3, 3, 10 and 30 ng/ml). In addition, glucose uptake, phosphorylated (p-)AKT and p-AS160 were examined ex vivo in extensor digitorum longus (EDL) dissected from C57BL/6J wild-type mice, at rest, following insulin alone, after muscle contraction followed by insulin and after muscle contraction followed by recombinant ucOC then insulin exposure. We observed protein expression of the likely receptor for ucOC, GPRC6A, in whole muscle sections and differentiated mouse myotubes. We observed reduced GPRC6A expression following siRNA transfection. ucOC significantly increased insulin-stimulated glucose uptake dose-dependently up to 10 ng/ml, in differentiated mouse C2C12 myotubes. Insulin increased EDL glucose uptake (∼30 %, p < 0.05) and p-AKT and p-AKT/AKT compared with rest (all p < 0.05). Contraction prior to insulin increased muscle glucose uptake (∼25 %, p < 0.05), p-AKT, p-AKT/AKT, p-AS160 and p-AS160/AS160 compared with contraction alone (all p < 0.05). ucOC after contraction increased insulin-stimulated muscle glucose uptake (∼12 % p < 0.05) and p-AS160 (<0.05) more than contraction plus insulin alone but without effect on p-AKT. In the absence of insulin and/or of contraction, ucOC had no significant effect on muscle glucose uptake. GPRC6A, the likely receptor of osteocalcin (OC), is expressed in mouse muscle. ucOC treatment augments insulin-stimulated skeletal muscle glucose uptake in C2C12 myotubes and following ex vivo muscle contraction. ucOC may partly account for the insulin sensitizing effect of exercise.

Impaired Muscle AMPK Activation in the Metabolic Syndrome May Attenuate Improved Insulin Action after Exercise Training

PubMed Central

Layne, Andrew S.; Nasrallah, Sami; South, Mark A.; Howell, Mary E. A.; McCurry, Melanie P.; Ramsey, Michael W.; Stone, Michael H.

2011-01-01

Context: Strength training induces muscle remodeling and may improve insulin responsiveness. Objective: This study will quantify the impact of resistance training on insulin sensitivity in subjects with the metabolic syndrome and correlate this with activation of intramuscular pathways mediating mitochondrial biogenesis and muscle fiber hypertrophy. Design: Ten subjects with the metabolic syndrome (MS) and nine sedentary controls underwent 8 wk of supervised resistance exercise training with pre- and posttraining anthropometric and muscle biochemical assessments. Setting: Resistance exercise training took place in a sports laboratory on a college campus. Main Outcome Measures: Pre- and posttraining insulin responsiveness was quantified using a euglycemic clamp. Changes in expression of muscle 5-AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathways were quantified using immunoblots. Results: Strength and stamina increased in both groups. Insulin sensitivity increased in controls (steady-state glucose infusion rate = 7.0 ± 2.0 mg/kg · min pretraining training vs. 8.7 ± 3.1 mg/kg · min posttraining; P < 0.01) but did not improve in MS subjects (3.3 ± 1.3 pre vs. 3.1 ± 1.0 post). Muscle glucose transporter 4 increased 67% in controls and 36% in the MS subjects. Control subjects increased muscle phospho-AMPK (43%), peroxisome proliferator-activated receptor γ coactivator 1α (57%), and ATP synthase (60%), more than MS subjects (8, 28, and 21%, respectively). In contrast, muscle phospho-mTOR increased most in the MS group (57 vs. 32%). Conclusion: Failure of resistance training to improve insulin responsiveness in MS subjects was coincident with diminished phosphorylation of muscle AMPK, but increased phosphorylation of mTOR, suggesting activation of the mTOR pathway could be involved in inhibition of exercise training-related increases in AMPK and its activation and downstream events. PMID:21508135

Changes in Bone Biomarkers, BMC, and Insulin Resistance Following a 10-Week Whole Body Vibration Exercise Program in Overweight Latino Boys.

PubMed

Erceg, David N; Anderson, Lindsey J; Nickles, Chun M; Lane, Christianne J; Weigensberg, Marc J; Schroeder, E Todd

2015-01-01

With the childhood obesity epidemic, efficient methods of exercise are sought to improve health. We tested whether whole body vibration (WBV) exercise can positively affect bone metabolism and improve insulin/glucose dynamics in sedentary overweight Latino boys. Twenty Latino boys 8-10 years of age were randomly assigned to either a control (CON) or 3 days/wk WBV exercise (VIB) for 10-wk. Significant increases in BMC (4.5 ± 3.2%; p=0.01) and BMD (1.3 ± 1.3%; p<0.01) were observed for the VIB group when compared to baseline values. For the CON group BMC significantly increased (2.0 ± 2.2%; p=0.02), with no change in BMD (0.8 ± 1.3%; p=0.11). There were no significant between group changes in BMC or BMD. No significant change was observed for osteocalcin and (collagen type I C-telopeptide) CTx for the VIB group. However, osteocalcin showed a decreasing trend (p=0.09) and CTx significantly increased (p<0.03) for the CON group. This increase in CTx was significantly different between groups (p<0.02) and the effect size of between-group difference in change was large (-1.09). There were no significant correlations between osteocalcin and measures of fat mass or insulin resistance for collapsed data. Although bone metabolism was altered by WBV training, no associations were apparent between osteocalcin and insulin resistance. These findings suggest WBV exercise may positively increase BMC and BMD by decreasing bone resorption in overweight Latino boys.

Exercise induced adipokine changes and the metabolic syndrome.

PubMed

Golbidi, Saeid; Laher, Ismail

2014-01-01

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

The response of circulating omentin-1 concentration to 16-week exercise training in male children with obesity.

PubMed

Zehsaz, Farzad; Farhangi, Negin; Ghahramani, Mehri

2016-11-01

The purpose of the present study was to investigate the effects of the 16-week exercise training program on serum omentin-1 in relation to change in insulin resistance in obese male children. Thirty-two obese male children, aged 9-12 years, were randomly assigned into Exercise Group (ExG; n = 16) and Control Group (CG; n = 16). ExG participated in a 16-week exercise training program which combined various forms of aerobic activities and resistance training. Body composition, body mass index (BMI), waist circumference (WC), fasting glucose and insulin, homeostasis model assessment estimate of insulin resistance (HOMA2-IR), blood lipids and serum omentin-1 were assessed before and after 16 weeks of training. Exercise training significantly decreased body mass (7.5%), BMI (7.6%), WC (4.3%), body fat % (15%), fasting insulin (18.5%), total cholesterol (TC) (5.4%), low-density lipoprotein cholesterol (LDL-C) (17%) and triglyceride (TG) (7.4%) compared to CG. Between-groups comparison showed a considerable exercise-induced upregulation in omentin-1 (ES = 89; P < 0.05) levels. Furthermore, in ExG serum omentin-1 levels were significantly increased from 24.5 ± 8.4 to 35.9 ± 9.3 ng/ml (45%; P < 0.001) after the training program, which was accompanied with significantly decreased fasting insulin (P < 0.001). The changes in omentin-1 concentrations correlated with the changes in BMI (r = -0.67, P < 0.001), WC (r = -0.62, P = 0.002), body fat % (r = -0.50, P = 0.004), insulin (r = -0.65, P = 0.001), HOMA2-IR (r = -0.60, P = 0.004), TC (r = -0.53, P = 0.004) and LDL-C (r = -0.51, P = 0.004) in ExG. BMI (β = -0.50, P = 0.009) and fasting insulin (β = -0.54, P = 0.006) changes were found to be independent predictors of omentin-1 increment in multiple regression analysis. Exercise training resulted in a significant increase in serum omentin-1 concentrations in children with obesity. The findings suggest that exercise-induced changes in omentin-1 may be associated with the beneficial effects of exercise on reduced insulin and weight lost.

The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity.

PubMed

Kelly, Karen R; Brooks, Latina M; Solomon, Thomas P J; Kashyap, Sangeeta R; O'Leary, Valerie B; Kirwan, John P

2009-06-01

Aging and obesity are characterized by decreased beta-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% Vo(2 max)) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 +/- 190, post: 1,269 +/- 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 +/- 1.5 yr), obese (34.4 +/- 1.7 kg/m(2)) adults with impaired glucose tolerance. In addition to GIP, plasma PYY(3-36), insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in Vo(2 max) (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (-8.3 +/- 1.1 vs. -2.8 +/- 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (DeltaI(0-30)/DeltaG(0-30)) and GIP (Delta(0-30)) secretion were correlated (r = 0.69, P = 0.05). The PYY(3-36) (Delta(0-30)) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY(3-36) response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults.

Effects of adding exercise to a 16-week very low-calorie diet in obese, insulin-dependent type 2 diabetes mellitus patients.

PubMed

Snel, Marieke; Gastaldelli, Amalia; Ouwens, D Margriet; Hesselink, Matthijs K C; Schaart, Gert; Buzzigoli, Emma; Frölich, Marijke; Romijn, Johannes A; Pijl, Hanno; Meinders, A Edo; Jazet, Ingrid M

2012-07-01

Reduction of 50% excess body weight, using a very low-calorie diet (VLCD; 450 kcal/d) improves insulin sensitivity in obese type 2 diabetes mellitus patients. The objective of the study was to evaluate whether adding exercise to the VLCD has additional benefits. This was a randomized intervention study. The study was conducted at a clinical research center in an academic medical center. Twenty-seven obese [body mass index 37.2 ± 0.9 kg/m(2) (mean ± sem)] insulin-treated type 2 diabetes mellitus patients. Patients followed a 16-wk VLCD. Thirteen of them simultaneously participated in an exercise program (E) consisting of 1-h, in-hospital training and four 30-min training sessions on a cycloergometer weekly. Insulin resistance was measured by a hyperinsulinemic euglycemic clamp. Insulin signaling, mitochondrial DNA (mtDNA) content, and intramyocellular lipid content was measured in skeletal muscle biopsies. Baseline characteristics were identical in both groups. Substantial weight loss occurred (-23.7 ± 1.7 kg VLCD-only vs. -27.2 ± 1.9 kg VLCD+E, P = NS within groups). The exercise group lost more fat mass. Insulin-stimulated glucose disposal increased similarly in both study groups [15.0 ± 0.9 to 39.2 ± 4.7 μmol/min(-1) · kg lean body mass (LBM(-1)) VLCD-only vs. 17.0 ± 1.0 to 37.5 ± 3.5 μmol/min(-1) · kg LBM(-1) in VLCD+E], as did phosphorylation of the phosphatidylinositol 3-kinase-protein kinase B/AKT insulin signaling pathway. In contrast, skeletal muscle mtDNA content increased only in the VLCD+E group (1211 ± 185 to 2288 ± 358, arbitrary units, P = 0.016 vs. 1397 ± 240 to 1196 ± 179, P = NS, VLCD-only group). Maximum aerobic capacity also only increased significantly in the VLCD+E group (+6.6 ± 1.7 ml/min(-1) · kg LBM(-1) vs. +0.7 ± 1.5 ml/min(-1) · kg LBM(-1) VLCD-only, P = 0.017). Addition of exercise to a 16-wk VLCD induces more fat loss. Exercise augments maximum aerobic capacity and skeletal muscle mtDNA content. These changes are, however, not reflected in a higher insulin-stimulated glucose disposal rate.

Effects of the dietary approaches to stop hypertension diet alone and in combination with exercise and caloric restriction on insulin sensitivity and lipids.

PubMed

Blumenthal, James A; Babyak, Michael A; Sherwood, Andrew; Craighead, Linda; Lin, Pao-Hwa; Johnson, Julie; Watkins, Lana L; Wang, Jenny T; Kuhn, Cynthia; Feinglos, Mark; Hinderliter, Alan

2010-05-01

This study examined the effects of the Dietary Approaches to Stop Hypertension (DASH) diet on insulin sensitivity and lipids. In a randomized control trial, 144 overweight (body mass index: 25 to 40) men (n=47) and women (n=97) with high blood pressure (130 to 159/85 to 99 mm Hg) were randomly assigned to one of the following groups: (1) DASH diet alone; (2) DASH diet with aerobic exercise and caloric restriction; or (3) usual diet controls (UC). Body composition, fitness, insulin sensitivity, and fasting lipids were measured before and after 4 months of treatment. Insulin sensitivity was estimated on the basis of glucose and insulin levels in the fasting state and after an oral glucose load. Participants in the DASH diet with aerobic exercise and caloric restriction condition lost weight (-8.7 kg [95% CI: -2.0 to -9.7 kg]) and exhibited a significant increase in aerobic capacity, whereas the DASH diet alone and UC participants maintained their weight (-0.3 kg [95% CI: -1.2 to 0.5 kg] and +0.9 kg [95% CI: 0.0 to 1.7 kg], respectively) and had no improvement in exercise capacity. DASH diet with aerobic exercise and caloric restriction demonstrated lower glucose levels after the oral glucose load, improved insulin sensitivity, and lower total cholesterol and triglycerides compared with both DASH diet alone and UC, as well as lower fasting glucose and low-density lipoprotein cholesterol compared with UC. DASH diet alone participants generally did not differ from UC in these measures. Combining the DASH diet with exercise and weight loss resulted in significant improvements in insulin sensitivity and lipids. Despite clinically significant reductions in blood pressure, the DASH diet alone, without caloric restriction or exercise, resulted in minimal improvements in insulin sensitivity or lipids.

Effects of exercise and lifestyle modification on fitness, insulin resistance, skeletal muscle oxidative phosphorylation and intramyocellular lipid content in obese children and adolescents.

PubMed

McCormack, S E; McCarthy, M A; Harrington, S G; Farilla, L; Hrovat, M I; Systrom, D M; Thomas, B J; Torriani, M; McInnis, K; Grinspoon, S K; Fleischman, A

2014-08-01

Obesity is associated with poor fitness and adverse metabolic consequences in children. To investigate how exercise and lifestyle modification may improve fitness and insulin sensitivity in this population. Randomized controlled trial, 21 obese (body mass index ≥ 95% percentile) subjects, ages 10 to 17 years. Subjects were given standardized healthful lifestyle advice for 8 weeks. In addition, they were randomized to an in-home supervised exercise intervention (n = 10) or control group (n = 11). Fasting laboratory studies (insulin, glucose, lipid profile) and assessments of fitness, body composition, skeletal muscle oxidative phosphorylation and intramyocellular lipid content (IMCL), were performed at baseline and study completion. Subjects were 13.0 ± 1.9 (standard deviation) years old, 72% female and 44% non-white. Exercise improved fitness (P = 0.03) and power (P = 0.01), and increased IMCL (P = 0.02). HOMA-IR decreased among all subjects in response to lifestyle modification advice (P = 0.01), regardless of exercise training assignment. In univariate analysis in all subjects, change in cardiovascular fitness was associated with change in HOMA-IR. In exploratory analyses, increased IMCL was associated with greater resting energy expenditure (r = 0.78, P = 0.005) and a decrease in fasting respiratory quotient (r = -0.70, P = 0.02) (n = 11). Change in fitness was found to be related to change in insulin resistance in response to lifestyle modification and exercise in obese children. IMCL increased with exercise in these obese children, which may reflect greater muscle lipid oxidative capacity. © 2013 The Authors. Pediatric Obesity © 2013 International Association for the Study of Obesity.

Minimal Intensity Physical Activity (Standing and Walking) of Longer Duration Improves Insulin Action and Plasma Lipids More than Shorter Periods of Moderate to Vigorous Exercise (Cycling) in Sedentary Subjects When Energy Expenditure Is Comparable

PubMed Central

Duvivier, Bernard M. F. M.; Schaper, Nicolaas C.; Bremers, Michelle A.; van Crombrugge, Glenn; Menheere, Paul P. C. A.; Kars, Marleen; Savelberg, Hans H. C. M.

2013-01-01

Background Epidemiological studies suggest that excessive sitting time is associated with increased health risk, independent of the performance of exercise. We hypothesized that a daily bout of exercise cannot compensate the negative effects of inactivity during the rest of the day on insulin sensitivity and plasma lipids. Methodology/Principal Findings Eighteen healthy subjects, age 21±2 year, BMI 22.6±2.6 kgm−2 followed randomly three physical activity regimes for four days. Participants were instructed to sit 14 hr/day (sitting regime); to sit 13 hr/day and to substitute 1 hr of sitting with vigorous exercise 1 hr (exercise regime); to substitute 6 hrs sitting with 4 hr walking and 2 hr standing (minimal intensity physical activity (PA) regime). The sitting and exercise regime had comparable numbers of sitting hours; the exercise and minimal intensity PA regime had the same daily energy expenditure. PA was assessed continuously by an activity monitor (ActivPAL) and a diary. Measurements of insulin sensitivity (oral glucose tolerance test, OGTT) and plasma lipids were performed in the fasting state, the morning after the 4 days of each regime. In the sitting regime, daily energy expenditure was about 500 kcal lower than in both other regimes. Area under the curve for insulin during OGTT was significantly lower after the minimal intensity PA regime compared to both sitting and exercise regimes 6727.3±4329.4 vs 7752.0±3014.4 and 8320.4±5383.7 mU•min/ml, respectively. Triglycerides, non-HDL cholesterol and apolipoprotein B plasma levels improved significantly in the minimal intensity PA regime compared to sitting and showed non-significant trends for improvement compared to exercise. Conclusions One hour of daily physical exercise cannot compensate the negative effects of inactivity on insulin level and plasma lipids if the rest of the day is spent sitting. Reducing inactivity by increasing the time spent walking/standing is more effective than one hour of physical exercise, when energy expenditure is kept constant. PMID:23418444

Involvement of bradykinin in acute exercise-induced increase of glucose uptake and GLUT-4 translocation in skeletal muscle: studies in normal and diabetic humans and rats.

PubMed

Taguchi, T; Kishikawa, H; Motoshima, H; Sakai, K; Nishiyama, T; Yoshizato, K; Shirakami, A; Toyonaga, T; Shirontani, T; Araki, E; Shichiri, M

2000-07-01

Acute exercise induces glucose uptake in skeletal muscle in vivo, but the molecular mechanism of this phenomenon remains to be identified. In this study, we evaluated the involvement of bradykinin in exercise-induced glucose uptake in humans and rats. In human studies, plasma bradykinin concentrations increased significantly during an ergometer exercise (20 minutes) in 8 healthy normoglycemic subjects and 6 well-controlled type 2 diabetic patients (mean hemoglobin A1c [HbA1c], 6.4% +/- 0.6%), but not in 6 poorly controlled type 2 diabetics (mean HbA1c, 11.6% +/- 2.6%). In rat studies, plasma bradykinin concentrations also significantly increased after 1 hour of swimming in nondiabetic and mildly diabetic (streptozotocin [STZ] 45 mg/kg intravenously [IV]) rats, but not in rats with severe diabetes (STZ 65 mg/kg IV). Glucose influx (maximum velocity [Vmax]) and GLUT-4 translocation in skeletal muscle of nondiabetic rats significantly increased after 1 hour of swimming, but these increases were abrogated by subcutaneous infusion of bradykinin B2 receptor antagonist HOE-140 (400 microg x kg(-1) x d(-1)). Insulin-stimulated tyrosine phosphorylation and phosphatidylinositol (PI) 3-kinase activity in response to insulin injection (20 U/kg IV) in the portal vein were significantly attenuated in exercised rats pretreated with HOE-140 compared with saline-treated exercised rats. Our results suggest that plasma bradykinin concentrations increase in response to acute exercise and this increase is affected by blood glucose status in diabetic patients. Moreover, the exercise-induced increase in bradykinin may be involved in modulating exercise-induced glucose transport through an increase of GLUT-4 translocation, as well as enhancement of the insulin signal pathway, during the postexercise period in skeletal muscle, resulting in a decrease of blood glucose.

Endurance exercise training and high-fat diet differentially affect composition of diacylglycerol molecular species in rat skeletal muscle.

PubMed

Kawanishi, Noriaki; Takagi, Kana; Lee, Hyeon-Cheol; Nakano, Daiki; Okuno, Toshiaki; Yokomizo, Takehiko; Machida, Shuichi

2018-06-01

Insulin resistance of peripheral muscle is implicated in the etiology of metabolic syndrome in obesity. Although accumulation of glycerolipids, such as triacylglycerol and diacylglycerol (DAG), in muscle contributes to insulin resistance in obese individuals, endurance-trained athletes also have higher glycerolipid levels but normal insulin sensitivity. We hypothesized that the difference in insulin sensitivity of skeletal muscle between athletes and obese individuals stems from changes in fatty acid composition of accumulated lipids. Here, we evaluated the effects of intense endurance exercise and high-fat diet (HFD) on the accumulation and composition of lipid molecular species in rat skeletal muscle using a lipidomic approach. Sprague-Dawley female rats were randomly assigned to three groups and received either normal diet (ND) in sedentary conditions, ND plus endurance exercise training, or HFD in sedentary conditions. Rats were fed ND or HFD between 4 and 12 wk of age. Rats in the exercise group ran on a treadmill for 120 min/day, 5 days/wk, for 8 wk. Soleus muscle lipidomic profiles were obtained using liquid chromatography/tandem mass spectrometry. Total DAG levels, particularly those of palmitoleate-containing species, were increased in muscle by exercise training. However, whereas the total DAG level in the muscle was also increased by HFD, the levels of DAG molecular species containing palmitoleate were decreased by HFD. The concentration of phosphatidylethanolamine molecular species containing palmitoleate was increased by exercise but decreased by HFD. Our results indicate that although DAG accumulation was similar levels in trained and sedentary obese rats, specific changes in molecular species containing palmitoleate were opposite.

Increased muscle blood supply and transendothelial nutrient and insulin transport induced by food intake and exercise: effect of obesity and ageing.

PubMed

Wagenmakers, Anton J M; Strauss, Juliette A; Shepherd, Sam O; Keske, Michelle A; Cocks, Matthew

2016-04-15

This review concludes that a sedentary lifestyle, obesity and ageing impair the vasodilator response of the muscle microvasculature to insulin, exercise and VEGF-A and reduce microvascular density. Both impairments contribute to the development of insulin resistance, obesity and chronic age-related diseases. A physically active lifestyle keeps both the vasodilator response and microvascular density high. Intravital microscopy has shown that microvascular units (MVUs) are the smallest functional elements to adjust blood flow in response to physiological signals and metabolic demands on muscle fibres. The luminal diameter of a common terminal arteriole (TA) controls blood flow through up to 20 capillaries belonging to a single MVU. Increases in plasma insulin and exercise/muscle contraction lead to recruitment of additional MVUs. Insulin also increases arteriolar vasomotion. Both mechanisms increase the endothelial surface area and therefore transendothelial transport of glucose, fatty acids (FAs) and insulin by specific transporters, present in high concentrations in the capillary endothelium. Future studies should quantify transporter concentration differences between healthy and at risk populations as they may limit nutrient supply and oxidation in muscle and impair glucose and lipid homeostasis. An important recent discovery is that VEGF-B produced by skeletal muscle controls the expression of FA transporter proteins in the capillary endothelium and thus links endothelial FA uptake to the oxidative capacity of skeletal muscle, potentially preventing lipotoxic FA accumulation, the dominant cause of insulin resistance in muscle fibres. © 2015 The Authors. The Journal of Physiology © 2015 The Physiological Society.

Dissociation between exercise-induced reduction in liver fat and changes in hepatic and peripheral glucose homoeostasis in obese patients with non-alcoholic fatty liver disease.

PubMed

Cuthbertson, Daniel J; Shojaee-Moradie, Fariba; Sprung, Victoria S; Jones, Helen; Pugh, Christopher J A; Richardson, Paul; Kemp, Graham J; Barrett, Mark; Jackson, Nicola C; Thomas, E Louise; Bell, Jimmy D; Umpleby, A Margot

2016-01-01

Non-alcoholic fatty liver disease (NAFLD) is associated with multi-organ (hepatic, skeletal muscle, adipose tissue) insulin resistance (IR). Exercise is an effective treatment for lowering liver fat but its effect on IR in NAFLD is unknown. We aimed to determine whether supervised exercise in NAFLD would reduce liver fat and improve hepatic and peripheral (skeletal muscle and adipose tissue) insulin sensitivity. Sixty nine NAFLD patients were randomized to 16 weeks exercise supervision (n=38) or counselling (n=31) without dietary modification. All participants underwent MRI/spectroscopy to assess changes in body fat and in liver and skeletal muscle triglyceride, before and following exercise/counselling. To quantify changes in hepatic and peripheral insulin sensitivity, a pre-determined subset (n=12 per group) underwent a two-stage hyperinsulinaemic euglycaemic clamp pre- and post-intervention. Results are shown as mean [95% confidence interval (CI)]. Fifty participants (30 exercise, 20 counselling), 51 years (IQR 40, 56), body mass index (BMI) 31 kg/m(2) (IQR 29, 35) with baseline liver fat/water % of 18.8% (IQR 10.7, 34.6) completed the study (12/12 exercise and 7/12 counselling completed the clamp studies). Supervised exercise mediated a greater reduction in liver fat/water percentage than counselling [Δ mean change 4.7% (0.01, 9.4); P<0.05], which correlated with the change in cardiorespiratory fitness (r=-0.34, P=0.0173). With exercise, peripheral insulin sensitivity significantly increased (following high-dose insulin) despite no significant change in hepatic glucose production (HGP; following low-dose insulin); no changes were observed in the control group. Although supervised exercise effectively reduced liver fat, improving peripheral IR in NAFLD, the reduction in liver fat was insufficient to improve hepatic IR. © 2016 Authors; published by Portland Press Limited.

Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

PubMed Central

Picklo, Matthew J.; Thyfault, John P.

2016-01-01

Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g α-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation. PMID:25761734

Upregulation of circulating IL-15 by treadmill running in healthy individuals: is IL-15 an endocrine mediator of the beneficial effects of endurance exercise?

PubMed

Tamura, Yoshiaki; Watanabe, Keiichi; Kantani, Tomomi; Hayashi, Junichi; Ishida, Nobuhiko; Kaneki, Masao

2011-01-01

The beneficial effects of endurance exercise include insulin-sensitization and reduction of fat mass. Limited knowledge is available about the mechanisms by which endurance exercise exerts the salutary effects. Myokines, cytokines secreted by skeletal muscle, have been recognized as a potential mediator. Recently, a role of skeletal muscle-derived interleukin-15 (IL-15) in improvement of fat-lean body mass composition and insulin sensitivity has been proposed. Yet, previous studies have reported that endurance training does not increase production or secretion of IL-15 in skeletal muscle. Here, we show that in opposition to previous findings, 30-min treadmill running at 70% of age-predicted maximum heart rate resulted in a significant increase in circulating IL-15 level in untrained healthy young men. These findings suggest that IL-15 might play a role in the systemic anti-obesogenic and insulin-sensitizing effects of endurance exercise, not only as a paracrine and autocrine but also as an endocrine factor.

A single bout of high-intensity interval exercise and work-matched moderate-intensity exercise has minimal effect on glucose tolerance and insulin sensitivity in 7- to 10-year-old boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Jackman, Sarah R; Bassi, Shikhar; Armstrong, Neil; Barker, Alan R

2018-01-01

The purpose of this study was to assess the acute effect of high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE) on glucose tolerance, insulin sensitivity and fat oxidation in young boys. Eleven boys (8.8 ± 0.8 y) completed three conditions: 1) HIIE; 2) work-matched MIE; and 3) rest (CON) followed by an oral glucose tolerance test (OGTT) to determine glucose tolerance and insulin sensitivity (Cederholm index). Fat oxidation was measured following the OGTT using indirect calorimetry. There was no effect for condition on plasma [glucose] and [insulin] area under the curve (AUC) responses following the OGTT (P > 0.09). However, there was a "trend" for a condition effect for insulin sensitivity with a small increase after HIIE (P = 0.04, ES = 0.28, 9.7%) and MIE (P = 0.07, ES = 0.21, 6.5%) compared to CON. There was an increase in fat oxidation AUC following HIIE (P = 0.008, ES = 0.79, 38.9%) compared to CON, but with no differences between MIE and CON and HIIE and MIE (P > 0.13). In conclusion, 7- to 10-year-old boys may have limited scope to improve insulin sensitivity and glucose tolerance after a single bout of HIIE and MIE. However, fat oxidation is augmented after HIIE but not MIE.

Algorithm that delivers an individualized rapid-acting insulin dose after morning resistance exercise counters post-exercise hyperglycaemia in people with Type 1 diabetes.

PubMed

Turner, D; Luzio, S; Gray, B J; Bain, S C; Hanley, S; Richards, A; Rhydderch, D C; Martin, R; Campbell, M D; Kilduff, L P; West, D J; Bracken, R M

2016-04-01

To develop an algorithm that delivers an individualized dose of rapid-acting insulin after morning resistance exercise to counter post-exercise hyperglycaemia in individuals with Type 1 diabetes. Eight people with Type 1 diabetes, aged 34 ± 7 years with HbA1c concentrations 72 ± 12 mmol/mol (8.7 ± 1.1%), attended our laboratory on two separate mornings after fasting, having taken their usual basal insulin the previous evening. These people performed a resistance exercise session comprising six exercises for two sets of 10 repetitions at 60% of the maximum amount of force that was generated in one maximal contraction (60% 1RM). In a randomized and counterbalanced order, the participants were administered an individualized dose of rapid-acting insulin (2 ± 1 units, range 0-4 units) immediately after resistance exercise (insulin session) by means of an algorithm or were not administered this (no-insulin session). Venous blood glucose concentrations were measured for 125 min after resistance exercise. Data (mean ± sem values) were analysed using anova (P ≤ 0.05). Participants had immediate post-resistance exercise hyperglycaemia (insulin session 13.0 ± 1.6 vs. no-insulin session 12.7 ± 1.5 mmol/l; P = 0.834). The decline in blood glucose concentration between peak and 125 min after exercise was greater in the insulin exercise session than in the no-insulin session (3.3 ± 1.0 vs. 1.3 ± 0.4 mmol/l: P = 0.015). There were no episodes of hypoglycaemia (blood glucose <3.9 mmol/l). Administration of rapid-acting insulin according to an individualized algorithm reduced the hyperglycaemia associated with morning resistance exercise without causing hypoglycaemia in the 2 h post-exercise period in people with Type 1 diabetes. © 2015 Diabetes UK.

Impact of Exercise and Dietary Fatty Acid Composition from a High-fat Diet on Markers of Hunger and Satiety

PubMed Central

Cooper, JA; Watras, AC; Paton, CM; Wegner, FH; Adams, AK; Schoeller, DA

2014-01-01

Objective To compare the effects of both dietary fatty acid composition and exercise vs. sedentary conditions on circulating levels of hunger and satiety hormones. Eight healthy males were randomized in a 2×2 crossover design. The four treatments were 3 days of HF diets (50% of energy) containing high saturated fat (22% of energy) with exercise (SE) or sedentary (SS) conditions, and high monounsaturated fat (30% of energy) with exercise (UE) or sedentary (US) conditions. Cycling exercise was completed at 45% of VO2max for 2h daily. On the third HF day, 20 blood specimens were drawn over a 24h period for each hormone (leptin, insulin, ghrelin, and peptide YY (PYY)). A visual analog scale (VAS) was completed hourly between 0800 and 2200. Average 24h leptin and insulin levels were lower while 24h PYY was higher during exercise vs sedentary conditions. FA composition did not differentially affect 24h hormone values. VAS scores for hunger and fullness did not differ between any treatment but did correlate with ghrelin, leptin, and insulin. High saturated or unsaturated fat diets did not differ with respect to markers of hunger or satiety. Exercise decreased 24h leptin and insulin while increasing PYY regardless of FA composition. PMID:21035513

Combined effects of endurance training and dietary unsaturated fatty acids on physical performance, fat oxidation and insulin sensitivity.

PubMed

Boss, Andreas; Lecoultre, Virgile; Ruffieux, Christiane; Tappy, Luc; Schneiter, Philippe

2010-04-01

Endurance training improves exercise performance and insulin sensitivity, and these effects may be in part mediated by an enhanced fat oxidation. Since n-3 and n-9 unsaturated fatty acids may also increase fat oxidation, we hypothesised that a diet enriched in these fatty acids may enhance the effects of endurance training on exercise performance, insulin sensitivity and fat oxidation. To assess this hypothesis, sixteen normal-weight sedentary male subjects were randomly assigned to an isoenergetic diet enriched with fish and olive oils (unsaturated fatty acid group (UFA): 52 % carbohydrates, 34 % fat (12 % SFA, 12 % MUFA, 5 % PUFA), 14 % protein), or a control diet (control group (CON): 62 % carbohydrates, 24 % fat (12 % SFA, 6 % MUFA, 2 % PUFA), 14 % protein) and underwent a 10 d gradual endurance training protocol. Exercise performance was evaluated by measuring VO2max and the time to exhaustion during a cycling exercise at 80 % VO2max; glucose homeostasis was assessed after ingestion of a test meal. Fat oxidation was assessed by indirect calorimetry at rest and during an exercise at 50 % VO2max. Training significantly increased time to exhaustion, but not VO2max, and lowered incremental insulin area under the curve after the test meal, indicating improved insulin sensitivity. Those effects were, however, of similar magnitude in UFA and CON. Fat oxidation tended to increase in UFA, but not in CON. This difference was, however, not significant. It is concluded that a diet enriched with fish- and olive oil does not substantially enhance the effects of a short-term endurance training protocol in healthy young subjects.

A 12-week sports-based exercise programme for inactive Indigenous Australian men improved clinical risk factors associated with type 2 diabetes mellitus.

PubMed

Mendham, Amy E; Duffield, Rob; Marino, Frank; Coutts, Aaron J

2015-07-01

This study assessed the effect of a 12-week sports-based exercise intervention on glucose regulation, anthropometry and inflammatory markers associated with the prevalence of type 2 diabetes mellitus (T2DM) in Indigenous Australian men. Twenty-six inactive Indigenous Australian men (48.6±6.6 years) were randomized into exercise (n=16) or control (n=10)conditions. Training included ∼2-3 days/week for 12 weeks of sports and gym exercises in a group environment, whilst control participants maintained normal activity and dietary patterns. Pre- and post-intervention testing included: anthropometry, peak aerobic capacity, fasting blood chemistry of inflammatory cytokines, adiponectin, leptin, cholesterol, glucose, insulin and C-peptide. An oral glucose tolerance test measured glucose, insulin and C-peptide 30, 60, 90 and 120min post 75g glucose ingestion. The exercise condition decreased insulin area under the curve (25±22%), increased estimated insulin sensitivity (35±62%) and decreased insulin resistance (9±35%; p<0.05), compared with control (p>0.05). The exercise condition decreased in body mass index, waist circumference and waist to hip ratio (p<0.05), compared to control (p>0.05). Leptin decreased in the exercise group, with no changes for adiponectin (p>0.05) or inflammatory markers (p>0.05) in either condition. Aerobic fitness variables showed significant increases in peak oxygen consumption for the exercise condition compared to no change in control (p>0.05). Findings indicate positive clinical outcomes in metabolic, anthropometric and aerobic fitness variables. This study provides evidence for sport and group-based activities leading to improved clinical risk factors associated with T2DM development in clinically obese Indigenous Australian men. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Exercise decreases CLK2 in the liver of obese mice and prevents hepatic fat accumulation.

PubMed

Muñoz, Vitor R; Gaspar, Rafael C; Kuga, Gabriel K; Nakandakari, Susana C B R; Baptista, Igor L; Mekary, Rania A; da Silva, Adelino S R; de Moura, Leandro P; Ropelle, Eduardo R; Cintra, Dennys E; Pauli, José R

2018-03-25

The accumulation of fatty acids in the liver associated with obesity condition is also known as nonalcoholic fatty liver disease (NAFLD). The impaired fat oxidation in obesity condition leads to increased hepatic fat accumulation and increased metabolic syndrome risk. On the other hand, physical exercise has been demonstrated as a potent strategy in the prevention of NAFLD. Also, these beneficial effects of exercise occur through different mechanisms. Recently, the Cdc2-like kinase (CLK2) protein was associated with the suppression of fatty acid oxidation and hepatic ketogenesis. Thus, obese animals demonstrated elevated levels of hepatic CLK2 and decreased fat acid oxidation. Here, we explored the effects of chronic physical exercise in the hepatic metabolism of obese mice. Swiss mice were distributed in Lean, Obese (fed with high-fat diet during 16 weeks) and Trained Obese group (fed with high-fat diet during 16 weeks and exercised (at 60% exhaustion velocity during 1 h/5 days/week) during 8 weeks. In our results, the obese animals showed insulin resistance, increased hepatic CLK2 content and increased hepatic fat accumulation compared to the Lean group. Otherwise, the chronic physical exercise improved insulin resistance state, prevented the increased CLK2 in the liver and attenuated hepatic fat accumulation. In summary, these data reveal a new protein involved in the prevention of hepatic fat accumulation after chronic physical exercise. More studies can evidence the negative role of CLK2 in the control of liver metabolism, contributing to the improvement of insulin resistance, obesity, and type 2 diabetes. © 2018 Wiley Periodicals, Inc.

Techniques for Exercise Preparation and Management in Adults with Type 1 Diabetes.

PubMed

Pinsker, Jordan E; Kraus, Amy; Gianferante, Danielle; Schoenberg, Benjamen E; Singh, Satbir K; Ortiz, Hallie; Dassau, Eyal; Kerr, David

2016-12-01

People with type 1 diabetes are at risk for early- and late-onset hypoglycemia following exercise. Reducing this risk may be possible with strategic modifications in carbohydrate intake and insulin use. We examined the exercise preparations and management techniques used by individuals with type 1 diabetes before and after physical activity and sought to determine whether use of differing diabetes technologies affects these health-related behaviours. We studied 502 adults from the Type 1 Diabetes Exchange's online patient community, Glu, who had completed an online survey focused on diabetes self-management and exercise. Many respondents reported increasing carbohydrate intake before (79%) and after (66%) exercise as well as decreasing their meal boluses before (53%) and after (46%) exercise. Most reported adhering to a target glucose level before starting exercise (77%). Despite these accommodations, the majority reported low blood glucose (BG) levels after exercise (70%). The majority of users of both insulin pump therapy (CSII) and continuous glucose monitoring (CGM) (Combined) reported reducing basal insulin around exercise (55%), with fewer participants adjusting basal insulin when using other devices (SMBG only = 20%; CGM = 34%; CSII = 42%; p<0.001). However, CSII and Combined users reported that exercise makes their BG levels harder to control (p<0.05) and makes them feel less able to predict their BG levels while exercising (p<0.001); they show agreement that fear of low BG levels keeps them from exercising (p<0.01). These findings highlight the need for exercise-management strategies tailored to individuals' overall diabetes management, for despite making exercise-specific adjustments for care, many people with type 1 diabetes still report significant difficulties with BG control when it comes to exercise. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions

PubMed Central

Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A.; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy

2010-01-01

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise. PMID:20739506

NF-κB activity in muscle from obese and type 2 diabetic subjects under basal and exercise-stimulated conditions.

PubMed

Tantiwong, Puntip; Shanmugasundaram, Karthigayan; Monroy, Adriana; Ghosh, Sangeeta; Li, Mengyao; DeFronzo, Ralph A; Cersosimo, Eugenio; Sriwijitkamol, Apiradee; Mohan, Sumathy; Musi, Nicolas

2010-11-01

NF-κB is a transcription factor that controls the gene expression of several proinflammatory proteins. Cell culture and animal studies have implicated increased NF-κB activity in the pathogenesis of insulin resistance and muscle atrophy. However, it is unclear whether insulin-resistant human subjects have abnormal NF-κB activity in muscle. The effect that exercise has on NF-κB activity/signaling also is not clear. We measured NF-κB DNA-binding activity and the mRNA level of putative NF-κB-regulated myokines interleukin (IL)-6 and monocyte chemotactic protein-1 (MCP-1) in muscle samples from T2DM, obese, and lean subjects immediately before, during (40 min), and after (210 min) a bout of moderate-intensity cycle exercise. At baseline, NF-κB activity was elevated 2.1- and 2.7-fold in obese nondiabetic and T2DM subjects, respectively. NF-κB activity was increased significantly at 210 min following exercise in lean (1.9-fold) and obese (2.6-fold) subjects, but NF-κB activity did not change in T2DM. Exercise increased MCP-1 mRNA levels significantly in the three groups, whereas IL-6 gene expression increased significantly only in lean and obese subjects. MCP-1 and IL-6 gene expression peaked at the 40-min exercise time point. We conclude that insulin-resistant subjects have increased basal NF-κB activity in muscle. Acute exercise stimulates NF-κB in muscle from nondiabetic subjects. In T2DM subjects, exercise had no effect on NF-κB activity, which could be explained by the already elevated NF-κB activity at baseline. Exercise-induced MCP-1 and IL-6 gene expression precedes increases in NF-κB activity, suggesting that other factors promote gene expression of these cytokines during exercise.

Update on the effects of physical activity on insulin sensitivity in humans

PubMed Central

Bird, Stephen R; Hawley, John A

2016-01-01

Purpose and methods This review presents established knowledge on the effects of physical activity (PA) on whole-body insulin sensitivity (SI) and summarises the findings of recent (2013–2016) studies. Discussion and conclusions Recent studies provide further evidence to support the notion that regular PA reduces the risk of insulin resistance, metabolic syndrome and type 2 diabetes, and SI improves when individuals comply with exercise and/or PA guidelines. Many studies indicate a dose response, with higher energy expenditures and higher exercise intensities, including high intensity interval training (HIIT), producing greater benefits on whole-body SI, although these findings are not unanimous. Aerobic exercise interventions can improve SI without an associated increase in cardiorespiratory fitness as measured by maximal or peak oxygen consumption. Both aerobic and resistance exercise can induce improvements in glycaemic regulation, with some suggestions that exercise regimens including both may be more efficacious than either exercise mode alone. Some studies report exercise-induced benefits to SI that are independent of habitual diet and weight loss, while others indicate an association with fat reduction, hence the debate over the relative importance of PA and weight loss continues. During exercise, muscle contraction stimulated improvements in SI are associated with increases in AMPK activity, which deactivates TCB1D1, promoting GLUT4 translocation to the cell membrane and thereby increasing glucose uptake. Postexercise, increases in Akt deactivate TCB1D4 and thereby increase GLUT4 translocation to the cell membrane. The reduction in intramuscular saturated fatty acids and concomitant reductions in ceramides, but not diacylglycerols, provide a potential link between intramuscular lipid content and SI. Increased skeletal muscle capillarisation provides another independent adaptation through which SI is improved, as does enhanced β cell activity. Recent studies are combining exercise interventions with dietary and feeding manipulations to investigate the potential for augmenting the exercise-induced improvements in SI and glycaemic control. PMID:28879026

Update on the effects of physical activity on insulin sensitivity in humans.

PubMed

Bird, Stephen R; Hawley, John A

2016-01-01

This review presents established knowledge on the effects of physical activity (PA) on whole-body insulin sensitivity (SI) and summarises the findings of recent (2013-2016) studies. Recent studies provide further evidence to support the notion that regular PA reduces the risk of insulin resistance, metabolic syndrome and type 2 diabetes, and SI improves when individuals comply with exercise and/or PA guidelines. Many studies indicate a dose response, with higher energy expenditures and higher exercise intensities, including high intensity interval training (HIIT), producing greater benefits on whole-body SI, although these findings are not unanimous. Aerobic exercise interventions can improve SI without an associated increase in cardiorespiratory fitness as measured by maximal or peak oxygen consumption. Both aerobic and resistance exercise can induce improvements in glycaemic regulation, with some suggestions that exercise regimens including both may be more efficacious than either exercise mode alone. Some studies report exercise-induced benefits to SI that are independent of habitual diet and weight loss, while others indicate an association with fat reduction, hence the debate over the relative importance of PA and weight loss continues. During exercise, muscle contraction stimulated improvements in SI are associated with increases in AMPK activity, which deactivates TCB1D1, promoting GLUT4 translocation to the cell membrane and thereby increasing glucose uptake. Postexercise, increases in Akt deactivate TCB1D4 and thereby increase GLUT4 translocation to the cell membrane. The reduction in intramuscular saturated fatty acids and concomitant reductions in ceramides, but not diacylglycerols, provide a potential link between intramuscular lipid content and SI. Increased skeletal muscle capillarisation provides another independent adaptation through which SI is improved, as does enhanced β cell activity. Recent studies are combining exercise interventions with dietary and feeding manipulations to investigate the potential for augmenting the exercise-induced improvements in SI and glycaemic control.

Diet, physical exercise and Orlistat administration increase serum anti-Müllerian hormone (AMH) levels in women with polycystic ovary syndrome (PCOS).

PubMed

Vosnakis, Christos; Georgopoulos, Neoklis A; Rousso, David; Mavromatidis, Georgios; Katsikis, Ilias; Roupas, Nikolaos D; Mamali, Irene; Panidis, Dimitrios

2013-03-01

The present study investigates the combined effect of diet, physical exercise and Orlistat for 24 weeks, on serum anti-Müllerian hormone (AMH) levels in overweight and obese women with polycystic ovary syndrome (PCOS) and in overweight and obese controls. Sixty-one (61) selected women with PCOS and 20 overweight and obese controls followed an energy-restricted diet, physical exercise plus Orlistat administration (120 mg, 3 times per day) for 24 weeks. At baseline, week 12 and week 24, serum levels of AMH, FSH, LH, PRL, androgens, sex hormone-binding globulin (SHBG), glucose, and insulin were measured and Free Androgen Index (FAI) and Insulin Resistance (IR) indices were calculated. In PCOS women, serum AMH levels increased after 12 and 24 weeks of treatment. After 12 weeks LH and SHBG were increased, while Testosterone decreased. After 12 and 24 weeks, FAI was decreased and all indices of IR were significantly improved. We concluded that in overweight and obese women with PCOS Orlistat administration, combined with diet and physical exercise, for 24 weeks, resulted in significant weight loss, improvement of hyperandrogenism and insulin sensitivity, and increased serum AMH levels.

Do youth with type 1 diabetes exercise safely? A focus on patient practices and glycemic outcomes.

PubMed

Roberts, Alissa J; Yi-Frazier, Joyce P; Aitken, Karen E; Mitrovich, Connor A; Pascual, Michael F; Taplin, Craig E

2017-08-01

Insulin adjustments have been shown to reduce glycemic excursions during and after exercise, but little is known about their use in youth with type 1 diabetes (T1D). We aimed to assess practices in youth with T1D around exercise, assess factors that influence practices, and examine associations between key behaviors and glycemic outcomes. We developed the 'Type 1 Diabetes Report of Exercise Practices Survey (T1D-REPS)' and piloted this tool in 100 youth with T1D on an insulin pump. Participants completed a 3-day physical activity recall and 30 days of pump/glucose data were collected. Chart review was conducted for key clinical measures. Eighty-four percent of participants modified their insulin regimen around exercise; only 40% reported adjusting prandial insulin immediately before exercise while 68% reported some modification (suspension or decrease) of basal insulin during exercise. Following exercise, only 10% reported reducing overnight basal insulin. Those who performed ≥ 5 glucose checks/day adjusted basal insulin during exercise more frequently than those with fewer daily glucose checks (33% vs. 13%, p = 0.05, chi-squared = 3.7), and were more likely to report decreasing insulin dose for the bedtime snack following exercise (50% vs. 17%, p = 0.004, chi-squared = 8.2). Despite several studies showing the frequency of hypoglycemia during and after exercise, many youth are not adjusting insulin for exercise. A tool designed to capture patient practices and provide clinicians with a framework for patient education may lead to improved safety around exercise in youth with T1D. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The effects of exercise-induced weight loss on appetite-related peptides and motivation to eat.

PubMed

Martins, C; Kulseng, B; King, N A; Holst, J J; Blundell, J E

2010-04-01

The magnitude of exercise-induced weight loss depends on the extent of compensatory responses. An increase in energy intake is likely to result from changes in the appetite control system toward an orexigenic environment; however, few studies have measured how exercise impacts on both orexigenic and anorexigenic peptides. The aim of the study was to investigate the effects of medium-term exercise on fasting/postprandial levels of appetite-related hormones and subjective appetite sensations in overweight/obese individuals. We conducted a longitudinal study in a university research center. Twenty-two sedentary overweight/obese individuals (age, 36.9 +/- 8.3 yr; body mass index, 31.3 +/- 3.3 kg/m(2)) took part in a 12-wk supervised exercise programme (five times per week, 75% maximal heart rate) and were requested not to change their food intake during the study. We measured changes in body weight and fasting/postprandial plasma levels of glucose, insulin, total ghrelin, acylated ghrelin (AG), peptide YY, and glucagon-like peptide-1 and feelings of appetite. Exercise resulted in a significant reduction in body weight and fasting insulin and an increase in AG plasma levels and fasting hunger sensations. A significant reduction in postprandial insulin plasma levels and a tendency toward an increase in the delayed release of glucagon-like peptide-1 (90-180 min) were also observed after exercise, as well as a significant increase (127%) in the suppression of AG postprandially. Exercise-induced weight loss is associated with physiological and biopsychological changes toward an increased drive to eat in the fasting state. However, this seems to be balanced by an improved satiety response to a meal and improved sensitivity of the appetite control system.

Effect of Combined Exercise Versus Aerobic-Only Training on Skeletal Muscle Lipid Metabolism in a Rodent Model of Type1 Diabetes.

PubMed

Dotzert, Michelle S; McDonald, Matthew W; Murray, Michael R; Nickels, J Zachary; Noble, Earl G; Melling, C W James

2017-12-04

Abnormal skeletal muscle lipid metabolism is associated with insulin resistance in people with type 1 diabetes. Although lipid metabolism is restored with aerobic exercise training, the risk for postexercise hypoglycemia is increased with this modality. Integrating resistance and aerobic exercise is associated with reduced hypoglycemic risk; however, the effects of this exercise modality on lipid metabolism and insulin resistance remain unknown. We compared the effects of combined (aerobic + resistance) versus aerobic exercise training on oxidative capacity and muscle lipid metabolism in a rat model of type 1 diabetes. Male Sprague-Dawley rats were divided into 4 groups: sedentary control (C), sedentary control + diabetes (CD), diabetes + high-intensity aerobic exercise (DAE) and diabetes + combined aerobic and resistance exercise (DARE). Following diabetes induction (20 mg/kg streptozotocin over five days), DAE rats ran for 12 weeks (5 days/week for 1 hour) on a motorized treadmill (27 m/min at a 6-degree grade), and DARE rats alternated daily between running and incremental weighted ladder climbing. After training, DAE showed reduced muscle CD36 protein content and lipid content compared to CD (p≤0.05). DAE rats also had significantly increased citrate synthase (CS) activity compared to CD (p≤0.05). DARE rats showed reduced CD36 protein content compared to CD and increased CS activity compared to CD and DAE rats (p≤0.05). DARE rats demonstrated increased skeletal muscle lipid staining, elevated lipin-1 protein content and insulin sensitivity (p≤0.05). Integration of aerobic and resistance exercise may exert a synergistic effect, producing adaptations characteristic of the "athlete's paradox," including increased capacity to store and oxidize lipids. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Beneficial effects of exercise on offspring obesity and insulin resistance are reduced by maternal high-fat diet

PubMed Central

Schreiber, Saskia; Klaus, Susanne; Kanzleiter, Isabel

2017-01-01

Scope We investigated the long-term effects of maternal high-fat consumption and post-weaning exercise on offspring obesity susceptibility and insulin resistance. Methods C57BL/6J dams were fed either a high-fat (HFD, 40% kcal fat) or low-fat (LFD, 10% kcal fat) semi-synthetic diet during pregnancy and lactation. After weaning, male offspring of both maternal diet groups (mLFD; mHFD) received a LFD. At week 7, half of the mice got access to a running wheel (+RW) as voluntary exercise training. To induce obesity, all offspring groups (mLFD +/-RW and mHFD +/-RW) received HFD from week 15 until week 25. Results Compared to mLFD, mHFD offspring were more prone to HFD-induced body fat gain and exhibited an increased liver mass which was not due to increased hepatic triglyceride levels. RW improved the endurance capacity in mLFD, but not in mHFD offspring. Additionally, mHFD offspring +RW exhibited higher plasma insulin levels during glucose tolerance test and an elevated basal pancreatic insulin production compared to mLFD offspring. Conclusion Taken together, maternal HFD reduced offspring responsiveness to the beneficial effects of voluntary exercise training regarding the improvement of endurance capacity, reduction of fat mass gain, and amelioration of HFD-induced insulin resistance. PMID:28235071

The Effect of Regular Exercise on Insulin Sensitivity in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis

PubMed Central

Hackett, Daniel A.; Baker, Michael K.

2016-01-01

The purpose of this study was to examine the effect of regular exercise training on insulin sensitivity in adults with type 2 diabetes mellitus (T2DM) using the pooled data available from randomised controlled trials. In addition, we sought to determine whether short-term periods of physical inactivity diminish the exercise-induced improvement in insulin sensitivity. Eligible trials included exercise interventions that involved ≥3 exercise sessions, and reported a dynamic measurement of insulin sensitivity. There was a significant pooled effect size (ES) for the effect of exercise on insulin sensitivity (ES, –0.588; 95% confidence interval [CI], –0.816 to –0.359; P<0.001). Of the 14 studies included for meta-analyses, nine studies reported the time of data collection from the last exercise bout. There was a significant improvement in insulin sensitivity in favour of exercise versus control between 48 and 72 hours after exercise (ES, –0.702; 95% CI, –1.392 to –0.012; P=0.046); and this persisted when insulin sensitivity was measured more than 72 hours after the last exercise session (ES, –0.890; 95% CI, –1.675 to –0.105; P=0.026). Regular exercise has a significant benefit on insulin sensitivity in adults with T2DM and this may persist beyond 72 hours after the last exercise session. PMID:27535644

Effect of cocoa flavanols and exercise on cardiometabolic risk factors in overweight and obese subjects.

PubMed

Davison, K; Coates, A M; Buckley, J D; Howe, P R C

2008-08-01

Impaired endothelial function in obesity may reduce blood flow to sites of metabolism, contributing to impaired fat oxidation and insulin resistance. This study investigated the effects of cocoa flavanols and regular exercise, interventions known to improve endothelial function, on cardiometabolic function and body composition in obese individuals. Overweight and obese adults were randomly assigned to high-flavanol cocoa (HF, 902 mg flavanols), HF and exercise, low-flavanol cocoa (LF, 36 mg flavanols), or LF and exercise for 12 weeks (exercise duration was 3 x 45 min per week at 75% of age-predicted maximum heart rate). Body composition was assessed by dual-energy X-ray absorptiometry at 0 and 12 weeks. Brachial artery flow-mediated dilatation (FMD), supine blood pressure (BP) and fasting plasma insulin, and glucose levels were assessed at 0, 6 and 12 weeks, respectively. Insulin sensitivity/resistance was determined using the modified homeostasis model assessment of insulin resistance (HOMA2). A total of 49 subjects (M=18; F=31) completed the intervention. Baseline averages were as follows: body mass index=33.5 kg/m(2); BP=123/76 mm Hg; HOMA2=2.4; FMD=4.3%; rate of fat oxidation during exercise=0.34 g min(-1); abdominal fat=45.7% of total abdominal mass. Compared to LF, HF increased FMD acutely (2 h post-dose) by 2.4% (P<0.01) and chronically (over 12 weeks; P<0.01) by 1.6% and reduced insulin resistance by 0.31% (P<0.05), diastolic BP by 1.6 mm Hg and mean arterial BP by 1.2 mm Hg (P<0.05), independent of exercise. Regular exercise increased fat oxidation during exercise by 0.10 g min(-1) (P<0.01) and reduced abdominal fat by 0.92% (P<0.05). Although HF consumption was shown to improve endothelial function, it did not enhance the effects of exercise on body fat and fat metabolism in obese subjects. However, it may be useful for reducing cardiometabolic risk factors in this population.

Atypical blood glucose response to continuous and interval exercise in a person with type 1 diabetes: a case report.

PubMed

Moser, Othmar; Tschakert, Gerhard; Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R; Koehler, Gerd; Eckstein, Max L; Bracken, Richard M; Hofmann, Peter

2017-06-30

Therapy must be adapted for people with type 1 diabetes to avoid exercise-induced hypoglycemia caused by increased exercise-related glucose uptake into muscles. Therefore, to avoid hypoglycemia, the preexercise short-acting insulin dose must be reduced for safety reasons. We report a case of a man with long-lasting type 1 diabetes in whom no blood glucose decrease during different types of exercise with varying exercise intensities and modes was found, despite physiological hormone responses. A Caucasian man diagnosed with type 1 diabetes for 24 years performed three different continuous high-intensity interval cycle ergometer exercises as part of a clinical trial (ClinicalTrials.gov identifier NCT02075567). Intensities for both modes of exercises were set at 5% below and 5% above the first lactate turn point and 5% below the second lactate turn point. Short-acting insulin doses were reduced by 25%, 50%, and 75%, respectively. Measurements taken included blood glucose, blood lactate, gas exchange, heart rate, adrenaline, noradrenaline, cortisol, glucagon, and insulin-like growth factor-1. Unexpectedly, no significant blood glucose decreases were observed during all exercise sessions (start versus end, 12.97 ± 2.12 versus 12.61 ± 2.66 mmol L -1 , p = 0.259). All hormones showed the expected response, dependent on the different intensities and modes of exercises. People with type 1 diabetes typically experience a decrease in blood glucose levels, particularly during low- and moderate-intensity exercises. In our patient, we clearly found no decline in blood glucose, despite a normal hormone response and no history of any insulin insensitivity. This report indicates that there might be patients for whom the recommended preexercise therapy adaptation to avoid exercise-induced hypoglycemia needs to be questioned because this could increase the risk of severe hyperglycemia and ketosis.

Exercise training decreases activation of the mitochondrial fission protein dynamin-related protein-1 in insulin-resistant human skeletal muscle.

PubMed

Fealy, Ciaran E; Mulya, Anny; Lai, Nicola; Kirwan, John P

2014-08-01

Defects in mitochondrial dynamics, the processes of fission, fusion, and mitochondrial autophagy, may contribute to metabolic disease including type 2 diabetes. Dynamin-related protein-1 (Drp1) is a GTPase protein that plays a central role in mitochondrial fission. We hypothesized that aerobic exercise training would decrease Drp1 Ser(616) phosphorylation and increase fat oxidation and insulin sensitivity in obese (body mass index: 34.6 ± 0.8 kg/m(2)) insulin-resistant adults. Seventeen subjects performed supervised exercise for 60 min/day, 5 days/wk at 80-85% of maximal heart rate for 12 wk. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp, and fat oxidation was determined by indirect calorimetry. Skeletal muscle biopsies were obtained from the vastus lateralis muscle before and after the 12-wk program. The exercise intervention increased insulin sensitivity 2.1 ± 0.2-fold (P < 0.01) and fat oxidation 1.3 ± 0.3-fold (P < 0.01). Phosphorylation of Drp1 at Ser(616) was decreased (pre vs. post: 0.81 ± 0.15 vs. 0.58 ± 0.14 arbitrary units; P < 0.05) following the intervention. Furthermore, reductions in Drp1 Ser(616) phosphorylation were negatively correlated with increases in fat oxidation (r = -0.58; P < 0.05) and insulin sensitivity (rho = -0.52; P < 0.05). We also examined expression of genes related to mitochondrial dynamics. Dynamin1-like protein (DNM1L; P < 0.01), the gene that codes for Drp1, and Optic atrophy 1 (OPA1; P = 0.05) were significantly upregulated following the intervention, while there was a trend towards an increase in expression of both mitofusin protein MFN1 (P = 0.08) and MFN2 (P = 0.07). These are the first data to suggest that lifestyle-mediated improvements in substrate metabolism and insulin sensitivity in obese insulin-resistant adults may be regulated through decreased activation of the mitochondrial fission protein Drp1. Copyright © 2014 the American Physiological Society.

Characterization of Exercise and Alcohol Self-Management Behaviors of Type 1 Diabetes Patients on Insulin Pump Therapy.

PubMed

Grando, Maria Adela; Groat, Danielle; Soni, Hiral; Boyle, Mary; Bailey, Marilyn; Thompson, Bithika; Cook, Curtiss B

2017-03-01

There is a lack of systematic ways to analyze how diabetes patients use their insulin pumps to self-manage blood glucose to compensate for alcohol ingestion and exercise. The objective was to analyze "real-life" insulin dosing decisions occurring in conjunction with alcohol intake and exercise among patients using insulin pumps. We recruited adult type 1 diabetes (T1D) patients on insulin pump therapy. Participants were asked to maintain their daily routines, including those related to exercising and consuming alcohol, and keep a 30-day journal on exercise performed and alcohol consumed. Thirty days of insulin pump data were downloaded. Participants' actual insulin dosing behaviors were compared against their self-reported behaviors in the setting of exercise and alcohol. Nineteen T1D patients were recruited and over 4000 interactions with the insulin pump were analyzed. The analysis exposed variability in how subjects perceived the effects of exercise/alcohol on their blood glucose, inconsistencies between self-reported and observed behaviors, and higher rates of blood glucose control behaviors for exercise versus alcohol. Compensation techniques and perceptions on how exercise and alcohol affect their blood glucose levels vary between patients. Improved individualized educational techniques that take into consideration a patient's unique life style are needed to help patients effectively apply alcohol and exercise compensation techniques.

Exercise rescues obese mothers' insulin sensitivity, placental hypoxia and male offspring insulin sensitivity.

PubMed

Fernandez-Twinn, Denise S; Gascoin, Geraldine; Musial, Barbara; Carr, Sarah; Duque-Guimaraes, Daniella; Blackmore, Heather L; Alfaradhi, Maria Z; Loche, Elena; Sferruzzi-Perri, Amanda N; Fowden, Abigail L; Ozanne, Susan E

2017-03-14

The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance. Maternal hyperinsulinemia (independent of maternal body weight and composition) strongly associated with offspring insulin resistance. To test causality, we implemented an exercise intervention that improved maternal insulin sensitivity without changing maternal body weight or composition. This maternal intervention prevented excess placental lipid deposition and hypoxia (independent of sex) and insulin resistance in male offspring. We conclude that hyperinsulinemia is a key programming factor and therefore an important interventional target during obese pregnancy, and propose moderate exercise as a promising strategy to improve metabolic outcome in both the obese mother and her offspring.

A novel, non-invasive transdermal fluid sampling methodology: IGF-I measurement following exercise

USDA-ARS?s Scientific Manuscript database

This study tested the hypothesis that transdermal fluid (TDF) provides a more sensitive and accurate measure of exercise-induced increases in insulin-like growth factor-I (IGF-I) than serum, and that these increases are detectable proximal, but not distal, to the exercising muscle. A novel, noninvas...

Randomized trial of a dual-hormone artificial pancreas with dosing adjustment during exercise compared with no adjustment and sensor-augmented pump therapy.

PubMed

Jacobs, P G; El Youssef, J; Reddy, R; Resalat, N; Branigan, D; Condon, J; Preiser, N; Ramsey, K; Jones, M; Edwards, C; Kuehl, K; Leitschuh, J; Rajhbeharrysingh, U; Castle, J R

2016-11-01

To test whether adjusting insulin and glucagon in response to exercise within a dual-hormone artificial pancreas (AP) reduces exercise-related hypoglycaemia. In random order, 21 adults with type 1 diabetes (T1D) underwent three 22-hour experimental sessions: AP with exercise dosing adjustment (APX); AP with no exercise dosing adjustment (APN); and sensor-augmented pump (SAP) therapy. After an overnight stay and 2 hours after breakfast, participants exercised for 45 minutes at 60% of their maximum heart rate, with no snack given before exercise. During APX, insulin was decreased and glucagon was increased at exercise onset, while during SAP therapy, subjects could adjust dosing before exercise. The two primary outcomes were percentage of time spent in hypoglycaemia (<3.9 mmol/L) and percentage of time spent in euglycaemia (3.9-10 mmol/L) from the start of exercise to the end of the study. The mean (95% confidence interval) times spent in hypoglycaemia (<3.9 mmol/L) after the start of exercise were 0.3% (-0.1, 0.7) for APX, 3.1% (0.8, 5.3) for APN, and 0.8% (0.1, 1.4) for SAP therapy. There was an absolute difference of 2.8% less time spent in hypoglycaemia for APX versus APN (p = .001) and 0.5% less time spent in hypoglycaemia for APX versus SAP therapy (p = .16). Mean time spent in euglycaemia was similar across the different sessions. Adjusting insulin and glucagon delivery at exercise onset within a dual-hormone AP significantly reduces hypoglycaemia compared with no adjustment and performs similarly to SAP therapy when insulin is adjusted before exercise. © 2016 John Wiley & Sons Ltd.

Homeostasis Model Assessment-Adiponectin: the role of different types of physical exercise in obese adolescents.

PubMed

da Silveira Campos, Raquel M; Landi Masquio, Deborah C; Campos Corgosinho, Flávia; de Lima Sanches, Priscila; de Piano, Aline; Carnier, June; Leão da Silva, Patrícia; Grotti Clemente, Ana P; de Castro Ferreira Vicente, Sofia E; Oyama, Lila M; da Penha Oller do Nascimento, Claudia M; Tock, Lian; Tufik, Sergio; de Mello, Marco T; Dâmaso, Ana R

2017-06-01

Homeostasis Model Assessment-Adiponectin (HOMA-AD) is suggesting a new biomarker of insulin resistance in obese population. In this way, the purpose of this study was to investigate the effects of different kinds of exercise in the sensitive index predictor of insulin resistance. A total of 148 obese adolescents were enrolled in the program. They aged 15-19 y, with Body Mass Index (BMI) ≥P95th and were submitted to 1 year of interdisciplinary weight loss therapy, randomized in two groups, aerobic training (AT) (N.=51) and aerobic plus resistance training (N.=97). Blood samples were collected to analyze adiponectin, glucose and insulin concentrations. The insulin resistance was measured by HOMA-AD and Homeostasis Model Assessment Insulin Resistance Index (HOMA-IR). Both kinds of exercise training promoted a decrease in body mass, body mass index, fat mass, visceral and subcutaneous fat. However, only aerobic plus resistance training was effective to reduce HOMA-AD, insulin and glucose concentration; and increase insulin sensibility and adiponectin concentration. The aerobic plus resistance training was more effective than AT alone to improve the HOMA-AD, suggesting clinical application on obesity, diabetes, atherosclerosis and metabolic syndrome control in the pediatric population.

The influence of nighttime feeding of carbohydrate or protein combined with exercise training on appetite and cardiometabolic risk in young obese women.

PubMed

Ormsbee, Michael J; Kinsey, Amber W; Eddy, Wyatt R; Madzima, Takudzwa A; Arciero, Paul J; Figueroa, Arturo; Panton, Lynn B

2015-01-01

Single macronutrient intake prior to sleep reduces appetite but may negatively impact insulin sensitivity in sedentary obese women. The present study examined the additive impact of nighttime feeding of whey (WH), casein (CAS), or carbohydrate (CHO) combined with exercise training on appetite, cardiometabolic health, and strength in obese women. Thirty-seven sedentary obese women (WH, n = 13, body mass index (BMI) 34.4 ± 1.3 kg/m(2); CAS, n = 14, BMI 36.5 ± 1.8 kg/m(2); CHO, n = 10, BMI 33.1 ± 1.7 kg/m(2)) consumed WH, CAS, or CHO (140-150 kcal/serving), every night of the week, within 30 min of sleep, for 4 weeks. Supervised exercise training (2 days of resistance training and 1 day of high-intensity interval training) was completed 3 days per week. Pre- and post-testing measurements included appetite ratings, mood state, resting metabolic rate, fasting lipids, glucose, and hormonal responses (insulin, leptin, adiponectin, hs-CRP, IGF-1, and cortisol), body composition, and strength. Nighttime intake of CAS significantly (p < 0.05) increased morning satiety (pretraining, 25 ± 5; post-training 41 ± 6) more than WH (pretraining, 34 ± 5; post-training, 35 ± 6) or CHO (pre 40 ± 8, post 43 ± 7). Exercise training increased lean mass and strength, decreased body fat, and improved mood state in all groups. No other differences were noted. Nighttime feeding of CAS combined with exercise training increased morning satiety more than WH or CHO. Nighttime feeding for 4 weeks did not impact insulin sensitivity (assessed via homeostatic model assessment of insulin resistance) when combined with exercise training in obese women. ClinicalTrial.gov: NCT01830946.

A Single Nucleotide Polymorphism Associates With the Response of Muscle ATP Synthesis to Long-Term Exercise Training in Relatives of Type 2 Diabetic Humans

PubMed Central

Kacerovsky-Bielesz, Gertrud; Kacerovsky, Michaela; Chmelik, Marek; Farukuoye, Michaela; Ling, Charlotte; Pokan, Rochus; Tschan, Harald; Szendroedi, Julia; Schmid, Albrecht Ingo; Gruber, Stephan; Herder, Christian; Wolzt, Michael; Moser, Ewald; Pacini, Giovanni; Smekal, Gerhard; Groop, Leif; Roden, Michael

2012-01-01

OBJECTIVE Myocellular ATP synthesis (fATP) associates with insulin sensitivity in first-degree relatives of subjects with type 2 diabetes. Short-term endurance training can modify their fATP and insulin sensitivity. This study examines the effects of moderate long-term exercise using endurance or resistance training in this cohort. RESEARCH DESIGN AND METHODS A randomized, parallel-group trial tested 16 glucose-tolerant nonobese relatives (8 subjects in the endurance training group and 8 subjects in the resistance training group) before and after 26 weeks of endurance or resistance training. Exercise performance was assessed from power output and oxygen uptake (Vo2) during incremental tests and from maximal torque of knee flexors (MaxTflex) and extensors (MaxText) using isokinetic dynamometry. fATP and ectopic lipids were measured with 1H/31P magnetic resonance spectroscopy. RESULTS Endurance training increased power output and Vo2 by 44 and 30%, respectively (both P < 0.001), whereas resistance training increased MaxText and MaxTflex by 23 and 40%, respectively (both P < 0.001). Across all groups, insulin sensitivity (382 ± 90 vs. 389 ± 40 mL ⋅ min−1 ⋅ m−2) and ectopic lipid contents were comparable after exercise training. However, 8 of 16 relatives had 26% greater fATP, increasing from 9.5 ± 2.3 to 11.9 ± 2.4 μmol ⋅ mL−1 ⋅ m−1 (P < 0.05). Six of eight responders were carriers of the G/G single nucleotide polymorphism rs540467 of the NDUFB6 gene (P = 0.019), which encodes a subunit of mitochondrial complex I. CONCLUSIONS Moderate exercise training for 6 months does not necessarily improve insulin sensitivity but may increase ATP synthase flux. Genetic predisposition can modify the individual response of the ATP synthase flux independently of insulin sensitivity. PMID:22190678

Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle

PubMed Central

Treebak, Jonas T; Pehmøller, Christian; Kristensen, Jonas M; Kjøbsted, Rasmus; Birk, Jesper B; Schjerling, Peter; Richter, Erik A; Goodyear, Laurie J; Wojtaszewski, Jørgen F P

2014-01-01

We investigated the phosphorylation signatures of two Rab-GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers exercised in the fasted or fed state and muscle biopsies were taken before and immediately after exercise. We identified TBC1D1/4 phospho-sites that (1) did not respond to exercise or postprandial increase in insulin (TBC1D4: S666), (2) responded to insulin only (TBC1D4: S318), (3) responded to exercise only (TBC1D1: S237, S660, S700; TBC1D4: S588, S751), and (4) responded to both insulin and exercise (TBC1D1: T596; TBC1D4: S341, T642, S704). In the insulin-stimulated leg, Akt phosphorylation of both T308 and S473 correlated significantly with multiple sites on both TBC1D1 (T596) and TBC1D4 (S318, S341, S704). Interestingly, in the exercised leg in the fasted state TBC1D1 phosphorylation (S237, T596) correlated significantly with the activity of the α2/β2/γ3 AMPK trimer, whereas TBC1D4 phosphorylation (S341, S704) correlated with the activity of the α2/β2/γ1 AMPK trimer. Our data show differential phosphorylation of TBC1D1 and TBC1D4 in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK regulated phosphorylation of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between species is problematic. Key points Phosphorylation signature patterns on TBC1D1 and TBC1D4 proteins in the insulin–glucose pathway were investigated in human skeletal muscle in response to physiological insulin and exercise. In response to postprandial increase in insulin, Akt phosphorylation of T308 and S473 correlated significantly with sites on TBC1D1 (T596) and TBC1D4 (S318, S341, S704). Exercise induced phosphorylation of TBC1D1 (S237, T596) that correlated significantly with activity of the α2/β2/γ3 AMPK trimer, whereas TBC1D4 phosphorylation (S341, S704) with exercise correlated with activity of the α2/β2/γ1 AMPK trimer. TBC1D1 phosphorylation signatures with exercise/muscle contraction were comparable between human and mouse skeletal muscle, and AMPK regulated phosphorylation of these sites in mouse muscle, whereas contraction and exercise elicited different TBC1D4 phosphorylation patterns in mouse compared with human muscle. Our results show differential phosphorylation of TBC1D1 and TBC1D4 in response to physiological stimuli in human skeletal muscle and indicate that Akt and AMPK may be upstream kinases. PMID:24247980

Insulin Management Strategies for Exercise in Diabetes.

PubMed

Zaharieva, Dessi P; Riddell, Michael C

2017-10-01

There is no question that regular exercise can be beneficial and lead to improvements in overall cardiovascular health. However, for patients with diabetes, exercise can also lead to challenges in maintaining blood glucose balance, particularly if patients are prescribed insulin or certain oral hypoglycemic agents. Hypoglycemia is the most common adverse event associated with exercise and insulin therapy, and the fear of hypoglycemia is also the greatest barrier to exercise for many patients. With the appropriate insulin dose adjustments and, in some cases, carbohydrate supplementation, blood glucose levels can be better managed during exercise and in recovery. In general, insulin strategies that help facilitate weight loss with regular exercise and recommendations around exercise adjustments to prevent hypoglycemia and hyperglycemia are often not discussed with patients because the recommendations can be complex and may differ from one individual to the next. This is a review of the current published literature on insulin dose adjustments and starting-point strategies for patients with diabetes in preparation for safe exercise. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

NMR studies of muscle glycogen synthesis in insulin-resistant offspring of parents with non-insulin-dependent diabetes mellitus immediately after glycogen-depleting exercise.

PubMed Central

Price, T B; Perseghin, G; Duleba, A; Chen, W; Chase, J; Rothman, D L; Shulman, R G; Shulman, G I

1996-01-01

To examine the impact of insulin resistance on the insulin-dependent and insulin-independent portions of muscle glycogen synthesis during recovery from exercise, we studied eight young, lean, normoglycemic insulin-resistant (IR) offspring of individuals with non-insulin-dependent diabetes mellitus and eight age-weight matched control (CON) subjects after plantar flexion exercise that lowered muscle glycogen to approximately 25% of resting concentration. After approximately 20 min of exercise, intramuscular glucose 6-phosphate and glycogen were simultaneously monitored with 31P and 13C NMR spectroscopies. The postexercise rate of glycogen resynthesis was nonlinear. Glycogen synthesis rates during the initial insulin independent portion (0-1 hr of recovery) were similar in the two groups (IR, 15.5 +/- 1.3 mM/hr and CON, 15.8 +/- 1.7 mM/hr); however, over the next 4 hr, insulin-dependent glycogen synthesis was significantly reduced in the IR group [IR, 0.1 +/- 0.5 mM/hr and CON, 2.9 +/- 0.2 mM/hr; (P < or = 0.001)]. After exercise there was an initial rise in glucose 6-phosphate concentrations that returned to baseline after the first hour of recovery in both groups. In summary, we found that following muscle glycogen-depleting exercise, IR offspring of parents with non-insulin-dependent diabetes mellitus had (i) normal rates of muscle glycogen synthesis during the insulin-independent phase of recovery from exercise and (ii) severely diminished rates of muscle glycogen synthesis during the subsequent recovery period (2-5 hr), which has previously been shown to be insulin-dependent in normal CON subjects. These data provide evidence that exercise and insulin stimulate muscle glycogen synthesis in humans by different mechanisms and that in the IR subjects the early response to stimulation by exercise is normal. PMID:8643574

Insulin and glucose responses during bed rest with isotonic and isometric exercise

NASA Technical Reports Server (NTRS)

Dolkas, C. B.; Greenleaf, J. E.

1977-01-01

The effects of daily intensive isotonic (68% maximum oxygen uptake) and isometric (21% maximum extension force) leg exercise on plasma insulin and glucose responses to an oral glucose tolerance test (OGTT) during 14-day bed-rest (BR) periods were investigated in seven young healthy men. The OGTT was given during ambulatory control and on day 10 of the no-exercise, isotonic, and isometric exercise BR periods during the 15-wk study. The subjects were placed on a controlled diet starting 10 days before each BR period. During BR, basal plasma glucose concentration remained unchanged with no exercise, but increased (P less 0.05) to 87-89 mg/100 ml with both exercise regimens on day 2, and then fell slightly below control levels on day 13. The fall in glucose content during BR was independent of the exercise regimen and was an adjustment for the loss of plasma volume. The intensity of the responses of insulin and glucose to the OGTT was inversely proportional to the total daily energy expenditure during BR. It was estimated that at least 1020 kcal/day must be provided by supplemental exercise to restore the hyperinsulinemia to control levels.

Whey protein hydrolysate increases translocation of GLUT-4 to the plasma membrane independent of insulin in wistar rats.

PubMed

Morato, Priscila Neder; Lollo, Pablo Christiano Barboza; Moura, Carolina Soares; Batista, Thiago Martins; Camargo, Rafael Ludemann; Carneiro, Everardo Magalhães; Amaya-Farfan, Jaime

2013-01-01

Whey protein (WP) and whey protein hydrolysate (WPH) have the recognized capacity to increase glycogen stores. The objective of this study was to verify if consuming WP and WPH could also increase the concentration of the glucose transporters GLUT-1 and GLUT-4 in the plasma membrane (PM) of the muscle cells of sedentary and exercised animals. Forty-eight Wistar rats were divided into 6 groups (n = 8 per group), were treated and fed with experimental diets for 9 days as follows: a) control casein (CAS); b) WP; c) WPH; d) CAS exercised; e) WP exercised; and f) WPH exercised. After the experimental period, the animals were sacrificed, muscle GLUT-1 and GLUT-4, p85, Akt and phosphorylated Akt were analyzed by western blotting, and the glycogen, blood amino acids, insulin levels and biochemical health indicators were analyzed using standard methods. Consumption of WPH significantly increased the concentrations of GLUT-4 in the PM and glycogen, whereas the GLUT-1 and insulin levels and the health indicators showed no alterations. The physical exercise associated with consumption of WPH had favorable effects on glucose transport into muscle. These results should encourage new studies dealing with the potential of both WP and WPH for the treatment or prevention of type II diabetes, a disease in which there is reduced translocation of GLUT-4 to the plasma membrane.

Cerebellar Insulin/IGF-1 signaling in diabetic rats: Effects of exercise training.

PubMed

Borges, Mariana Eiras; Ribeiro, Alessandra Mussi; Pauli, José Rodrigo; Arantes, Luciana Mendonça; Luciano, Eliete; de Moura, Leandro Pereira; de Almeida Leme, José Alexandre Curiacos; Medeiros, Alessandra; Bertolini, Natália Oliveira; Sibuya, Clarice Yoshiko; Gomes, Ricardo José

2017-02-03

The Diabetes Mellitus (DM) is a chronic disease associated with loss of brain regions such as the cerebellum, increasing the risk of developing neurodegenerative diseases such as Parkinson's disease (PD). In the brain of diabetic and PD organisms the insulin/IGF-1 signaling is altered. Exercise training is an effective intervention for the prevention of neurodegerative diseases since it release neurotrophic factors and regulating insulin/IGF-1 signaling in the brain. This study aimed to evaluate the proteins involved in the insulin/IGF-1 pathway in the cerebellum of diabetic rats subjected to exercise training protocol. Wistar rats were distributed in four groups: sedentary control (SC), trained control (TC), sedentary diabetic (SD) and trained diabetic (TD). Diabetes was induced by Alloxan (ALX) (32mg/kgb.w.). The training program consisted in swimming 5days/week, 1h/day, during 6 weeks, supporting an overload corresponding to 90% of the anaerobic threshold. At the end, cerebellum was extracted to determinate the protein expression of GSK-3β, IRβ and IGF-1R and the phosphorylation of β-amyloid, Tau, ERK1+ERK2 by Western Blot analysis. All dependent variables were analyzed by one-way analysis of variance with significance level of 5%. Diabetes causes hyperglycemia in both diabetic groups; however, in TD, there was a reduction in hyperglycemia compared to SD. Diabetes increased Tau and β-amyloid phosphorylation in both SD and TD groups. Furthermore, aerobic exercise increased ERK1+ERK2 expression in TC. The data showed that in cerebellum of diabetic rats induced by alloxan there are some proteins expression like Parkinson cerebellum increased, and the exercise training was not able to modulate the expression of these proteins. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The glucose-dependent insulinotropic polypeptide and glucose-stimulated insulin response to exercise training and diet in obesity

PubMed Central

Kelly, Karen R.; Brooks, Latina M.; Solomon, Thomas P. J.; Kashyap, Sangeeta R.; O'Leary, Valerie B.; Kirwan, John P.

2009-01-01

Aging and obesity are characterized by decreased β-cell sensitivity and defects in the potentiation of nutrient-stimulated insulin secretion by GIP. Exercise and diet are known to improve glucose metabolism and the pancreatic insulin response to glucose, and this effect may be mediated through the incretin effect of GIP. The purpose of this study was to assess the effects of a 12-wk exercise training intervention (5 days/wk, 60 min/day, 75% V̇o2 max) combined with a eucaloric (EX, n = 10) or hypocaloric (EX-HYPO, pre: 1,945 ± 190, post: 1,269 ± 70, kcal/day; n = 9) diet on the GIP response to glucose in older (66.8 ± 1.5 yr), obese (34.4 ± 1.7 kg/m2) adults with impaired glucose tolerance. In addition to GIP, plasma PYY3–36, insulin, and glucose responses were measured during a 3-h, 75-g oral glucose tolerance test. Both interventions led to a significant improvement in V̇o2 max (P < 0.05). Weight loss (kg) was significant in both groups but was greater after EX-HYPO (−8.3 ± 1.1 vs. −2.8 ± 0.5, P = 0.002). The glucose-stimulated insulin response was reduced after EX-HYPO (P = 0.02), as was the glucose-stimulated GIP response (P < 0.05). Furthermore, after the intervention, changes in insulin (ΔI0–30/ΔG0–30) and GIP (Δ0–30) secretion were correlated (r = 0.69, P = 0.05). The PYY3–36 (Δ0–30) response to glucose was increased after both interventions (P < 0.05). We conclude that 1) a combination of caloric restriction and exercise reduces the GIP response to ingested glucose, 2) GIP may mediate the attenuated glucose-stimulated insulin response after exercise/diet interventions, and 3) the increased PYY3–36 response represents an improved capacity to regulate satiety and potentially body weight in older, obese, insulin-resistant adults. PMID:19351807

Pumping Insulin during Exercise: What Healthcare Providers and Diabetic Patients Need To Know.

ERIC Educational Resources Information Center

Colberg, Sheri R.; Walsh, John

2002-01-01

Exercise can decrease insulin resistance. Insulin pumps deliver precise insulin adjustments that improve fuel availability and provide glycemic control to help people with diabetes overcome obstacles to exercise. Physicians, patients, and healthcare providers should be familiar with the features and nuances of specific pump models and follow basic…

Exercise Training-Induced Adaptations Associated with Increases in Skeletal Muscle Glycogen Content

PubMed Central

Manabe, Yasuko; Gollisch, Katja S.C.; Holton, Laura; Kim, Young–Bum; Brandauer, Josef; Fujii, Nobuharu L.; Hirshman, Michael F.; Goodyear, Laurie J.

2012-01-01

Chronic exercise training results in numerous skeletal muscle adaptations, including increases in insulin sensitivity and glycogen content. To understand the mechanism for increased muscle glycogen, we studied the effects of exercise training on glycogen regulatory proteins in rat skeletal muscle. Female Sprague Dawley rats performed voluntary wheel running for 1, 4, or 7 weeks. After 7 weeks of training, insulin-stimulated glucose uptake was increased in epitrochlearis muscle. Compared to sedentary control rats, muscle glycogen did not change after 1 week of training, but increased significantly after 4 and 7 weeks. The increases in muscle glycogen were accompanied by elevated glycogen synthase activity and protein expression. To assess the regulation of glycogen synthase, we examined its major activator, protein phosphatase 1 (PP1), and its major deactivator, glycogen synthase kinase 3 (GSK3). Consistent with glycogen synthase activity, PP1 activity was unchanged after 1 week of training but significantly increased after 4 and 7 weeks of training. Protein expression of RGL(GM), another regulatory PP1 subunit, significantly decreased after 4 and 7 weeks of training. Unlike PP1, GSK3 phosphorylation did not follow the pattern of glycogen synthase activity. The ~40% decrease in GSK-3α phosphorylation after 1 week of exercise training persisted until 7 weeks and may function as a negative feedback to elevated glycogen. Our findings suggest that exercise training-induced increases in muscle glycogen content could be regulated by multiple mechanisms including enhanced insulin sensitivity, glycogen synthase expression, allosteric activation of glycogen synthase and PP1activity. PMID:23206309

Glycemic control during consecutive days with prolonged walking exercise in individuals with type 1 diabetes mellitus.

PubMed

van Dijk, Jan-Willem; Eijsvogels, Thijs M; Nyakayiru, Jean; Schreuder, Tim H A; Hopman, Maria T; Thijssen, Dick H; van Loon, Luc J C

2016-07-01

Despite its general benefits for health, exercise complicates the maintenance of stable blood glucose concentrations in individuals with type 1 diabetes. The aim of the current study was to examine changes in food intake, insulin administration, and 24-h glycemic control in response to consecutive days with prolonged walking exercise (∼8h daily) in individuals with type 1 diabetes. Ten individuals with type 1 diabetes participating in the worlds' largest walking event were recruited for this observational study. Simultaneous measurements of 24-h glycemic control (continuous glucose monitoring), insulin administration and food intake were performed during a non-walking day (control) and during three subsequent days with prolonged walking exercise (daily distance 40 or 50km). Despite an increase in daily energy (31±18%; p<0.01) and carbohydrate (82±71g; p<0.01) intake during walking days, subjects lowered their insulin administration by 26±16% relative to the control day (p<0.01). Average 24-h blood glucose concentrations, the prevalence of hyperglycemia (blood glucose >10 mmol/L) and hypoglycemia (blood glucose <3.9mmol/L) did not differ between the control day and walking days (p>0.05 for all variables). The prolonged walking exercise was associated with a modest increase in glycemic variability compared with the control day (p<0.05). Prolonged walking exercise allows for profound reductions in daily insulin administration in persons with type 1 diabetes, despite large increments in energy and carbohydrate intake. When taking such adjustments into account, prolonged moderate-intensity exercise does not necessarily impair 24-h glycemic control. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

PubMed

Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

2010-01-01

Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

Influence of Acute and Chronic Exercise on Glucose Uptake

PubMed Central

Röhling, Martin; Herder, Christian; Stemper, Theodor; Müssig, Karsten

2016-01-01

Insulin resistance plays a key role in the development of type 2 diabetes. It arises from a combination of genetic predisposition and environmental and lifestyle factors including lack of physical exercise and poor nutrition habits. The increased risk of type 2 diabetes is molecularly based on defects in insulin signaling, insulin secretion, and inflammation. The present review aims to give an overview on the molecular mechanisms underlying the uptake of glucose and related signaling pathways after acute and chronic exercise. Physical exercise, as crucial part in the prevention and treatment of diabetes, has marked acute and chronic effects on glucose disposal and related inflammatory signaling pathways. Exercise can stimulate molecular signaling pathways leading to glucose transport into the cell. Furthermore, physical exercise has the potential to modulate inflammatory processes by affecting specific inflammatory signaling pathways which can interfere with signaling pathways of the glucose uptake. The intensity of physical training appears to be the primary determinant of the degree of metabolic improvement modulating the molecular signaling pathways in a dose-response pattern, whereas training modality seems to have a secondary role. PMID:27069930

High intensity interval training improves liver and adipose tissue insulin sensitivity.

PubMed

Marcinko, Katarina; Sikkema, Sarah R; Samaan, M Constantine; Kemp, Bruce E; Fullerton, Morgan D; Steinberg, Gregory R

2015-12-01

Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine-alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

Leptin and leptin receptor gene polymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals: the HERITAGE family study.

PubMed

Lakka, Timo A; Rankinen, Tuomo; Weisnagel, S John; Chagnon, Yvon C; Lakka, Hanna-Maaria; Ukkola, Olavi; Boulé, Normand; Rice, Treva; Leon, Arthur S; Skinner, James S; Wilmore, Jack H; Rao, D C; Bergman, Richard; Bouchard, Claude

2004-06-01

We recently reported that a genomic region close to the leptin locus was linked to fasting insulin response to exercise training in nondiabetic white subjects. We tested the hypothesis that common exonic variants in the leptin (LEP) and leptin receptor (LEPR) genes modify the effects of regular physical activity on glucose homeostasis in nondiabetic whites (n = 397) and blacks (n = 143). In whites, exercise increased insulin sensitivity index (P = 0.041) and disposition index (P = 0.046) in the LEPR 109R allele carriers but not in the K109K homozygotes, increased glucose disappearance index more in the R109R homozygotes than in the K109 allele carriers (P = 0.039), and decreased fasting glucose only in the 109R allele carriers (P = 0.018). We also found an interaction between the LEP A19G and LEPR K109R polymorphisms on the change in fasting insulin in whites (P = 0.010). The association between the LEP A19G polymorphism and the change in insulin was evident only in the LEPR 109R carriers (P = 0.019). The decrease in insulin was strongest in the LEP A19A homozygotes who carried the LEPR 109R allele. Similar interaction was observed in blacks (P = 0.046). Variations in the LEP and LEPR genes are associated with the magnitude of the effects of regular exercise on glucose homeostasis in nondiabetic individuals.

Restoration of muscle mitochondrial function and metabolic flexibility in type 2 diabetes by exercise training is paralleled by increased myocellular fat storage and improved insulin sensitivity.

PubMed

Meex, Ruth C R; Schrauwen-Hinderling, Vera B; Moonen-Kornips, Esther; Schaart, Gert; Mensink, Marco; Phielix, Esther; van de Weijer, Tineke; Sels, Jean-Pierre; Schrauwen, Patrick; Hesselink, Matthijs K C

2010-03-01

Mitochondrial dysfunction and fat accumulation in skeletal muscle (increased intramyocellular lipid [IMCL]) have been linked to development of type 2 diabetes. We examined whether exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2 diabetes. Eighteen male type 2 diabetic and 20 healthy male control subjects of comparable body weight, BMI, age, and VO2max participated in a 12-week combined progressive training program (three times per week and 45 min per session). In vivo mitochondrial function (assessed via magnetic resonance spectroscopy), insulin sensitivity (clamp), metabolic flexibility (indirect calorimetry), and IMCL content (histochemically) were measured before and after training. Mitochondrial function was lower in type 2 diabetic compared with control subjects (P = 0.03), improved by training in control subjects (28% increase; P = 0.02), and restored to control values in type 2 diabetic subjects (48% increase; P < 0.01). Insulin sensitivity tended to improve in control subjects (delta Rd 8% increase; P = 0.08) and improved significantly in type 2 diabetic subjects (delta Rd 63% increase; P < 0.01). Suppression of insulin-stimulated endogenous glucose production improved in both groups (-64%; P < 0.01 in control subjects and -52% in diabetic subjects; P < 0.01). After training, metabolic flexibility in type 2 diabetic subjects was restored (delta respiratory exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects (delta respiratory exchange ratio 7% increase; P = 0.22). Starting with comparable pretraining IMCL levels, training tended to increase IMCL content in type 2 diabetic subjects (27% increase; P = 0.10), especially in type 2 muscle fibers. Exercise training restored in vivo mitochondrial function in type 2 diabetic subjects. Insulin-mediated glucose disposal and metabolic flexibility improved in type 2 diabetic subjects in the face of near-significantly increased IMCL content. This indicates that increased capacity to store IMCL and restoration of improved mitochondrial function contribute to improved muscle insulin sensitivity.

Restoration of Muscle Mitochondrial Function and Metabolic Flexibility in Type 2 Diabetes by Exercise Training Is Paralleled by Increased Myocellular Fat Storage and Improved Insulin Sensitivity

PubMed Central

Meex, Ruth C.R.; Schrauwen-Hinderling, Vera B.; Moonen-Kornips, Esther; Schaart, Gert; Mensink, Marco; Phielix, Esther; van de Weijer, Tineke; Sels, Jean-Pierre; Schrauwen, Patrick; Hesselink, Matthijs K.C.

2010-01-01

OBJECTIVE Mitochondrial dysfunction and fat accumulation in skeletal muscle (increased intramyocellular lipid [IMCL]) have been linked to development of type 2 diabetes. We examined whether exercise training could restore mitochondrial function and insulin sensitivity in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Eighteen male type 2 diabetic and 20 healthy male control subjects of comparable body weight, BMI, age, and Vo2max participated in a 12-week combined progressive training program (three times per week and 45 min per session). In vivo mitochondrial function (assessed via magnetic resonance spectroscopy), insulin sensitivity (clamp), metabolic flexibility (indirect calorimetry), and IMCL content (histochemically) were measured before and after training. RESULTS Mitochondrial function was lower in type 2 diabetic compared with control subjects (P = 0.03), improved by training in control subjects (28% increase; P = 0.02), and restored to control values in type 2 diabetic subjects (48% increase; P < 0.01). Insulin sensitivity tended to improve in control subjects (delta Rd 8% increase; P = 0.08) and improved significantly in type 2 diabetic subjects (delta Rd 63% increase; P < 0.01). Suppression of insulin-stimulated endogenous glucose production improved in both groups (−64%; P < 0.01 in control subjects and −52% in diabetic subjects; P < 0.01). After training, metabolic flexibility in type 2 diabetic subjects was restored (delta respiratory exchange ratio 63% increase; P = 0.01) but was unchanged in control subjects (delta respiratory exchange ratio 7% increase; P = 0.22). Starting with comparable pretraining IMCL levels, training tended to increase IMCL content in type 2 diabetic subjects (27% increase; P = 0.10), especially in type 2 muscle fibers. CONCLUSIONS Exercise training restored in vivo mitochondrial function in type 2 diabetic subjects. Insulin-mediated glucose disposal and metabolic flexibility improved in type 2 diabetic subjects in the face of near–significantly increased IMCL content. This indicates that increased capacity to store IMCL and restoration of improved mitochondrial function contribute to improved muscle insulin sensitivity. PMID:20028948

Aerobic Exercise and Weight Loss Reduce Vascular Markers of Inflammation and Improve Insulin Sensitivity in Obese Women

PubMed Central

Ryan, Alice S.; Ge, Shealinna; Blumenthal, Jacob B.; Serra, Monica C.; Prior, Steven J.; Goldberg, Andrew P.

2014-01-01

Background/Objectives To examine the relationships of plasma and tissue markers of systemic and vascular inflammation to obesity and insulin resistance and determine the effects of aerobic exercise training+weight loss (AEX+WL) and weight loss (WL) on these biomarkers. Design Prospective controlled study. Participants Seventy-seven overweight and obese sedentary postmenopausal women. Interventions Six months, 3d/wk AEX+WL (n=37) or WL (n=40). Measurements Total body dual-energy x-ray absorptiometry, abdominal computed tomography scans, hyperinsulinemic-euglycemic clamps, adipose tissue biopsies (n=28), and blood for Homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule (sICAM-1) and vascular CAM-1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Results Body weight, %fat, visceral fat, triglyceride levels and systolic blood pressure decreased comparably after WL and AEX+WL (P<0.05). VO2max increased 16% after AEX+WL (P<0.001). Insulin resistance decreased in both groups (P<0.01). Glucose utilization increased 10% (P< 0.05) after AEX+WL and 8% with WL (P=0.07). AEX+WL and WL decreased CRP by 29% and 21%, (P<0.05). SAA levels decreased two-fold more after AEX+WL (−19%, P<0.05) than with WL (−9%, P=0.08). Plasma sICAM-1 and sVCAM-1 levels did not change; however, women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose, insulin and insulin resistance (P<0.05). Gluteal ICAM mRNA levels decreased 27% after AEX+WL (P<0.05) and did not change after WL. Conclusion Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP and SAA and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women. PMID:24635342

Metabolic Syndrome and Insulin Resistance: Underlying Causes and Modification by Exercise Training

PubMed Central

Roberts, Christian K.; Hevener, Andrea L.; Barnard, R. James

2014-01-01

Metabolic syndrome (MS) is a collection of cardiometabolic risk factors that includes obesity, insulin resistance, hypertension, and dyslipidemia. Although there has been significant debate regarding the criteria and concept of the syndrome, this clustering of risk factors is unequivocally linked to an increased risk of developing type 2 diabetes and cardiovascular disease. Regardless of the true definition, based on current population estimates, nearly 100 million have MS. It is often characterized by insulin resistance, which some have suggested is a major underpinning link between physical inactivity and MS. The purpose of this review is to: (i) provide an overview of the history, causes and clinical aspects of MS, (ii) review the molecular mechanisms of insulin action and the causes of insulin resistance, and (iii) discuss the epidemiological and intervention data on the effects of exercise on MS and insulin sensitivity. PMID:23720280

Effects of cross-training on markers of insulin resistance/hyperinsulinemia.

PubMed

Wallace, M B; Mills, B D; Browning, C L

1997-09-01

This study examined, through a randomized controlled trial, the effects of cross-training (combined resistance and endurance exercise) on markers of insulin resistance, (e.g., dyslipidemia, intra-abdominal obesity, hyperinsulinemia, and hypertension), body composition, and performance in hyperinsulinemic individuals. Sedentary adult males characterized as hyperinsulinemic (fasting insulin > 2 OuU.mL-1), randomly assigned to two groups (N = 8 each), completed 14 wk of training at 3 d.wk-1. An endurance-only (E) group performed both continuous cycle exercise and walking (30 min each at 60-70% heart rate reserve). A cross-training (C) group performed both endurance and resistance exercise (8 exercises, 4 sets/exercise, 8-12 repetitions/set) in a single session. Both E and C groups demonstrated similar increases in VO2max (25% and 27%) while only C demonstrated an increase in 1 RM bench press (19%) and leg press (25%). The changes induced by C training were significantly greater than those from E training alone in percent fat (6.9 +/- 1.3 vs 1.4 +/- 1.4), insulin concentration (8.5 +/- 2.7 vs 3.0 +/- 1.3 uU.mL-1), glucose levels (11.1 +/- 2.9 vs 5.9 +/- 2.6 mg.dL-1), HDL-C levels (5.1 +/- 1.3 vs 2.9 +/- 1.6 mg.dL-1), triglyceride concentration (43.8 +/- 13.6 mg.dL-1), and systolic blood pressure (14.6 +/- 5.5 vs 8.3 +/- 6.8 mm Hg). Results indicate that the addition of resistance training to an endurance training program will induce significantly greater differences in markers of insulin resistance and body composition in individuals with hyperinsulinemia than endurance training alone.

Effects of insulin and exercise on rat hindlimb muscles after simulated microgravity

NASA Technical Reports Server (NTRS)

Stump, Craig S.; Balon, Thomas W.; Tipton, Charles M.

1992-01-01

The effect of simulated microgravity on the insulin- and exercise-stimulated glucose uptake and metabolism in the hindlimb muscles of rats was investigated using three groups of rats suspended at 45 head-down tilt (SUS) for 14 days: (1) cage control, (2) exercising (treadmill running) control, and (3) rats subjected to suspension followed by exercise (SUS-E). It was found that the suspension of rats with hindlimbs non-weight bearing led to enhanced muscle responses to insulin and exercise, when these stimuli were applied separately. However, the insulin affect appeared to be impaired after exercise for the SUS-E rats, especially for the soleus muscle.

Improvements in insulin sensitivity are blunted by subclinical hypothyroidism.

PubMed

Amati, Francesca; Dubé, John J; Stefanovic-Racic, Maja; Toledo, Frederico G; Goodpaster, Bret H

2009-02-01

Exercise- and weight loss-induced improvements in insulin resistance (IR) are variable; some individuals experience robust enhancements in insulin sensitivity, whereas others do not. Thyroid hormone status is related to IR, but it is not clear whether subclinical hypothyroidism may help to explain the variability in improvements in IR with diet and exercise. The purpose of this study was to examine whether thyroid hormone status is related to the improvement in insulin sensitivity and physical fitness after weight loss and exercise training. By retrospective nested case-control analysis, eight subclinical hypothyroid (sHT) subjects and eight matched euthyroid controls underwent a euglycemic hyperinsulinemic clamp and peak oxygen uptake test, before and after a 16-wk program of moderate aerobic exercise combined with diet-induced weight loss. All subjects were middle-aged (57.3 +/- 3.3 yr), were overweight to obese (body mass index = 33.1 +/- 0.8 kg m(-2)), and had impaired glucose tolerance. The improvement in insulin sensitivity was significantly lower (P < 0.05) in the sHT group than in the euthyroid group. Both groups performed similar amounts of regular exercise and lost a significant amount of body weight during the intervention. VO(2peak) tended to improve in the euthyroid group but not in the sHT group. Subclinical hypothyroidism may interfere with beneficial adaptations on muscle metabolism and physical fitness that typically occur with weight loss and increased physical activity. These results may have significant clinical implications because of the high prevalence of both hypothyroidism and insulin resistance in the aging population.

[Physical exercise is a help for lean women with polycystic ovary syndrome].

PubMed

Bisgaard, Helene; Dela, Flemming

2017-06-05

Polycystic ovary syndrome (PCOS) affects 12-21% of women in the childbearing age and is the most common cause of hyperandrogenaemia and anovulatory infertility. There is an increase in insulin resistance in both overweight and lean women with PCOS. Exercise treatment is mandatory among the overweight women due to sufficient evidence that it can improve the signs and symptoms of PCOS. This has not been fully investigated among the lean. However, new randomized controlled trials show that structured physical exercise can also improve insulin sensitivity, hyperandrogenaemia and menstrual frequency in lean women with PCOS.

Strength exercise improves muscle mass and hepatic insulin sensitivity in obese youth

USDA-ARS?s Scientific Manuscript database

Data on the metabolic effects of resistance exercise (strength training) in adolescents are limited. The objective of this study was to determine whether a controlled resistance exercise program without dietary intervention or weight loss reduces body fat accumulation, increases lean body mass, and ...

Glucose Transporter Type 4 Redistribution on the Membrane Induced by Insulin through Akt in Hydrocortisone Treatment in Rat Skeletal Muscles.

PubMed

Chen, Chien-Min; Chiu, Lian; Chen, Hung-Chi; Cheng, Chun-Yuan; Shyu, Woei-Cherng; Chou, Chii-Wen; Lu, Cheng-You; Lin, Chung-Tien

2015-10-31

Hydrocortisone is a growth hormone frequently used in the treatment of low back pain. Hydrocortisone treatment has an anti-inflammation effect, which also inactivates glucose transporter type 4 (GLUT4) by p38 mitogen-activated protein kinase (MAPK) inhibition. Translocation of GLUT4 regulates body glucose homeostasis and muscle repair and is induced by insulin. In this study, 56 SD rats were divided into seven groups, and were treated with insulin or hydrocortisone in sedentary or exercise training groups. The muscle proteins and biochemical blood parameters were analyzed after 7 days of treatments. The results showed that the serum glucose increased in hydrocortisone treatment accompanied by GLUT4 inactivation in both the sedentary and exercise training rats. In the exercise training groups, GLUT4 was redistributed on the plasma membrane on co-treatment with insulin and hydrocortisone through Akt phosphorylation. Insulin treatment exerted a compensatory feedback effect on the GLUT4 translocation on hydrocortisone co-treatment, which was the cause of GLUT4 inactivation.

Melatonin supplementation plus exercise behavior ameliorate insulin resistance, hypertension and fatigue in a rat model of type 2 diabetes mellitus.

PubMed

Rahman, Md Mahbubur; Kwon, Han-Sol; Kim, Myung-Jin; Go, Hyeon-Kyu; Oak, Min-Ho; Kim, Do-Hyung

2017-08-01

The objective was to investigate the effects of melatonin and exercise on insulin resistance (IR), hypertension and fatigue syndrome in a rat model of type 2 diabetes mellitus (T2DM). Rats were divided into 5 groups namely normal control (NC), T2DM control group (DC), diabetes plus exercise (DE), diabetes plus oral melatonin supplement (DM) and diabetes plus melatonin and exercise (DME) groups. Melatonin was administered orally 5mg/kg twice daily and 40min swimming/day 5days/week were regimented after diabetes induction. Blood pressure, fasting blood glucose, insulin, IR, serum leptin, lipid profiles, inflammatory cytokines, lipid peroxidation increased significantly (P<0.01) while serum adiponectin, antioxidant activities (superoxide dismutase, glutathione), exercise performance significantly decreased (P<0.001) in the DC group compared with the control group. Combined effects of exercise and melatonin ameliorated markedly hypertension, IR, biochemical alteration induced by diabetes and significantly increased exercise performance (P<0.01). The expression glucose transporter type 4 (GLUT4) mitochondrial biogenesis related proteins such as peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1 α), nuclear respiratory factor (NRFs) and mitochondrial transcription factor-A were up-regulated skeletal and cardiac muscle in the DME group. Melatonin supplementation in combination with exercise behavior may ameliorate IR, hypertension and exercise performance or fatigue possibly by improving antioxidative activities, hyperlipidemia, inflammatory cytokines via up-regulation of GLUT4, PGC-1 α and mitochondrial biogenesis in T2DM rats. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Exercise and nutritional interventions for improving aging muscle health.

PubMed

Forbes, Scott C; Little, Jonathan P; Candow, Darren G

2012-08-01

Skeletal muscle mass declines with age (i.e., sarcopenia) resulting in muscle weakness and functional limitations. Sarcopenia has been associated with physiological changes in muscle morphology, protein and hormonal kinetics, insulin resistance, inflammation, and oxidative stress. The purpose of this review is to highlight how exercise and nutritional intervention strategies may benefit aging muscle. It is well known that resistance exercise training increases muscle strength and size and evidence also suggests that resistance training can increase mitochondrial content and decrease oxidative stress in older adults. Recent findings suggest that fast-velocity resistance exercise may be an effective intervention for older adults to enhance muscle power and functional capacity. Aerobic exercise training may also benefit aging skeletal muscle by enhancing mitochondrial bioenergetics, improving insulin sensitivity, and/or decreasing oxidative stress. In addition to exercise, creatine monohydrate, milk-based proteins, and essential fatty acids all have biological effects which could enhance some of the physiological adaptations from exercise training in older adults. Additional research is needed to determine whether skeletal muscle adaptations to increased activity in older adults are further enhanced with effective nutritional interventions and whether this is due to enhanced muscle protein synthesis, improved mitochondrial function, and/or a reduced inflammatory response.

Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

PubMed

Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

2006-03-01

Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

Short-term weight loss attenuates local tissue inflammation and improves insulin sensitivity without affecting adipose inflammation in obese mice.

PubMed

Jung, Dae Young; Ko, Hwi Jin; Lichtman, Eben I; Lee, Eunjung; Lawton, Elizabeth; Ong, Helena; Yu, Kristine; Azuma, Yoshihiro; Friedline, Randall H; Lee, Ki Won; Kim, Jason K

2013-05-01

Obesity is a major cause of insulin resistance, and weight loss is shown to improve glucose homeostasis. But the underlying mechanism and the role of inflammation remain unclear. Male C57BL/6 mice were fed a high-fat diet (HFD) for 12 wk. After HFD, weight loss was induced by changing to a low-fat diet (LFD) or exercise with continuous HFD. The weight loss effects on energy balance and insulin sensitivity were determined using metabolic cages and hyperinsulinemic euglycemic clamps in awake mice. Diet and exercise intervention for 3 wk caused a modest weight loss and improved glucose homeostasis. Weight loss dramatically reduced local inflammation in skeletal muscle, liver, and heart but not in adipose tissue. Exercise-mediated weight loss increased muscle glucose metabolism without affecting Akt phosphorylation or lipid levels. LFD-mediated weight loss reduced lipid levels and improved insulin sensitivity selectively in liver. Both weight loss interventions improved cardiac glucose metabolism. These results demonstrate that a short-term weight loss with exercise or diet intervention attenuates obesity-induced local inflammation and selectively improves insulin sensitivity in skeletal muscle and liver. Our findings suggest that local factors, not adipose tissue inflammation, are involved in the beneficial effects of weight loss on glucose homeostasis.

Nuclear Receptors and AMPK: Can Exercise Mimetics Cure Diabetes?

PubMed Central

Wall, Christopher E.; Yu, Ruth T.; Atkins, Anne R.; Downes, Michael; Evans, Ronald M.

2016-01-01

Endurance exercise can lead to systemic improvements in insulin sensitivity and metabolic homeostasis, and is an effective approach to combat metabolic diseases. Pharmacological compounds that recapitulate the beneficial effects of exercise, also known as “exercise mimetics,” have the potential to improve disease symptoms of metabolic syndrome. These drugs, which can increase energy expenditure, suppress hepatic gluconeogenesis, and induce insulin sensitization, have accordingly been highly scrutinized for their utility in treating metabolic diseases including diabetes. Nevertheless, the identity of an efficacious exercise mimetic still remains elusive. In this article, we will highlight several nuclear receptors and cofactors that are putative molecular targets for exercise mimetics, and review recent studies that provide advancements in our mechanistic understanding of how exercise mimetics exert their beneficial effects. We will also discuss evidence from clinical trials utilizing these compounds in human subjects to evaluate their efficacy in treating diabetes. PMID:27106806

Aspartame in conjunction with carbohydrate reduces insulin levels during endurance exercise

PubMed Central

2012-01-01

Background As most sport drinks contain some form of non-nutritive sweetener (e.g. aspartame), and with the variation in blood glucose regulation and insulin secretion reportedly associated with aspartame, a further understanding of the effects on insulin and blood glucose regulation during exercise is warranted. Therefore, the aim of this preliminary study was to profile the insulin and blood glucose responses in healthy individuals after aspartame and carbohydrate ingestion during rest and exercise. Findings Each participant completed four trials under the same conditions (45 min rest + 60 min self-paced intense exercise) differing only in their fluid intake: 1) carbohydrate (2% maltodextrin and 5% sucrose (C)); 2) 0.04% aspartame with 2% maltodextrin and 5% sucrose (CA)); 3) water (W); and 4) aspartame (0.04% aspartame with 2% maltodextrin (A)). Insulin levels dropped significantly for CA versus C alone (43%) between pre-exercise and 30 min, while W and A insulin levels did not differ between these time points. Conclusions Aspartame with carbohydrate significantly lowered insulin levels during exercise versus carbohydrate alone. PMID:22853297

Role of O-GlcNAcylation in nutritional sensing, insulin resistance and in mediating the benefits of exercise.

PubMed

Myslicki, Jason P; Belke, Darrell D; Shearer, Jane

2014-11-01

The purpose of this review is to highlight the role of O-linked β-N-acetylglucosamine (O-GlcNAc) protein modification in metabolic disease states and to summarize current knowledge of how exercise affects this important post-translational signalling pathway. O-GlcNAc modification is an intracellular tool capable of integrating energy supply with demand. The accumulation of excess energy associated with obesity and insulin resistance is mediated, in part, by the hexosamine biosynthetic pathway (HBP), which results in the O-GlcNAcylation of a myriad of proteins, thereby affecting their respective function, stability, and localization. Insulin resistance is related to the excessive O-GlcNAcylation of key metabolic proteins causing a chronic blunting of insulin signalling pathways and precipitating the accompanying pathologies, such as heart and kidney disease. Lifestyle modifications such as diet and exercise also modify the pathway. Exercise is a front-line and cost-effective therapeutic approach for insulin resistance, and recent work shows that the intervention can alter O-GlcNAc gene expression, signalling, and protein modification. However, there is currently no consensus on the effect of frequency, intensity, type, and duration of exercise on O-GlcNAc modification, the HBP, and its related enzymes. On one end of the spectrum, mild, prolonged swim training reduces O-GlcNAcylation, while on the other end, higher intensity treadmill running increases cardiac protein O-GlcNAc modification. Clearly, a balance between acute and chronic stress of exercise is needed to reap the benefits of the intervention on O-GlcNAc signalling.

Intact Regulation of the AMPK Signaling Network in Response to Exercise and Insulin in Skeletal Muscle of Male Patients With Type 2 Diabetes: Illumination of AMPK Activation in Recovery From Exercise.

PubMed

Kjøbsted, Rasmus; Pedersen, Andreas J T; Hingst, Janne R; Sabaratnam, Rugivan; Birk, Jesper B; Kristensen, Jonas M; Højlund, Kurt; Wojtaszewski, Jørgen F P

2016-05-01

Current evidence on exercise-mediated AMPK regulation in skeletal muscle of patients with type 2 diabetes (T2D) is inconclusive. This may relate to inadequate segregation of trimeric complexes in the investigation of AMPK activity. We examined the regulation of AMPK and downstream targets ACC-β, TBC1D1, and TBC1D4 in muscle biopsy specimens obtained from 13 overweight/obese patients with T2D and 14 weight-matched male control subjects before, immediately after, and 3 h after exercise. Exercise increased AMPK α2β2γ3 activity and phosphorylation of ACCβ Ser(221), TBC1D1 Ser(237)/Thr(596), and TBC1D4 Ser(704) Conversely, exercise decreased AMPK α1β2γ1 activity and TBC1D4 Ser(318)/Thr(642) phosphorylation. Interestingly, compared with preexercise, 3 h into exercise recovery, AMPK α2β2γ1 and α1β2γ1 activity were increased concomitant with increased TBC1D4 Ser(318)/Ser(341)/Ser(704) phosphorylation. No differences in these responses were observed between patients with T2D and control subjects. Subjects were also studied by euglycemic-hyperinsulinemic clamps performed at rest and 3 h after exercise. We found no evidence for insulin to regulate AMPK activity. Thus, AMPK signaling is not compromised in muscle of patients with T2D during exercise and insulin stimulation. Our results reveal a hitherto unrecognized activation of specific AMPK complexes in exercise recovery. We hypothesize that the differential regulation of AMPK complexes plays an important role for muscle metabolism and adaptations to exercise. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Higher Circulating Leukocytes in Women with PCOS is Reversed by Aerobic Exercise

PubMed Central

Covington, Jeffrey D.; Tam, Charmaine S.; Pasarica, Magdalena; Redman, Leanne M.

2014-01-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r= -0.73, p=0.03; and r= -0.82, p=0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. PMID:25446648

Attenuation of exercise-induced heat shock protein 72 expression blunts improvements in whole-body insulin resistance in rats with type 2 diabetes.

PubMed

Tsuzuki, Takamasa; Kobayashi, Hiroyuki; Yoshihara, Toshinori; Kakigi, Ryo; Ichinoseki-Sekine, Noriko; Naito, Hisashi

2017-03-01

Heat shock proteins (HSPs) play an important role in insulin resistance and improve the cellular stress response via HSP induction by exercise to treat type 2 diabetes. In this study, the effects of exercise-induced HSP72 expression levels on whole-body insulin resistance in type 2 diabetic rats were investigated. Male 25-week-old Otsuka Long-Evans Tokushima Fatty rats were divided into three groups: sedentary (Sed), trained in a thermal-neutral environment (NTr: 25 °C), and trained in a cold environment (CTr: 4 °C). Exercise training was conducted 5 days/week for 10 weeks. Rectal temperature was measured following each bout of exercise. An intraperitoneal glucose tolerance test (IPGTT) was performed after the training sessions. The serum, gastrocnemius muscle, and liver were sampled 48 h after the final exercise session. HSP72 and heat shock cognate protein 73 expression levels were analyzed by Western blot, and serum total cholesterol, triglyceride (TG), and free fatty acid (FFA) levels were measured. NTr animals exhibited significantly higher body temperatures following exercise, whereas, CTr animals did not. Exercise training increased HSP72 levels in the gastrocnemius muscle and liver, whereas, HSP72 expression was significantly lower in the CTr group than that in the NTr group (p < 0.05). Glucose tolerance improved equally in both trained animals; however, insulin levels during the IPGTT were higher in CTr animals than those in NTr animals (p < 0.05). In addition, the TG and FFA levels decreased significantly only in NTr animals compared with those in Sed animals. These results suggest that attenuation of exercise-induced HSP72 expression partially blunts improvement in whole-body insulin resistance and lipid metabolism in type 2 diabetic rats.

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice

PubMed Central

Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-01-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day−1). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training. PMID:22674717

Consumption of a high-fat diet, but not regular endurance exercise training, regulates hypothalamic lipid accumulation in mice.

PubMed

Borg, Melissa L; Omran, Simin Fallah; Weir, Jacquelyn; Meikle, Peter J; Watt, Matthew J

2012-09-01

Obesity is characterised by increased storage of fatty acids in an expanded adipose tissue mass and in peripheral tissues such as the skeletal muscle and liver, where it is associated with the development of insulin resistance. Insulin resistance also develops in the central nervous system with high-fat feeding. The capacity for hypothalamic cells to accumulate/store lipids, and the effects of obesity remain undefined. The aims of this study were (1) to examine hypothalamic lipid content in mice with increased dietary fat intake and in obese ob/ob mice fed a low-fat diet, and (2) to determine whether endurance exercise training could reduce hypothalamic lipid accumulation in high-fat fed mice. Male C57BL/6 mice were fed a low- (LFD) or high-fat diet (HFD) for 12 weeks; ob/ob mice were maintained on a chow diet. HFD-exercise (HFD-ex) mice underwent 12 weeks of high-fat feeding with 6 weeks of treadmill exercise training (increasing from 30 to 70 min day(-1)). Hypothalamic lipids were assessed by unbiased mass spectrometry. The HFD increased body mass and hepatic lipid accumulation, and induced glucose intolerance, while the HFD-ex mice had reduced body weight and improved glucose tolerance. A total of 335 lipid molecular species were identified and quantified. Lipids known to induce insulin resistance, including ceramide (22%↑), diacylglycerol (25%↑), lysophosphatidylcholine (17%↑), cholesterol esters (60%↑) and dihexosylceramide (33%↑), were increased in the hypothalamus of HFD vs. LFD mice. Hypothalamic lipids were unaltered with exercise training and in the ob/ob mice, suggesting that obesity per se does not alter hypothalamic lipids. Overall, hypothalamic lipid accumulation is regulated by dietary lipid content and is refractory to change with endurance exercise training.

Effects of a brief high-fat diet and acute exercise on the mTORC1 and IKK/NF-κB pathways in rat skeletal muscle

PubMed Central

Castorena, Carlos M.; Arias, Edward B.; Sharma, Naveen; Cartee, Gregory D.

2016-01-01

One exercise session can improve subsequent insulin-stimulated glucose uptake by skeletal muscle in healthy and insulin-resistant individuals. Our first aim was to determine whether a brief (2 weeks) high-fat diet (HFD) that caused muscle insulin resistance would activate the mammalian target of rapamycin complex 1 (mTORC1) and/or inhibitor of κB kinase/nuclear factor κB (IKK/NF-κB) pathways, which are potentially linked to induction of insulin resistance. Our second aim was to determine whether acute exercise that improved insulin-stimulated glucose uptake by muscles would attenuate activation of these pathways. We compared HFD-fed rats with rats fed a low-fat diet (LFD). Some animals from each diet group were sedentary and others were studied 3 h postexercise, when insulin-stimulated glucose uptake was increased. The results did not provide evidence that brief HFD activated either the mTORC1 (including phosphorylation of mTORSer2448, TSC2Ser939, p70S6KThr412, and RPS6Ser235/236) or the IKK/NF-κB (including abundance of IκBα or phosphorylation of NF-κBSer536, IKKα/βSer177/181, and IκBSer32) pathway in insulin-resistant muscles. Exercise did not oppose the activation of either pathway, as evidenced by no attenuation of phosphorylation of key proteins in the IKK/NF-κB pathway (NF-κBSer536, IKKα/βSer177/181, and IκBSer32), unaltered IκBα abundance, and no attenuation of phosphorylation of key proteins in the mTORC1 pathway (mTORSer2448, TSC2Ser939, and RPS6Ser235/236). Instead, exercise induced greater phosphorylation of 2 proteins of the mTORC1 pathway (PRAS40Thr246 and p70S6KThr412) in insulin-stimulated muscles, regardless of diet. Insulin resistance induced by a brief HFD was not attributable to greater activation of the mTORC1 or the IKK/NF-κB pathway in muscle, and exercise-induced improvement in insulin sensitivity was not attributable to attenuated activation of these pathways in muscle. PMID:25706655

Effects of exercise training and diet on lipid kinetics during free fatty acid-induced insulin resistance in older obese humans with impaired glucose tolerance

PubMed Central

Solomon, Thomas P. J.; Haus, Jacob M.; Marchetti, Christine M.; Stanley, William C.; Kirwan, John P.

2009-01-01

Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFAox) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; −598 ± 125 kcal/day, 66 ± 1 yr, 32.8 ± 1.8 kg/m2) or a eucaloric (n = 8; 67 ± 2 yr, 35.3 ± 2.1 kg/m2) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-14C]palmitate) were assessed throughout a 7-h, 40 mU·m−2·min−1 hyperinsulinemic euglycemic clamp, during which insulin resistance was induced in the last 5 h by a sustained elevation in plasma FFA (intralipid/heparin infusion). Despite greater weight loss in the hypocaloric group (−7.7 ± 0.5 vs. −3.3 ± 0.7%, P < 0.001), FFA-induced peripheral insulin resistance was improved equally in both groups. However, circulating FFA concentrations (2,123 ± 261 vs. 1,764 ± 194 μmol/l, P < 0.05) and FFA turnover (3.20 ± 0.58 vs. 2.19 ± 0.58 μmol·kg FFM−1·min−1, P < 0.01) during hyperlipemia were suppressed only in the hypocaloric group. In contrast, whole body FFAox was improved in both groups at rest and during hyperlipemia. These changes were driven by increases in intracellular lipid-derived FFAox (12.3 ± 7.7 and 14.7 ± 7.8%, P < 0.05). We conclude that the exercise-induced improvement in FFA-induced insulin resistance is independent of the magnitude of weight loss and FFA turnover, yet it is linked to increased intracellular FFA utilization. PMID:19531640

The effect of endurance training and subsequent physical inactivity on glycaemic control after oral glucose load and physical exercise in healthy men

NASA Astrophysics Data System (ADS)

Radikova, Zofia; Ksinantova, Lucia; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Vigas, Milan; Koska, Juraj

2007-02-01

Physical inactivity during space flight has a profound effect on glucose metabolism. The aim of this study was to test whether endurance training (ET) may improve a negative effect of subsequent -6∘ head-down bed rest (HDBR) on glucose metabolism. Fourteen healthy males completed the study consisting of 6 weeks lasting ET followed by 6 days HDBR. Treadmill exercise at 80% of pre-training VO2max and 75 g oral glucose tolerance test (OGTT) were performed before and after ET as well as after HDBR. ET increased VO2max by 11%. ET significantly lowered while HDBR had no effect on fasting and OGTT plasma glucose levels. ET had no effect while HDBR was followed by an augmentation of insulin and C-peptide response to OGTT. Insulin sensitivity tended to increase after ET and to decrease during HDBR, however, mostly without statistical significance. Plasma glucose, insulin and C-peptide response to exercise were elevated after HDBR only. Our study shows that antecedent physical training could ameliorate a negative effect of simulated microgravity on insulin-mediated glucose metabolism.

High intensity interval exercise is an effective alternative to moderate intensity exercise for improving glucose tolerance and insulin sensitivity in adolescent boys.

PubMed

Cockcroft, Emma J; Williams, Craig A; Tomlinson, Owen W; Vlachopoulos, Dimitris; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2015-11-01

High-intensity interval exercise (HIIE) may offer a time efficient means to improve health outcomes compared to moderate-intensity exercise (MIE). This study examined the acute effect of HIIE compared to a work-matched bout of MIE on glucose tolerance, insulin sensitivity (IS), resting fat oxidation and exercise enjoyment in adolescent boys. Within-measures design with counterbalanced experimental conditions. Nine boys (14.2 ± 0.4 years) completed three conditions on separate days in a counterbalanced order: (1) HIIE; (2) work matched MIE, both on a cycle ergometer; and (3) rest (CON). An oral glucose tolerance test (OGTT) was performed after exercise or rest and the area under curve (AUC) responses for plasma [glucose] and [insulin] were calculated, and IS estimated (Cederholm index). Energy expenditure and fat oxidation were measured following the OGTT using indirect calorimetry. Exercise enjoyment was assessed using the Physical Activity Enjoyment Scale. The incremental AUC (iAUC) for plasma [glucose] was reduced following both MIE (-23.9%, P = 0.013, effect size [ES] = -0.64) and HIIE (-28.9%, P=0.008, ES = -0.84) compared to CON. The iAUC for plasma [insulin] was lower for HIIE (-24.2%, P = 0.021, ES = -0.71) and MIE (-29.1%, P = 0.012, ES = -0.79) compared to CON. IS increased by 11.2% after HIIE (P = 0.03, ES = 0.76) and 8.4% after MIE (P = 0.10, ES = 0.58). There was a trend for an increase in fat oxidation following HIIE (P = 0.097, ES = 0.70). Both HIIE and MIE were rated as equally enjoyable (P > 0.05, ES < 0.01). A single bout of time efficient HIIE is an effective alternative to MIE for improving glucose tolerance and IS in adolescent boys immediately after exercise. Copyright © 2014 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

Sustained, Low-Intensity Exercise Achieved by a Dynamic Feeding System Decreases Body Fat in Ponies.

PubMed

de Laat, M A; Hampson, B A; Sillence, M N; Pollitt, C C

2016-09-01

Obesity in horses is increasing in prevalence and can be associated with insulin insensitivity and laminitis. Current treatment strategies for obesity include dietary restriction and exercise. However, whether exercise alone is effective for decreasing body fat is uncertain. Our hypothesis was that twice daily use of a dynamic feeding system for 3 months would induce sustained, low-intensity exercise thereby decreasing adiposity and improving insulin sensitivity (SI). Eight, university-owned, mixed-breed, adult ponies with body condition scores (BCS) ≥5/9 were used. Two treatments ("feeder on" or "feeder off") were administered for a 3-month period by a randomized, crossover design (n = 4/treatment). An interim equilibration period of 6 weeks at pasture separated the 2 study phases. Measurements of body mass (body weight, BCS, cresty neck score [CrNS], and morphometry), body fat (determined before and after the "feeder on" treatment only), triglycerides, and insulin sensitivity (SI; combined glucose-insulin test) were undertaken before and after treatments. The dynamic feeding system induced a 3.7-fold increase in the daily distance travelled (n = 6), compared to with a stationary feeder, which significantly decreased mean BCS (6.53 ± 0.94 to 5.38 ± 1.71), CrNS (2.56 ± 1.12 to 1.63 ± 1.06) and body fat (by 4.95%). An improvement in SI did not occur in all ponies. A dynamic feeding system can be used to induce sustained (daily), low-intensity exercise that promotes weight loss in ponies. However, this exercise may not be sufficient to substantially improve SI. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Pre-exercise blood glucose affects glycemic variation of aerobic exercise in patients with type 2 diabetes treated with continuous subcutaneous insulin infusion.

PubMed

Hu, Yun; Zhang, Dan-Feng; Dai, Lu; Li, Zheng; Li, Hui-Qin; Li, Feng-Fei; Liu, Bing-Li; Sun, Xiao-Juan; Ye, Lei; He, Ke; Ma, Jian-Hua

2018-05-03

Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC 0-60 min ). The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC 0-60 min (standardized β = -0.386, P < 0.001) and incremental AUC of blood glucose ≤ 4.4 mmol/L (standardized β = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P < 0.001). The Δglucose AUC 0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P < 0.05 for all). PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. ChiCTR-ONC-17010400, www.chictr.org.cn. Copyright © 2018 Elsevier B.V. All rights reserved.

High intensity interval training improves liver and adipose tissue insulin sensitivity

PubMed Central

Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

2015-01-01

Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

AMPK and Exercise: Glucose Uptake and Insulin Sensitivity

PubMed Central

2013-01-01

AMPK is an evolutionary conserved sensor of cellular energy status that is activated during exercise. Pharmacological activation of AMPK promotes glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and insulin sensitivity; processes that are reduced in obesity and contribute to the development of insulin resistance. AMPK deficient mouse models have been used to provide direct genetic evidence either supporting or refuting a role for AMPK in regulating these processes. Exercise promotes glucose uptake by an insulin dependent mechanism involving AMPK. Exercise is important for improving insulin sensitivity; however, it is not known if AMPK is required for these improvements. Understanding how these metabolic processes are regulated is important for the development of new strategies that target obesity-induced insulin resistance. This review will discuss the involvement of AMPK in regulating skeletal muscle metabolism (glucose uptake, glycogen synthesis, and insulin sensitivity). PMID:23441028

The function of androgen/androgen receptor and insulin growth factor‑1/insulin growth factor‑1 receptor on the effects of Tribulus terrestris extracts in rats undergoing high intensity exercise.

PubMed

Wu, Yin; Yang, Hongfang; Wang, Xiaohui

2017-09-01

Our previous study demonstrated that treatment with Tribulus terrestris (TT) extracts (120 mg/kg) promoted the muscle weight gain and performance of rats undergoing high intensity exercise. The present study was designed to explore the mechanisms underlying the effect of treatment with TT extracts and the involvement of androgens, the androgen receptor (AR), insulin growth factor‑1 (IGF‑1) and the IGF‑1 receptor (IGF‑1R). A total of 32 Sprague‑Dawley rats were randomly divided into groups as follows: Control; TT, treated with TT extracts, E, high intensity exercise; E+TT, high intensity exercise plus TT treatment. The rats of the E and E+TT groups underwent high intensity exercise with a progressively increasing load for 5 weeks, and TT extracts were intragastrically administered in the TT and E+TT rats 30 min prior to training. TT extract composition was analyzed using ultra‑high performance liquid chromatography‑quadrupole‑time of flight mass spectrometry. Testosterone and IGF‑1 plasma levels and AR, IGF‑1R and myosin heavy chain (MHC) protein levels in muscles were determined by ELISA and western blotting, respectively. The saponins tigogenin and diosgenin comprised ~71.35% of the total peak area. Compared with the E group, TT extracts increased the testosterone and IGF‑1 plasma levels, and AR, IGF‑1R and MHC protein levels in the gastrocnemius of rats undergoing high intensity exercise, accompanied with increased body weight and gastrocnemius weight. In conclusion, the effect of TT extracts on the performance of high intensity exercise rats may be attributed to increased levels of circulating testosterone and IGF‑1 and increased AR and IGF‑1R protein expression levels in the gastrocnemius, resulting in increased muscle weight and increased MHC in the gastrocnemius. The present study provided preliminary evidence supporting the use of TT extracts as a dietary supplement for the promotion of skeletal muscle mass increase and the enhancement of athletic performance in humans performing high intensity exercise.

Exercise improves adipose function and inflammation and ameliorates fatty liver disease in obese diabetic mice.

PubMed

Haczeyni, Fahrettin; Barn, Vanessa; Mridha, Auvro R; Yeh, Matthew M; Estevez, Emma; Febbraio, Mark A; Nolan, Christopher J; Bell-Anderson, Kim S; Teoh, Narci C; Farrell, Geoffrey C

2015-09-01

Adipose inflammation and dysfunction underlie metabolic obesity. Exercise improves glycemic control and metabolic indices, but effects on adipose function and inflammation are less clear. Accordingly, it was hypothesized that exercise improves adipose morphometry to reduce adipose inflammation in hyperphagic obese mice. Alms1 mutant foz/foz mice housed in pairs were fed an atherogenic or chow diet; half the cages were fitted with a computer-monitored wheel for voluntary exercise. Insulin-induced AKT-phosphorylation, adipocyte size distribution, and inflammatory recruitment were studied in visceral versus subcutaneous depots, and severity of fatty liver disease was determined. Exercise prevented obesity and diabetes development in chow-fed foz/foz mice and delayed their onset in atherogenic-fed counterparts. Insulin-stimulated phospho-AKT levels in muscle were improved with exercise, but not in adipose or liver. Exercise suppressed adipose inflammatory recruitment, particularly in visceral adipose, associated with an increased number of small adipocyte subpopulations, and enhanced expression of beige adipocyte factor PRDM16 in subcutaneous fat. In atherogenic-fed foz/foz mice liver, exercise suppressed development of nonalcoholic steatohepatitis and related liver fibrosis. Exercise confers metabo-protective effects in atherogenic-fed hyperphagic mice by preventing early onset of obesity and diabetes in association with enhanced muscle insulin sensitivity, improved adipose morphometry, and suppressed adipose and liver inflammation. © 2015 The Obesity Society.

Effects of active recovery during interval training on plasma catecholamines and insulin.

PubMed

Nalbandian, Harutiun M; Radak, Zsolt; Takeda, Masaki

2018-06-01

BACKGROUNDː Active recovery has been used as a method to accelerate the recovery during intense exercise. It also has been shown to improve performance in subsequent exercises, but little is known about its acute effects on the hormonal and metabolic profile. The aim of this research was to study the effects of active recovery on plasma catecholamines and plasma insulin during a high-intensity interval exercise. METHODSː Seven subjects performed two high-intensity interval training protocols which consisted of three 30-second high-intensity bouts (constant intensity), separated by a recovery of 4 minutes. The recovery was either active recovery or passive recovery. During the main test blood samples were collected and plasma insulin, plasma catecholamines and blood lactate were determined. Furthermore, respiratory gasses were also measured. RESULTSː Plasma insulin and blood lactate were significantly higher in the passive recovery trial, while plasma adrenaline was higher in the active recovery. Additionally, VO2 and VCO2 were significantly more increased during the active recovery trials. CONCLUSIONSː These results suggest that active recovery affects the hormonal and metabolic responses to high-intensity interval exercise. Active recovery produces a hormonal environment which may favor lipolysis and oxidative metabolism, while passive recovery may be favoring glycolysis.

Skeletal muscle neuronal nitric oxide synthase micro protein is reduced in people with impaired glucose homeostasis and is not normalized by exercise training.

PubMed

Bradley, Scott J; Kingwell, Bronwyn A; Canny, Benedict J; McConell, Glenn K

2007-10-01

Skeletal muscle inducible nitric oxide synthase (NOS) protein is greatly elevated in people with type 2 diabetes mellitus, whereas endothelial NOS is at normal levels. Diabetic rat studies suggest that skeletal muscle neuronal NOS (nNOS) micro protein expression may be reduced in human insulin resistance. The aim of this study was to determine whether skeletal muscle nNOSmicro protein expression is reduced in people with impaired glucose homeostasis and whether exercise training increases nNOSmicro protein expression in these individuals because exercise training increases skeletal muscle nNOSmicro protein in rats. Seven people with type 2 diabetes mellitus or prediabetes (impaired fasting glucose and/or impaired glucose tolerance) and 7 matched (sex, age, fitness, body mass index, blood pressure, lipid profile) healthy controls aged 36 to 60 years participated in this study. Vastus lateralis muscle biopsies for nNOSmicro protein determination were obtained, aerobic fitness was measured (peak pulmonary oxygen uptake [Vo(2) peak]), and glucose tolerance and insulin homeostasis were assessed before and after 1 and 4 weeks of cycling exercise training (60% Vo(2) peak, 50 minutes x 5 d wk(-1)). Skeletal muscle nNOSmicro protein was significantly lower (by 32%) in subjects with type 2 diabetes mellitus or prediabetes compared with that in controls before training (17.7 +/- 1.2 vs 26.2 +/- 3.4 arbitrary units, P < .05). The Vo(2) peak and indicators of insulin sensitivity improved with exercise training in both groups (P < .05), but there was no effect of exercise training on skeletal muscle nNOSmicro protein in either group. In conclusion, individuals with impaired glucose homeostasis have reduced skeletal muscle nNOSmicro protein content. However, because exercise training improves insulin sensitivity without influencing skeletal muscle nNOSmicro protein expression, it seems that changes in skeletal muscle nNOSmicro protein are not central to the control of insulin sensitivity in humans and therefore may be a consequence rather than a cause of diabetes.

Two weeks of moderate-intensity continuous training, but not high-intensity interval training, increases insulin-stimulated intestinal glucose uptake

PubMed Central

Savolainen, Anna M.; Eskelinen, Jari-Joonas; Toivanen, Jussi; Ishizu, Tamiko; Yli-Karjanmaa, Minna; Virtanen, Kirsi A.; Parkkola, Riitta; Kapanen, Jukka; Grönroos, Tove J.; Haaparanta-Solin, Merja; Solin, Olof; Savisto, Nina; Ahotupa, Markku; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K.

2017-01-01

Similar to muscles, the intestine is also insulin resistant in obese subjects and subjects with impaired glucose tolerance. Exercise training improves muscle insulin sensitivity, but its effects on intestinal metabolism are not known. We studied the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on intestinal glucose and free fatty acid uptake from circulation in humans. Twenty-eight healthy, middle-aged, sedentary men were randomized for 2 wk of HIIT or MICT. Intestinal insulin-stimulated glucose uptake and fasting free fatty acid uptake from circulation were measured using positron emission tomography and [18F]FDG and [18F]FTHA. In addition, effects of HIIT and MICT on intestinal GLUT2 and CD36 protein expression were studied in rats. Training improved aerobic capacity (P = 0.001) and whole body insulin sensitivity (P = 0.04), but not differently between HIIT and MICT. Insulin-stimulated glucose uptake increased only after the MICT in the colon (HIIT = 0%; MICT = 37%) (P = 0.02 for time × training) and tended to increase in the jejunum (HIIT = −4%; MICT = 13%) (P = 0.08 for time × training). Fasting free fatty acid uptake decreased in the duodenum in both groups (HIIT = −6%; MICT = −48%) (P = 0.001 time) and tended to decrease in the colon in the MICT group (HIIT = 0%; MICT = −38%) (P = 0.08 for time × training). In rats, both training groups had higher GLUT2 and CD36 expression compared with control animals. This study shows that already 2 wk of MICT enhances insulin-stimulated glucose uptake, while both training modes reduce fasting free fatty acid uptake in the intestine in healthy, middle-aged men, providing an additional mechanism by which exercise training can improve whole body metabolism. NEW & NOTEWORTHY This is the first study where the effects of exercise training on the intestinal substrate uptake have been investigated using the most advanced techniques available. We also show the importance of exercise intensity in inducing these changes. PMID:28183816

Acute exercise and physiological insulin induce distinct phosphorylation signatures on TBC1D1 and TBC1D4 proteins in human skeletal muscle.

PubMed

Treebak, Jonas T; Pehmøller, Christian; Kristensen, Jonas M; Kjøbsted, Rasmus; Birk, Jesper B; Schjerling, Peter; Richter, Erik A; Goodyear, Laurie J; Wojtaszewski, Jørgen F P

2014-01-15

We investigated the phosphorylation signatures of two Rab-GTPase activating proteins TBC1D1 and TBC1D4 in human skeletal muscle in response to physical exercise and physiological insulin levels induced by a carbohydrate rich meal using a paired experimental design. Eight healthy male volunteers exercised in the fasted or fed state and muscle biopsies were taken before and immediately after exercise. We identified TBC1D1/4 phospho-sites that (1) did not respond to exercise or postprandial increase in insulin (TBC1D4: S666), (2) responded to insulin only (TBC1D4: S318), (3) responded to exercise only (TBC1D1: S237, S660, S700; TBC1D4: S588, S751), and (4) responded to both insulin and exercise (TBC1D1: T596; TBC1D4: S341, T642, S704). In the insulin-stimulated leg, Akt phosphorylation of both T308 and S473 correlated significantly with multiple sites on both TBC1D1 (T596) and TBC1D4 (S318, S341, S704). Interestingly, in the exercised leg in the fasted state TBC1D1 phosphorylation (S237, T596) correlated significantly with the activity of the α2/β2/γ3 AMPK trimer, whereas TBC1D4 phosphorylation (S341, S704) correlated with the activity of the α2/β2/γ1 AMPK trimer. Our data show differential phosphorylation of TBC1D1 and TBC1D4 in response to physiological stimuli in human skeletal muscle and support the idea that Akt and AMPK are upstream kinases. TBC1D1 phosphorylation signatures were comparable between in vitro contracted mouse skeletal muscle and exercised human muscle, and we show that AMPK regulated phosphorylation of these sites in mouse muscle. Contraction and exercise elicited a different phosphorylation pattern of TBC1D4 in mouse compared with human muscle, and although different circumstances in our experimental setup may contribute to this difference, the observation exemplifies that transferring findings between species is problematic.

Potential Mechanisms of Exercise in Gestational Diabetes

PubMed Central

Golbidi, Saeid; Laher, Ismail

2013-01-01

Gestational diabetes mellitus (GDM) is defined as glucose intolerance first diagnosed during pregnancy. This condition shares same array of underlying abnormalities as occurs in diabetes outside of pregnancy, for example, genetic and environmental causes. However, the role of a sedentary lifestyle and/or excess energy intake is more prominent in GDM. Physically active women are less likely to develop GDM and other pregnancy-related diseases. Weight gain in pregnancy causes increased release of adipokines from adipose tissue; many adipokines increase oxidative stress and insulin resistance. Increased intramyocellular lipids also increase cellular oxidative stress with subsequent generation of reactive oxygen species. A well-planned program of exercise is an important component of a healthy lifestyle and, in spite of old myths, is also recommended during pregnancy. This paper briefly reviews the role of adipokines in gestational diabetes and attempts to shed some light on the mechanisms by which exercise can be beneficial as an adjuvant therapy in GDM. In this regard, we discuss the mechanisms by which exercise increases insulin sensitivity, changes adipokine profile levels, and boosts antioxidant mechanisms. PMID:23691290

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats

PubMed Central

Moreira, Veridiana Mota; da Silva Franco, Claudinéia Conationi; Prates, Kelly Valério; Gomes, Rodrigo Mello; de Moraes, Ana Maria Praxedes; Ribeiro, Tatiane Aparecida; Martins, Isabela Peixoto; Previate, Carina; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Almeida, Douglas Lopes; Francisco, Flávio Andrade; Malta, Ananda; Tófolo, Laize Peron; da Silva Silveira, Sandra; Saavedra, Lucas Paulo Jacinto; Machado, Katia; da Silva, Paulo Henrique Olivieri; Fabrício, Gabriel S.; Palma-Rigo, Kesia; de Souza, Helenir Medri; de Fátima Silva, Flaviane; Biazi, Giuliana Regina; Pereira, Taís Susane; Vieira, Elaine; Miranda, Rosiane Aparecida; de Oliveira, Júlio Cezar; da Costa Lima, Luiz Delmar; Rinaldi, Wilson; Ravanelli, Maria Ida; de Freitas Mathias, Paulo Cezar

2018-01-01

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55–65% VO2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

Aerobic Exercise Training Attenuates Tumor Growth and Reduces Insulin Secretion in Walker 256 Tumor-Bearing Rats.

PubMed

Moreira, Veridiana Mota; da Silva Franco, Claudinéia Conationi; Prates, Kelly Valério; Gomes, Rodrigo Mello; de Moraes, Ana Maria Praxedes; Ribeiro, Tatiane Aparecida; Martins, Isabela Peixoto; Previate, Carina; Pavanello, Audrei; Matiusso, Camila Cristina Ianoni; Almeida, Douglas Lopes; Francisco, Flávio Andrade; Malta, Ananda; Tófolo, Laize Peron; da Silva Silveira, Sandra; Saavedra, Lucas Paulo Jacinto; Machado, Katia; da Silva, Paulo Henrique Olivieri; Fabrício, Gabriel S; Palma-Rigo, Kesia; de Souza, Helenir Medri; de Fátima Silva, Flaviane; Biazi, Giuliana Regina; Pereira, Taís Susane; Vieira, Elaine; Miranda, Rosiane Aparecida; de Oliveira, Júlio Cezar; da Costa Lima, Luiz Delmar; Rinaldi, Wilson; Ravanelli, Maria Ida; de Freitas Mathias, Paulo Cezar

2018-01-01

Aerobic exercise training can improve insulin sensitivity in many tissues; however, the relationship among exercise, insulin, and cancer cell growth is unclear. We tested the hypothesis that aerobic exercise training begun during adolescence can attenuate Walker 256 tumor growth in adult rats and alter insulin secretion. Thirty-day-old male Wistar rats engaged in treadmill running for 8 weeks, 3 days/week, 44 min/day, at 55-65% VO 2max until they were 90 days old (TC, Trained Control). An equivalently aged group was kept inactive during the same period (SC, Sedentary Control). Then, half the animals of the SC and TC groups were reserved as the control condition and the other half were inoculated with Walker 256 cancer cells, yielding two additional groups (Sedentary Walker and Trained Walker). Zero mortalities were observed in tumor-bearing rats. Body weight (BW), food intake, plasma glucose, insulin levels, and peripheral insulin sensitivity were analyzed before and after tumor cell inoculation. We also evaluated tumor growth, metastasis and cachexia. Isolated pancreatic islets secretory activity was analyzed. In addition, we evaluated mechanic sensibility. Our results showed improved physical performance according to the final workload and VO 2max and reduced BW in trained rats at the end of the running protocol. Chronic adaptation to the aerobic exercise training decreased tumor weight, cachexia and metastasis and were associated with low glucose and insulin levels and high insulin sensitivity before and after tumor cell inoculation. Aerobic exercise started at young age also reduced pancreatic islet insulin content and insulin secretion in response to a glucose stimulus, without impairing islet morphology in trained rats. Walker 256 tumor-bearing sedentary rats also presented reduced pancreatic islet insulin content, without changing insulin secretion through isolated pancreatic islets. The mechanical sensitivity test indicated that aerobic exercise training did not cause injury or trigger inflammatory processes prior to tumor cell inoculation. Taken together, the current study suggests that aerobic exercise training applied during adolescence may mitigate tumor growth and related disorders in Walker 256 tumor-bearing adult rats. Improved insulin sensibility, lower glucose and insulin levels and/or reduced insulin secretion stimulated by glucose may be implicated in this tumor attenuation.

Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

PubMed Central

Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

2014-01-01

Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

[Moderate exercise and intake of either high or low glycemic index carbohydrates in sedentary women].

PubMed

Ortiz-Rodríguez, Briseidy; De León, Lidia G; Esparza-Romero, Julián; Carrasco-Legleu, Claudia E; Candia-Luján, Ramón

2018-05-25

To analyze changes in blood glucose, insulin and triglyceride concentrations in relation to a moderate aerobic exercise in sedentary women of different body weight, exposed to either a high or low glycemic index carbohydrates diet. DISEñO: Cross-over type. SITE: Research was performed in the Exercise Physiology Laboratory at Facultad de Ciencias de la Cultura Física, Universidad Autónoma de Chihuahua, México. Twenty-six young sedentary women who did not exercise in the last year participated in the study. Four of adequate weight (AW) and 2 with obesity (OB) were excluded for not consuming the suggested carbohydrates (1gr/kg of weight) nor completed the programed exercise. There were n=10 in each group (AW/OB). Two treatments of 55minutes of aerobic exercise each were applied one day after consuming either high or low glycemic index carbohydrates. Plasmatic glucose, insulin, and triglycerides were determined before and after the scheduled exercise. Glucose, insulin, and triglycerides were higher in OB than in AW at baseline. Glucose was normalized in OB from 5.8±0.35 to 5.3±0.23 mmol/L (P=.001), only by eating foods with low glycemic index; triglycerides increased from 139.5±66.0 to 150.8±67.2mg/dl (P=.004) at the end of the exercise, after consumption of low glycemic index carbohydrates. Elevation of triglycerides secondary to exercise after consumption of low glycemic index seems to indicate an increase of lipid oxidation in OB. Copyright © 2018 The Authors. Publicado por Elsevier España, S.L.U. All rights reserved.

Antidiabetic effect of Euterpe oleracea Mart. (açaí) extract and exercise training on high-fat diet and streptozotocin-induced diabetic rats: A positive interaction

PubMed Central

de Bem, Graziele Freitas; Costa, Cristiane Aguiar; Santos, Izabelle Barcellos; Cristino Cordeiro, Viviane da Silva; de Carvalho, Lenize Costa Reis Marins; de Souza, Marcelo Augusto Vieira; Soares, Ricardo de Andrade; Sousa, Pergentino José da Cunha; Ognibene, Dayane Teixeira; de Moura, Roberto Soares

2018-01-01

A growing body of evidence suggests a protective role of polyphenols and exercise training on the disorders of type 2 diabetes mellitus (T2DM). We aimed to assess the effect of the açaí seed extract (ASE) associated with exercise training on diabetic complications induced by high-fat (HF) diet plus streptozotocin (STZ) in rats. Type 2 diabetes was induced by feeding rats with HF diet (55% fat) for 5 weeks and a single dose of STZ (35 mg/kg i.p.). Control (C) and Diabetic (D) animals were subdivided into four groups each: Sedentary, Training, ASE Sedentary, and ASE Training. ASE (200 mg/kg/day) was administered by gavage and the exercise training was performed on a treadmill (30min/day; 5 days/week) for 4 weeks after the diabetes induction. In type 2 diabetic rats, the treatment with ASE reduced blood glucose, insulin resistance, leptin and IL-6 levels, lipid profile, and vascular dysfunction. ASE increased the expression of insulin signaling proteins in skeletal muscle and adipose tissue and plasma GLP-1 levels. ASE associated with exercise training potentiated the reduction of glycemia by decreasing TNF-α levels, increasing pAKT and adiponectin expressions in adipose tissue, and IR and pAMPK expressions in skeletal muscle of type 2 diabetic rats. In conclusion, ASE treatment has an antidiabetic effect in type 2 diabetic rats by activating the insulin-signaling pathway in muscle and adipose tissue, increasing GLP-1 levels, and an anti-inflammatory action. Exercise training potentiates the glucose-lowering effect of ASE by activating adiponectin-AMPK pathway and increasing IR expression. PMID:29920546

Voluntary post weaning exercise restores metabolic homeostasis in offspring of obese rats.

PubMed

Rajia, S; Chen, H; Morris, M J

2013-06-01

Physical exercise reduces obesity, insulin resistance and dyslipidemia. We previously found that maternal obesity alters central appetite circuits and contributes to increased adiposity, glucose intolerance and metabolic disease in offspring. Here we hypothesized that voluntary exercise would ameliorate the adverse metabolic effects of maternal obesity on offspring. Sprague-Dawley females fed chow (C) or high-fat diet HFD (H) were mated. Female offspring from C dams were weaned onto chow (CC); those from H dams recieved chow (HC) or HFD (HH). Half of each group was provided with running wheels (CC(EX), HC(EX), HH(EX); n=10-12). Maternal obesity increased body weight (12%), adiposity, plasma lipids and induced glucose intolerance (HC vs CC; P<0.05). These were exaggerated by postweaning HFD (HH vs HC; P<0.01), showed doubled energy intake, a 37% increase in body weight, insulin resistance and glucose intolerance (HH vs HC; P<0.01). Exercise reduced fat mass, plasma lipids, HOMA and fasting glucose in HC(EX) (vs HC; P<0.05) and HH(EX) (vs HH; P<0.01). Values in HC(EX) were indistinguishable from CC, however in HH(EX) these metabolic parameters remained higher than the sedentary HC and CC rats (P<0.01). mRNA expression of hypothalamic pro-opiomelanocortin, and adipose tumour necrosis factor α and 11β-hydroxysteroid dehydrogenase type 1 were reduced by exercise in HH(EX) (vs HH; P<0.05). While voluntary exercise almost completely reversed the metabolic effects of maternal obesity in chow fed offspring, it did not fully attenuate the increased adiposity, glucose intolerance and insulin resistance in offspring weaned onto HFD. Crown Copyright © 2011. Published by Elsevier B.V. All rights reserved.

Exercise Increases and Browns Muscle Lipid in High-Fat Diet-Fed Mice.

PubMed

Morton, Tiffany L; Galior, Kornelia; McGrath, Cody; Wu, Xin; Uzer, Gunes; Uzer, Guniz Bas; Sen, Buer; Xie, Zhihui; Tyson, David; Rubin, Janet; Styner, Maya

2016-01-01

Muscle lipid increases with high-fat feeding and diabetes. In trained athletes, increased muscle lipid is not associated with insulin resistance, a phenomenon known as the athlete's paradox. To understand if exercise altered the phenotype of muscle lipid, female C57BL/6 mice fed CTL or high-fat diet (HFD for 6 or 18 weeks) were further divided into sedentary or exercising groups (CTL-E or HFD-E) with voluntary access to running wheels for the last 6 weeks of experiments, running 6 h/night. Diet did not affect running time or distance. HFD mice weighed more than CTL after 18 weeks (p < 0.01). Quadriceps muscle TG was increased in running animals and in sedentary mice fed HFD for 18 weeks (p < 0.05). In exercised animals, markers of fat, Plin1, aP2, FSP27, and Fasn, were increased significantly in HFD groups. Ucp1 and Pgc1a, markers for brown fat, increased with exercise in the setting of high fat feeding. Fndc5, which encodes irisin, and CytC were sensitive to exercise regardless of diet. Plin5 was increased with HFD and unaffected by exercise; the respiratory exchange ratio was 15% lower in the 18-week HFD group compared with CTL (p < 0.001) and 10% lower in 18 weeks HFD-E compared with CTL-E (p < 0.001). Increased Ucp1 and Pgc1a in exercised muscle of running mice suggests that a beige/brown fat phenotype develops, which differs from the fat phenotype that induces insulin resistance in high fat feeding. This suggests that increased muscle lipid may develop a "brown" phenotype in the setting of endurance exercise training, a shift that is further promoted by HFD.

Effects of Exercise Training and Weight Loss on Plasma Fetuin-A Levels and Insulin Sensitivity in Overweight Older Men.

PubMed

Blumenthal, Jacob B; Gitterman, Anna; Ryan, Alice S; Prior, Steven J

2017-01-01

Aerobic exercise training and weight loss (AEX+WL) improves insulin sensitivity in overweight adults; however, the underlying pathways are incompletely understood. Fetuin-A, a hepatokine that inhibits insulin signaling, may be involved in the salutary effects of AEX+WL. Therefore, we examined the effects of 6-month AEX+WL on plasma fetuin-A levels (36-48 hours after the last bout of exercise), aerobic capacity (VO 2max ), body composition, glucose tolerance, and insulin sensitivity (M) in 16 sedentary, overweight-obese older men (age = 60 ± 2 years, BMI = 31 ± 1 kg/m 2 ) with no history of cardiovascular disease or diabetes. At baseline, fetuin-A levels correlated directly with adiposity and had a borderline inverse correlation with M. After AEX+WL, body weight decreased by ~10 kg, while both VO 2max and M increased by 16% ( P < 0.005 for all). Contrary to our hypothesis, plasma fetuin-A levels increased after AEX+WL (1.16 ± 0.10 g/L versus 1.70 ± 0.19 g/L, P = 0.006). This increase was unrelated to changes in body composition or glucose metabolism, but directly correlated with changes in VO 2max ( r = 0.57, P < 0.05). Thus, in overweight-to-obese older men, AEX+WL appears to increase plasma fetuin-A levels. Although not associated with improvements in insulin sensitivity, this increase in fetuin-A was related to improvements in aerobic capacity and could be representative of the cardioprotective effects of AEX+WL in older men.

Postnatal PPARdelta activation and myostatin inhibition exert distinct yet complimentary effects on the metabolic profile of obese insulin-resistant mice.

PubMed

Bernardo, Barbara L; Wachtmann, Timothy S; Cosgrove, Patricia G; Kuhn, Max; Opsahl, Alan C; Judkins, Kyle M; Freeman, Thomas B; Hadcock, John R; LeBrasseur, Nathan K

2010-06-25

Interventions for T2DM have in part aimed to mimic exercise. Here, we have compared the independent and combined effects of a PPARdelta agonist and endurance training mimetic (GW501516) and a myostatin antibody and resistance training mimetic (PF-879) on metabolic and performance outcomes in obese insulin resistant mice. Male ob/ob mice were treated for 6 weeks with vehicle, GW501516, PF-879, or GW501516 in combination with PF-879. The effects of the interventions on body composition, glucose homeostasis, glucose tolerance, energy expenditure, exercise capacity and metabolic gene expression were compared at the end of study. GW501516 attenuated body weight and fat mass accumulation and increased the expression of genes of oxidative metabolism. In contrast, PF-879 increased body weight by driving muscle growth and altered the expression of genes involved in insulin signaling and glucose metabolism. Despite their differences, both interventions alone improved glucose homeostasis. Moreover, GW501516 more effectively improved serum lipids, and PF-879 uniquely increased energy expenditure, exercise capacity and adiponectin levels. When combined the robust effects of GW501516 and/or PF-879 on body weight, adiposity, muscle mass, glycemia, serum lipids, energy expenditure and exercise capacity were highly conserved. The data, for the first time, demonstrate postnatal inhibition of myostatin not only promotes gains in muscle mass similar to resistance training,but improves metabolic homeostasis. In several instances, these effects were either distinct from or complimentary to those of GW501516. The data further suggest that strategies to increase muscle mass, and not necessarily oxidative capacity, may effectively counter insulin resistance and T2DM.

Weight Loss, Exercise, or Both and Cardiometabolic Risk Factors in Obese Older Adults: Results of a Randomized Controlled Trial

PubMed Central

Bouchonville, Matthew; Armamento-Villareal, Reina; Shah, Krupa; Napoli, Nicola; Sinacore, David R.; Qualls, Clifford; Villareal, Dennis T.

2013-01-01

Background Obesity exacerbates the age-related decline in insulin sensitivity and is associated with risk for cardiometabolic syndrome in older adults; however, the appropriate treatment for obese older adults is controversial. Objective To determine the independent and combined effects of weight loss and exercise on cardiometabolic risk factors in obese older adults. Design One-hundred-seven obese (BMI≥30 kg/m2) older (≥65 yrs) adults with physical frailty were randomized to control group, diet group, exercise group, and diet-exercise group for 1 year. Outcomes for this study included change in insulin sensitivity index (ISI), glucose tolerance, central obesity, adipocytokines, and cardiometabolic syndrome. Results Although similar increases in ISI occurred in the diet-exercise and diet groups at 6 months, the ISI improved more in the diet-exercise than in the diet group at 12 months (2.4 vs. 1.2; between-group difference, 1.2; 95% CI, 0.2-2.1); no changes in ISI occurred in both exercise and control groups. The diet-exercise and diet groups had similar improvements in insulin area under the curve (AUC) (−2.9 and −2.9 ×103mg.min/dl), glucose AUC (−1.4 and −2.2×103mg.min/dl), visceral fat (−787 and −561 cm3), tumor-necrosis factor (−17.0 and −12.8 pg/mL), adiponectin (5.0 and 4.0 ng/mL), waist circumference (−8.2 and −8.4 cm), triglyceride (−30.7 and −24.3 g/dL), and systolic/diastolic BP (−15.9 and −13.1/−4.9 and −6.7 mmHg), while no changes in these parameters occurred in both exercise and control groups. The cardiometabolic syndrome prevalence decreased by 40% in the diet-exercise and by 15% in the diet group. Body weight decreased similarly in the diet-exercise and diet groups (−8.6 and −9.7kg) but not in the exercise and control groups. Conclusions In frail, obese older adults, lifestyle interventions associated with weight loss improve insulin sensitivity and other cardiometabolic risk factors, but continued improvement in insulin sensitivity is only achieved when exercise training is added to weight loss. PMID:23823329

A randomized controlled exercise training trial on insulin sensitivity in African American men: The ARTIIS study: Major category: study design, statistical design, study protocols.

PubMed

Newton, Robert L; Johnson, William D; Hendrick, Chelsea; Harris, Melissa; Andrews, Emanuel; Johannsen, Neil; Rodarte, Ruben Q; Hsia, Daniel S; Church, Timothy S

2015-07-01

Lack of regular physical activity at prescribed intensity levels is a modifiable risk factor for insulin resistance and the development of diabetes. African American men are at increased risk for developing diabetes and most African American men are not meeting the current recommended levels of physical activity. The primary objective of the Aerobic Plus Resistance Training and Insulin Resistance in African American Men (ARTIIS) study is to determine the effectiveness of an exercise training intervention aimed at reducing diabetes risk factors in African American men at risk for developing diabetes. Insufficiently active 35-70 year old African American men with a family history of diabetes were eligible for the study. The 5-month randomized controlled trial assigns 116 men to an exercise training or healthy living control arm. The exercise training arm combines aerobic and resistance training according to the current national physical activity recommendations and is conducted in community (YMCA) facilities. The healthy living arm receives information promoting healthy lifestyle changes. Insulin response to an oral glucose load is the primary outcome measure, and changes in physiological parameters, cardiorespiratory fitness, strength, body composition, and psychological well-being comprise the secondary outcomes. The ARTIIS study is one of the first adequately powered, rigorously designed studies to investigate the effects of an aerobic plus resistance exercise training program and to assess adherence to exercise training in community facilities, in African American men. Copyright © 2015 Elsevier Inc. All rights reserved.

Postprandial improvement in insulin sensitivity after a single exercise session in adolescents with low aerobic fitness and physical activity.

PubMed

Short, Kevin R; Pratt, Lauren V; Teague, April M; Man, Chiara Dalla; Cobelli, Claudio

2013-03-01

The purpose of this study was to determine the acute and residual impact of a single exercise bout on meal glucose control in adolescents with habitually low physical activity. Twelve adolescents (seven females/five males, 14 ± 2 yr) completed three trials. One trial [No Exercise (No Ex)] was completed after refraining from vigorous activity for ≥ 3 d. On the other two trials, a 45-min aerobic exercise bout at 75% peak heart rate was performed either 17-h Prior Day Exercise (Prior Day Ex) trial or 1-h Same Day Exercise (Same Day Ex) trial before consuming the test meal (2803 kJ, 45/40/15% energy as carbohydrate/fat/protein, respectively). Compared to No Ex, insulin sensitivity (SI) (minimal model analysis) was increased by 45% (p < 0.03) and 78% (p < 0.01) on the Prior Day Ex and Same Day Ex trials, respectively. This improvement in glucose control was supported by corresponding reductions in the net area under the curve for glucose, insulin, and c-peptide, although there was no change in postprandial suppression of fatty acids. These results show that SI is improved with a single bout of moderate intensity exercise in adolescents with habitually low physical activity and that the residual beneficial effect of exercise lasts at least 17 h. This finding highlights the plasticity of exercise responses in youth and the importance of daily exercise for metabolic health. © 2012 John Wiley & Sons A/S.

Effects Ala54Thr polymorphism of FABP2 on obesity index and biochemical variable in response to a aerobic exercise training

PubMed Central

Han, Tae Kyung

2013-01-01

The purpose of the current study was to investigate whether or not the FABP2 gene polymorphism modulated obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers through 12-week aerobic exercise training in abdominal obesity group of Korean mid-life women. A total of 243 abdominally obese subjects of Korean mid-life women voluntarily participated in aerobic exercise training program for 12 weeks. Polymerase Chain Reaction with Restriction Fragment Length Polymorphism (PCR-RFLP) assay was used to assess the FABP2 genotype of the participants (117 of AA homozygotes, 100 of AT heterozygotes, 26 of TT homozygotes). Prior to the participation of the exercise training program, baseline obesity indices, hemodynamic factor, blood lipid factor, and insulin resistance markers were measured. All the measurements were replicated following the 12-week aerobic exercise training program, and then the following results were found. After 12-week aerobic exercise training program, wild type (Ala54Ala) and mutant type (Ala54Thr+Thr54Thr) significantly decreased weight (P > .001), BMI (P > .001), %bf (P > .001), waist circumference (P > .001), WHR (P > .001), muscle mass (wild type p < .022; mutant type P > .001), RHR (P > .001), viseceral adipose area (wild type p < .005; mutant type P > .001), subcutaneous area (P > .001), insulin (wild type p < .005; mutant type P > .001) and significantly increased VO2max (P > .001). And wild type significantly decresed NEFA (P > .05), glucose (P > .05), OGTT 120min glucose (P > .05) and significantly increased HDLC (p > .005). Mutant type significantly decreased SBP (P > .001), DBP (P > .01), TC (P > .01), LPL (P > .05), LDL (P > .001), HOMA index (P > .01). The result of the present study represents that regular aerobic exercise training may beneficially prevent obesity index, blood pressure, blood lipids and insulin resistance markers independent of FABP Ala54Thr wild type and mutant type. PMID:25566432

Effects of crocin and voluntary exercise, alone or combined, on heart VEGF-A and HOMA-IR of HFD/STZ induced type 2 diabetic rats.

PubMed

Ghorbanzadeh, V; Mohammadi, M; Dariushnejad, H; Chodari, L; Mohaddes, G

2016-10-01

Hyperglycemia is the main risk factor for microvascular complications in type 2 diabetes. Crocin and voluntary exercise have anti-hyperglycemic effects in diabetes. In this research, we evaluated the effects of crocin and voluntary exercise alone or combined on glycemia control and heart level of VEGF-A. Animals were divided into eight groups as: control (con), diabetes (Dia), crocin (Cro), voluntary exercise (Exe), crocin and voluntary exercise (Cro-Exe), diabetic-crocin (Dia-Cro), diabetic-voluntary exercise (Dia-Exe), diabetic-crocin-voluntary exercise (Dia-Cro-Exe). Type 2 diabetes was induced by a high-fat diet (4 weeks) and injection of streptozotocin (STZ) (i.p, 35 mg/kg). Animals received oral administration of crocin (50 mg/kg) or performed voluntary exercise alone or together for 8 weeks. Oral glucose tolerance test (OGTT) was performed on overnight fasted control, diabetic and treated rats after 8 weeks of treatment. Then, serum insulin and heart VEGF-A protein levels were measured. Crocin combined with voluntary exercise significantly decreased blood glucose levels (p < 0.001) and insulin resistance (HOMA-IR) (p < 0.001) compared to diabetic group. VEGF-A level was significantly (p < 0.01) lower in Dia group compared to control group. The combination of crocin and voluntary exercise significantly enhanced VEGF-A protein levels in Dia-Cro-Exe and Cro-Exe group compared to diabetic and control groups, respectively; p < 0.001 and p < 0.05. Crocin combined with voluntary exercise improved insulin resistance (HOMA-IR) and reduced glucose levels in diabetic rats. Since both crocin and voluntary exercise can increase VEGF-A protein expression in heart tissue, they probably are able to increase angiogenesis in diabetic animals.

Effects of continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content in rat skeletal muscle.

PubMed

Kubota, M; Koshinaka, K; Kawata, Y; Koike, T; Oshida, Y

2008-01-01

Stimulation of AMPK and decreased glycogen levels in skeletal muscle have a deep involvement in enhanced insulin action and GLUT-4 protein content after exercise training. The present study examined the chronic effects of a continuous low-carbohydrate diet after long-term exercise on GLUT-4 protein content, glycogen content, AMPK, and insulin signaling in skeletal muscle. Rats were divided randomly into four groups: normal chow diet sedentary (N-Sed), low carbohydrate diet sedentary (L-Sed), normal chow diet exercise (N-Ex), and low carbohydrate diet exercise (L-Ex) groups. Rats in the exercise groups (N-Ex and L-Ex) were exercised by swimming for 6 hours/day in two 3-hour bouts separated by 45 minutes of rest. The 10-day exercise training resulted in a significant increase in the GLUT-4 protein content (p<0.01). Additionally, the GLUT-4 protein content in L-Ex rats was increased by 29% above that in N-Ex rats (p<0.01). Finally, the glycogen content in skeletal muscle of L-Ex rats was decreased compared with that of N-Ex rats. Taken together, we suggest that the maintenance of glycogen depletion after exercise by continuous low carbohydrate diet results in the increment of the GLUT-4 protein content in skeletal muscle.

Exercise and dietary change ameliorate high fat diet induced obesity and insulin resistance via mTOR signaling pathway.

PubMed

Bae, Ju Yong; Shin, Ki Ok; Woo, Jinhee; Woo, Sang Heon; Jang, Ki Soeng; Lee, Yul Hyo; Kang, Sunghwun

2016-06-01

The purpose of this study was to investigate the effect of exercise and dietary change on obesity and insulin resistance and mTOR signaling protein levels in skeletal muscles of obese rats. Sixty male Sprague-Dawley rats were divided into CO (Normal diet) and HF (High Fat diet) groups in order to induce obesity for 15 weeks. The rats were then subdivided into CO, COT (CO + Training), HF, HFT (HF + Training), HFND (Dietary change), and HFNDT (HFND + Training) groups (10 rats / group). The training groups underwent moderate-intensity treadmill exercise for 8 weeks, after which soleus muscles were excised and analyzed. Data was statistically analyzed by independent t-test and One-way ANOVA tests with a 0.05 significance level. Fasting blood glucose, plasma insulin, and HOMA-IR in the HF group were significantly higher, as compared with other groups (p <.05). Protein levels of insulin receptor subunit-1 (IRS-1), IRS-2, and p-Akt were significantly higher in the HFT, HFND, and HFNDT groups, as compared with HF group. In addition, the protein levels of the mammalian target of rapamycin complex 1 (mTORC1) and ribosomal S6 protein kinase 1 were significantly decreased by exercise and dietary change (p <.05). However, mTORC2 and phosphoinositide 3-kinase were significantly increased (p <.05). In summary, despite the negative impact of continuous high fat intake, regular exercise and dietary change showed a positive effect on insulin resistance and mTOR signaling protein levels.

Association of exercise-induced hyperinsulinaemic hypoglycaemia with MCT1-expressing insulinoma.

PubMed

Marquard, J; Welters, A; Buschmann, T; Barthlen, W; Vogelgesang, S; Klee, D; Krausch, M; Raffel, A; Otter, S; Piemonti, L; Mayatepek, E; Otonkoski, T; Lammert, E; Meissner, T

2013-01-01

Exercise-induced hyperinsulinism (EIHI) is a hypoglycaemic disorder characterised by inappropriate insulin secretion following anaerobic exercise or pyruvate load. Activating promoter mutations in the MCT1 gene (also known as SCLA16A1), coding for monocarboxylate transporter 1 (MCT1), were shown to associate with EIHI. Recently, transgenic Mct1 expression in pancreatic beta cells was shown to introduce EIHI symptoms in mice. To date, MCT1 has not been demonstrated in insulin-producing cells from an EIHI patient. In vivo insulin secretion was studied during an exercise test before and after the resection of an insulinoma. The presence of MCT1 was analysed using immunohistochemistry followed by laser scanning microscopy, western blot analysis and real-time RT-PCR of MCT1. The presence of MCT1 protein was analysed in four additional insulinoma patients. Clinical testing revealed massive insulin secretion induced by anaerobic exercise preoperatively, but not postoperatively. MCT1 protein was not detected in the patient's normal islets. In contrast, immunoreactivity was clearly observed in the insulinoma tissue. Western blot analysis and real-time RT-PCR showed a four- to fivefold increase in MCT1 in the insulinoma tissue of the EIHI patient compared with human pancreatic islets. MCT1 protein was detected in three of four additional insulinomas. We show for the first time that an MCT1-expressing insulinoma was associated with EIHI and that MCT1 might be present in most insulinomas. Our data suggest that MCT1 expression in human insulin-producing cells can lead to EIHI and warrant further studies on the role of MCT1 in human insulinoma patients.

Short-term HIIT and Fat max training increase aerobic and metabolic fitness in men with class II and III obesity.

PubMed

Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Capodaglio, Paolo; Brunani, Amelia; Fanari, Paolo; Salvadori, Alberto; Malatesta, Davide

2015-10-01

To compare the effects of two different 2-week-long training modalities [continuous at the intensity eliciting the maximal fat oxidation (Fatmax) versus high-intensity interval training (HIIT)] in men with class II and III obesity. Nineteen men with obesity (BMI ≥ 35 kg · m(-2)) were assigned to Fatmax group (GFatmax) or to HIIT group (GHIIT). Both groups performed eight cycling sessions matched for mechanical work. Aerobic fitness and fat oxidation rates (FORs) during exercise were assessed prior and following the training. Blood samples were drawn to determine hormones and plasma metabolites levels. Insulin resistance was assessed by the homeostasis model assessment of insulin resistance (HOMA2-IR). Aerobic fitness and FORs during exercise were significantly increased in both groups after training (P ≤ 0.001). HOMA2-IR was significantly reduced only for GFatmax (P ≤ 0.001). Resting non-esterified fatty acids (NEFA) and insulin decreased significantly only in GFatmax (P ≤ 0.002). Two weeks of HIIT and Fatmax training are effective for the improvement of aerobic fitness and FORs during exercise in these classes of obesity. The decreased levels of resting NEFA only in GFatmax may be involved in the decreased insulin resistance only in this group. © 2015 The Obesity Society.

Aerobic exercise + weight loss decreases skeletal muscle myostatin expression and improves insulin sensitivity in older adults.

PubMed

Ryan, A S; Li, G; Blumenthal, J B; Ortmeyer, H K

2013-07-01

To determine whether aerobic exercise training + weight loss (AEX + WL) would affect the expression of myostatin and its relationship with insulin sensitivity in a longitudinal, clinical intervention study. Thirty-three obese sedentary postmenopausal women and men (n = 17 and 16, age: 61 ± 1 years, body mass index: 31 ± 1 kg/m(2) , VO2 max: 21.9 ± 1.0 mL/kg/min, X ± Standard error of the mean (SEM)) completed 6 months of 3 days/week AEX + WL. During an 80 mU m(-2) min(-1) hyperinsulinemic-euglycemic clamp, we measured glucose utilization (M), myostatin, myogenin, and MyoD gene expression by real-time RT-PCR in vastus lateralis muscle at baseline and 2 h. Body weight (-8%) and fat mass (-17%) decreased after AEX + WL (P < 0.001). Fat-free mass (FFM) and mid-thigh muscle area by computed tomography did not change but muscle attenuation increased (P < 0.05). VO2 max increased 14% (P < 0.001). AEX + WL increased M by 18% (P < 0.01). Myostatin gene expression decreased 19% after AEX + WL (P < 0.05). Basal mRNA myostatin levels were negatively associated with M before the intervention (r = -0.43, P < 0.05). Insulin infusion increased myoD and myogenin expression before and after AEX + WL (both P < 0.001) but basal levels did not change. The insulin effect on myostatin expression was associated with the change in M after AEX + WL (r = 0.56, P < 0.005). Exercise and weight loss results in a downregulation of myostatin mRNA and an improvement in insulin sensitivity in obese older men and women. Copyright © 2012 The Obesity Society.

Effectiveness of resistance exercise compared to aerobic exercise without insulin therapy in patients with type 2 diabetes mellitus: a meta-analysis.

PubMed

Nery, Cybelle; Moraes, Silvia Regina Arruda De; Novaes, Karyne Albino; Bezerra, Márcio Almeida; Silveira, Patrícia Verçoza De Castro; Lemos, Andrea

Physical exercise has been used to mitigate the metabolic effects of diabetes mellitus. To evaluate the effect of resistance exercise when compared to aerobic exercise without insulin therapy on metabolic and clinical outcomes in patients with type 2 diabetes mellitus. Papers were searched on the databases MEDLINE/PubMed, CINAHL, SPORTDiscus, LILACS, and SCIELO, without language or date of publication limits. Clinical trials that compared resistance exercise to aerobic exercise in adults with type 2 diabetes mellitus who did not use insulin therapy were included. The quality of evidence and risk of bias were assessed using the GRADE system and the Cochrane Risk of Bias tool, respectively. Meta-analysis was also used, whenever possible. Two reviewers extracted the data independently. Eight eligible articles were included in this study, with a total of 336 individuals, with a mean age of 48-58 years. The protocols of aerobic and resistance exercise varied in duration from eight to 22 weeks, 30-60min/day, three to five times/week. Overall the available evidence came from a very low quality of evidence and there was an increase in Maximal oxygen consumption (mean difference: -2.86; 95% CI: -3.90 to -1.81; random effect) for the resistance exercise and no difference was found in Glycated hemoglobin, Body mass index, High-density lipoprotein cholesterol, Low-density lipoprotein cholesterol, triglycerides, and total cholesterol. Resistance exercise appears to be more effective in promoting an increase in Maximal oxygen consumption in protocols longer than 12 weeks and there is no difference in the control of glycemic and lipid levels between the two types of exercise. Copyright © 2017 Associação Brasileira de Pesquisa e Pós-Graduação em Fisioterapia. Publicado por Elsevier Editora Ltda. All rights reserved.

Higher circulating leukocytes in women with PCOS is reversed by aerobic exercise.

PubMed

Covington, Jeffrey D; Tam, Charmaine S; Pasarica, Magdalena; Redman, Leanne M

2016-05-01

Polycystic ovary syndrome (PCOS) is characterized by insulin resistance, elevated circulating leukocytes, and hypothesized to have higher adipose tissue inflammation. Aerobic exercise reduces circulating leukocytes and improves insulin sensitivity in obese individuals, but the effect of exercise on inflammation in PCOS is not known. We investigated circulating leukocytes, insulin sensitivity by euglycemic-hyperinsulinemic clamp, serum pro- and anti-inflammatory markers (hsCRP, TNF-α, total and high molecular weight adiponectin), and abdominal subcutaneous adipose tissue (SAT) gene expression of proinflammatory markers in 8 PCOS women and 8 obese control females matched for BMI. Additionally, in a prospective study, the 8 women with PCOS underwent a 16-week aerobic exercise regimen with the same measures performed post-intervention. Compared to controls, white blood cell counts (WBC) were 30% higher (p = 0.04) and circulating total adiponectin levels were 150% lower (p = 0.03) in women with PCOS at baseline/pre-exercise conditions. SAT gene expression of macrophage migration inhibitory factor (MIF, p < 0.01) and interleukin-6 (IL-6, p < 0.05) were also lower in women with PCOS. In response to 16 weeks of aerobic exercise, insulin sensitivity improved (p < 0.01) and WBC counts decreased (p = 0.02). The exercise-induced change in WBC and circulating neutrophils correlated inversely with changes in glucose disposal rate (r = -0.73, p = 0.03; and r = -0.82, p = 0.01, respectively). Aerobic exercise reduced serum leptin (p < 0.05) after 4 weeks, trended to reduce the ratio of leptin-to-high molecular weight adiponectin (p < 0.1) by the 8th week, and significantly increased serum dehydroepiandrosterone sulfate (DHEA-S, p < 0.001) after 16 weeks. In conclusion, women with PCOS have higher circulating leukocytes compared to controls, which can be reversed by aerobic exercise and is associated with improvements in insulin sensitivity. Copyright © 2014 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

The Role of Skeletal Muscle Glycogen Breakdown for Regulation of Insulin Sensitivity by Exercise

PubMed Central

Jensen, Jørgen; Rustad, Per Inge; Kolnes, Anders Jensen; Lai, Yu-Chiang

2011-01-01

Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g). Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycemic clamp, 70–90% of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen’s main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70% of maximal oxygen uptake (Vo2max⁡) and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favor glycogen repletion and preparation for new “fight or flight” events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channeled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type 2 diabetes. PMID:22232606

The role of skeletal muscle glycogen breakdown for regulation of insulin sensitivity by exercise.

PubMed

Jensen, Jørgen; Rustad, Per Inge; Kolnes, Anders Jensen; Lai, Yu-Chiang

2011-01-01

Glycogen is the storage form of carbohydrates in mammals. In humans the majority of glycogen is stored in skeletal muscles (∼500 g) and the liver (∼100 g). Food is supplied in larger meals, but the blood glucose concentration has to be kept within narrow limits to survive and stay healthy. Therefore, the body has to cope with periods of excess carbohydrates and periods without supplementation. Healthy persons remove blood glucose rapidly when glucose is in excess, but insulin-stimulated glucose disposal is reduced in insulin resistant and type 2 diabetic subjects. During a hyperinsulinemic euglycemic clamp, 70-90% of glucose disposal will be stored as muscle glycogen in healthy subjects. The glycogen stores in skeletal muscles are limited because an efficient feedback-mediated inhibition of glycogen synthase prevents accumulation. De novo lipid synthesis can contribute to glucose disposal when glycogen stores are filled. Exercise physiologists normally consider glycogen's main function as energy substrate. Glycogen is the main energy substrate during exercise intensity above 70% of maximal oxygen uptake ([Formula: see text]) and fatigue develops when the glycogen stores are depleted in the active muscles. After exercise, the rate of glycogen synthesis is increased to replete glycogen stores, and blood glucose is the substrate. Indeed insulin-stimulated glucose uptake and glycogen synthesis is elevated after exercise, which, from an evolutional point of view, will favor glycogen repletion and preparation for new "fight or flight" events. In the modern society, the reduced glycogen stores in skeletal muscles after exercise allows carbohydrates to be stored as muscle glycogen and prevents that glucose is channeled to de novo lipid synthesis, which over time will causes ectopic fat accumulation and insulin resistance. The reduction of skeletal muscle glycogen after exercise allows a healthy storage of carbohydrates after meals and prevents development of type 2 diabetes.

Aerobic exercise is necessary to improve glucose utilization with moderate weight loss in women.

PubMed

Ryan, Alice S; Nicklas, Barbara J; Berman, Dora M

2006-06-01

To determine the effects of weight loss (WL) alone and combined with aerobic exercise on visceral adipose tissue (VAT), intramuscular fat, insulin-stimulated glucose uptake, and the rate of decline in free fatty acid (FFA) concentrations during hyperinsulinemia. We studied 33 sedentary, obese (BMI = 32 +/- 1 kg/m(2)) postmenopausal women who completed a 6-month (three times per week) program of either WL alone (n = 16) or WL + aerobic exercise (AEX) (n = 17). Glucose utilization (M) was measured during a 3-hour hyperinsulinemic-euglycemic clamp (40 mU/m(2) per minute). M/I, the amount of glucose metabolized per unit of plasma insulin (I), was used as an index of insulin sensitivity. Body weight, total fat mass, and percentage fat decreased similarly in both groups (p < 0.01). VAT, subcutaneous abdominal adipose tissue, mid-thigh subcutaneous fat, and intramuscular fat decreased to a similar extent in both groups and between 14% and 27% after WL and WL+AEX (p < 0.05). WL alone did not change M or M/I; however, M and M/I increased 15% and 21% after WL+AEX (p < 0.05). Fasting concentrations and rate of decline of FFA did not change in either group. In stepwise regression models to determine the independent predictors of changes in M and M/I, the change in VAT was the single independent predictor of M (r(2) = 0.30) and M/I (r(2) = 0.33). Intramuscular fat decreases similarly with 6 months of moderate WL alone or with aerobic exercise in postmenopausal women. In contrast, only WL combined with exercise results in increased glucose utilization and insulin sensitivity. These findings should be validated in a larger population.

Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise

PubMed Central

Mankowski, Robert T.; Anton, Stephen D.; Buford, Thomas W.; Leeuwenburgh, Christiaan

2015-01-01

Adaptive responses to exercise training (ET) are crucial in maintaining physiological homeostasis and health span. Exercise-induced aerobic bioenergetic reactions in mitochondria and cytosol increase production of reactive oxygen species (ROSs), where excess of ROS can be scavenged by enzymatic as well as non-enzymatic antioxidants to protect against deleterious oxidative stress. Free radicals, however, have recently been recognized as crucial signaling agents that promote adaptive mechanisms to ET, such as mitochondrial biogenesis, antioxidant (AO) enzyme activity defense system upregulation, insulin sensitivity, and glucose uptake in skeletal muscle. Commonly used non-enzymatic AO supplements, such as vitamins C and E, a-lipoic acid, and polyphenols, in combination with ET, have been proposed as ways to prevent exercise-induced oxidative stress and hence improve adaptation responses to endurance training. Preclinical and clinical studies to date have shown inconsistent results indicating either positive or negative effects of endurance training combined with different blends of AO supplements (mostly vitamins C and E and a-lipoic acid) on redox status, mitochondrial biogenesis pathways, and insulin sensitivity. Preclinical reports on ET combined with resveratrol, however, have shown consistent positive effects on exercise performance, mitochondrial biogenesis, and insulin sensitivity, with clinical trials reporting mixed effects. Relevant clinical studies have been few and have used inconsistent results and methodology (types of compounds, combinations, and supplementation time). The future studies would investigate the effects of specific antioxidants and other popular supplements, such as a-lipoic acid and resveratrol, on training effects in humans. Of particular importance are older adults who may be at higher risk of age-related increased oxidative stress, an impaired AO enzyme defense system, and comorbidities such as hypertension, insulin resistance, and diabetes. PMID:25606815

Only minor additional metabolic health benefits of high as opposed to moderate dose physical exercise in young, moderately overweight men.

PubMed

Reichkendler, M H; Rosenkilde, M; Auerbach, P L; Agerschou, J; Nielsen, M B; Kjaer, A; Hoejgaard, L; Sjödin, A; Ploug, T; Stallknecht, B

2014-05-01

The dose-response effects of exercise training on insulin sensitivity, metabolic risk, and quality of life were examined. Sixty-one healthy, sedentary (VO₂max: 35 ± 5 ml/kg/min), moderately overweight (BMI: 27.9 ± 1.8), young (age: 29 ± 6 years) men were randomized to sedentary living (sedentary control group; n = 18), moderate (moderate dose training group [MOD]: 300 kcal/day, n = 21), or high (high dose training group [HIGH]: 600 kcal/day, n = 22) dose physical exercise for 11 weeks. The return rate for post-intervention testing was 82-94% across groups. Weekly exercise amounted to 2,004 ± 24 and 3,774 ± 68 kcal, respectively, in MOD and HIGH. Cardiorespiratory fitness increased (P < 0.001) 18 ± 3% in MOD and 17 ± 3% in HIGH, and fat percentage decreased (P < 0.001) similarly in both exercise groups (MOD: 32 ± 1 to 29 ± 1%; HIGH: 30 ± 1 to 27 ± 1%). Peripheral insulin sensitivity increased (P < 0.01) (MOD: 28 ± 7%; HIGH: 36 ± 8%) and the homeostasis model assessment of insulin resistance decreased (P < 0.05) (MOD: -17 ± 7%; HIGH: -18 ± 10%). The number of subjects meeting the criteria of the metabolic syndrome decreased by 78% in MOD (P < 0.01) and by 80% in HIGH (P < 0.05). General health assessed by questionnaire increased similarly in MOD (P < 0.05) and HIGH (P < 0.01). Only minor additional health benefits were found when exercising ∼3,800 as opposed to ∼2,000 kcal/week in young moderately overweight men. This finding may have important public health implications. Copyright © 2012 The Obesity Society.

Pioglitazone ameliorates the lowered exercise capacity and impaired mitochondrial function of the skeletal muscle in type 2 diabetic mice.

PubMed

Takada, Shingo; Hirabayashi, Kagami; Kinugawa, Shintaro; Yokota, Takashi; Matsushima, Shouji; Suga, Tadashi; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Mizushima, Wataru; Masaki, Yoshihiro; Furihata, Takaaki; Katsuyama, Ryoichi; Okita, Koichi; Tsutsui, Hiroyuki

2014-10-05

We have reported that exercise capacity is reduced in high fat diet (HFD)-induced diabetic mice, and that this reduction is associated with impaired mitochondrial function in skeletal muscle (SKM). However, it remains to be clarified whether the treatment of diabetes ameliorates the reduced exercise capacity. Therefore, we examined whether an insulin-sensitizing drug, pioglitazone, could improve exercise capacity in HFD mice. C57BL/6J mice were fed a normal diet (ND) or HFD, then treated with or without pioglitazone (3 mg/kg/day) to yield the following 4 groups: ND+vehicle, ND+pioglitazone, HFD+vehicle, and HFD+pioglitazone (n=10 each). After 8 weeks, body weight, plasma glucose, and insulin in the HFD+vehicle were significantly increased compared to the ND+vehicle group. Pioglitazone normalized the insulin levels in HFD-fed mice, but did not affect the body weight or plasma glucose. Exercise capacity determined by treadmill tests was significantly reduced in the HFD+vehicle, and this reduction was almost completely ameliorated in HFD+pioglitazone mice. ADP-dependent mitochondrial respiration, complex I and III activities, and citrate synthase activity were significantly decreased in the SKM of the HFD+vehicle animals, and these decreases were also attenuated by pioglitazone. NAD(P)H oxidase activity was significantly increased in the HFD+vehicle compared with the ND+vehicle, and this increase was ameliorated in HFD+pioglitazone mice. Pioglitazone improved the exercise capacity in diabetic mice, which was due to the improvement in mitochondrial function and attenuation of oxidative stress in the SKM. Our data suggest that pioglitazone may be useful as an agent for the treatment of diabetes mellitus. Copyright © 2014 Elsevier B.V. All rights reserved.

Variations in the four and a half LIM domains 1 gene (FHL1) are associated with fasting insulin and insulin sensitivity responses to regular exercise.

PubMed

Teran-Garcia, M; Rankinen, T; Rice, T; Leon, A S; Rao, D C; Skinner, J S; Bouchard, C

2007-09-01

The expression of the four and a half LIM domains 1 gene (FHL1) is increased in the muscle of individuals who show an improvement in insulin sensitivity index (S(I)) after 20 weeks of exercise training. The aim of the present study was to investigate associations between three FHL1 single nucleotide polymorphisms (SNPs) and variables derived from an IVGTT, both in the sedentary state and in response to exercise training, in participants in the HERITAGE Family Study. SNPs were typed using fluorescence polarisation methodology. Analyses were performed separately by sex and in black and white individuals. In black participants, no associations were found with any of the SNPs. In white women (n = 207), SNP rs9018 was associated with the disposition index (D(I)), which is calculated as S(I) generated from the MINMOD program (x10(-4) min(-1)[microU/ml](-1)) multiplied by acute insulin response to glucose (AIR(g); pmol/l x 10 min), and the glucose disappearance index (K(g)) training responses (p = 0.016 and p = 0.008, respectively). In white men (n = 222), all SNPs were associated with fasting glucose levels (p < or = 0.05) and SNP rs2180062 with the insulin sensitivity index (S(I)) (p = 0.04) in the sedentary state. Two SNPs were associated with fasting insulin training response. Fasting insulin decreased to a greater extent in carriers of the rs2180062 C allele (p = 0.01) and rs9018 T allele (p = 0.04). With exercise training, S(I) (x10(-4) min(-1)[microU/ml](-1): 0.68 +/- 0.20 vs -0.77 +/- 0.44, p = 0.046), D(I) (319 +/- 123 vs -528 +/- 260, p = 0.006) and K(g) (per 100 min: 0.09 +/- 0.04 vs -0.14 +/- 0.8, p = 0.03) improved more in the C allele carriers at rs2180062 than in the T allele carriers. Fasting insulin and S(I) responses to exercise training were associated with DNA sequence variation in FHL1 in white men. Whether these associations exist only in white men remains to be investigated.

Aerobic exercise and weight loss reduce vascular markers of inflammation and improve insulin sensitivity in obese women.

PubMed

Ryan, Alice S; Ge, Shealinna; Blumenthal, Jacob B; Serra, Monica C; Prior, Steven J; Goldberg, Andrew P

2014-04-01

To examine the relationships between plasma and tissue markers of systemic and vascular inflammation and obesity and insulin resistance and determine the effects of aerobic exercise training plus weight loss (AEX+WL) and weight loss (WL) alone on these biomarkers. Prospective controlled study. Veterans Affairs Medical Center and University research setting. Overweight and obese sedentary postmenopausal women (N = 77). Six months, 3 d/wk AEX+WL (n = 37) or WL (n = 40). Total-body dual-energy X-ray absorptiometry, abdominal computed tomography, hyperinsulinemic-euglycemic clamps (a criterion standard method of assessing insulin sensitivity), adipose tissue biopsies (n = 28), and blood for homeostasis model assessment-insulin resistance, and soluble forms of intracellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), C-reactive protein (CRP), and serum amyloid A (SAA). Body weight (P < .001), percentage of fat (P < .001), visceral fat (P < .005), triglyceride levels (P < .001), and systolic blood pressure decreased comparably after WL and AEX+WL (P = .04). Maximal oxygen consumption increased 16% after AEX+WL (P < .001). Insulin resistance decreased in both groups (P = .005). Glucose utilization according to the clamp increased 10% (P = .04) with AEX+WL and 8% with WL (P = .07). AEX+WL decreased CRP by 29% (P < .001) and WL by 21% (P = .02). SAA levels decreased twice as much after AEX+WL (-19%, P = .02) as after WL (-9%, P = .08). Plasma sICAM-1 and sVCAM-1 levels did not change, but women with the greatest reduction in plasma sICAM-1 levels had the greatest reductions in fasting glucose (P = .02), insulin (P = .02), and insulin resistance (P = .004). Gluteal ICAM messenger ribonucleic acid levels decreased 27% after AEX+WL (P = .02) and did not change after WL. Obesity and insulin resistance worsen markers of systemic and vascular inflammation. A reduction in plasma sICAM-1 is important to improve insulin sensitivity. CRP, SAA, and tissue ICAM decrease with exercise and weight loss, suggesting that exercise training is a necessary component of lifestyle modification in obese postmenopausal women. © Published 2014. This article is a U.S. Government work and is in the public domain in the U.S.A.

Proteomics of Skeletal Muscle: Focus on Insulin Resistance and Exercise Biology

PubMed Central

Deshmukh, Atul S.

2016-01-01

Skeletal muscle is the largest tissue in the human body and plays an important role in locomotion and whole body metabolism. It accounts for ~80% of insulin stimulated glucose disposal. Skeletal muscle insulin resistance, a primary feature of Type 2 diabetes, is caused by a decreased ability of muscle to respond to circulating insulin. Physical exercise improves insulin sensitivity and whole body metabolism and remains one of the most promising interventions for the prevention of Type 2 diabetes. Insulin resistance and exercise adaptations in skeletal muscle might be a cause, or consequence, of altered protein expressions profiles and/or their posttranslational modifications (PTMs). Mass spectrometry (MS)-based proteomics offer enormous promise for investigating the molecular mechanisms underlying skeletal muscle insulin resistance and exercise-induced adaptation; however, skeletal muscle proteomics are challenging. This review describes the technical limitations of skeletal muscle proteomics as well as emerging developments in proteomics workflow with respect to samples preparation, liquid chromatography (LC), MS and computational analysis. These technologies have not yet been fully exploited in the field of skeletal muscle proteomics. Future studies that involve state-of-the-art proteomics technology will broaden our understanding of exercise-induced adaptations as well as molecular pathogenesis of insulin resistance. This could lead to the identification of new therapeutic targets. PMID:28248217

Metabolomic Response of Skeletal Muscle to Aerobic Exercise Training in Insulin Resistant Type 1 Diabetic Rats.

PubMed

Dotzert, Michelle S; Murray, Michael R; McDonald, Matthew W; Olver, T Dylan; Velenosi, Thomas J; Hennop, Anzel; Noble, Earl G; Urquhart, Brad L; Melling, C W James

2016-05-20

The etiology of insulin resistance in Type 1 Diabetes (T1D) is unknown, however it affects approximately 20% of T1D patients. Intramyocellular lipids (IMCL) have been identified as a mechanism of insulin resistance. We examined skeletal muscle of T1D rats to determine if alterations in lipid metabolism were evident and whether aerobic exercise training improves IMCL and insulin resistance. To do so, 48 male Sprague-Dawley rats were divided into control (C), sedentary diabetes (D) and diabetes exercise (DX) groups. Following multiple low-dose Streptozotocin (STZ) injections (20 mg/kg), glycemia (9-15 mM) was maintained using insulin treatment. DX were treadmill trained at high intensity (~75% V02max; 5days/week) for 10 weeks. The results demonstrate that D exhibited insulin resistance compared with C and DX, indicated by decreased glucose infusion rate during a hyperinsulinemic-euglycemic clamp (p < 0.05). There were no differences between C and DX, suggesting that exercise improved insulin resistance (p < 0.05). Metabolomics analysis revealed a significant shift in lipid metabolism whereby notable fatty acid metabolites (arachidonic acid, palmitic acid and several polyunsaturated fatty acids) were significantly elevated in D compared to C and DX. Based on the intermediates observed, insulin resistance in T1D is characterized by an insulin-desensitizing intramyocellular fatty acid metabolite profile that is ameliorated with exercise training.

What Are the Safety Considerations for Insulin Control for Athletes?

ERIC Educational Resources Information Center

McDaniel, Larry W.; Olson, Sara; Gaudet, Laura; Jackson, Allen

2010-01-01

Athletes diagnosed with diabetes may have difficulty with their blood sugar levels fluctuating during intense exercise. Considerations for athletes with insulin concerns may range anywhere from exercise rehabilitation to the use of an automatic insulin pump. The automatic insulin pump is a small battery-operated device about the size of a pager.…

PPARgamma gene polymorphism is associated with exercise-mediated changes of insulin resistance in healthy men.

PubMed

Kahara, Toshio; Takamura, Toshinari; Hayakawa, Tetsuo; Nagai, Yukihiro; Yamaguchi, Hiromi; Katsuki, Tatsuo; Katsuki, Ken-Ichi; Katsuki, Michio; Kobayashi, Ken-Ichi

2003-02-01

Exercise training improves insulin sensitivity, but individual responses vary greatly. Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a regulator of adipose cell differentiation and plays an important role in systemic insulin action. We investigated whether PPARgamma gene polymorphism affects insulin resistance in response to exercise in Japanese healthy men. The exercise program at an individual intensity of 50% of the maximal heart rate was performed for 20 to 60 min/d, and 2 to 3 days per week to attain a level of physical activity of 700 kcal/wk. The program was conducted for 3 months without any dietary intervention, and the clinical and metabolic characteristics were examined before and after the exercise program. Body mass index (BMI) did not change significantly after the exercise program, whereas percentage of body fat (% body fat), fasting plasma glucose (FPG), and serum leptin levels decreased significantly. Pro12Ala polymorphism in PPARgamma gene was performed on genomic DNA isolated from human leukocytes and examined with polymerase chain reaction (PCR) and subsequent restriction enzyme analysis using BstU-I. In this study, the Ala allele did not correlate with fasting immunoreactive insulin (IRI) and homeostasis model assessment-insulin resistance index (HOMA-R) at baseline, but did so with the changes in IRI and HOMA-R after exercise (DeltaIRI, Pro/Pro 0.55 +/- 3.49 microU/mL v Pro/Ala -2.83 +/- 1.47 microU/mL, P <.05; DeltaHOMA-R, Pro/Pro 0.09 +/- 0.86 v Pro/Ala -0.61 +/- 0.32, P <.05). This result suggests that the Ala allele is associated with improvement in insulin resistance after exercise. We conclude that PPARgamma gene polymorphism may be a reliable indicator of whether exercise will have a beneficial effect as part of the treatment of insulin resistance syndrome. Copyright 2003, Elsevier Science (USA). All rights reserved.

Exercise training, glucose transporters, and glucose transport in rat skeletal muscles

NASA Technical Reports Server (NTRS)

Rodnick, K. J.; Henriksen, E. J.; James, D. E.; Holloszy, J. O.

1992-01-01

It was previously found that voluntary wheel running induces an increase in the insulin-sensitive glucose transporter, i.e., the GLUT4 isoform, in rat plantaris muscle (K. J. Rodnick, J. O. Holloszy, C. E. Mondon, and D. E. James. Diabetes 39: 1425-1429, 1990). The present study was undertaken to determine whether 1) the increase in muscle GLUT4 protein is associated with an increase in maximally stimulated glucose transport activity, 2) a conversion of type IIb to type IIa or type I muscle fibers plays a role in the increase in GLUT4 protein, and 3) an increase in the GLUT1 isoform is a component of the adaptation of muscle to endurance exercise. Five weeks of voluntary wheel running that resulted in a 33% increase in citrate synthase activity induced a 50% increase in GLUT4 protein in epitrochlearis muscles of female Sprague-Dawley rats. The rate of 2-deoxy-glucose transport maximally stimulated with insulin or insulin plus contractions was increased approximately 40% (P less than 0.05). There was no change in muscle fiber type composition, evaluated by myosin ATPase staining, in the epitrochlearis. There was also no change in GLUT1 protein concentration. We conclude that an increase in GLUT4, but not of GLUT1 protein, is a component of the adaptive response of muscle to endurance exercise and that the increase in GLUT4 protein is associated with an increased capacity for glucose transport.

Whole-Body Vibration Mimics the Metabolic Effects of Exercise in Male Leptin Receptor–Deficient Mice

PubMed Central

McGee-Lawrence, Meghan E.; Wenger, Karl H.; Misra, Sudipta; Davis, Catherine L.; Pollock, Norman K.; Elsalanty, Mohammed; Ding, Kehong; Isales, Carlos M.; Hamrick, Mark W.; Wosiski-Kuhn, Marlena; Arounleut, Phonepasong; Mattson, Mark P.; Cutler, Roy G.; Yu, Jack C.

2017-01-01

Whole-body vibration (WBV) has gained attention as a potential exercise mimetic, but direct comparisons with the metabolic effects of exercise are scarce. To determine whether WBV recapitulates the metabolic and osteogenic effects of physical activity, we exposed male wild-type (WT) and leptin receptor–deficient (db/db) mice to daily treadmill exercise (TE) or WBV for 3 months. Body weights were analyzed and compared with WT and db/db mice that remained sedentary. Glucose and insulin tolerance testing revealed comparable attenuation of hyperglycemia and insulin resistance in db/db mice following TE or WBV. Both interventions reduced body weight in db/db mice and normalized muscle fiber diameter. TE or WBV also attenuated adipocyte hypertrophy in visceral adipose tissue and reduced hepatic lipid content in db/db mice. Although the effects of leptin receptor deficiency on cortical bone structure were not eliminated by either intervention, exercise and WBV increased circulating levels of osteocalcin in db/db mice. In the context of increased serum osteocalcin, the modest effects of TE and WBV on bone geometry, mineralization, and biomechanics may reflect subtle increases in osteoblast activity in multiple areas of the skeleton. Taken together, these observations indicate that WBV recapitulates the effects of exercise on metabolism in type 2 diabetes. PMID:28323991

Role of insulin on exercise-induced GLUT-4 protein expression and glycogen supercompensation in rat skeletal muscle.

PubMed

Kuo, Chia-Hua; Hwang, Hyonson; Lee, Man-Cheong; Castle, Arthur L; Ivy, John L

2004-02-01

The purpose of this study was to investigate the role of insulin on skeletal muscle GLUT-4 protein expression and glycogen storage after postexercise carbohydrate supplementation. Male Sprague-Dawley rats were randomly assigned to one of six treatment groups: sedentary control (Con), Con with streptozocin (Stz/C), immediately postexercise (Ex0), Ex0 with Stz (Stz/Ex0), 5-h postexercise (Ex5), and Ex5 with Stz (Stz/Ex5). Rats were exercised by swimming (2 bouts of 3 h) and carbohydrate supplemented immediately after each exercise session by glucose intubation (1 ml of a 50% wt/vol). Stz was administered 72-h before exercise, which resulted in hyperglycemia and elimination of the insulin response to the carbohydrate supplement. GLUT-4 protein of Ex0 rats was 30% above Con in fast-twitch (FT) red and 21% above Con in FT white muscle. In Ex5, GLUT-4 protein was 52% above Con in FT red and 47% above Con in FT white muscle. Muscle glycogen in FT red and white muscle was also increased above Con in Ex5 rats. Neither GLUT-4 protein nor muscle glycogen was increased above Con in Stz/Ex0 or Stz/Ex5 rats. GLUT-4 mRNA in FT red muscle of Ex0 rats was 61% above Con but only 33% above Con in Ex5 rats. GLUT-4 mRNA in FT red muscle of Stz/C and Stz/Ex0 rats was similar but significantly elevated in Ex5/Stz rats. These results suggest that insulin is essential for the increase in GLUT-4 protein expression following postexercise carbohydrate supplementation.

Effect of exercise on serum vitamin D and tissue vitamin D receptors in experimentally induced type 2 Diabetes Mellitus.

PubMed

Aly, Yosria E; Abdou, Azza S; Rashad, Mona M; Nassef, Menatallah M

2016-09-01

This work aimed to study the effect of swimming exercise on serum vitamin D level and tissue vitamin D receptors in experimentally induced type 2 Diabetes Mellitus. Sixty adult male rats were divided into control and diabetic groups. Each was further subdivided into sedentary and exercised subgroups. Diabetes Mellitus was induced by a single intraperitoneal dose of streptozotocin (50 mg/kg) dissolved in cold 0.01 M citrate buffer (pH 4.5). The exercised subgroups underwent swimming for 60 min, 5 times a week for 4 weeks. Serum glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), lipids, vitamin D and tissue Vitamin D receptors (VDR) were evaluated. Significant increase in serum glucose, insulin, HOMA-IR, cholesterol, triglycerides, and low density lipoprotein (LDL) levels in sedentary diabetic rats was detected. On the other hand, high density lipoprotein (HDL), free fatty acids, serum vitamin D and pancreatic, adipose, and muscular VDR showed a significant decrease in the same group. It is evident that all these parameters were reversed by swimming exercise indicating its beneficial role in type 2 Diabetes. In diabetic groups; serum vitamin D was found to be correlated negatively with serum glucose, insulin, HOMA, cholesterol, triglycerides, and LDL and positively correlated with HDL and tissue VDR. In conclusion, Disturbed vitamin D is associated with metabolic impairments in sedentary diabetic rats. Moderate swimming exercise is beneficial in improving these consequences through modulation of vitamin D status. Future studies could be designed to investigate the effect of the combination of vitamin D intake with exercise in diabetic patients.

Functional high intensity exercise training ameliorates insulin resistance and cardiometabolic risk factors in type 2 diabetes.

PubMed

Fealy, Ciarán E; Nieuwoudt, Stephan; Foucher, Julie A; Scelsi, Amanda R; Malin, Steve K; Pagadala, Mangesh; Cruz, Lauren A; Li, Miranda; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

2018-05-15

Functional high intensity training (F-HIT) is a novel fitness paradigm that integrates simultaneous aerobic and resistance training in sets of constantly varied movements, based on real-world situational exercises, performed at high intensity in workouts that range from ∼8-20 min/session. We hypothesized that F-HIT would be an effective exercise mode for reducing insulin resistance in type 2 diabetes (T2D). We recruited 13 overweight/obese adults (5 males, 8 females; 53 ± 7 years; BMI 34.5 ± 3.6 kg•m -2 , Mean ± SD) with T2D to participate in a 6 week (3d/wk) supervised F-HIT program. An oral glucose tolerance test was used to derive measures of insulin sensitivity. F-HIT significantly reduced fat mass (43.8 ± 83.8 vs 41.6 ± 7.9 kg; P < 0.01), diastolic blood pressure (80.2 ± 7.1 vs 74.5 ± 5.8; P < 0.01), blood lipids (triglyceride and VLDL, both P < 0.05) and metabolic syndrome z-score (6.4 ± 4.5 vs -0.2 ± 5.2 AU; P < 0.001), and increased basal fat oxidation (FOX: 0.08 ± 0.03 vs 0.10 ± 0.04 g•min -1 ; P = 0.05), and HMW adiponectin (214.4 ± 88.9 vs 288.8 ± 127.4 ng•mL -1 ; P < 0.01). Importantly, F-HIT also increased insulin sensitivity (0.037 ± 0.010 vs 0.042 ± 0.010 AU; P < 0.05). Increases in HMW adiponectin and FOX correlated with the change in insulin sensitivity (rho: 0.75; P < 0.05, rho: 0.81; P < 0.01, respectively). Compliance with the training program was > 95% and no injuries or adverse events were reported. These data suggest that F-HIT may be an effective exercise mode for managing T2D. The increase in insulin sensitivity addresses a key defect in T2D and is consistent with improvements observed after more traditional aerobic exercise programs in overweight/obese adults with T2D. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

High Intensity Aerobic Exercise Training Improves Deficits of Cardiovascular Autonomic Function in a Rat Model of Type 1 Diabetes Mellitus with Moderate Hyperglycemia

PubMed Central

Grisé, Kenneth N.; Olver, T. Dylan; McDonald, Matthew W.; Dey, Adwitia; Jiang, Mao; Lacefield, James C.; Shoemaker, J. Kevin; Noble, Earl G.; Melling, C. W. James

2016-01-01

Indices of cardiovascular autonomic neuropathy (CAN) in experimental models of Type 1 diabetes mellitus (T1DM) are often contrary to clinical data. Here, we investigated whether a relatable insulin-treated model of T1DM would induce deficits in cardiovascular (CV) autonomic function more reflective of clinical results and if exercise training could prevent those deficits. Sixty-four rats were divided into four groups: sedentary control (C), sedentary T1DM (D), control exercise (CX), or T1DM exercise (DX). Diabetes was induced via multiple low-dose injections of streptozotocin and blood glucose was maintained at moderate hyperglycemia (9–17 mM) through insulin supplementation. Exercise training consisted of daily treadmill running for 10 weeks. Compared to C, D had blunted baroreflex sensitivity, increased vascular sympathetic tone, increased serum neuropeptide Y (NPY), and decreased intrinsic heart rate. In contrast, DX differed from D in all measures of CAN (except NPY), including heart rate variability. These findings demonstrate that this T1DM model elicits deficits and exercise-mediated improvements to CV autonomic function which are reflective of clinical T1DM. PMID:26885531

Modulation of leptin, insulin, and growth hormone in obese pony mares under chronic nutritional restriction and supplementation with ractopamine hydrochloride.

PubMed

Buff, Preston R; Johnson, Philip J; Wiedmeyer, Charles E; Ganjam, Venkataseshu K; Messer Iv, Nat T; Keisler, Duane H

2006-01-01

Horses fed beyond their nutritional requirement and that are physically inactive will develop obesity, which is often accompanied by insulin resistance and heightened risk of laminitis. The use of pharmacologic agents in combination with nutritional restriction may promote weight loss in obese horses unable to exercise because of laminitic pain. This study shows that reducing feed intake of brome grass hay to 75% of ad libitum intake in obese pony mares reduces body weight without induced exercise. Additional supplementation of ractopamine hydrochloride for 6 weeks resulted in a tendency for increased weight loss. Subsequent modulation of obesity-associated hormones, leptin and insulin, as a result of caloric restriction was observed.

Skeletal muscle phosphatidylcholine and phosphatidylethanolamine respond to exercise and influence insulin sensitivity in men.

PubMed

Lee, Sindre; Norheim, Frode; Gulseth, Hanne L; Langleite, Torgrim M; Aker, Andreas; Gundersen, Thomas E; Holen, Torgeir; Birkeland, Kåre I; Drevon, Christian A

2018-04-25

Phosphatidylcholine (PC) and phosphatidylethanolamine (PE) composition in skeletal muscle have been linked to insulin sensitivity. We evaluated the relationships between skeletal muscle PC:PE, physical exercise and insulin sensitivity. We performed lipidomics and measured PC and PE in m. vastus lateralis biopsies obtained from 13 normoglycemic normal weight men and 13 dysglycemic overweight men at rest, immediately after 45 min of cycling at 70% maximum oxygen uptake, and 2 h post-exercise, before as well as after 12 weeks of combined endurance- and strength-exercise intervention. Insulin sensitivity was monitored by euglycemic-hyperinsulinemic clamp. RNA-sequencing was performed on biopsies, and mitochondria and lipid droplets were quantified on electron microscopic images. Exercise intervention for 12 w enhanced insulin sensitivity by 33%, skeletal muscle levels of PC by 21%, PE by 42%, and reduced PC:PE by 16%. One bicycle session reduced PC:PE by 5%. PC:PE correlated negatively with insulin sensitivity (β = -1.6, P < 0.001), percent area of mitochondria (ρ = -0.52, P = 0.035), and lipid droplet area (ρ = 0.55, P = 0.017) on EM pictures, and negatively with oxidative phosphorylation and mTOR based on RNA-sequencing. In conclusion, PC and PE contents of skeletal muscle respond to exercise, and PC:PE is inversely related to insulin sensitivity.

Home-based exercise may not decrease the insulin resistance in individuals with metabolic syndrome.

PubMed

Chen, Chiao-Nan; Chuang, Lee-Ming; Korivi, Mallikarjuna; Wu, Ying-Tai

2015-01-01

This study investigated the differences in exercise self-efficacy, compliance, and effectiveness of home-based exercise in individuals with and without metabolic syndrome (MetS). One hundred and ten individuals at risk for diabetes participated in this study. Subjects were categorized into individuals with MetS and individuals without MetS. Metabolic risk factors and exercise self-efficacy were evaluated for all subjects before and after 3 months of home-based exercise. Univariate analysis of variance was used to compare the effectiveness of a home-based exercise program between individuals with and without MetS. The home-based exercise program improved body mass index and lipid profile in individuals at risk for diabetes, regardless of MetS status at baseline. Individuals without MetS had higher exercise self-efficacy at baseline and performed greater exercise volume compared with individuals with MetS during the intervention. The increased exercise volume in individuals without MetS may contribute to their better control of insulin resistance than individuals with MetS. Furthermore, baseline exercise self-efficacy was correlated with exercise volume executed by subjects at home. We conclude that home-based exercise programs are beneficial for individuals at risk for diabetes. However, more intensive and/or supervised exercise intervention may be needed for those with MetS.

Sleep Duration, Exercise, Shift Work and Polycystic Ovarian Syndrome-Related Outcomes in a Healthy Population: A Cross-Sectional Study.

PubMed

Lim, Audrey J R; Huang, Zhongwei; Chua, Seok Eng; Kramer, Michael S; Yong, Eu-Leong

2016-01-01

Few studies have examined the associations between sleep duration, shiftwork, and exercise to the infrequent menstruation, hyperandrogenism, and ovarian morphological changes observed in women with polycystic ovarian syndrome (PCOS). To examine whether lifestyle factors, including short sleep duration, insufficient exercise, and shiftwork, alone or in combination, are associated with the reproductive and metabolic abnormalities typical of PCOS in a healthy population. Prospective cross-sectional study of 231 women, including healthcare workers recruited for an annual health screen, healthy referral patients from the Women's Clinic and volunteers from the university community at the National University Hospital, Singapore, from 2011 to 2015. The women completed a questionnaire, including their menstrual cycle length, sleep length, frequency of exercise and shift work. Hyperandrogenism (hirsutism score, testosterone, sex hormone binding globulin (SHBG)), ovarian morphology and function (anthral follicle count, ovarian volume, anti-mullerian hormone (AMH)), and metabolic measures (body mass index (BMI), waist hip ratio (WHR), blood pressure, fasting glucose, fasting insulin and fasting lipids) were examined through anthropometric measurements, transvaginal ultrasound scans, and blood tests. No significant associations were observed between shift work, exercise or sleep duration and the androgenic and ovarian measures that define PCOS. However, women reporting fewer than 6 hours of sleep were more likely to report abnormal (short or long) menstrual cycle lengths (OR = 2.1; 95% CI, 1.1 to 4.2). Women who reported fewer than 6 hours of sleep had increased fasting insulin levels (difference in means = 2.13; 95% CI, 0.27 to 3.99 mU/L) and higher odds of insulin resistance (OR = 2.58; CI, 1.16 to 5.76). Lack of regular exercise was associated with higher mean fasting insulin (difference in means = 2.3 mU/L; 95% CI, 0.5 to 4.1) and HOMA-IR (difference in means = 0.49; 95% CI, 0.09 to 0.90) levels. Women with insufficient sleep are at increased risk of menstrual disturbances and insulin resistance, but do not have the hyperandrogenism and polycystic ovarian morphology typical of PCOS. Improved sleep duration may help reduce the risks of diabetes or infertility. Shift work, exercise or sleep duration appear not to impact the androgenic and ovarian measures that define PCOS.

The TRPC1 Ca2+-permeable channel inhibits exercise-induced protection against high-fat diet-induced obesity and type II diabetes.

PubMed

Krout, Danielle; Schaar, Anne; Sun, Yuyang; Sukumaran, Pramod; Roemmich, James N; Singh, Brij B; Claycombe-Larson, Kate J

2017-12-15

The transient receptor potential canonical channel-1 (TRPC1) is a Ca 2+ -permeable channel found in key metabolic organs and tissues, including the hypothalamus, adipose tissue, and skeletal muscle. Loss of TRPC1 may alter the regulation of cellular energy metabolism resulting in insulin resistance thereby leading to diabetes. Exercise reduces insulin resistance, but it is not known whether TRPC1 is involved in exercise-induced insulin sensitivity. The role of TRPC1 in adiposity and obesity-associated metabolic diseases has not yet been determined. Our results show that TRPC1 functions as a major Ca 2+ entry channel in adipocytes. We have also shown that fat mass and fasting glucose concentrations were lower in TRPC1 KO mice that were fed a high-fat (HF) (45% fat) diet and exercised as compared with WT mice fed a HF diet and exercised. Adipocyte numbers were decreased in both subcutaneous and visceral adipose tissue of TRPC1 KO mice fed a HF diet and exercised. Finally, autophagy markers were decreased and apoptosis markers increased in TRPC1 KO mice fed a HF diet and exercised. Overall, these findings suggest that TRPC1 plays an important role in the regulation of adiposity via autophagy and apoptosis and that TRPC1 inhibits the positive effect of exercise on type II diabetes risk under a HF diet-induced obesity environment.

The Effects of Sympathetic Inhibition on Metabolic and Cardiopulmonary Responses to Exercise in Hypoxic Conditions.

PubMed

Scalzo, Rebecca L; Peltonen, Garrett L; Binns, Scott E; Klochak, Anna L; Szallar, Steve E; Wood, Lacey M; Larson, Dennis G; Luckasen, Gary J; Irwin, David; Schroeder, Thies; Hamilton, Karyn L; Bell, Christopher

2015-12-01

Pre-exertion skeletal muscle glycogen content is an important physiological determinant of endurance exercise performance: low glycogen stores contribute to premature fatigue. In low-oxygen environments (hypoxia), the important contribution of carbohydrates to endurance performance is further enhanced as glucose and glycogen dependence is increased; however, the insulin sensitivity of healthy adult humans is decreased. In light of this insulin resistance, maintaining skeletal muscle glycogen in hypoxia becomes difficult, and subsequent endurance performance is impaired. Sympathetic inhibition promotes insulin sensitivity in hypoxia but may impair hypoxic exercise performance, in part due to suppression of cardiac output. Accordingly, we tested the hypothesis that hypoxic exercise performance after intravenous glucose feeding in a low-oxygen environment will be attenuated when feeding occurs during sympathetic inhibition. On 2 separate occasions, while breathing a hypoxic gas mixture, 10 healthy men received 1 hour of parenteral carbohydrate infusion (20% glucose solution in saline; 75 g), after which they performed stationary cycle ergometer exercise (~65% maximal oxygen uptake) until exhaustion. Forty-eight hours before 1 visit, chosen randomly, sympathetic inhibition via transdermal clonidine (0.2 mg/d) was initiated. The mean time to exhaustion after glucose feeding both with and without sympathetic inhibition was not different (22.7 ± 5.4 minutes vs 23.5 ± 5.1 minutes; P = .73). Sympathetic inhibition protects against hypoxia-mediated insulin resistance without influencing subsequent hypoxic endurance performance. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Changes in the heart rate recovery to endurance effort after high intensity interval, strength, and concurrent exercise training in patients with insulin resistance.

PubMed

Álvarez, Cristian; Ramírez-Campillo, Rodrigo; Martínez, Cristian; Castro-Sepúlveda, Mauricio; Cano-Montoya, Johnathan; Mancilla, Rodrigo; Flores-Opazo, Marcelo

2017-11-01

The aim of this study was to assess the effects of three exercise training programs in the adaptation of the heart rate recovery of patients with insulin resistance. We studied 43 women with insulin resistance, which were assigned to three training groups: 1) high intensity interval training (HIT, age 39.0±10 years); 2) strength training (ST, age 33.9±9.4 years); 3) HIT+ST (MIXT, age 43.3±8.1 years); and 4) control group (CG, age 40.1±11 years). Heart rate was measured at rest (HRrest), during the 2-km-walking-test (UKKT) for mean (HRDE), and maximum (HRMDE) values, and during the recovery at one, two, and three minutes after the UKKT. Additionally, anthropometric measurements (body mass and body mass index) were assessed. HIT significantly decreased HRrest and HRDE (-4.5% and -2% respectively, P<0.05). MIXT training also decreased HRDE in -3% whilst both average and maximal HR during UKK were significantly increased in the control group HRDE (+2% and +3% respectively). Moreover, there were significant reductions in HR recovery at 1, 2 and 3 minutes after both HIT and MIXT training, whereas these values were increased in control group. Our findings suggest that HIT induces meaningful cardiovascular adaptations in patient with insulin resistance, reducing heart rate at rest, as well as during and after exercise, and that complementary strength training increases these adaptations.

The IL-6 Paradox: Context Dependent Interplay of SOCS3 and AMPK

PubMed Central

Sarvas, Jessica L; Khaper, Neelam; Lees, Simon J

2013-01-01

Insulin resistance is the principle step towards the progression of type 2 diabetes, and has been linked to increased circulating levels of cytokines, leading to chronic low-grade inflammation. Specifically, in chronic disease states increased IL-6 is thought to play a critical role in the regulation of insulin resistance in the peripheral tissues, and has been used as a marker of insulin resistance. There is also an endogenous up-regulation of IL-6 in response to exercise, which has been linked to improved insulin sensitivity. This leads to the question “how can elevated IL-6 lead to the development of insulin resistance, and yet also lead to increased insulin sensitivity?” Resolving the dual role of IL-6 in regulating insulin resistance/sensitivity is critical to the development of potential therapeutic interventions. This review summarizes the literature on the seemingly paradoxical role of elevated IL-6 on insulin signalling, including the activation of AMPK and the involvement of leptin and SOCS3. PMID:24244888

Supervised exercise training counterbalances the adverse effects of insulin therapy in overweight/obese subjects with type 2 diabetes.

PubMed

Balducci, Stefano; Zanuso, Silvano; Cardelli, Patrizia; Salerno, Gerardo; Fallucca, Sara; Nicolucci, Antonio; Pugliese, Giuseppe

2012-01-01

To examine the effect of supervised exercise on traditional and nontraditional cardiovascular risk factors in sedentary, overweight/obese insulin-treated subjects with type 2 diabetes from the Italian Diabetes Exercise Study (IDES). The study randomized 73 insulin-treated patients to twice weekly supervised aerobic and resistance training plus structured exercise counseling (EXE) or to counseling alone (CON) for 12 months. Clinical and laboratory parameters were assessed at baseline and at the end of the study. The volume of physical activity was significantly higher in the EXE versus the CON group. Values for hemoglobin A(1c), BMI, waist circumference, high-sensitivity C-reactive protein, blood pressure, LDL cholesterol, and the coronary heart disease risk score were significantly reduced only in the EXE group. No major adverse events were observed. In insulin-treated subjects with type 2 diabetes, supervised exercise is safe and effective in improving glycemic control and markers of adiposity and inflammation, thus counterbalancing the adverse effects of insulin on these parameters.

Evaluation of treadmill exercise effect on muscular lipid profiles of diabetic fatty rats by nanoflow liquid chromatography-tandem mass spectrometry

NASA Astrophysics Data System (ADS)

Lee, Jong Cheol; Kim, Il Yong; Son, Yeri; Byeon, Seul Kee; Yoon, Dong Hyun; Son, Jun Seok; Song, Han Sol; Song, Wook; Seong, Je Kyung; Moon, Myeong Hee

2016-07-01

We compare comprehensive quantitative profiling of lipids at the molecular level from skeletal muscle tissues (gastrocnemius and soleus) of Zucker diabetic fatty rats and Zucker lean control rats during treadmill exercise by nanoflow liquid chromatography-tandem mass spectrometry. Because type II diabetes is caused by decreased insulin sensitivity due to excess lipids accumulated in skeletal muscle tissue, lipidomic analysis of muscle tissues under treadmill exercise can help unveil the mechanism of lipid-associated insulin resistance. In total, 314 lipid species, including phospholipids, sphingolipids, ceramides, diacylglycerols (DAGs), and triacylglycerols (TAGs), were analyzed to examine diabetes-related lipid species and responses to treadmill exercise. Most lysophospholipid levels increased with diabetes. While DAG levels (10 from the gastrocnemius and 13 from the soleus) were >3-fold higher in diabetic rats, levels of most of these decreased after exercise in soleus but not in gastrocnemius. Levels of 5 highly abundant TAGs (52:1 and 54:3 in the gastrocnemius and 48:2, 50:2, and 52:4 in the soleus) displaying 2-fold increases in diabetic rats decreased after exercise in the soleus but not in the gastrocnemius in most cases. Thus, aerobic exercise has a stronger influence on lipid levels in the soleus than in the gastrocnemius in type 2 diabetic rats.

Physical exercise introduced after weaning enhances pancreatic islet responsiveness to glucose and potentiating agents in adult MSG-obese rats.

PubMed

Ribeiro, R A; Bonfleur, M L; Vanzela, E C; Zotti, A I; Scomparin, D X; Boschero, A C; Balbo, S L

2014-08-01

Physical exercise represents an alternative way to prevent and/or ameliorate chronic metabolic diseases. Disruption of sympathetic nervous system (SNS) activity contributes to adiposity in obese subjects. Here, we verified the preventive effect of swimming training upon adiposity, adrenal catecholamine storage, and pancreatic islet function in obese monosodium glutamate (MSG)-treated rats. Male neonatal Wistar rats received MSG (4 mg/g body weight) during the first 5 days of life and, at weaning, half of the rats were submitted to swimming training, 30 min/day, 3 days a week, until 90 days of age (exercised rats: MSGex). Half of the rats were used as controls (sedentary group, MSGsd). Exercise training (ET) decreased insulinemia and fat deposition in MSGex, and increased adrenal catecholamine content, compared with MSGsd rats. Insulinemia during the ivGTT was lower in MSGex rats, despite a lack of difference in glycemia. Swimming training enhanced insulin release in islets challenged by 2.8-8.3 mmol/l glucose, whereas, at supraphysiological glucose concentrations (11.1-16.7 mmol/l), MSGex islets secreted less insulin than MSGsd. No differences in insulin secretion were observed following l-arginine (Arg) or K(+) stimuli. In contrast, islets from MSGex rats secreted more insulin when exposed to carbachol (100 μmol/l), forskolin (10 μmol/l), or IBMX (1 mmol/l) at 8.3 mmol/l glucose. Additionally, MSGex islets presented a better epinephrine inhibition upon insulin release. These results demonstrate that ET prevented the onset of obesity in MSG rats, probably by enhancing adrenal catecholamine levels. ET ameliorates islet responsiveness to several compounds, as well as insulin peripheral action. © Georg Thieme Verlag KG Stuttgart · New York.

Importance of Lean Muscle Maintenance to Improve Insulin Resistance by Body Weight Reduction in Female Patients with Obesity.

PubMed

Fukushima, Yaeko; Kurose, Satoshi; Shinno, Hiromi; Cao Thu, Ha; Takao, Nana; Tsutsumi, Hiromi; Kimura, Yutaka

2016-04-01

It has recently been suggested that skeletal muscle has an important role in insulin resistance in obesity, in addition to exercise tolerance and the fat index. The aim of this study was to identify body composition factors that contribute to improvement of insulin resistance in female patients with obesity who reduce body weight. We studied 92 female obese patients (age 40.9±10.4 years, body mass index 33.2±4.6 kg/m²) who reduced body weight by ≥5% after an intervention program including diet, exercise therapy, and cognitive behavioral therapy. Before and after the intervention, body composition was evaluated by dual-energy X-ray absorptiometry to examine changes in skeletal muscle mass. Homeostasis model assessment of insulin resistance (HOMA-IR) was measured as an index of insulin resistance. Cardiopulmonary exercise was also performed by all patients. There were significant improvements in body weight (-10.3%±4.5%), exercise tolerance (anaerobic threshold oxygen uptake 9.1%±18.4%, peak oxygen uptake 11.0%±14.2%), and HOMA-IR (-20.2%±38.3%). Regarding body composition, there were significant decreases in total body fat (-19.3%±9.6%), total fat-free mass (-2.7%±4.3%), and % body fat (-10.1%±7.5%), whereas % skeletal muscle significantly increased (8.9%±7.2%). In stepwise multiple linear regression analysis with change in HOMA-IR as the dependent variable, the change in % skeletal muscle was identified as an independent predictor (β=-0.280, R²=0.068, P<0.01). Improvement of insulin resistance in female obese patients requires maintenance of skeletal muscle mass.

Relationship of visfatin level to pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index in overweight women who performed hydraulic resistance exercise.

PubMed

Ha, Chang Ho; Swearingin, Brenda; Jeon, Yong Kyun

2015-09-01

[Purpose] This study aimed to examine the correlation of visfatin level to pancreatic endocrine hormone level, homeostasis model assessment of insulin resistance (HOMA-IR) index, and HOMA β-cell index in hydraulic resistance exercise. Furthermore, it investigated the relationship between visfatin level and other variables affected by exercise in overweight women. [Subjects and Methods] The exercise group trained for 12 weeks, 70 minutes/day, 5 days/week. Visfatin level, pancreatic endocrine hormone level, HOMA-IR index, and HOMA β-cell index were measured before and after the intervention. Based on the blood insulin and glucose concentrations, HOMA-IR index, the indicator of insulin resistance, and HOMA β-cell index, the indicator of insulin secretion level, were assessed. [Results] Interaction effects on visfatin level, insulin level, HOMA-IR index, and HOMA β-cell index were observed. Interaction effects on glucagon and glucose levels were not observed between the intervention groups. The correlations of visfatin level to insulin, glucagon, and glucose levels, and HOMA-IR and HOMA β-cell indexes were not significant for any of the subjects. [Conclusion] Therefore, the 12-week resistance exercise affected body composition, visfatin level, insulin level, HOMA-IR index, and HOMA β-cell index. Finally, visfatin was not related to insulin, glucagon, and glucose levels, and HOMA-IR and HOMA β-cell indexes.

Exploration of the Performance of a Hybrid Closed Loop Insulin Delivery Algorithm That Includes Insulin Delivery Limits Designed to Protect Against Hypoglycemia.

PubMed

de Bock, Martin; Dart, Julie; Roy, Anirban; Davey, Raymond; Soon, Wayne; Berthold, Carolyn; Retterath, Adam; Grosman, Benyamin; Kurtz, Natalie; Davis, Elizabeth; Jones, Timothy

2017-01-01

Hypoglycemia remains a risk for closed loop insulin delivery particularly following exercise or if the glucose sensor is inaccurate. The aim of this study was to test whether an algorithm that includes a limit to insulin delivery is effective at protecting against hypoglycemia under those circumstances. An observational study on 8 participants with type 1 diabetes was conducted, where a hybrid closed loop system (HCL) (Medtronic™ 670G) was challenged with hypoglycemic stimuli: exercise and an overreading glucose sensor. There was no overnight or exercise-induced hypoglycemia during HCL insulin delivery. All daytime hypoglycemia was attributable to postmeal bolused insulin in those participants with a more aggressive carbohydrate factor. HCL systems rely on accurate carbohydrate ratios and carbohydrate counting to avoid hypoglycemia. The algorithm that was tested against moderate exercise and an overreading glucose sensor performed well in terms of hypoglycemia avoidance. Algorithm refinement continues in preparation for long-term outpatient trials.

A prospective, multicenter pilot study to investigate the feasibility and safety of a 1-year controlled exercise training after adjuvant chemotherapy in colorectal cancer patients.

PubMed

Piringer, Gudrun; Fridrik, Michael; Fridrik, Alfred; Leiherer, Andreas; Zabernigg, August; Greil, Richard; Eisterer, Wolfgang; Tschmelitsch, Jörg; Lang, Alois; Frantal, Sophie; Burgstaller, Sonja; Gnant, Michael; Thaler, Josef

2018-04-01

Despite advances in adjuvant chemotherapy, 20-30% of patients in stages II-III colorectal cancer will eventually relapse. Observational studies showed a reduction in relapse rate, colon cancer-specific mortality, and overall mortality by physical activity. Results from prospective randomized interventional studies to confirm these observational data are lacking. The aims of this prospective single-arm multicenter pilot study are to evaluate feasibility and safety of exercise training after adjuvant chemotherapy in colorectal cancer patients. The training was performed three times per week for 1 year and was increased gradually in three phases until reaching 18 metabolic equivalent task hours per week. Overall, 30 patients were included. The planned training intensity could be achieved in all three phases. Patients experienced a performance increase of median 35.5 watt, a weight-loss of a median of 3.0 kg, and a reduction in body fat content of median 1.0% during this exercise training. The analysis showed early study termination due to non-compliance in 10/30 patients (33.3%), disease progression in 4 patients (13.3%), and serious adverse events in 2 patients (6.7%). About half of patients (46.7%) completed the pilot study as planned. Biomarker analysis from 20 patients showed a non-significant reduction in insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and insulin-like growth factor binding protein 3 (IGF-BP3) levels, significant increases in adiponectin and leptin levels, and a non-significant increase in C-peptide levels. Exercise training is feasible in patients with colorectal cancer after completion of adjuvant chemotherapy. The main problem encountered during the study was compliance. To improve compliance of exercise training, several measures were adapted for the upcoming prospective randomized ABCSG C08 Exercise II study.

Aerobic exercise regulates blood lipid and insulin resistance via the toll‑like receptor 4‑mediated extracellular signal‑regulated kinases/AMP‑activated protein kinases signaling pathway.

PubMed

Wang, Mei; Li, Sen; Wang, Fubaihui; Zou, Jinhui; Zhang, Yanfeng

2018-06-01

Diabetes mellitus is a complicated metabolic disease with symptoms of hyperglycemia, insulin resistance, chronic damage and dysfunction of tissues, and metabolic syndrome for insufficient insulin production. Evidence has indicated that exercise treatments are essential in the progression of type‑ІІ diabetes mellitus, and affect insulin resistance and activity of islet β‑cells. In the present study, the efficacy and signaling mechanism of aerobic exercise on blood lipids and insulin resistance were investigated in the progression of type‑ІІ diabetes mellitus. Body weight, glucose metabolism and insulin serum levels were investigated in mouse models of type‑ІІ diabetes mellitus following experienced aerobic exercise. Expression levels of inflammatory factors, interleukin (IL)‑6, high‑sensitivity C‑reactive protein, tumor necrosis factor‑α and leucocyte differentiation antigens, soluble CD40 ligand in the serum were analyzed in the experimental mice. In addition, expression levels of toll‑like receptor 4 (TLR‑4) were analyzed in the liver cells of experimental mice. Changes of oxidative stress indicators, including reactive oxygen species, superoxide dismutase, glutathione and catalase were examined in the liver cells of experimental mice treated by aerobic exercise. Expression levels and activity of extracellular signal‑regulated kinases (ERK) and AMP‑activated protein kinase (AMPK) signaling pathways were investigated in the liver cells of mouse models of type‑ІІ diabetes mellitus after undergoing aerobic exercise. Aerobic exercise decreased the expression levels of inflammatory factors in the serum of mouse models of type‑ІІ diabetes mellitus. The results indicated that aerobic exercise downregulated oxidative stress indicators in liver cells from mouse models of type‑ІІ diabetes mellitus. In addition, the ERK and AMPK signaling pathways were inactivated by aerobic exercise in liver cells in mouse models of type‑ІІ diabetes mellitus. The activity of ERK and AMPK, and the function of islet β‑cells were observed to be improved in experimental mice treated with aerobic exercise. Furthermore, blood lipid metabolism and insulin resistance were improved by treatment with aerobic exercise. Body weight and glucose concentration of serology was markedly improved in mouse models of type‑ІІ diabetes mellitus. Furthermore, TLR‑4 inhibition markedly promoted ERK and AMPK expression levels and activity. Thus, these results indicate that aerobic exercise may improve blood lipid metabolism, insulin resistance and glucose plasma concentration in mouse models of type‑ІІ diabetes mellitus. Thus indicating aerobic exercise is beneficial for improvement of blood lipid and insulin resistance via the TLR‑4‑mediated ERK/AMPK signaling pathway in the progression of type‑ІІ diabetes mellitus.

Randomized trial on the effects of a 7-d low-glycemic diet and exercise intervention on insulin resistance in older obese humans123

PubMed Central

Solomon, Thomas PJ; Haus, Jacob M; Kelly, Karen R; Cook, Marc D; Riccardi, Michelle; Rocco, Michael; Kashyap, Sangeeta R; Barkoukis, Hope

2009-01-01

Background: The optimal combination of diet and exercise that produces the greatest reversal of obesity-related insulin resistance is unknown. Objectives: We examined the effects of a combined 7-d low–glycemic index (low-GI) diet and exercise training intervention on insulin sensitivity in older obese humans. Design: Participants [n = 32; mean (±SEM) age: 66 ± 1 y; body mass index (in kg/m2): 33.8 ± 0.7] were randomly assigned to a parallel, double-blind, controlled-feeding trial and underwent supervised aerobic exercise (EX; 60 min/d at 80–85% maximum heart rate) in combination with either a low-GI (LoGI + EX: 41.1 ± 0.4) or a high-GI (HiGI + EX: 80.9 ± 0.6) diet. All meals were provided and were isocaloric to individual energy requirements. Insulin sensitivity and hepatic glucose production were assessed with a 40–mU ⋅ m−2 · min−1 hyperinsulinemic euglycemic clamp combined with a [6,6-2H2]-glucose infusion. Results: After the intervention, small decreases were observed in body weight (−1.6 ± 0.2 kg; P < 0.0001) and fat mass (−1.7 ± 0.9%; P = 0.004) in both groups. Maximal aerobic capacity (V̇O2max) also improved slightly (0.06 ± 0.02 L/min; P = 0.004). Resting systolic blood pressure, fasting glucose, insulin, triglycerides, and cholesterol all decreased after the study (all P < 0.05). Larger changes in systolic blood pressure and V̇O2max were seen in the LoGI + EX group. Insulin-stimulated glucose disposal (P < 0.001), insulin suppression of hepatic glucose production (P = 0.004), and postabsorptive fat oxidation (P = 0.03) improved equally in both groups after the intervention. Conclusions: These findings suggest that the metabolic improvements after short-term exercise training in older obese individuals are dependent on increased physical activity and are not influenced by a low-GI diet. However, a low-GI diet has added benefit in alleviating hypertension, thus reducing the risk of diabetic and vascular complications. PMID:19793849

Insulin resistance influences weight loss in non-obese women who followed a home-based exercise program and slight caloric restriction.

PubMed

Mediano, Mauro Felippe Felix; Sichieri, Rosely

2011-06-01

This study aimed to evaluate the influence of insulin resistance status on weight changes in non-obese women who followed a home-based exercise program and slight caloric restriction over a period of 12 months. Middle-aged (25-45 year), non-obese (body mass index of 23-29.9 kg/m(2)) women were randomly assigned to control (CG) or home-based exercise group (HB). The HB group received a booklet explaining the physical exercises to be practiced at home at least three times per week (40 min/session). Both groups were required to follow a small energy restriction of 100-300 calories per day. For the analysis, women were stratified in two groups according to baseline insulin sensitivity: NIR (non-insulin resistant; n = 121) and IR (insulin resistant; n = 64). Women classified as IR at baseline had greater weight loss after 12 months of follow-up (-1.6 kg vs. -1.1 kg; p = 0.01), and HB exercise helped to reduce weight only among NIR women (-1.5 vs. -0.7; p = 0.04); no differences were observed between intervention groups for IR women (-1.5 vs. -1.7; p = 0.24). There were no differences between IR and NIR groups for lipid profile after adjustment for weight changes. Insulin resistance facilitated weight loss, and home-based exercise promoted greater weight loss only in non-insulin resistance women. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Battling insulin resistance in elderly obese people with type 2 diabetes: bring on the heavy weights.

PubMed

Willey, Karen A; Singh, Maria A Fiatarone

2003-05-01

Exercise improves insulin resistance and has beneficial effects in preventing and treating type 2 diabetes. However, aerobic exercise is hindered in many type 2 diabetic patients because of advancing age, obesity, and other comorbid conditions. Weight lifting or progressive resistance training (PRT) offers a safe and effective exercise alternative for these people. PRT promotes favorable energy balance and reduced visceral fat deposition through enhanced basal metabolism and activity levels while counteracting age- and disease-related muscle wasting. PRT improves insulin sensitivity and glycemic control; increases muscle mass, strength, and endurance; and has positive effects on bone density, osteoarthritic symptoms, mobility impairment, self-efficacy, hypertension, and lipid profiles. PRT also alleviates symptoms of anxiety, depression, and insomnia in individuals with clinical depression and improves exercise tolerance in individuals with cardiac ischemic disease and congestive heart failure; all of these aspects are relevant to the care of diabetic elders. Moreover, PRT is safe and well accepted in many complex patient populations, including very frail elderly individuals and those with cardiovascular disease. The greater feasibility of using PRT over aerobic exercise in elderly obese type 2 diabetic individuals because of concomitant cardiovascular, arthritic, and other disease provides a solid rationale for investigating the global benefits of PRT in the management of diabetes.

The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise

PubMed Central

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-01-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. PMID:25875578

What is the relationship between exercise and metabolic abnormalities? A review of the metabolic syndrome.

PubMed

Carroll, Sean; Dudfield, Mike

2004-01-01

Prevention of the metabolic syndrome and treatment of its main characteristics are now considered of utmost importance in order to combat the epidemic of type 2 diabetes mellitus and to reduce the increased risk of cardiovascular disease and all-cause mortality. Insulin resistance/hyperinsulinaemia are consistently linked with a clustering of multiple clinical and subclinical metabolic risk factors. It is now widely recognised that obesity (especially abdominal fat accumulation), hyperglycaemia, dyslipidaemia and hypertension are common metabolic traits that, concurrently, constitute the distinctive insulin resistance or metabolic syndrome. Cross-sectional and prospective data provide an emerging picture of associations of both physical activity habits and cardiorespiratory fitness with the metabolic syndrome. The metabolic syndrome, is a disorder that requires aggressive multi-factorial intervention. Recent treatment guidelines have emphasised the clinical utility of diagnosis and an important treatment role for 'therapeutic lifestyle change', incorporating moderate physical activity. Several previous narrative reviews have considered exercise training as an effective treatment for insulin resistance and other components of the syndrome. However, the evidence cited has been less consistent for exercise training effects on several metabolic syndrome variables, unless combined with appropriate dietary modifications to achieve weight loss. Recently published randomised controlled trial data concerning the effects of exercise training on separate metabolic syndrome traits are evaluated within this review. Novel systematic review and meta-analysis evidence is presented indicating that supervised, long-term, moderate to moderately vigorous intensity exercise training, in the absence of therapeutic weight loss, improves the dyslipidaemic profile by raising high density lipoprotein-cholesterol and lowering triglycerides in overweight and obese adults with characteristics of the metabolic syndrome. Lifestyle interventions, including exercise and dietary-induced weight loss may improve insulin resistance and glucose tolerance in obesity states and are highly effective in preventing or delaying the onset of type 2 diabetes in individuals with impaired glucose regulation. Randomised controlled trial evidence also indicates that exercise training decreases blood pressure in overweight/obese individuals with high normal blood pressure and hypertension. These evidence-based findings continue to support recommendations that supervised or partially supervised exercise training is an important initial adjunctive step in the treatment of individuals with the metabolic syndrome. Exercise training should be considered an essential part of 'therapeutic lifestyle change' and may concurrently improve insulin resistance and the entire cluster of metabolic risk factors. Copyright 2004 Adis Data Information BV

Plasma Irisin Modestly Increases during Moderate and High-Intensity Afternoon Exercise in Obese Females

PubMed Central

Winn, Nathan C.; Grunewald, Zachary I.; Liu, Ying; Heden, Timothy D.; Nyhoff, Lauren M.; Kanaley, Jill A.

2017-01-01

Background and Purpose Irisin is an exercise-responsive myokine that has been proposed to exert anti-obesity benefits; yet its response during exercise in obese women is not described. This study characterized plasma irisin levels during a single bout of afternoon isocaloric-exercise of different intensities (moderate- vs high-intensity) in obese females. Methods Eleven obese females participated in 3 randomized study days beginning at 1600h: 1) no exercise (NoEx), 2) moderate exercise (ModEx; 55%VO2max) and 3) high intensity interval exercise (IntEx; 4 min (80%VO2max)/3 min (50% VO2max). Frequent blood samples were analyzed for glucose and lactate (whole-blood), and insulin, c-peptide, glucagon, and irisin (plasma) throughout 190 min of testing. Results Plasma irisin increased above baseline during ModEx and IntEx (P<0.05), but not NoEx (P>0.05). Peak irisin levels during ModEx and IntEx exercise were 11.9± 3.4% and 12.3 ± 4.1% relative to baseline (P<0.05), respectively, with no differences between exercise intensities (P>0.05). Irisin levels remained elevated above resting for 125 minutes post-exercise during ModEx, whereas levels returned to baseline within 15 minutes post-exercise during IntEx. Similarly, no associations were found between plasma irisin levels and circulating lactate, glucose, insulin, c-peptide, or glucagon among study days (P>0.05). However, there was an inverse association between basal irisin and lean mass (r = -0.70, P = 0.01). Conclusion A single bout of moderate and high intensity afternoon exercise induces modest increases in circulating irisin concentrations during exercise; however the regulation post-exercise appears to be dimorphic between exercise intensity in obese females. Future studies are needed to compare morning and afternoon exercise on irisin secretion. PMID:28125733

Clinical trial to assess the effect of physical exercise on endothelial function and insulin resistance in pregnant women

PubMed Central

2009-01-01

Background Preeclampsia (PE) is a common maternal disease that complicates 5 to 10% of pregnancies and remains as the major cause of maternal and neonatal mortality. Cost-effective interventions aimed at preventing the development of preeclampsia are urgently needed. However, the pathogenesis of PE is not well known. Multiple mechanisms such as oxidative stress, endothelial dysfunction and insulin resistance may contribute to its development. Regular aerobic exercise recovers endothelial function; improves insulin resistance and decreases oxidative stress. Therefore the purpose of this clinical trial is to determine the effect of regular aerobic exercise on endothelial function, on insulin resistance and on pregnancy outcome. Methods and design 64 pregnant women will be included in a blind, randomized clinical trial, and parallel assignment. The exercise group will do regular aerobic physical exercise: walking (10 minutes), aerobic exercise (30 minutes), stretching (10 minutes) and relaxation exercise (10 minutes) in three sessions per week. Control group will do the activities of daily living (bathing, dressing, eating, and walking) without counselling from a physical therapist. Trial registration NCT00741312. PMID:19919718

The Benefits of Exercise and Metabolic Interventions for the Prevention and Early Treatment of Alzheimer's Disease.

PubMed

Maliszewska-Cyna, Ewelina; Lynch, Madelaine; Oore, Jonathan Jordan; Nagy, Paul Michael; Aubert, Isabelle

2017-01-01

Alzheimer's disease (AD) is characterized by neuronal degeneration, vascular pathology and cognitive decline. Furthermore, deficits in cerebral glucose metabolism and insulin resistance are being increasingly recognized in AD. Many lifestyle-modifying approaches, including diet and exercise, have yielded promising results in modulating brain morphology and function for the prevention and early treatment of AD. This review focuses on the effects of physical exercise on rescuing cognition and limiting the progression of AD pathology. Specifically, the impact of exercise, in human and animal models of AD, on the stimulation and preservation of cognition, neurotransmission, neurogenesis, vasculature, glucose metabolism and insulin signaling is discussed. Studies have highlighted the potential of physical activity to improve overall brain health, which could delay or lessen AD-related cognitive deficits and pathology. Physical activity influences cognitive function, vascular health and brain metabolism, which taken together offers benefits for the aging population, including AD patients.

Nutrition and exercise in individuals with diabetes.

PubMed

Zinker, B A

1999-07-01

Individuals with type 1 (insulin-dependent diabetes mellitus [IDDM]) and type 2 (non-insulin-dependent diabetes mellitus [NIDDM]) diabetes should be encouraged to exercise. Although there is an absence of consistent evidence that adaptations to routine exercise improve glucose control in type 1 diabetes, there is evidence that shows improved glucose control in individuals with type 2 diabetes. Although both groups benefit from exercise, the merit and suitability of routine exercise is measured by the extent to which the advantageous adaptive effects of regular exercise surpass the risks of a sole bout of exercise. In addition, when considering acute versus routine exercise, special considerations must be given to children with diabetes and older adults at risk for insulin resistance. Finally, a greater research focus is needed on engaging in competitive and recreational sports so that children and adults with diabetes may participate safely in activities such as baseball, swimming, basketball, soccer, and hockey.

Nutritional concerns in the diabetic athlete.

PubMed

Jensen, Jørgen

2004-08-01

The etiology of type I and type II diabetes differs and so do the nutritional challenges during and after exercise. For type I diabetics, exercise may cause hypoglycemia. To avoid hypoglycemia, a carbohydrate-rich meal should be eaten 1 to 3 hours prior to exercise and the insulin dose reduced. During exercise, at least 40 g glucose per hour should be ingested; more if the insulin dose is not reduced. After exercise, it is important to rebuild the glycogen stores to reduce the risk for hypoglycemia. Carbohydrates should always be available during training and in the recovery period. Despite these difficulties, exercise is recommended for type I diabetics and competition at high level is possible. Exercise prevents development of type II diabetes and improves metabolic regulation. For type II diabetics, exercise is normally performed to improve insulin sensitivity and to reduce body weight. Carbohydrates should only be supplied to prevent hypoglycemia.

Endocrinology and Adolescence: aerobic exercise reduces insulin resistance markers in obese youth: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, Antonio; Saavedra, Jose M; Escalante, Yolanda; Sánchez-López, Mairena; Martínez-Vizcaíno, Vicente

2014-10-01

The purpose of this meta-analysis was to examine the evidence for the effectiveness of aerobic exercise interventions on reducing insulin resistance markers in obese children and/or adolescents. A secondary outcome was change in percentage of body fat. A computerized search was made from seven databases: CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, ERIC, MEDLINE, PsycINFO, and Science Citation Index. The analysis was restricted to randomized controlled trials that examined the effect of aerobic exercise on insulin resistance markers in obese youth. Two independent reviewers screened studies and extracted data. Effect sizes (ES) and 95% confidence interval (CI) were calculated, and the heterogeneity of the studies was estimated using Cochran's Q-statistic. Nine studies were selected for meta-analysis as they fulfilled the inclusion criteria (n=367). Aerobic exercise interventions resulted in decreases in fasting glucose (ES=-0.39; low heterogeneity) and insulin (ES=-0.40; low heterogeneity) and in percentage of body fat (ES=-0.35; low heterogeneity). These improvements were specifically accentuated in adolescents (only in fasting insulin), or through programs lasting more than 12 weeks, three sessions per week, and over 60 min of aerobic exercise per session. This meta-analysis provides insights into the effectiveness of aerobic exercise interventions on insulin resistance markers in the obese youth population. © 2014 European Society of Endocrinology.

Effects of aerobic versus resistance exercise without caloric restriction on abdominal fat, intrahepatic lipid, and insulin sensitivity in obese adolescent boys: a randomized, controlled trial

USDA-ARS?s Scientific Manuscript database

The optimal exercise modality for reductions of abdominal obesity and risk factors for type 2 diabetes in youth is unknown. We examined the effects of aerobic exercise (AE) versus resistance exercise (RE) without caloric restriction on abdominal adiposity, ectopic fat, and insulin sensitivity and se...

Effects of short-term training on insulin sensitivity and skeletal muscle glucose metabolism in standardbred horses.

PubMed

Stewart-Hunt, L; Geor, R J; McCutcheon, L J

2006-08-01

Increased insulin sensitivity occurs after a period of exercise training, but the mechanisms underlying this training-associated increase in insulin action have not been investigated. To examine the effects of short-term endurance training (7 consecutive days) and a subsequent period of inactivity (5 days) on whole body insulin sensitivity and GLUT-4 protein and the activities of glycogen synthase (GS) and hexokinase (HK) in skeletal muscle. It was hypothesised that training would increase insulin sensitivity in association with increased GLUT-4 protein and activities of GS and HK, but that these changes would be transient, returning to baseline after 5 days of inactivity. Seven mature Standardbred horses completed training consisting of 7 consecutive days of 45 min of treadmill exercise at a speed that elicited 55% of pretraining maximal aerobic capacity (VO2peak). Insulin sensitivity was determined by rate of glucose disposal (M) during the last 60 min of a 120 min euglycaemic-hyperinsulinaemic clamp (EHC) performed before (-2 days) and at 1 and 6 days following training. VO2peak was measured before (UT) and after (TR) training and the period of inactivity (IA). Training resulted in a 9% increase in mean VO2peak (P<0.05) that was maintained following inactivity (IA). Mean M values were more than 2-fold higher (P<0.05) in TR than in UT. Mean M was also higher (P<0.05) in IA when compared to UT. GLUT-4 protien abundancewas more than 10-fold higher in TR and IA (P<0.001) than in UT. Pre-EHC GS activity and GS fractional velocity were increased (P<0.05) in TR when compared to UT and IA. Pre-EHC HK activity was increased (P<0.05) in IA when compared to UT and TR. Muscle glycogen was 66% lower (P<0.05) in TR than in UT and IA. Short-term training resulted in increases in whole body insulin sensitivity, and GLUT-4 protein content and glycogen synthase activity in skeletal muscle. The enhancements in insulin sensitivity, GLUT-4 protein and glycogen synthase activity were still evident after 5 days of inactivity. Insulin resistance in equids has been associated with obesity and predisposition to laminitis. Regular physical activity may mitigate risk of these conditions via enhancement of insulin sensitivity and/or control of bodyweight.

The Higher the Insulin Resistance the Lower the Cardiac Output in Men with Type 1 Diabetes During the Maximal Exercise Test.

PubMed

Niedzwiecki, Pawel; Naskret, Dariusz; Pilacinski, Stanislaw; Pempera, Maciej; Uruska, Aleksandra; Adamska, Anna; Zozulinska-Ziolkiewicz, Dorota

2017-06-01

The aim of this study was to assess the hemodynamic parameters analyzed in bioimpedance cardiography during maximal exercise in patients with type 1 diabetes differing in insulin resistance. The study group consisted of 40 men with type 1 diabetes. Tissue sensitivity to insulin was assessed on the basis of the glucose disposal rate (GDR) analyzed during hyperinsulinemic-euglycemic clamp. Patients were divided into groups with GDR <4.5 mg/kg/min (G1 group-lower insulin sensitivity) and GDR ≥4.5 mg/kg/min (G2 group-higher insulin sensitivity). During the exercise test, the heart rate, systolic volume, cardiac output, cardiac index were measured by the impedance meter (PhysioFlow). Compared with the G2 group, the G1 group had a lower cardiac output (CO): during exercise 8.6 (IQR 7.7-10.0) versus 12.8 (IQR 10.8-13.7) L/min; P < 0.0001, at the maximal effort 13.1 (IQR 12.2-16.7) versus 18.6 (IQR 16.9-20.2) L/min; P = 0.001, and during observation after exercise 8.4 (IQR 6.3-9.6) versus 11.9 (IQR 10.1-13.1) L/min; P < 0.0001. We noticed a positive correlation of GDR and cardiac output: during the exercise test (r = 0.63, P = 0.0002), at the maximal effort (Rs 0.56, P = 0.001), and during observation after the exercise test (r = 0.72, P < 0.0001). In multivariate logistic regression, cardiac output during exercise and during observation was associated with high GDR, regardless of the age and duration of diabetes [OR: 1.98 (95% CI 1.10-3.56), P = 0.02 and OR: 1.91 (95% CI 1.05-3.48), P = 0.03; respectively]. In nonobese subjects with type 1 diabetes, with good metabolic control, insulin resistance is associated with cardiac hemodynamic parameters assessed during and after exercise. The higher the insulin resistance the lower the cardiac output during maximal exercise in men with type 1 diabetes.

Exercise initiated after the onset of insulin resistance improves trabecular microarchitecture and cortical bone biomechanics of the tibia in hyperphagic Otsuka Long Evans Tokushima Fatty rats.

PubMed

Ortinau, Laura C; Linden, Melissa A; Dirkes, Rebecca K; Rector, R Scott; Hinton, Pamela S

2017-10-01

The present study extends our previous findings that exercise, which prevents the onset of insulin resistance and type 2 diabetes (T2D), also prevents the detrimental effects of T2D on whole-bone and tissue-level strength. Our objective was to determine whether exercise improves bone's structural and material properties if insulin resistance is already present in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The OLETF rat is hyperphagic due to a loss-of-function mutation in cholecystokinin-1 receptor (CCK-1 receptor), which leads to progressive obesity, insulin resistance and T2D after the majority of skeletal growth is complete. Because exercise reduces body mass, which is a significant determinant of bone strength, we used a body-mass-matched caloric-restricted control to isolate body-mass-independent effects of exercise on bone. Eight-wk old, male OLETF rats were fed ad libitum until onset of hyperglycemia (20weeks of age), at which time they were randomly assigned to three groups: ad libitum fed, sedentary (O-SED); ad libitum fed, treadmill running (O-EX); or, sedentary, mild caloric restriction to match body mass of O-EX (O-CR). Long-Evans Tokushima Otsuka rats served as the normophagic, normoglycemic controls (L-SED). At 32weeks of age, O-SED rats had T2D as evidenced by hyperglycemia and a significant reduction in fasting insulin compared to OLETFs at 20weeks of age. O-SED rats also had reduced total body bone mineral content (BMC), increased C-terminal telopeptide of type I collagen (CTx)/tartrate resistant acid phosphatase isoform 5b (TRAP5b), decreased N-terminal propeptide of type I procollagen (P1NP), reduced percent cancellous bone volume (BV/TV), trabecular number (Tb.N) and increased trabecular separation (Tb.Sp) and structural model index (SMI) of the proximal tibia compared to L-SED. T2D also adversely affected biomechanical properties of the tibial diaphysis, and serum sclerostin was increased and β-catenin, runt-related transcription factor 2 (Runx2) and insulin-like growth factor-I (IGF-I) protein expression in bone were reduced in O-SED vs. L-SED. O-EX or O-CR had greater total body bone mineral density (BMD) and BMC, and BV/TV, Tb.N, Tb.Sp, and SMI compared to O-SED. O-EX had lower CTx and CR greater P1NP relative to O-SED. O-EX, not O-CR, had greater cortical thickness and area, and improved whole-bone and tissue-level biomechanical properties associated with a 4-fold increase in cortical bone β-catenin protein expression vs. O-SED. In summary, EX or CR initiated after the onset of insulin resistance preserved cancellous bone volume and structure, and EX elicited additional benefits in cortical bone. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of exercise training and food restriction on endothelium-dependent relaxation in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous NIDDM.

PubMed

Sakamoto, S; Minami, K; Niwa, Y; Ohnaka, M; Nakaya, Y; Mizuno, A; Kuwajima, M; Shima, K

1998-01-01

We investigated whether endothelial function may be impaired in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat, a model of spontaneous NIDDM. The effect of exercise training and food restriction on endothelial function was also studied. OLETF rats were divided into three groups at age 16 weeks: sedentary, exercise trained, and food restricted (70% of the food intake of sedentary rats). Otsuka Long-Evans Tokushima rats were used as the age-matched nondiabetic controls. Endothelium-dependent relaxation of the thoracic aorta induced by histamine was significantly attenuated in the sedentary or food-restricted rats, and exercise training improved endothelial function. Relaxation induced by sodium nitroprusside, a donor of nitric oxide, did not differ significantly among groups. Both exercise training and food restriction significantly suppressed plasma levels of glucose and insulin and serum levels of triacylglycerol and cholesterol and reduced the accumulation of abdominal fat. Insulin sensitivity, as measured by the hyperinsulinemic-euglycemic clamp technique, was significantly decreased in sedentary rats but was enhanced in exercise-trained and food-restricted rats. The urinary excretion of nitrite was significantly decreased in sedentary and food-restricted rats compared with nondiabetic rats and was significantly increased in exercise-trained rats. These results indicate that exercise training, but not food restriction, prevents endothelial dysfunction in NIDDM rats, presumably due to the exercise-induced increase in the production of nitric oxide.

GLUT4 translocation is not impaired after acute exercise in skeletal muscle of women with obesity and polycystic ovary syndrome.

PubMed

Dantas, Wagner Silva; Marcondes, José Antonio Miguel; Shinjo, Samuel Katsuyuki; Perandini, Luiz Augusto; Zambelli, Vanessa Olzon; Neves, Willian Das; Barcellos, Cristiano Roberto Grimaldi; Rocha, Michele Patrocínio; Yance, Viviane Dos Reis Vieira; Pereira, Renato Tavares Dos Santos; Murai, Igor Hisashi; Pinto, Ana Lucia De Sá; Roschel, Hamilton; Gualano, Bruno

2015-11-01

The aim of this study was to examine the effects of acute exercise on insulin signaling in skeletal muscle of women with polycystic ovary syndrome (PCOS) and controls (CTRL). Fifteen women with obesity and PCOS and 12 body mass index-matched CTRL participated in this study. Subjects performed a 40-min single bout of exercise. Muscle biopsies were performed before and 60 min after exercise. Selected proteins were assessed by Western blotting. CTRL, but not PCOS, showed a significant increase in PI3-k p85 and AS160 Thr 642 after a single bout of exercise (P = 0.018 and P = 0.018, respectively). Only PCOS showed an increase in Akt Thr 308 and AMPK phosphorylation after exercise (P = 0.018 and P = 0.018, respectively). Total GLUT4 expression was comparable between groups (P > 0.05). GLUT4 translocation tended to be significantly higher in both groups after exercise (PCOS: P = 0.093; CTRL: P = 0.091), with no significant difference between them (P > 0.05). A single bout of exercise elicited similar GLUT4 translocation in skeletal muscle of PCOS and CTRL, despite a slightly differential pattern of protein phosphorylation. The absence of impairment in GLUT4 translocation suggests that PCOS patients with obesity and insulin resistance may benefit from exercise training. © 2015 The Obesity Society.

IGF-1 colocalizes with muscle satellite cells following acute exercise in humans.

PubMed

Grubb, Amanda; Joanisse, Sophie; Moore, Daniel R; Bellamy, Leeann M; Mitchell, Cameron J; Phillips, Stuart M; Parise, Gianni

2014-04-01

Insulin-like growth factor-1 (IGF-1) regulates stem cell proliferation and differentiation in vitro. The aim of this study was to quantify the change in satellite cell (SC) specific IGF-1 colocalization following exercise. We observed a significant increase (p < 0.05) in the percentage of SC with IGF-1 colocalization from baseline to 72 h after a bout of resistance exercise. This strongly supports a role for IGF-1 in human SC function following exercise.

Acute regulation of IGF-I by alterations in post-exercise macronutrients.

PubMed

Foster, E B; Fisher, G; Sartin, J L; Elsasser, T H; Wu, G; Cowan, W; Pascoe, D D

2012-04-01

This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise nutritional protocols: (1) placebo (EX); (2) carbohydrate only (CHO); and (3) essential amino acid/carbohydrate (EAA/CHO). Samples were analyzed for growth hormone (GH), free IGF-I, IGFBP-1, IGFBP-2, insulin, hematocrit, hemoglobin, serum leucine, matrix metalloproteinase-9 (MMP-9) proteolytic activity, and presence of IGFBP-3 protease activity. No evidence for IGFBP-3 proteolysis was observed. Significant increases in [free IGF-I] and [leucine] were observed in the EAA/CHO group only. Significant differences were noted in [IGFBP-1] and [IGFBP-2] across conditions. Significant increases in [GH] and MMP-9 activity were observed in all groups. These results indicate that post-exercise macronutrient ratio is a determinant of [free IGF-I], [IGFBP-1 and -2] and may play a role in modulating the IGF-I axis in vivo.

Metabolic signals and innate immune activation in obesity and exercise.

PubMed

Ringseis, Robert; Eder, Klaus; Mooren, Frank C; Krüger, Karsten

2015-01-01

The combination of a sedentary lifestyle and excess energy intake has led to an increased prevalence of obesity which constitutes a major risk factor for several co-morbidities including type 2 diabetes and cardiovascular diseases. Intensive research during the last two decades has revealed that a characteristic feature of obesity linking it to insulin resistance is the presence of chronic low-grade inflammation being indicative of activation of the innate immune system. Recent evidence suggests that activation of the innate immune system in the course of obesity is mediated by metabolic signals, such as free fatty acids (FFAs), being elevated in many obese subjects, through activation of pattern recognition receptors thereby leading to stimulation of critical inflammatory signaling cascades, like IκBα kinase/nuclear factor-κB (IKK/NF- κB), endoplasmic reticulum (ER) stress-induced unfolded protein response (UPR) and NOD-like receptor P3 (NLRP3) inflammasome pathway, that interfere with insulin signaling. Exercise is one of the main prescribed interventions in obesity management improving insulin sensitivity and reducing obesity- induced chronic inflammation. This review summarizes current knowledge of the cellular recognition mechanisms for FFAs, the inflammatory signaling pathways triggered by excess FFAs in obesity and the counteractive effects of both acute and chronic exercise on obesity-induced activation of inflammatory signaling pathways. A deeper understanding of the effects of exercise on inflammatory signaling pathways in obesity is useful to optimize preventive and therapeutic strategies to combat the increasing incidence of obesity and its comorbidities. Copyright © 2015 International Society of Exercise and Immunology. All rights reserved.

Acylcarnitines as markers of exercise-associated fuel partitioning, xenometabolism, and potential signals to muscle afferent neurons.

PubMed

Zhang, Jie; Light, Alan R; Hoppel, Charles L; Campbell, Caitlin; Chandler, Carol J; Burnett, Dustin J; Souza, Elaine C; Casazza, Gretchen A; Hughen, Ronald W; Keim, Nancy L; Newman, John W; Hunter, Gary R; Fernandez, Jose R; Garvey, W Timothy; Harper, Mary-Ellen; Fiehn, Oliver; Adams, Sean H

2017-01-01

What is the central question of this study? Does improved metabolic health and insulin sensitivity following a weight-loss and fitness intervention in sedentary, obese women alter exercise-associated fuel metabolism and incomplete mitochondrial fatty acid oxidation (FAO), as tracked by blood acylcarnitine patterns? What is the main finding and its importance? Despite improved fitness and blood sugar control, indices of incomplete mitochondrial FAO increased in a similar manner in response to a fixed load acute exercise bout; this indicates that intramitochondrial muscle FAO is inherently inefficient and is tethered directly to ATP turnover. With insulin resistance or type 2 diabetes mellitus, mismatches between mitochondrial fatty acid fuel delivery and oxidative phosphorylation/tricarboxylic acid cycle activity may contribute to inordinate accumulation of short- or medium-chain acylcarnitine fatty acid derivatives [markers of incomplete long-chain fatty acid oxidation (FAO)]. We reasoned that incomplete FAO in muscle would be ameliorated concurrent with improved insulin sensitivity and fitness following a ∼14 week training and weight-loss intervention in obese, sedentary, insulin-resistant women. Contrary to this hypothesis, overnight-fasted and exercise-induced plasma C4-C14 acylcarnitines did not differ between pre- and postintervention phases. These metabolites all increased robustly with exercise (∼45% of pre-intervention peak oxygen consumption) and decreased during a 20 min cool-down. This supports the idea that, regardless of insulin sensitivity and fitness, intramitochondrial muscle β-oxidation and attendant incomplete FAO are closely tethered to absolute ATP turnover rate. Acute exercise also led to branched-chain amino acid acylcarnitine derivative patterns suggestive of rapid and transient diminution of branched-chain amino acid flux through the mitochondrial branched-chain ketoacid dehydrogenase complex. We confirmed our prior novel observation that a weight-loss/fitness intervention alters plasma xenometabolites [i.e. cis-3,4-methylene-heptanoylcarnitine and γ-butyrobetaine (a co-metabolite possibly derived in part from gut bacteria)], suggesting that host metabolic health regulated gut microbe metabolism. Finally, we considered whether acylcarnitine metabolites signal to muscle-innervating afferents; palmitoylcarnitine at concentrations as low as 1-10 μm activated a subset (∼2.5-5%) of these neurons ex vivo. This supports the hypothesis that in addition to tracking exercise-associated shifts in fuel metabolism, muscle acylcarnitines act as signals of exertion to short-loop somatosensory-motor circuits or to the brain. © 2016 The Authors. Experimental Physiology © 2016 The Physiological Society.

Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise?

PubMed

da Silva, Márcia F; Natali, Antônio J; da Silva, Edson; Gomes, Gilton J; Teodoro, Bruno G; Cunha, Daise N Q; Drummond, Lucas R; Drummond, Filipe R; Moura, Anselmo G; Belfort, Felipe G; de Oliveira, Alessandro; Maldonado, Izabel R S C; Alberici, Luciane C

2015-07-15

We tested the effects of swimming training and insulin therapy, either alone or in combination, on the intracellular calcium ([Ca(2+)]i) homeostasis, oxidative stress, and mitochondrial functions in diabetic rat hearts. Male Wistar rats were separated into control, diabetic, or diabetic plus insulin groups. Type 1 diabetes mellitus was induced by streptozotocin (STZ). Insulin-treated groups received 1 to 4 UI of insulin daily for 8 wk. Each group was divided into sedentary or exercised rats. Trained groups were submitted to swimming (90 min/day, 5 days/wk, 8 wk). [Ca(2+)]i transient in left ventricular myocytes (LVM), oxidative stress in LV tissue, and mitochondrial functions in the heart were assessed. Diabetes reduced the amplitude and prolonged the times to peak and to half decay of the [Ca(2+)]i transient in LVM, increased NADPH oxidase-4 (Nox-4) expression, decreased superoxide dismutase (SOD), and increased carbonyl protein contents in LV tissue. In isolated mitochondria, diabetes increased Ca(2+) uptake, susceptibility to permeability transition pore (MPTP) opening, uncoupling protein-2 (UCP-2) expression, and oxygen consumption but reduced H2O2 release. Swimming training corrected the time course of the [Ca(2+)]i transient, UCP-2 expression, and mitochondrial Ca(2+) uptake. Insulin replacement further normalized [Ca(2+)]i transient amplitude, Nox-4 expression, and carbonyl content. Alongside these benefits, the combination of both therapies restored the LV tissue SOD and mitochondrial O2 consumption, H2O2 release, and MPTP opening. In conclusion, the combination of swimming training with insulin replacement was more effective in attenuating intracellular Ca(2+) disruptions, oxidative stress, and mitochondrial dysfunctions in STZ-induced diabetic rat hearts. Copyright © 2015 the American Physiological Society.

Myostatin in relation to physical activity and dysglycaemia and its effect on energy metabolism in human skeletal muscle cells.

PubMed

Hjorth, M; Pourteymour, S; Görgens, S W; Langleite, T M; Lee, S; Holen, T; Gulseth, H L; Birkeland, K I; Jensen, J; Drevon, C A; Norheim, F

2016-05-01

Some health benefits of exercise may be explained by an altered secretion of myokines. Because previous focus has been on upregulated myokines, we screened for downregulated myokines and identified myostatin. We studied the expression of myostatin in relation to exercise and dysglycaemia in skeletal muscle, adipose tissue and plasma. We further examined some effects of myostatin on energy metabolism in primary human muscle cells and Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. Sedentary men with or without dysglycaemia underwent a 45-min acute bicycle test before and after 12 weeks of combined endurance and strength training. Blood samples and biopsies from m. vastus lateralis and adipose tissue were collected. Myostatin mRNA expression was reduced in skeletal muscle after acute as well as long-term exercise and was even further downregulated by acute exercise on top of 12-week training. Furthermore, the expression of myostatin at baseline correlated negatively with insulin sensitivity. Myostatin expression in the adipose tissue increased after 12 weeks of training and correlated positively with insulin sensitivity markers. In cultured muscle cells but not in SGBS cells, myostatin promoted an insulin-independent increase in glucose uptake. Furthermore, muscle cells incubated with myostatin had an enhanced rate of glucose oxidation and lactate production. Myostatin was differentially expressed in the muscle and adipose tissue in relation to physical activity and dysglycaemia. Recombinant myostatin increased the consumption of glucose in human skeletal muscle cells, suggesting a complex regulatory role of myostatin in skeletal muscle homeostasis. © 2015 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Physical training in the prophylaxis and treatment of obesity, hypertension and diabetes.

PubMed

Krotkiewski, M

1983-01-01

The results of physical training in 600 obese and 100 diabetic patients are described and discussed. Three months of physical training (55 min 3 times/week) without dietary restriction did not result in any change in body weight and composition either in obese or diabetic female patients. However, the male patients remained their body weight unchanged and body fat decreased and lean body mass increased after training. The combination of exercise with a very low calorie diet in obese women neither prevents the erosion of lean body mass nor the diet-induced decrease in oxygen uptake. Local exercise could not evoke a local decrease in the thickness of adipose tissue. The addition of physical training to the low calorie diet leads to better social and psychological compliance and a more equal distribution of adipose tissue. A close relationship has been found between the muscle morphology and glucose metabolism in obese patients. Insulin concentration appeared to be positively correlated to the percentage of FTb fibers and inversely correlated to the capillary density. The decrease in the percentage of FTb muscle fibers and the increase in the number of capillaries were correlated to the decrease in plasma insulin levels. The capillary density appeared to be reduced with decreasing degrees of glucose tolerance. In patients with diabetes type I it was found diminished so much that the diffusion distance in muscle increased after training. The most interesting results related to glucose metabolism were found otherwise as follows: The sum of insulin (276.4 +/- 20.1 before and 255.1 +/- 19.0 after p less than 0.05) and glucose levels (but not fasting values) decreased (28.3 +/- 1.6 before and 27.8 +/- 1.4 after p less than 0.01) after training in obesity. In obese and diabetic patients with initially high insulin values physical training resulted in a decrease in insulin level, while in those patients with initially low values it resulted in an increase. As judged from the insulin C-peptide ratio, patients who decreased their insulin levels after training increased their liver uptake of insulin. The increased hepatic extraction of insulin without the decrease of insulin production was also noted in patients with diabetes type II. After training both obese patients and those with diabetes I and II increased their glucose metabolism (disposal rate) during insulin euglycemic clamp. Patients with diabetes type II showed initially lower basal and insulin-stimulated glucose incorporation into triglycerides.(ABSTRACT TRUNCATED AT 400 WORDS)

Combination of exercise training and diet restriction normalizes limited exercise capacity and impaired skeletal muscle function in diet-induced diabetic mice.

PubMed

Suga, Tadashi; Kinugawa, Shintaro; Takada, Shingo; Kadoguchi, Tomoyasu; Fukushima, Arata; Homma, Tsuneaki; Masaki, Yoshihiro; Furihata, Takaaki; Takahashi, Masashige; Sobirin, Mochamad A; Ono, Taisuke; Hirabayashi, Kagami; Yokota, Takashi; Tanaka, Shinya; Okita, Koichi; Tsutsui, Hiroyuki

2014-01-01

Exercise training (EX) and diet restriction (DR) are essential for effective management of obesity and insulin resistance in diabetes mellitus. However, whether these interventions ameliorate the limited exercise capacity and impaired skeletal muscle function in diabetes patients remains unexplored. Therefore, we investigated the effects of EX and/or DR on exercise capacity and skeletal muscle function in diet-induced diabetic mice. Male C57BL/6J mice that were fed a high-fat diet (HFD) for 8 weeks were randomly assigned for an additional 4 weeks to 4 groups: control, EX, DR, and EX+DR. A lean group fed with a normal diet was also studied. Obesity and insulin resistance induced by a HFD were significantly but partially improved by EX or DR and completely reversed by EX+DR. Although exercise capacity decreased significantly with HFD compared with normal diet, it partially improved with EX and DR and completely reversed with EX+DR. In parallel, the impaired mitochondrial function and enhanced oxidative stress in the skeletal muscle caused by the HFD were normalized only by EX+DR. Although obesity and insulin resistance were completely reversed by DR with an insulin-sensitizing drug or a long-term intervention, the exercise capacity and skeletal muscle function could not be normalized. Therefore, improvement in impaired skeletal muscle function, rather than obesity and insulin resistance, may be an important therapeutic target for normalization of the limited exercise capacity in diabetes. In conclusion, a comprehensive lifestyle therapy of exercise and diet normalizes the limited exercise capacity and impaired muscle function in diabetes mellitus.

Growth hormone-insulin-like growth factor-1 and inflammatory response to a single exercise bout in children and adolescents.

PubMed

Nemet, Dan; Eliakim, Alon

2010-01-01

Physical activity plays an important role in tissue anabolism, growth and development, but the mechanisms that link patterns of exercise with tissue anabolism are not completely understood. The effectiveness of physical training depends on the training load and on the individual ability to tolerate it, and an imbalance between the two may lead to under or over-training. Therefore, many efforts have been made to find objective parameters to quantify the balance between training load and the athlete's tolerance. One of the unique features of exercise is that it leads to a simultaneous increase of antagonistic mediators. On the one hand, exercise stimulates anabolic components of the growth hormone (GH) → IGF-1 (insulin-like growth factor-1) axis. On the other hand, exercise elevates catabolic pro-inflammatory cytokines such as interleukin-6 (IL-6), IL-1 and tumor necrosis factor-α (TNF-α). This emphasizes probably the importance of optimal adaptation to exercise in particularly during adolescence. The very fine balance between the anabolic and inflammatory/catabolic response to exercise will determine the effectiveness of exercise training and the health consequences of exercise. If the anabolic response is stronger, exercise will probably lead ultimately to increased muscle mass and improved fitness. A greater catabolic response, in particularly if persists for long duration, may lead to overtraining. Therefore, changes in the anabolic-catabolic hormonal balance and in circulating inflammatory cytokines can be used by adolescent athletes and/or their coaches to gauge the training intensity in individual and team sports. Copyright © 2010 S. Karger AG, Basel.

Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

USDA-ARS?s Scientific Manuscript database

Controversy exists as to whether supplementation with the antioxidants vitamin E (VE) and vitamin C (VC) blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial (MT) function and induces insulin resistance ...

The Effects of Basal Insulin Suspension at the Start of Exercise on Blood Glucose Levels During Continuous Versus Circuit-Based Exercise in Individuals with Type 1 Diabetes on Continuous Subcutaneous Insulin Infusion.

PubMed

Zaharieva, Dessi; Yavelberg, Loren; Jamnik, Veronica; Cinar, Ali; Turksoy, Kamuran; Riddell, Michael C

2017-06-01

Exercise causes glycemic disturbances in individuals with type 1 diabetes (T1D). Continuous moderate-intensity aerobic exercise (CON) generally lowers blood glucose (BG) levels and often leads to hypoglycemia. In comparison, circuit-based exercise (CIRC) may attenuate the drop in BG. The goal of this study is to contrast the effects of basal insulin suspension at the onset of two different forms of exercise (CON vs. CIRC). Twelve individuals (six men and six women) with T1D on insulin pump therapy were recruited for the study. All participants completed a maximal aerobic fitness test and two 40-min exercise sessions, consisting of either continuous treadmill walking or a circuit workout. Basal insulin infusion was stopped at the onset of exercise and resumed in recovery. After providing an initial reference value, volunteers were blinded to their [BG] and were asked to estimate their levels during exercise. Oxygen consumption (47.5 ± 7.5 vs. 54.5 ± 13.5 mL·kg -1 ·min -1 , P = 0.03) and heart rate (122 ± 20 vs. 144 ± 20 bpm, P = 0.003) were lower in CON vs. CIRC. Despite the lower workload, BG levels dropped more with CON vs. CIRC (delta BG = -3.8 ± 1.5 vs. -0.5 ± 3.0 mmol/L for CON vs. CIRC, respectively, P = 0.001). Participants were able to estimate their BG more accurately during CON (r = 0.83) vs. CIRC (r = 0.33) based on a regression analysis. Despite a lower intensity of exercise, with full basal insulin suspension at the start of exercise, CON results in a larger drop in BG vs. CIRC. These findings have implications for single hormone-based artificial pancreas development for exercise. While this study does not negate the importance of frequent capillary BG monitoring during exercise, it does suggest that if persons are knowledgeable about their pre-exercise BG levels, they can accurately perceive the changes in BG during CON, but not during CIRC.

Adiponectin and markers of metabolic syndrome in obese children and adolescents: impact of 8-mo regular physical exercise program.

PubMed

Nascimento, Henrique; Costa, Elísio; Rocha, Susana; Lucena, Clarice; Rocha-Pereira, Petronila; Rêgo, Carla; Mansilha, Helena Ferreira; Quintanilha, Alexandre; Aires, Luísa; Mota, Jorge; Santos-Silva, Alice; Belo, Luís

2014-08-01

Adiponectin circulates as low-, medium-, and high-molecular-weight multimers (LMW, MMW, and HMW) and influences lipid profile and insulin resistance (IR), HMW being considered as the most biologically active form. We aimed to study the relation between adiponectin and markers of metabolic syndrome (MS) in pediatric obesity, and the impact of physical exercise. The study consisted of a cross-sectional part and an 8-mo physical exercise program. Lipid profile, insulin, glucose, C-reactive protein (CRP), total adiponectin (TA), and homeostasis model assessment IR (HOMA-IR) were measured. Adiponectin multimers were studied in a prepubertal group. Obesity is associated with increased dyslipidemia, IR, and inflammation. TA is correlated inversely with adiposity, triglycerides, HOMA-IR, and CRP, and positively with high-density lipoprotein cholesterol (HDLc)/total cholesterol (TC) ratio. HMW mimicked TA associations. The intervention program led to a reduction of TC, low-density lipoprotein cholesterol (LDLc), insulin, HOMA-IR, and trunk percentage of fat, and an increase of HDLc/TC ratio, in the obese group. BMI improvements prevented adiponectin reduction and correlated with increments in HMW and MMW. Obesity-related increase in MS features might be linked to lower adiponectin. HMW and MMW were the multimers that most explained the MS features. The intervention program improved the lipid profile and IR, and prevented the reduction of adiponectin.

Saffron with resistance exercise improves diabetic parameters through the GLUT4/AMPK pathway in-vitro and in-vivo

PubMed Central

Dehghan, Firouzeh; Hajiaghaalipour, Fatemeh; Yusof, Ashril; Muniandy, Sekaran; Hosseini, Seyed Ali; Heydari, Sedigheh; Salim, Landa Zeenelabdin Ali; Azarbayjani, Mohammad Ali

2016-01-01

Saffron is consumed as food and medicine to treat several illnesses. This study elucidates the saffron effectiveness on diabetic parameters in-vitro and combined with resistance exercise in-vivo. The antioxidant properties of saffron was examined. Insulin secretion and glucose uptake were examined by cultured RIN-5F and L6 myotubes cells. The expressions of GLUT2, GLUT4, and AMPKα were determined by Western blot. Diabetic and non-diabetic male rats were divided into: control, training, extract treatment, training + extract treatment and metformin. The exercise and 40 mg/kg/day saffron treatments were carried out for six weeks. The antioxidant capacity of saffron was higher compare to positive control (P < 0.01). High dose of saffron stimulated insulin release in RIN-5F cells and improved glucose uptake in L6 myotubes. GLUT4 and AMPKα expressions increased in both doses of saffron (P < 0.01), whereas GLUT2 not changed (p > 0.05). Serum glucose, cholesterol, triglyceride, low-density lipoprotein, very low-density lipoprotein, insulin resistance, and glycated hemoglobin levels decreased in treated rats compared to untreated (p < 0.01). However, no significant differences were observed in the high-density lipoprotein, insulin, adiponectin, and leptin concentration levels in all groups (p > 0.05). The findings suggest that saffron consuming alongside exercise could improve diabetic parameters through redox-mediated mechanisms and GLUT4/AMPK pathway to entrap glucose uptake. PMID:27122001

The role of weight loss and exercise in correcting skeletal muscle mitochondrial abnormalities in obesity, diabetes and aging.

PubMed

Toledo, Frederico G S; Goodpaster, Bret H

2013-10-15

Mitochondria within skeletal muscle have been implicated in insulin resistance of obesity and type 2 diabetes mellitus as well as impaired muscle function with normal aging. Evaluating the potential of interventions to improve mitochondria is clearly relevant to the prevention or treatment of metabolic diseases and age-related dysfunction. This review provides an overview and critical evaluation of the effects of weight loss and exercise interventions on skeletal muscle mitochondria, along with implications for insulin resistance, obesity, type 2 diabetes and aging. The available literature strongly suggests that the lower mitochondrial capacity associated with obesity, type 2 diabetes and aging is not an irreversible lesion. However, weight loss does not appear to affect this response, even when the weight loss is extreme. In contrast, increasing physical activity improves mitochondrial content and perhaps the function of individual mitochondrion. Despite the consistent effect of exercise to improve mitochondrial capacity, studies mechanistically linking mitochondria to insulin resistance, reductions in intramyocellular lipid or improvement in muscle function remain inconclusive. In summary, studies of diet and exercise training have advanced our understanding of the link between mitochondrial oxidative capacity and insulin resistance in obesity, type 2 diabetes and aging. Nevertheless, additional inquiry is necessary to establish the significance and clinical relevance of those perturbations, which could lead to targeted therapies for a myriad of conditions and diseases involving mitochondria. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Exercise training with weight loss and either a high or low glycemic diet reduces metabolic syndrome severity in older adults

PubMed Central

Malin, Steven K.; Niemi, Nicole; Solomon, Thomas P.J.; Haus, Jacob M.; Kelly, Karen R.; Filion, Julianne; Rocco, Michael; Kashyap, Sangeeta R.; Barkoukis, Hope; Kirwan, John P.

2012-01-01

Background The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low or high glycemic diet on metabolic syndrome severity (Z-score). Methods Twenty-one adults (66.2 ± 1.1 yr; BMI = 35.3 ± 0.9 kg/m2) with metabolic syndrome were randomized to 12 weeks of exercise (60 minutes/d for 5 d/week at ~85% HRmax) and provided a low-glycemic (n=11; LoGIx) or high glycemic (n=10; HiGIx) diet. Z-scores were determined from: blood pressure, triglycerides (TG), high-density lipoproteins (HDL), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and non-esterfied fatty acid (NEFA) suppression were also assessed. Results LoGIx and HiGIx decreased body mass and insulin resistance and increased aerobic fitness comparably (p < 0.05). LoGIx and HiGIx decreased the Z-score similarly, as each intervention decreased blood pressure, TG, FPG, and WC (p < 0.05). HiGIx tended to suppress NEFA during insulin stimulation compared to LoGIx (p = 0.06). Conclusions Our findings highlight that exercise with weight loss reduces metabolic syndrome severity whether individuals were randomized to a high or low glycemic index diet. PMID:23036993

Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

PubMed

Van Proeyen, Karen; Ramaekers, Monique; Pischel, Ivo; Hespel, Peter

2012-08-01

The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t₀) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t₆₀. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t₃₀ and t₆₀ (p < .05). Furthermore, a higher serum insulin concentration was noted after OFI intake at baseline and at t₃₀ (p < .05). In OGTT(EX), blood glucose at t₆₀ was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p < .05). However, insulin values and AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs.

PubMed

Jankord, Ryan; Ganjam, Venkataseshu K; Turk, James R; Hamilton, Marc T; Laughlin, M Harold

2008-06-01

Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo-pituitary-adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16-20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the blunted ACTH response to an acute stressor in sedentary animals, but cannot explain the exaggerated response in exercise trained animals.

Exercise training alters effect of high-fat feeding on the ACTH stress response in pigs

PubMed Central

Jankord, Ryan; Ganjam, Venkataseshu K.; Turk, James R.; Hamilton, Marc T.; Laughlin, M. Harold

2009-01-01

Eating and physical activity behaviors influence neuroendocrine output. The purpose of this study was to test, in an animal model of diet-induced cardiovascular disease, the effects of high-fat feeding and exercise training on hypothalamo–pituitary–adrenocortical (HPA) axis activity. We hypothesized that a high-fat diet would increase circulating free fatty acids (FFAs) and decrease the adrenocorticotropic hormone (ACTH) and cortisol response to an acute stressor. We also hypothesized that exercise training would reverse the high-fat diet-induced changes in FFAs and thereby restore the ACTH and cortisol response. Pigs were placed in 1 of 4 groups (normal diet, sedentary; normal diet, exercise training; high-fat diet, sedentary; high-fat diet, exercise training; n = 8/group). Animals were placed on their respective dietary and activity treatments for 16–20 weeks. After completion of the treatments animals were anesthetized and underwent surgical intubation. Blood samples were collected after surgery and the ACTH and cortisol response to surgery was determined and the circulating concentrations of FFAs, glucose, cholesterol, insulin, and IGF-1 were measured. Consistent with our hypothesis, high-fat feeding increased FFAs by 200% and decreased the ACTH stress response by 40%. In exercise-trained animals, the high-fat diet also increased FFA; however, the increase in FFA in exercise-trained pigs was accompanied by a 60% increase in the ACTH response. The divergent effect of high-fat feeding on ACTH response was not expected, as exercise training alone had no effect on the ACTH response. Results demonstrate a significant interaction between diet and exercise and their effect on the ACTH response. The divergent effects of high-fat diet could not be explained by changes in weight gain, blood glucose, insulin, or IGF-1, as these were altered by high-fat feeding, but unaffected by exercise training. Thus, the increase in FFA with high-fat feeding may explain the blunted ACTH response to an acute stressor in sedentary animals, but cannot explain the exaggerated response in exercise trained animals. PMID:18461098

Swimming training alleviated insulin resistance through Wnt3a/β-catenin signaling in type 2 diabetic rats

PubMed Central

Yang, Qiang; Wang, Wen-wen; Ma, Pu; Ma, Zhong-xuan; Hao, Meng; Adelusi, Temitope I; Lei-Du; Yin, Xiao-Xing; Lu, Qian

2017-01-01

Objective(s): Increasing evidence suggests that regular physical exercise improves type 2 diabetes mellitus (T2DM). However, the potential beneficial effects of swimming on insulin resistance and lipid disorder in T2DM, and its underlying mechanisms remain unclear. Materials and Methods: Rats were fed with high fat diet and given a low dosage of Streptozotocin (STZ) to induce T2DM model, and subsequently treated with or without swimming exercise. An 8-week swimming program (30, 60 or 120 min per day, 5 days per week) decreased body weight, fasting blood glucose and fasting insulin. Results: Swimming ameliorated lipid disorder, improved muscular atrophy and revealed a reduced glycogen deposit in skeletal muscles of diabetic rats. Furthermore, swimming also inhibited the activation of Wnt3a/β-catenin signaling pathway, decreased Wnt3a mRNA and protein level, upregulated GSK3β phosphorylation activity and reduced the expression of β-catenin phosphorylation in diabetic rats. Conclusion: The trend of the result suggests that swimming exercise proved to be a potent ameliorator of insulin resistancein T2DM through the modulation of Wnt3a/β-catenin pathway and therefore, could present a promising therapeutic measure towards the treatment of diabetes and its relatives. PMID:29299199

The integrative role of leptin, oestrogen and the insulin family in obesity-associated breast cancer: potential effects of exercise.

PubMed

Schmidt, S; Monk, J M; Robinson, L E; Mourtzakis, M

2015-06-01

Obesity is an established risk factor for postmenopausal breast cancer. The mechanisms through which obesity influences the development and progression of breast cancer are not fully elucidated; however, several factors such as increased oestrogen, concentrations of various members of the insulin family and inflammation that are associated with adiposity are purported to be important factors in this relationship. Emerging research has also begun to focus on the role of adipokines, (i.e. adipocyte secreted factors), in breast cancer. Leptin secretion is directly related to adiposity and is believed to promote breast cancer directly and independently, as well as through involvement with the oestrogen and insulin signalling pathways. As leptin is secreted from white adipose tissue, any intervention that reduces adiposity may be favourable. However, it is also important to consider that energy expenditure through exercise, independent of fat loss, may improve leptin regulation. The purpose of this narrative review was to explore the role of leptin in breast cancer development and progression, identify key interactions with oestrogen and the insulin family, and distinguish the potential effects of exercise on these interactions. © 2015 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity.

Exercise activates the PI3K-AKT signal pathway by decreasing the expression of 5α-reductase type 1 in PCOS rats.

PubMed

Wu, Chuyan; Jiang, Feng; Wei, Ke; Jiang, Zhongli

2018-05-22

Hyperandrogenism and hyperinsulinemia are main clinical endocrine features of PCOS. Exercise can adjust the androgen level, as well as increase the sensitivity of insulin by activating PI3K-Akt insulin signaling pathways. 5αR1 has certain effects on insulin resistance and can synthesize dihydrotestosterone by metabolizing testosterone. So 5αR1 may be the target of androgen and insulin for exercise-induced regulation. To investigate the role of 5αR1 in the PI3K-Akt signaling pathway in skeletal muscle of PCOS rats activated by exercise, fifty-four female rats were randomly divided into the PCOS group (n = 42) and the control group(n = 12). After injection of testosterone propionate for 28 days, the remaining 36 rats in the PCOS group were randomly assigned to six groups: the sedentary group (PS, n = 6), sedentary and 5αRI (5α-reductase inhibitor) group (PS + RI, n = 6), sedentary and 5αR2I (5α-reductase type 2 selective inhibitor) group (PS + R2I, n = 6), exercise group (PE, n = 6), exercise and 5αRI group (PE + RI, n = 6), and exercise and 5αR2I group (PE + R2I, n = 6). The rats undergoing exercise were trained to swim for 14 days. Finasteride (5α-reductase type 2 selective inhibitor) and dutasteride (5α-reductase inhibitor) were administered once daily and were dosed based on weight. At the end, the expression of 5αR1 proteins, the phosphorylation level of PI3K and AKT, were determined by Western blot. The PCOS non-exercise group and the PE + RI group displayed significantly lower phosphorylation of Akt, PI3K p85 and GLUT4 expression, while in the PE + R2I group, the level of Akt phosphorylation and PI3K p85 expression was significantly higher than that of the PCOS non-exercise group and the PE + RI group. In summary, our study demonstrated that exercise can activate the PI3K/AKT signal pathway of PCOS rats by decreasing the expression of 5αR1.

Depression-like behaviors in mice subjected to co-treatment of high-fat diet and corticosterone are ameliorated by AICAR and exercise.

PubMed

Liu, Weina; Zhai, Xiaofeng; Li, Haipeng; Ji, Liu

2014-03-01

Major depressive disorder (MDD) and type II diabetes mellitus (T2DM) are highly co-morbid, and there may be a bi-directional connection between the two. Herein, we have described a mouse model of a depression-like and insulin-resistant (DIR) state induced by the co-treatment of high-fat diet (HFD) and corticosterone (CORT). 5-Aminoimidazole-4-carboxamide-1-β-d- ribofuranoside (AICAR), a pharmacological activator of AMP-activated protein kinase (AMPK), was originally used to improve insulin resistance (IR). Interestingly, our results show a clear potential for AICAR as a putative antidepressant with a chronic action on the DIR mice. In contrast to the traditional antidepressants, AICAR as a promising antidepressant avoids reducing insulin actions of skeletal muscle in the context of long-term HFD. Exercise also produced antidepressant effects. Our data suggest that the effects of AICAR and exercise on DIR may further increase our understanding on the link between depression and diabetes. Copyright © 2013 Elsevier B.V. All rights reserved.

Exercise in obese female rats has beneficial effects on maternal and male and female offspring metabolism

PubMed Central

Vega, Claudia C; Reyes-Castro, Luis A; Bautista, Claudia J; Larrea, Fernando; Nathanielsz, Peter W; Zambrano, Elena

2013-01-01

BACKGROUND Maternal obesity (MO) impairs maternal and offspring health. Mechanisms and interventions to prevent adverse maternal and offspring outcomes need to be determined. Human studies are confounded by socio-economic status providing the rationale for controlled animal data on effects of maternal exercise (MEx) intervention on maternal (F0) and offspring (F1) outcomes in MO. HYPOTHESIS MO produces metabolic and endocrine dysfunction, increases maternal and offspring glucocorticoid exposure, oxidative stress and adverse offspring outcomes by postnatal day (PND) 36. MEx prevents these outcomes. METHODS F0 female rats ate either control or obesogenic diet from weaning through lactation. Half of each group wheel ran (from day ninety of life through pregnancy beginning day 120) providing four groups (n=8/group) – i) controls, ii) obese, iii) exercised controls and iv) exercised obese. After weaning, PND 21, F1 offspring ate a control diet. Metabolic parameters of F0 prepregnancy and end of lactation and F1 offspring at PND 36 were analyzed. RESULTS Exercise did not change maternal weight. Before breeding, MO elevated F0 glucose, insulin, triglycerides, cholesterol, leptin, fat and oxidative stress. Exercise completely prevented the triglyceride rise and partially glucose, insulin, cholesterol and oxidative stress increases. MO decreased fertility, recovered by exercise. At the end of lactation, exercise returned all metabolic variables except leptin to control levels. Exercise partially prevented MO elevated corticosterone. F1 Offspring weights were similar at birth. At PND 36 MO increased F1 male but not female offspring leptin, triglycerides and fat mass. In controls exercise reduced male and female offspring glucose, prevented the offspring leptin increase and partially the triglyceride rise. CONCLUSIONS MEx before and during pregnancy has beneficial effects on maternal and offspring metabolism and endocrine function occurring with no weight change in mothers and offspring indicating the importance of body composition rather than weight in evaluations of metabolic status. PMID:23949616

Rosiglitazone lowers resting and blood pressure response to exercise in men with type 2 diabetes: A 1-year randomized study.

PubMed

Piché, Marie-Eve; Laberge, Anne-Sophie; Brassard, Patrice; Arsenault, Benoit J; Bertrand, Olivier F; Després, Jean-Pierre; Costerousse, Olivier; Poirier, Paul

2018-07-01

We aimed to determine the effect of 1-year treatment with the insulin sensitizer peroxisome proliferator-activated receptor (PPAR)-γ agonist rosiglitazone on exercise capacity and blood pressure (BP) response to exercise in men with coronary artery disease (CAD) and type 2 diabetes (T2D). A total of 116 men (age, 64 ± 7 years; body mass index, 30.0 ± 4.4 kg/m 2 ) with CAD and T2D were randomized to receive rosiglitazone or placebo for 1 year. Exercise capacity (VO 2peak ) and BP response to exercise were assessed with a maximal treadmill test, prior to the intervention and at 1-year follow-up. Exercise-induced hypertension (EIH) was defined as maximal systolic BP ≥ 220 mm Hg and/or diastolic BP ≥ 100 mm Hg. PPAR-γ agonist-treated patients showed improvements in fasting glucose, HbA1c and insulin sensitivity (Homeostasis model assessment of insulin resistance [HOMA-IR]) (all P < .05). Resting BPs, maximal exercise diastolic BP and resting rate-pressure product (RPP) were all reduced in the PPAR-γ agonist group (P < .05). Maximal exercise duration was unchanged. T2D patients who displayed the greatest improvement in insulin sensitivity (HOMA-IR) under PPAR-γ agonist treatment experienced a greater reduction in exercise BP and RPP (P < .05). The proportion of men with EIH decreased in the PPAR-γ agonist group during follow-up (39.00% ± 0.06% vs 21.00% ± 0.05%). In the subgroup with EIH that was treated with a PPAR-γ agonist, resting and exercise diastolic BP, as well as resting RPP, were all reduced at 1-year follow-up (P < .05). The insulin sensitizer rosiglitazone has a beneficial effect on resting and BP response to exercise in men with CAD and T2D, especially in those with an exaggerated BP response to exercise. © 2018 John Wiley & Sons Ltd.

Lifelong exercise and locally produced insulin-like growth factor-1 (IGF-1) have a modest influence on reducing age-related muscle wasting in mice.

PubMed

McMahon, C D; Chai, R; Radley-Crabb, H G; Watson, T; Matthews, K G; Sheard, P W; Soffe, Z; Grounds, M D; Shavlakadze, T

2014-12-01

The age-related loss of skeletal muscle mass and function is termed sarcopenia and has been attributed to a decline in concentrations of insulin-like growth factor-1 (IGF-1). We hypothesized that constitutively expressed IGF-1 within skeletal muscles with or without exercise would prevent sarcopenia. Male transgenic mice that overexpress IGF-1 Ea in skeletal muscles were compared with wild-type littermates. Four-month-old mice were assigned to be sedentary, or had access to free-running wheels, until 18 or 28 months of age. In wild-type mice, the mass of the quadriceps muscles was reduced at 28 months and exercise prevented such loss, without affecting the diameter of myofibers. Conversely, increased IGF-1 alone was ineffective, whereas the combination of exercise and IGF-1 was additive in maintaining the diameter of myofibers in the quadriceps muscles. For other muscles, the combination of IGF-1 and exercise was variable and either increased or decreased the mass at 18 months of age, but was ineffective thereafter. Despite an increase in the diameter of myofibers, grip strength was not improved. In conclusion, our data show that exercise and IGF-1 have a modest effect on reducing aged-related wasting of skeletal muscle, but that there is no improvement in muscle function when assessed by grip strength. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effects of insulin resistance on skeletal muscle growth and exercise capacity in type 2 diabetic mouse models

PubMed Central

Ostler, Joseph E.; Maurya, Santosh K.; Dials, Justin; Roof, Steve R.; Devor, Steven T.; Ziolo, Mark T.

2014-01-01

Type 2 diabetes mellitus is associated with an accelerated muscle loss during aging, decreased muscle function, and increased disability. To better understand the mechanisms causing this muscle deterioration in type 2 diabetes, we assessed muscle weight, exercise capacity, and biochemistry in db/db and TallyHo mice at prediabetic and overtly diabetic ages. Maximum running speeds and muscle weights were already reduced in prediabetic db/db mice when compared with lean controls and more severely reduced in the overtly diabetic db/db mice. In contrast to db/db mice, TallyHo muscle size dramatically increased and maximum running speed was maintained during the progression from prediabetes to overt diabetes. Analysis of mechanisms that may contribute to decreased muscle weight in db/db mice demonstrated that insulin-dependent phosphorylation of enzymes that promote protein synthesis was severely blunted in db/db muscle. In addition, prediabetic (6-wk-old) and diabetic (12-wk-old) db/db muscle exhibited an increase in a marker of proteasomal protein degradation, the level of polyubiquitinated proteins. Chronic treadmill training of db/db mice improved glucose tolerance and exercise capacity, reduced markers of protein degradation, but only mildly increased muscle weight. The differences in muscle phenotype between these models of type 2 diabetes suggest that insulin resistance and chronic hyperglycemia alone are insufficient to rapidly decrease muscle size and function and that the effects of diabetes on muscle growth and function are animal model-dependent. PMID:24425761

Effect of Exercise Training on Cardiac Biomarkers in At-Risk Populations: A Systematic Review.

PubMed

Glenney, Susan Sullivan; Brockemer, Derrick Paul; Ng, Andy C; Smolewski, Michael A; Smolgovskiy, Vladimir M; Lepley, Adam S

2017-12-01

Studies have demonstrated beneficial effects of exercise on cardiovascular disease biomarkers for healthy individuals; however, a comprehensive review regarding the effect of exercise on cardiovascular disease biomarkers in at-risk populations is lacking. A literature search was performed to identify studies meeting the following criteria: randomized controlled study, participants with pathology/activity limitations, biomarker outcome (total cholesterol, high-density lipoprotein, low-density lipoprotein, C-reactive protein, insulin, triglycerides, or glucose), and exercise intervention. Means and standard deviations from each biomarker were used to calculate standardized Cohen's d effect sizes with 95% confidence intervals. In total, 37 articles were included. The majority (44/57; 77%) of data points demonstrated moderate to strong effects for the reduction in total cholesterol, triglycerides, and low-density lipoprotein, and elevation in high-density lipoprotein following exercise. The majority of data points demonstrated strong effects for reductions in blood glucose (24/30; 80%) and insulin (23/24; 96%) levels following exercise intervention. Evidence is heterogeneous regarding the influence of exercise on cardiovascular disease biomarkers in at-risk patients, which does not allow a definitive conclusion. Favorable effects include reductions in triglycerides, total cholesterol, low-density lipoprotein, glucose, and insulin, and elevation in high-density lipoprotein following exercise intervention. The strongest evidence indicates that exercise is favorable for the reduction in glucose and cholesterol levels among obese patients, and reduction of insulin regardless of population.

Pigment epithelium-derived factor, insulin sensitivity, and adiposity in polycystic ovary syndrome: impact of exercise training.

PubMed

Joham, Anju E; Teede, Helena J; Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Strauss, Boyd J; Paul, Eldho; Watt, Matthew J

2012-12-01

Pigment epithelium-derived factor (PEDF) is upregulated in obese rodents and is involved in the development of insulin resistance (IR). We aim to explore the relationships between PEDF, adiposity, insulin sensitivity, and cardiovascular risk factors in obese women with polycystic ovary syndrome (PCOS) and weight-matched controls and to examine the impact of endurance exercise training on PEDF. This prospective cohort intervention study was based at a tertiary medical center. Twenty obese PCOS women and 14 non-PCOS weight-matched women were studied at baseline. PEDF, cardiometabolic markers, detailed body composition, and euglycemic-hyperinsulinemic clamps were performed and measures were repeated in 10 PCOS and 8 non-PCOS women following 12 weeks of intensified aerobic exercise. Mean glucose infusion rate (GIR) was 31.7% lower (P = 0.02) in PCOS compared to controls (175.6 ± 96.3 and 257.2 ± 64.3 mg.m(-2).min(-1)) at baseline, yet both PEDF and BMI were similar between groups. PEDF negatively correlated to GIR (r = -0.41, P = 0.03) and high-density lipoprotein (HDL) (r = -0.46, P = 0.01), and positively to cardiovascular risk factors, systolic (r = 0.41, P = 0.02) and diastolic blood pressure (r = 0.47, P = 0.01) and triglycerides (r = 0.49, P = 0.004). The correlation with GIR was not significant after adjusting for fat mass (P = 0.07). Exercise training maintained BMI and increased GIR in both groups; however, plasma PEDF was unchanged. In summary, PEDF is not elevated in PCOS, is not associated with IR when adjusted for fat mass, and is not reduced by endurance exercise training despite improved insulin sensitivity. PEDF was associated with cardiovascular risk factors, suggesting PEDF may be a marker of cardiovascular risk status.

The effects of aerobic, resistance, and combination training on insulin sensitivity and secretion in overweight adults from STRRIDE AT/RT: a randomized trial.

PubMed

AbouAssi, Hiba; Slentz, Cris A; Mikus, Catherine R; Tanner, Charles J; Bateman, Lori A; Willis, Leslie H; Shields, A Tamlyn; Piner, Lucy W; Penry, Lorrie E; Kraus, Erik A; Huffman, Kim M; Bales, Connie W; Houmard, Joseph A; Kraus, William E

2015-06-15

Most health organizations recommend a combination of aerobic training (AT) and resistance training (RT), yet few studies have compared their acute (within 24 h of the last exercise bout) and sustained (after 14 days of no exercise training) effects alone and in combination on glucose metabolism. The present study (Studies Targeting Risk Reduction Interventions through Defined Exercise-Aerobic Training and/or Resistance Training) compared the effects of AT, RT, and the combination (AT/RT) on insulin action at both acute and sustained phases. Subjects (N = 196) were 18-70 yr old (mean age = 50 yr), overweight (mean body mass index = 30 kg/m2), sedentary with moderate dyslipidemia, and were randomized into one of three 8-mo exercise groups: 1) RT: 3 days/wk, 8 exercises, 3 sets/exercise, 8-12 repetitions/set; 2) AT: equivalent to ∼19.2 km/wk (12 miles/wk) at 75% peak O2 consumption; 3) AT/RT: the combination of AT and RT. One hundred forty-four subjects completed the intervention. Eighty-eight subjects completed all pre- and postintervention testing visits. Insulin sensitivity, glucose effectiveness, and disposition index were measured via a frequently sampled intravenous glucose tolerance test with subsequent minimal model analyses. AT/RT resulted in greater improvements in insulin sensitivity, β-cell function (disposition index), and glucose effectiveness than either AT or RT alone (all P < 0.05). Approximately 52% of the improvement in insulin sensitivity by AT/RT was retained 14 days after the last exercise training bout. Neither AT or RT led to acute or chronic improvement in sensitivity index. In summary, only AT/RT (which required twice as much time as either alone) led to significant acute and sustained benefits in insulin sensitivity

Effects of menopause and high-intensity training on insulin sensitivity and muscle metabolism.

PubMed

Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael; Enevoldsen, Lotte Hahn; Kjær, Andreas; Clemmensen, Andreas E; Christensen, Anders Nymark; Suetta, Charlotte; Frikke-Schmidt, Ruth; Steenberg, Dorte Enggaard; Wojtaszewski, Jørgen F P; Hellsten, Ylva; Stallknecht, Bente M

2018-02-01

To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n = 20) women were included in a 3-month high-intensity exercise training intervention. Body composition was assessed by magnetic resonance imaging and dual-energy x-ray absorptiometry, whole body glucose disposal rate (GDR) by hyperinsulinemic euglycemic clamp (40 mU/m/min), and femoral muscle glucose uptake by positron emission tomography/computed tomography, using the glucose analog fluorodeoxyglucose, expressed as estimated metabolic rate (eMR). Insulin signaling was investigated in muscle biopsies. Age difference between groups was 4.5 years, and no difference was observed in body composition. Training increased lean body mass (estimate [95% confidence interval] 0.5 [0.2-0.9] kg, P < 0.01) and thigh muscle mass (0.2 [-0.1 to 0.6] kg, P < 0.01), and decreased fat percentage (1.0 [0.5-1.5]%, P < 0.01) similarly in the two groups. The postmenopausal women had lower eMR in vastus lateralis muscle than the premenopausal women (-14.0 [-26.0 to -2.0] μmol/min/kg, P = 0.02), and tended to have lower eMR in femoral muscles (-11.2 [-22.7 to 0.4] μmol/min/kg, P = 0.06), and also GDR (-59.3 [-124.8 to 6.3] mg/min, P = 0.08), but increased similarly in both groups with training (eMR vastus lateralis muscle: 27.8 [19.6-36.0] μmol/min/kg, P < 0.01; eMR femoral muscle: 20.0 [13.1-26.7] μmol/min/kg, P < 0.01, respectively; GDR: 43.6 [10.4-76.9] mg/min, P = 0.01). Potential mechanisms underlying the training-induced increases in insulin sensitivity included increased expression of hexokinase (19.2 [5.0-24.7] AU, P = 0.02) and glycogen synthase (32.4 [15.0-49.8] AU, P < 0.01), and also increased insulin activation of Akt2 (20.6 [3.4-29.0], P = 0.03) and dephosphorylation of glycogen synthase (-41.8 [-82.9 to -0.7], P = 0.05). Insulin sensitivity was reduced in early postmenopausal women. However, postmenopausal women increased peripheral insulin sensitivity, skeletal muscle insulin-stimulated glucose uptake, and skeletal muscle mass to the same extent as premenopausal women after 3 months of high-intensity exercise training.

A review of obesity, insulin resistance, and the role of exercise in breast cancer patients.

PubMed

Ghose, Abhimanyu; Kundu, Ria; Toumeh, Anis; Hornbeck, Catherine; Mohamed, Iman

2015-01-01

Breast cancer, the most common female malignancy in the world, has a strong association with obesity and insulin resistance. The importance of these risk factors goes up significantly in patients already affected by this cancer as they negatively affect the prognosis, recurrence rate, and survival by various mechanisms. The literature on the role of physical activity and aerobic exercise on modifying the above risks is debatable with data both for and against it. In this article, we have reviewed the risks of obesity and insulin resistance in breast cancer patients and the controversy associated with the impact of exercise. Ultimately, we have concluded that a randomized control trial is necessary with an individualized aerobic exercise program for a minimum duration of 20 wk on breast cancer patients, who are undergoing or recently completed chemotherapy, to study its effects on insulin resistance, weight, and clinical outcome.

Illness and treatment perceptions are associated with adherence to medications, diet, and exercise in diabetic patients.

PubMed

Broadbent, Elizabeth; Donkin, Liesje; Stroh, Julia C

2011-02-01

To investigate diabetic patients' perceptions of illness and treatments, and explore relationships to adherence and blood glucose control. Forty-nine type 1 and one hundred and eight type 2 diabetic patients completed questionnaires assessing illness perceptions, treatment beliefs, and adherence to medications, diet, and exercise. Blood glucose control was assessed from blood tests. Patients rated medication more important than diet and exercise, and reported higher adherence to medications. Insulin was perceived as more helpful for diabetes, while antihypertensives and cholesterol medication were perceived more helpful for preventing heart problems. Perceptions were associated with adherence to insulin, cholesterol and antihypertensive medications, exercise, and diet. Blood glucose control in type 1 diabetic patients was associated with insulin adherence and perceived personal control, and in type 2 diabetic patients to being prescribed insulin or antihypertensives, and perceived personal control. Patients hold specific mental models about diabetes treatments, which are associated with adherence.

The Effect of Metformin and Standard Therapy Versus Standard Therapy Alone in Nondiabetic Patients with Insulin Resistance and Nonalcoholic Steatohepatitis (NASH): A Pilot Trial

DTIC Science & Technology

2009-01-01

histology in nondiabetic patients with insulin resistance and NASH. Decrease in BMI through diet and exercise significantly improved HOMA - IR scores, serum...BMI through diet and exercise significantly improved HOMA - IR scores, serum aminotransferases and liver histology. 15. SUBJECT TERMS 16. SECURITY...insulin resistance (or HOMA - IR ) score was calculated using the formula: fasting insulin (mIU/ml) fasting glu- cose (mg/dl)/405 [Matthews et al. 1985

Strength training alters MCT1-protein expression and exercise-induced translocation in erythrocytes of men with non-insulin-dependent type-2 diabetes.

PubMed

Opitz, David; Kreutz, Thorsten; Lenzen, Edward; Dillkofer, Benedict; Wahl, Patrick; Montiel-Garcia, Gracia; Graf, Christine; Bloch, Wilhelm; Brixius, Klara

2014-03-01

We investigated the cellular distribution of lactate transporter (MCT1) and its chaperone CD147 (using immunohistochemistry and fluorescence-activated cell sorting) in the erythrocytes of men with non-insulin-dependent type-2 diabetes (NIDDM, n = 11, 61 ± 8 years of age) under acute exercise (ergometer cycling test, World Health Organisation scheme) performed before and after a 3-month strength training program. Cytosolic MCT1 distribution and membraneous CD147 density did not change after acute exercise (ergometer). After the 3-month strength training, MCT1-density was increased and the reaction of MCT1 (but not that of CD147) towards acute exercise (ergometer) was altered. MCT1 localisation was shifted from the centre to the cellular membrane. This resulted in a decrease in the immunohistochemically measured cytosolic MCT1-density. We conclude that strength training alters the acute exercise reaction of MCT1 but not that of CD147 in erythrocytes in patients with NIDDM. This reaction may contribute to long-term normalisation and stabilisation of the regulation of lactate plasma concentration in NIDDM.

Evaluation of Jump into Action: A Program to Reduce the Risk of Non-Insulin Dependent Diabetes Mellitus in School Children on the Texas-Mexico Border.

ERIC Educational Resources Information Center

Holcomb, J. David; Lira, Juanita; Kingery, Paul M.; Smith, D. W.; Lane, Dorothy; Goodway, Jackie

1998-01-01

Evaluated Jump into Action, a non-insulin dependent diabetes mellitus (NIDDM)-prevention program that encouraged students to eat well and exercise regularly to reduce NIDDM risks. Surveys of predominantly Hispanic fifth graders and their teachers at Texas-Mexico border schools indicated that the program increased NIDDM-prevention knowledge and…

Skeletal Muscle Triglycerides, Diacylglycerols, and Ceramides in Insulin Resistance

PubMed Central

Amati, Francesca; Dubé, John J.; Alvarez-Carnero, Elvis; Edreira, Martin M.; Chomentowski, Peter; Coen, Paul M.; Switzer, Galen E.; Bickel, Perry E.; Stefanovic-Racic, Maja; Toledo, Frederico G.S.; Goodpaster, Bret H.

2011-01-01

OBJECTIVE Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance. PMID:21873552

The association among skeletal muscle phosphocreatine recovery, adiposity, and insulin resistance in children.

PubMed

Wells, Greg D; Banks, Laura; Caterini, Jessica E; Thompson, Sara; Noseworthy, Michael D; Rayner, Tammy; Syme, Catriona; McCrindle, Brian W; Hamilton, Jill

2017-04-01

Obesity is associated with cardiometabolic disturbances, which may have significant implications for musculoskeletal health and exercise tolerance. We sought to determine the association between muscle structure, function, and metabolism in adolescents across the weight spectrum. This cross-sectional case-control study included overweight and obese participants (n = 24) 8-18 years of age with a body mass index (BMI) ≥ 85th percentile for age and gender, and non-obese participants (n = 24) with a BMI < 85 th percentile. Body composition, physical activity, peak aerobic capacity, cardiometabolic blood markers and insulin resistance (measured by the homeostatic model assessment of insulin resistance, HOMA-IR), skeletal muscle mitochondrial oxidative capacity (via 31 Phosphorous-Magnetic Resonance Spectroscopy, 31 P-MRS, to assess phosphocreatine (PCr) recovery after exercise), and extramyocellular and intramyocellular lipid (IMCL) levels (via 1 Hydrogen-MRS) were assessed. Stepwise regression was performed to examine the factors associated with oxidative capacity. bese and overweight patients had similar age, height, and physical activity to non-obese controls, but obese and overweight participants exhibited higher insulin resistance. Obese and overweight participants had longer PCr recovery than non-obese controls following 5x30s of moderate-intensity exercise (51.2 ± 20.1 s vs. 23.9 ± 7.5 s, p = 0.004). In univariate correlation analysis, impaired PCr recovery was associated with a higher BMI z-score (r s  = 0.51, p < 0.001), circulating triglycerides (r s  = 0.41, p = 0.005), and HOMA-IR (r s  = 0.46, p = 0.001). In stepwise multivariate regression analysis, impaired PCr recovery was associated with a higher BMI z-score (β = 0.47, p = 0.002), but not insulin resistance (β = 0.07, p = 0.07) or circulating triglycerides (β = 0.16 p = 0.33). A slower phosphocreatine recovery following aerobic exercise is strongly associated with increasing adiposity. A slower metabolic recovery following aerobic exercise stress suggests that endurance exercise training in obese adolescents may be an optimal strategy to target exercise intolerance in this cohort. © 2016 World Obesity Federation.

Maternal low intensity physical exercise prevents obesity in offspring rats exposed to early overnutrition.

PubMed

Ribeiro, Tatiane Aparecida; Tófolo, Laize Peron; Martins, Isabela Peixoto; Pavanello, Audrei; de Oliveira, Júlio Cezar; Prates, Kelly Valério; Miranda, Rosiane Aparecida; da Silva Franco, Claudinéia Conationi; Gomes, Rodrigo Mello; Francisco, Flávio Andrade; Alves, Vander Silva; de Almeida, Douglas Lopes; Moreira, Veridiana Mota; Palma-Rigo, Kesia; Vieira, Elaine; Fabricio, Gabriel Sergio; da Silva Rodrigues, Marcos Ricardo; Rinaldi, Wilson; Malta, Ananda; de Freitas Mathias, Paulo Cezar

2017-08-09

Low intensity exercise during pregnancy and lactation may create a protective effect against the development of obesity in offspring exposed to overnutrition in early life. To test these hypotheses, pregnant rats were randomly assigned into 2 groups: Sedentary and Exercised, low intensity, on a rodent treadmill at 30% VO 2Max /30-minute/session/3x/week throughout pregnancy and the lactation. Male offspring were raised in small litters (SL, 3 pups/dam) and normal litters (NL, 9 pups/dam) as models of early overnutrition and normal feed, respectively. Exercised mothers showed low mesenteric fat pad stores and fasting glucose and improved glucose-insulin tolerance, VO 2max during lactation and sympathetic activity. Moreover, the breast milk contained elevated levels of insulin. In addition, SL of sedentary mothers presented metabolic dysfunction and glucose and insulin intolerance and were hyperglycemic and hyperinsulinemic in adulthood. SL of exercised mothers showed lower fat tissue accretion and improvements in glucose tolerance, insulin sensitivity, insulinemia and glycemia. The results suggest that maternal exercise during the perinatal period can have a possible reprogramming effect to prevent metabolic dysfunction in adult rat offspring exposed to early overnutrition, which may be associated with the improvement in maternal health caused by exercise.

Effect of Exercise and Calorie Restriction on Tissue Acylcarnitines, Tissue Desaturase Indices, and Fat Accumulation in Diet-Induced Obese Rats

PubMed Central

Gopalan, Venkatesh; Michael, Navin; Ishino, Seigo; Lee, Swee Shean; Yang, Adonsia Yating; Bhanu Prakash, K. N.; Yaligar, Jadegoud; Sadananthan, Suresh Anand; Kaneko, Manami; Zhou, Zhihong; Satomi, Yoshinori; Hirayama, Megumi; Kamiguchi, Hidenori; Zhu, Bin; Horiguchi, Takashi; Nishimoto, Tomoyuki; Velan, S. Sendhil

2016-01-01

Both exercise and calorie restriction interventions have been recommended for inducing weight-loss in obese states. However, there is conflicting evidence on their relative benefits for metabolic health and insulin sensitivity. This study seeks to evaluate the differential effects of the two interventions on fat mobilization, fat metabolism, and insulin sensitivity in diet-induced obese animal models. After 4 months of ad libitum high fat diet feeding, 35 male Fischer F344 rats were grouped (n = 7 per cohort) into sedentary control (CON), exercise once a day (EX1), exercise twice a day (EX2), 15% calorie restriction (CR1) and 30% calorie restriction (CR2) cohorts. Interventions were carried out over a 4-week period. We found elevated hepatic and muscle long chain acylcarnitines with both exercise and calorie restriction, and a positive association between hepatic long chain acylcarnitines and insulin sensitivity in the pooled cohort. Our result suggests that long chain acylcarnitines may not indicate incomplete fat oxidation in weight loss interventions. Calorie restriction was found to be more effective than exercise in reducing body weight. Exercise, on the other hand, was more effective in reducing adipose depots and muscle triglycerides, favorably altering muscle/liver desaturase activity and improving insulin sensitivity. PMID:27197769

Heterotypic endosomal fusion as an initial trigger for insulin-induced glucose transporter 4 (GLUT4) translocation in skeletal muscle.

PubMed

Hatakeyama, Hiroyasu; Kanzaki, Makoto

2017-08-15

Comprehensive imaging analyses of glucose transporter 4 (GLUT4) behaviour in mouse skeletal muscle was conducted. Quantum dot-based single molecule nanometry revealed that GLUT4 molecules in skeletal myofibres are governed by regulatory systems involving 'static retention' and 'stimulus-dependent liberation'. Vital imaging analyses and super-resolution microscopy-based morphometry demonstrated that insulin liberates the GLUT4 molecule from its static state by triggering acute heterotypic endomembrane fusion arising from the very small GLUT4-containing vesicles in skeletal myofibres. Prior exposure to exercise-mimetic stimuli potentiated this insulin-responsive endomembrane fusion event involving GLUT4-containing vesicles, suggesting that this endomembranous regulation process is a potential site related to the effects of exercise. Skeletal muscle is the major systemic glucose disposal site. Both insulin and exercise facilitate translocation of the glucose transporter glucose transporter 4 (GLUT4) via distinct signalling pathways and exercise also enhances insulin sensitivity. However, the trafficking mechanisms controlling GLUT4 mobilization in skeletal muscle remain poorly understood as a resuly of technical limitations. In the present study, which employs various imaging techniques on isolated skeletal myofibres, we show that one of the initial triggers of insulin-induced GLUT4 translocation is heterotypic endomembrane fusion arising from very small static GLUT4-containing vesicles with a subset of transferrin receptor-containing endosomes. Importantly, pretreatment with exercise-mimetic stimuli potentiated the susceptibility to insulin responsiveness, as indicated by these acute endomembranous activities. We also found that AS160 exhibited stripe-like localization close to sarcomeric α-actinin and that insulin induced a reduction of the stripe-like localization accompanying changes in its detergent solubility. The results of the present study thus provide a conceptual framework indicating that GLUT4 protein trafficking via heterotypic fusion is a critical feature of GLUT4 translocation in skeletal muscles and also suggest that the efficacy of the endomembranous fusion process in response to insulin is involved in the benefits of exercise. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

Effects of exercise intensity on plasma concentrations of appetite-regulating hormones: Potential mechanisms.

PubMed

Hazell, Tom J; Islam, Hashim; Townsend, Logan K; Schmale, Matt S; Copeland, Jennifer L

2016-03-01

The physiological control of appetite regulation involves circulating hormones with orexigenic (appetite-stimulating) and anorexigenic (appetite-inhibiting) properties that induce alterations in energy intake via perceptions of hunger and satiety. As the effectiveness of exercise to induce weight loss is a controversial topic, there is considerable interest in the effect of exercise on the appetite-regulating hormones such as acylated ghrelin, peptide YY (PYY), glucagon-like peptide-1 (GLP-1), and pancreatic polypeptide (PP). Research to date suggests short-term appetite regulation following a single exercise session is likely affected by decreases in acylated ghrelin and increases in PYY, GLP-1, and PP. Further, this exercise-induced response may be intensity-dependent. In an effort to guide future research, it is important to consider how exercise alters the circulating concentrations of these appetite-regulating hormones. Potential mechanisms include blood redistribution, sympathetic nervous system activity, gastrointestinal motility, cytokine release, free fatty acid concentrations, lactate production, and changes in plasma glucose and insulin concentrations. This review of relevant research suggests blood redistribution during exercise may be important for suppressing ghrelin, while other mechanisms involving cytokine release, changes in plasma glucose and insulin concentrations, SNS activity, and muscle metabolism likely mediate changes in the anorexigenic signals PYY and GLP-1. Overall, changes in appetite-regulating hormones following acute exercise appear to be intensity-dependent, with increasing intensity leading to a greater suppression of orexigenic signals and greater stimulation of anorexigenic signals. However, there is less research on how exercise-induced responses in appetite-regulating hormones differ between sexes or different age groups. A better understanding of how exercise intensity and workload affect appetite across the sexes and life stages will be a powerful tool in developing more successful strategies for managing weight. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of dietary fats with odd or even numbers of carbon atoms on metabolic response and muscle damage with exercise in Quarter Horse-type horses with type 1 polysaccharide storage myopathy.

PubMed

Borgia, Lisa A; Valberg, Stephanie J; McCue, Molly E; Pagan, Joe D; Roe, Charles R

2010-03-01

To evaluate effects of fats with odd and even numbers of carbon atoms on muscle metabolism in exercising horses with polysaccharide storage myopathy (PSSM). 8 horses with PSSM (6 females and 2 males; mean +/- SD age, 6.3 +/- 3.9 years). Isocaloric diets (grain, triheptanoin, corn oil, and high-fat, low-starch [HFLS] feed) were fed for 3 weeks each; horses performed daily treadmill exercise. Grain was fed to establish an exercise target, and HFLS feed was fed as a negative control diet. Daily plasma samples were obtained. For each diet, a 15-minute exercise test was performed, and gluteus medius muscle specimens and blood samples were obtained before and after exercise. Feeding triheptanoin, compared with the corn oil diet, resulted in exercise intolerance; higher plasma creatine kinase (CK) activity and concentrations of C3:0- and C7:0-acylcarnitine and insulin; and lower concentrations of nonesterified fatty acids (NEFA) and C16:0-, C18:1-, and C18:2-acylcarnitine, without changes in concentrations of plasma glucose or resting muscle substrates and metabolites. Feeding grain induced higher CK activity and insulin concentrations and lower NEFA concentrations than did corn oil or HFLS feed. Feeding grain induced higher glucose concentrations than did triheptanoin and corn oil. In muscle, feeding grain resulted in lower glucose-6-phosphate, higher citrate, and higher postexercise lactate concentrations than did the other diets. Triheptanoin had detrimental effects, reflecting decreased availability of NEFA, increased insulin stimulation of glycogen synthesis, and potential inhibition of lipid oxidation. Long-chain fats are the best dietetic for PSSM.

Energy balance, insulin-resistance biomarkers and breast cancer risk

PubMed Central

Fair, Alecia Malin; Dai, Qi; Shu, Xiao-Ou; Matthews, Charles E.; Yu, Herbert; Jin, Fan; Gao, Yu-Tang; Zheng, Wei

2007-01-01

Background American women are five times more likely to be at risk for breast cancer than women from Asian countries. Epidemiologic studies have linked energy balance to an increased risk of breast cancer, yet few studies have investigated potential mediators of this association with Chinese women. We examined the above association by blood levels of insulin-like growth factors, binding proteins, and C-peptide in the Shanghai Breast Cancer Study (SBCS), a case-control study conducted among 1459 breast cancer cases and 1556 healthy Chinese women from 1996 and 1998. Methods In-person surveys were used to collect data on energy intake, anthropometric measures, exercise/sport activity, and occupational activity. The present analyses consisted of 397 cases and 397 controls whose blood samples were measured for levels of insulin-like growth factors ( IGFs), insulin growth-factor binding protein 3, (IGFBP-3) C-peptide and the relationship with physical activity status, total energy intake, and body fat distribution. Results Body mass index [BMI] and waist-to-hip ratio [WHR] were significantly positively correlated with IGFBP-3 and C-peptide. Adult exercise/sport activity was significantly negatively correlated with insulin-like growth factor 1(IGF-I). C-peptide levels increased with increasing quartiles of WHR (p for trend <0.01). Additional analyses were performed to evaluate whether the association of energy balance measures with breast cancer risk changed after adjustment for IGFs, IGFBP-3 and C-peptide biomarkers. The associations attenuated, but none of them changed substantially. Conclusions Insulin resistance biomarkers may partially explain the association between positive energy balance and breast cancer risk, but future studies are needed to identify the underlying complex biological mechanisms of action for breast cancer prevention. PMID:17646056

Exercise effects on fitness, lipids, glucose tolerance and insulin levels in young adults.

PubMed

Israel, R G; Davidson, P C; Albrink, M J; Krall, J M

1981-07-01

The effect of 3 different physical training programs on cardiorespiratory (cr) fitness, fasting plasma lipids, glucose and insulin levels, and scapular skinfold thickness was assessed in 64 healthy college men. Training sessions were held 4 times a week for 5 weeks. The cr fitness improved significantly and skinfold thickness decreased following the aerobic, the pulse workout (interval training), and the anaerobic training compared to the control group. Skinfold thickness, plasma insulin, and triglyceride concentrations were significantly intercorrelated before and after training. The exercise programs had no significant effect on plasma cholesterol, triglycerides, phospholipids, glucose tolerance, or insulin levels. Change in adipose mass was thus dissociated from change in plasma insulin and triglyceride concentrations. It was concluded that in young men plasma triglycerides, the lipid component mostly readily reduced by exercise, were too low to be reduced further by a physical training program.

Muscle glycogen storage postexercise: effect of mode of carbohydrate administration.

PubMed

Reed, M J; Brozinick, J T; Lee, M C; Ivy, J L

1989-02-01

The primary purpose of this study was to determine whether gastric emptying limits the rate of muscle glycogen storage during the initial 4 h after exercise when a carbohydrate supplement is provided. A secondary purpose was to determine whether liquid (L) and solid (S) carbohydrate (CHO) feedings result in different rates of muscle glycogen storage after exercise. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. After each exercise bout they received 3 g CHO/kg body wt in L (50% glucose polymer) or S (rice/banana cake) form or by intravenous infusion (I; 20% sterile glucose). The L and S supplements were divided into two equal doses and administered immediately after and 120 min after exercise, whereas the I supplement was administered continuously during the first 235 min of the 240-min recovery period. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately after and 120 and 240 min after exercise. Blood glucose and insulin declined during exercise and increased significantly above preexercise levels during recovery in all treatments. The increase in blood glucose during the I treatment, however, was three times greater than during the L or S treatments. The average insulin response of the L treatment (61.7 +/- 4.9 microU/ml) was significantly greater than that of the S treatment (47.5 +/- 4.2 microU/ml) but not that of the I (55.3 +/- 4.5 microU/ml) treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Resistance exercise improves hippocampus-dependent memory

PubMed Central

Cassilhas, R.C.; Lee, K.S.; Venâncio, D.P.; Oliveira, M.G.M.; Tufik, S.; de Mello, M.T.

2012-01-01

It has been demonstrated that resistance exercise improves cognitive functions in humans. Thus, an animal model that mimics this phenomenon can be an important tool for studying the underlying neurophysiological mechanisms. Here, we tested if an animal model for resistance exercise was able to improve the performance in a hippocampus-dependent memory task. In addition, we also evaluated the level of insulin-like growth factor 1/insulin growth factor receptor (IGF-1/IGF-1R), which plays pleiotropic roles in the nervous system. Adult male Wistar rats were divided into three groups (N = 10 for each group): control, SHAM, and resistance exercise (RES). The RES group was submitted to 8 weeks of progressive resistance exercise in a vertical ladder apparatus, while the SHAM group was left in the same apparatus without exercising. Analysis of a cross-sectional area of the flexor digitorum longus muscle indicated that this training period was sufficient to cause muscle fiber hypertrophy. In a step-through passive avoidance task (PA), the RES group presented a longer latency than the other groups on the test day. We also observed an increase of 43 and 94% for systemic and hippocampal IGF-1 concentration, respectively, in the RES group compared to the others. A positive correlation was established between PA performance and systemic IGF-1 (r = 0.46, P < 0.05). Taken together, our data indicate that resistance exercise improves the hippocampus-dependent memory task with a concomitant increase of IGF-1 level in the rat model. This model can be further explored to better understand the effects of resistance exercise on brain functions. PMID:22930413

Effect of exercise on the pseudodiabetes of bed rest

NASA Technical Reports Server (NTRS)

Greenleaf, J. E.

1982-01-01

The effect of intensive isotonic exercise and isometric exercise (with its low metabolic rate) during bed rest on plasma insulin and glucose tolerance test was investigated. The subjects were seven healthy men, 19 to 22 years in age, 166 to 188 cm in height, and 62.40 to 103.80 kg in weight; maximal oxygen uptakes ranged from 3.36 to 4.38 liters/min. It appears that bed-rest-induced glucose intolerance is diminished with increasing energy expenditure during both bed rest and recovery.

Exercise training with weight loss and either a high- or low-glycemic index diet reduces metabolic syndrome severity in older adults.

PubMed

Malin, Steven K; Niemi, Nicole; Solomon, Thomas P J; Haus, Jacob M; Kelly, Karen R; Filion, Julianne; Rocco, Michael; Kashyap, Sangeeta R; Barkoukis, Hope; Kirwan, John P

2012-01-01

The efficacy of combining carbohydrate quality with exercise on metabolic syndrome risk is unclear. Thus, we determined the effects of exercise training with a low (LoGIx)- or high (HiGIx)-glycemic index diet on the severity of the metabolic syndrome (Z-score). Twenty-one adults (66.2±1.1 years; BMI=35.3±0.9 kg/m2) with the metabolic syndrome were randomized to 12 weeks of exercise (60 min/day for 5 days/week at about 85% HRmax) and provided a LoGIx (n=11) or HiGIx (n=10) diet. Z-scores were determined from: blood pressure, triglycerides (TGs), high-density lipoproteins (HDLs), fasting plasma glucose (FPG), and waist circumference (WC) before and after the intervention. Body composition, aerobic fitness, insulin resistance, and nonesterfied fatty acid (NEFA) suppression were also assessed. LoGIx and HiGIx diets decreased body mass and insulin resistance and increased aerobic fitness comparably (p<0.05). LoGIx and HiGIx diets decreased the Z-score similarly as each intervention decreased blood pressure, TGs, FPG and WC (p<0.05). The HiGIx diet tended to suppress NEFA during insulin stimulation compared with the LoGIx diet (p=0.06). Our findings highlight that exercise with weight loss reduces the severity of the metabolic syndrome whether individuals were randomized to a HiGIx or a LoGIx diet.

The Online Big Blue Test for Promoting Exercise: Health, Self-Efficacy, and Social Support.

PubMed

Gómez-Zúñiga, Beni; Pousada, Modesta; Hernandez, Manny M; Colberg, Sheri; Gabarrón, Elia; Armayones, Manuel

2015-10-01

Recent articles have documented the influence of self-efficacy and social support on exercising. Simultaneously, insulin use is also related to the perception of self-efficacy and social support in patients with diabetes. We combine these two ideas through the Big Blue Test experience in a social networking site and propose to analyze whether a change in blood sugar levels after completion of the Big Blue Test and insulin use are related to the perception of self-efficacy and social support in patients with diabetes. To undergo the Big Blue Test, 3,926 participants voluntarily joined the Diabetes Hands Foundation. Responses were analyzed using descriptive analysis. The participants who reduced their blood glucose after exercise the least were those with lower self-efficacy and also with lower perceived social support. There seems to have been no relationship between changes in blood sugar level and the explicit intention of doing exercise in the future. Insulin-dependent participants demonstrated a lower perception of self-efficacy and social support than non-insulin-dependent participants. Change in blood glucose level or being insulin-dependent or not do not explain completely a health behavior such as exercise. Hence, self-efficacy and social support have an impact on behavioral change such as exercise to become a habit in people with diabetes, and this experience through a social networking site is an important tool for this behavioral change. For exercise to become a habit in people with diabetes, it is necessary to consider not only the crucial physiological variables, but also those psychological variables that clearly have an impact on behavioral change.

The insulin-like growth factor system is modulated by exercise in breast cancer survivors: a systematic review and meta-analysis.

PubMed

Meneses-Echávez, José Francisco; Jiménez, Emilio González; Río-Valle, Jacqueline Schmidt; Correa-Bautista, Jorge Enrique; Izquierdo, Mikel; Ramírez-Vélez, Robinson

2016-08-25

Insulin-like growth factors (IGF´s) play a crucial role in controlling cancer cell proliferation, differentiation and apoptosis. Exercise has been postulated as an effective intervention in improving cancer-related outcomes and survival, although its effects on IGF´s are not well understood. This meta-analysis aimed to determine the effects of exercise in modulating IGF´s system in breast cancer survivors. Databases of PuMed, EMBASE, Cochrane Central Register of Controlled Trials, EMBASE, ClinicalTrials.gov, SPORTDiscus, LILACS and Scopus were systematically searched up to November 2014. Effect estimates were calculated through a random-effects model of meta-analysis according to the DerSimonian and Laird method. Heterogeneity was evaluated with the I (2) test. Risk of bias and methodological quality were evaluated using the PEDro score. Five randomized controlled trials (n = 235) were included. Most women were post-menopausal. High-quality and low risk of bias were found (mean PEDro score = 6.2 ± 1). Exercise resulted in significant improvements on IGF-I, IGF-II, IGFBP-I, IGFBP-3, Insulin and Insulin resistance (P < 0.05). Non-significant differences were found for Glucose. Aerobic exercise improved IGF-I, IGFBP-3 and Insulin. No evidence of publication bias was detected by Egger´s test (p = 0.12). Exercise improved IGF´s in breast cancer survivors. These findings provide novel insight regarding the molecular effects of exercise on tumoral microenvironment, apoptosis and survival in breast cancer survivors.

Long-term AICAR administration and exercise prevents diabetes in ZDF rats.

PubMed

Pold, Rasmus; Jensen, Lasse S; Jessen, Niels; Buhl, Esben S; Schmitz, Ole; Flyvbjerg, Allan; Fujii, Nobuharu; Goodyear, Laurie J; Gotfredsen, Carsten F; Brand, Christian L; Lund, Sten

2005-04-01

Lifestyle interventions including exercise programs are cornerstones in the prevention of obesity-related diabetes. The AMP-activated protein kinase (AMPK) has been proposed to be responsible for many of the beneficial effects of exercise on glucose and lipid metabolism. The effects of long-term exercise training or 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside (AICAR) treatment, both known AMPK activators, on the development of diabetes in male Zucker diabetic fatty (ZDF) rats were examined. Five-week-old, pre-diabetic ZDF rats underwent daily treadmill running or AICAR treatment over an 8-week period and were compared with an untreated group. In contrast to the untreated, both the exercised and AICAR-treated rats did not develop hyperglycemia during the intervention period. Whole-body insulin sensitivity, as assessed by a hyperinsulinemic-euglycemic clamp at the end of the intervention period, was markedly increased in the exercised and AICAR-treated animals compared with the untreated ZDF rats (P < 0.01). In addition, pancreatic beta-cell morphology was almost normal in the exercised and AICAR-treated animals, indicating that chronic AMPK activation in vivo might preserve beta-cell function. Our results suggest that activation of AMPK may represent a therapeutic approach to improve insulin action and prevent a decrease in beta-cell function associated with type 2 diabetes.

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes.

PubMed

Kahleova, H; Matoulek, M; Malinska, H; Oliyarnik, O; Kazdova, L; Neskudla, T; Skoch, A; Hajek, M; Hill, M; Kahle, M; Pelikanova, T

2011-05-01

The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [-6.2 kg (95% CI -6.6 to -5.3) vs. -3.2 kg (95% CI -3.7 to -2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5-39) vs. 20% (95% CI 14-25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet. © 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes

PubMed Central

Kahleova, H; Matoulek, M; Malinska, H; Oliyarnik, O; Kazdova, L; Neskudla, T; Skoch, A; Hajek, M; Hill, M; Kahle, M; Pelikanova, T

2011-01-01

Aims The aim of this study was to compare the effects of calorie-restricted vegetarian and conventional diabetic diets alone and in combination with exercise on insulin resistance, visceral fat and oxidative stress markers in subjects with Type 2 diabetes. Methods A 24-week, randomized, open, parallel design was used. Seventy-four patients with Type 2 diabetes were randomly assigned to either the experimental group (n = 37), which received a vegetarian diet, or the control group (n = 37), which received a conventional diabetic diet. Both diets were isocaloric, calorie restricted (-500 kcal/day). All meals during the study were provided. The second 12 weeks of the diet were combined with aerobic exercise. Participants were examined at baseline, 12 weeks and 24 weeks. Primary outcomes were: insulin sensitivity measured by hyperinsulinaemic isoglycaemic clamp; volume of visceral and subcutaneous fat measured by magnetic resonance imaging; and oxidative stress measured by thiobarbituric acid reactive substances. Analyses were by intention to treat. Results Forty-three per cent of participants in the experimental group and 5% of participants in the control group reduced diabetes medication (P < 0.001). Body weight decreased more in the experimental group than in the control group [–6.2 kg (95% CI –6.6 to –5.3) vs. –3.2 kg (95% CI –3.7 to –2.5); interaction group × time P = 0.001]. An increase in insulin sensitivity was significantly greater in the experimental group than in the control group [30% (95% CI 24.5–39) vs. 20% (95% CI 14–25), P = 0.04]. A reduction in both visceral and subcutaneous fat was greater in the experimental group than in the control group (P = 0.007 and P = 0.02, respectively). Plasma adiponectin increased (P = 0.02) and leptin decreased (P = 0.02) in the experimental group, with no change in the control group. Vitamin C, superoxide dismutase and reduced glutathione increased in the experimental group (P = 0.002, P < 0.001 and P = 0.02, respectively). Differences between groups were greater after the addition of exercise training. Changes in insulin sensitivity and enzymatic oxidative stress markers correlated with changes in visceral fat. Conclusions A calorie-restricted vegetarian diet had greater capacity to improve insulin sensitivity compared with a conventional diabetic diet over 24 weeks. The greater loss of visceral fat and improvements in plasma concentrations of adipokines and oxidative stress markers with this diet may be responsible for the reduction of insulin resistance. The addition of exercise training further augmented the improved outcomes with the vegetarian diet. PMID:21480966

Elevated Muscle TLR4 Expression and Metabolic Endotoxemia in Human Aging

PubMed Central

Ghosh, Sangeeta; Lertwattanarak, Raweewan; Garduño, Jose de Jesus; Galeana, Joaquin Joya; Li, Jinqi; Zamarripa, Frank; Lancaster, Jack L.; Mohan, Sumathy; Hussey, Sophie

2015-01-01

Aging is associated with alterations in glucose metabolism and sarcopenia that jointly contribute to a higher risk of developing type 2 diabetes. Because aging is considered as a state of low-grade inflammation, in this study we examined whether older, healthy (lean, community-dwelling) participants have altered signaling flux through toll-like receptor 4 (TLR4), a key mediator of innate and adaptive immune responses. We also examined whether a 4-month aerobic exercise program would have an anti-inflammatory effect by reducing TLR4 expression and signaling. At baseline, muscle TLR4, nuclear factor κB p50 and nuclear factor κB p65 protein content, and c-Jun N-terminal kinase phosphorylation were significantly elevated in older versus young participants. The plasma concentration of the TLR4 agonist lipopolysaccharide and its binding protein also were significantly elevated in older participants, indicative of metabolic endotoxemia, which is a recently described phenomenon of increased plasma endotoxin level in metabolic disease. These alterations in older participants were accompanied by decreased insulin sensitivity, quadriceps muscle volume, and muscle strength. The exercise training program increased insulin sensitivity, without affecting quadriceps muscle volume or strength. Muscle TLR4, nuclear factor κB, and c-Jun N-terminal kinase, and plasma lipopolysaccharide and lipopolysaccharide binding protein were not changed by exercise. In conclusion, insulin resistance and sarcopenia of aging are associated with increased TLR4 expression/signaling, which may be secondary to metabolic endotoxemia. PMID:24846769

Low energy availability in exercising men is associated with reduced leptin and insulin but not with changes in other metabolic hormones.

PubMed

Koehler, Karsten; Hoerner, Neele R; Gibbs, Jenna C; Zinner, Christoph; Braun, Hans; De Souza, Mary Jane; Schaenzer, Wilhelm

2016-10-01

Low energy availability, defined as low caloric intake relative to exercise energy expenditure, has been linked to endocrine alterations frequently observed in chronically energy-deficient exercising women. Our goal was to determine the endocrine effects of low energy availability in exercising men. Six exercising men (VO2peak: 49.3 ± 2.4 ml · kg(-1) · min(-1)) underwent two conditions of low energy availability (15 kcal · kg(-1) fat-free mass [FFM] · day(-1)) and two energy-balanced conditions (40 kcal · kg(-1) FFM · day(-1)) in randomised order. During one low energy availability and one balanced condition, participants exercised to expend 15 kcal · kg(-1) FFM · day(-1); no exercise was conducted during the other two conditions. Metabolic hormones were assessed before and after each 4-day period. Following both low energy availability conditions, leptin (-53% to -56%) and insulin (-34% to -38%) were reduced (P < 0.05). Reductions in leptin and insulin were independent of whether low energy availability was attained with or without exercise (P > 0.80). Low energy availability did not significantly impact ghrelin, triiodothyronine, testosterone and IGF-1 (all P > 0.05). The observed reductions in leptin and insulin were in the same magnitude as changes previously reported in sedentary women. Further research is needed to understand why other metabolic hormones are more robust against low energy availability in exercising men than those in sedentary and exercising women.

Concentric and eccentric exercise, glycemic responses to a postexercise meal, and inflammation in women with high versus low waist circumference.

PubMed

Miles, Mary P; Horrigan, Laura C; Jay, Sara E; Brown, Karen M; Porter, Jay W; Steward, Andrea N

2016-12-01

Carbohydrate ingestion and level of concentric versus eccentric muscle activity may alter exercise-induced health benefits for individuals who have high waist circumference as a metabolic risk factor. The purpose of this study was to determine whether metabolic and inflammation responses to an exercise recovery meal differ between women with lower (Lo-WC, <80 cm) compared with higher (Hi-WC) waist circumference when the exercise is primarily concentric (uphill walking; UPHILL) versus primarily eccentric (downhill walking; DOWNHILL). Recreationally active women (age, 18-39 years; body mass index, 19-35.4 m·kg -2 ; Lo-WC, n = 13; Hi-WC, n = 10) completed UPHILL, DOWNHILL, and resting (CONTROL) conditions followed 30 min later by a mixed meal tolerance test (MMTT) with carbohydrates to protein ratio of 4:1, and blood glucose, insulin, and inflammation markers were compared across conditions. Compared with Lo-WC, the Hi-WC group had higher (p < 0.05) (i) insulin during the MMTT in CONTROL (mean ± SE; 48.5 ± 8.2 vs 22.9 ± 2.8 pmol·L -1 ), (ii) baseline (0.7 ± 0.4 vs 2.0 ± 1.7 pg·mL -1 ) interleukin-6 (IL-6), and (iii) IL-6 responses 8 h after UPHILL and CONTROL. Both groups had (i) increases in IL-6 at 0 h after UPHILL and at 8 h after DOWNHILL, and (ii) lower glycemic responses in UPHILL. Women with Hi-WC had higher IL-6 at rest and delayed increases in IL-6 after a high-carbohydrate meal in all conditions. This is consistent with an inflammation response to the meal and or uphill walking exercise. However, both concentrically and eccentrically biased exercises offered benefits to insulin responses to a high carbohydrate meal for Hi-WC.

Influence of muscle mass and work on post-exercise glucose and insulin responses in young untrained subjects.

PubMed

Brambrink, J K; Fluckey, J D; Hickey, M S; Craig, B W

1997-11-01

The 18 h post-exercise glucose and insulin responses of six male and six female subjects were measured following one- or two-leg cycling to determine the influence of muscle mass involvement and work. Each subject performed three exercise trials on a Cybex Met 100 cycle ergometer: (1) two-leg exercise for 30 min at 60% of the two-leg VO2 max; (2) one-leg exercise for 30 min at 60% of one-leg VO2 max; and (3) one-leg exercise (one-leg TW) at 60% of the one-leg VO2 max with the total work performed equal to that of the two-leg trial (duration approximately 50 min). These trials were preceded by 2 days of inactivity and followed by an 18 h post-exercise 75 g oral glucose tolerance test (OGTT). The glucose response during the baseline OGTT demonstrated that the subjects had normal glucose tolerance with fasting serum glucose levels of 5.1 mM, and 1 and 2 h serum glucose less than 7.8 mM, respectively. The 18 h post-exercise glucose responses were significantly lower following the two-leg trial (P < 0.05), with the area under the curve values being 129.9 mM h-1 less than the resting control level. The 18 h post-exercise insulin AUC response of the two-leg trial was significantly lower than either of the one-leg responses (14.7 pM below the one-leg and 5.0 pM below the one-leg TW) but was not associated with a change in C-peptide. The 18 h post-exercise insulin levels of the one-leg and one-leg TW trials were above or near the resting control values, but were not accompanied by a significant change in C-peptide. In conclusion, the data presented here show that the amount of muscle tissue utilized during an exercise bout can influence both the glucose and insulin responses, whereas the amount of total work employed during the exercise had no effect on either of these parameters.

Effects of High-Intensity Interval Exercise versus Moderate Continuous Exercise on Glucose Homeostasis and Hormone Response in Patients with Type 1 Diabetes Mellitus Using Novel Ultra-Long-Acting Insulin

PubMed Central

Mueller, Alexander; Groeschl, Werner; Pieber, Thomas R.; Obermayer-Pietsch, Barbara; Koehler, Gerd; Hofmann, Peter

2015-01-01

Introduction We investigated blood glucose (BG) and hormone response to aerobic high-intensity interval exercise (HIIE) and moderate continuous exercise (CON) matched for mean load and duration in type 1 diabetes mellitus (T1DM). Material and Methods Seven trained male subjects with T1DM performed a maximal incremental exercise test and HIIE and CON at 3 different mean intensities below (A) and above (B) the first lactate turn point and below the second lactate turn point (C) on a cycle ergometer. Subjects were adjusted to ultra-long-acting insulin Degludec (Tresiba/ Novo Nordisk, Denmark). Before exercise, standardized meals were administered, and short-acting insulin dose was reduced by 25% (A), 50% (B), and 75% (C) dependent on mean exercise intensity. During exercise, BG, adrenaline, noradrenaline, dopamine, cortisol, glucagon, and insulin-like growth factor-1, blood lactate, heart rate, and gas exchange variables were measured. For 24 h after exercise, interstitial glucose was measured by continuous glucose monitoring system. Results BG decrease during HIIE was significantly smaller for B (p = 0.024) and tended to be smaller for A and C compared to CON. No differences were found for post-exercise interstitial glucose, acute hormone response, and carbohydrate utilization between HIIE and CON for A, B, and C. In HIIE, blood lactate for A (p = 0.006) and B (p = 0.004) and respiratory exchange ratio for A (p = 0.003) and B (p = 0.003) were significantly higher compared to CON but not for C. Conclusion Hypoglycemia did not occur during or after HIIE and CON when using ultra-long-acting insulin and applying our methodological approach for exercise prescription. HIIE led to a smaller BG decrease compared to CON, although both exercises modes were matched for mean load and duration, even despite markedly higher peak workloads applied in HIIE. Therefore, HIIE and CON could be safely performed in T1DM. Trial Registration ClinicalTrials.gov NCT02075567 http://www.clinicaltrials.gov/ct2/show/NCT02075567 PMID:26317981

Physical exercise enhances protein kinase C delta activity and insulin receptor tyrosine phosphorylation in diabetes-prone psammomys obesus.

PubMed

Heled, Yuval; Shapiro, Yair; Shani, Yoav; Moran, Dani S; Langzam, Leah; Braiman, Liora; Sampson, Sanford R; Meyerovitch, Joseph

2003-08-01

We recently reported that physical exercise prevents the progression of type 2 diabetes mellitus in Psammomys obesus, an animal model of nutritionally induced type 2 diabetes mellitus. In the present study we characterized the effect of physical exercise on protein kinase C delta (PKC delta) activity, as a mediator of the insulin-signaling cascade in vivo. Three groups of Psammomys obesus were exposed to a 4-week protocol: high-energy diet (HE/C), high-energy diet and exercise (HE/EX), or low-energy diet (LE/C). None of the animals in the HE/EX group became diabetic, whereas all the animals in the HE/C group became diabetic. After overnight fast, intraperitoneal (IP) insulin (1U) caused a greater reduction in blood glucose levels in the HE/EX and LE/C groups compared to the HE/C group. Tyrosine phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3 kinase (PI3 kinase) was significantly higher in the HE/EX and LE/C groups compared with the HE/C group. Finally, IR-associated PKC delta was higher in the HE/EX and LE/C groups compared to the HE/C group. Coprecipitation of PKC delta with IR was higher in the HE/EX and LE/C groups compared to the HE/C group. Thus, we suggest that 4 weeks of physical exercise results in improved insulin-signaling response in Psammomys obesus accompanied by a direct connection between PKC delta and IR. We conclude that this mechanism may be involved in the preventive effect of exercise on type 2 diabetes mellitus in Psammomys obesus.

Short term exercise induces PGC-1α, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.

PubMed

Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy

2013-01-01

PGC-1α, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1α is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1α on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1α without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNFα) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1α such as NRF-1 and several respiratory genes. Such mismatch between PGC-1α and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1α expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1α mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age.

Tocotrienols and Whey Protein Isolates Substantially Increase Exercise Endurance Capacity in Diet -Induced Obese Male Sprague-Dawley Rats

PubMed Central

Aguila, Jay; McConell, Glenn K.; McAinch, Andrew J.; Mathai, Michael L.

2016-01-01

Background and Aims Obesity and impairments in metabolic health are associated with reductions in exercise capacity. Both whey protein isolates (WPIs) and vitamin E tocotrienols (TCTs) exert favorable effects on obesity-related metabolic parameters. This research sought to determine whether these supplements improved exercise capacity and increased glucose tolerance in diet-induced obese rats. Methods Six week old male rats (n = 35) weighing 187 ± 32g were allocated to either: Control (n = 9), TCT (n = 9), WPI (n = 8) or TCT + WPI (n = 9) and placed on a high-fat diet (40% of energy from fat) for 10 weeks. Animals received 50mg/kg body weight and 8% of total energy intake per day of TCTs and/or WPIs respectively. Food intake, body composition, glucose tolerance, insulin sensitivity, exercise capacity, skeletal muscle glycogen content and oxidative enzyme activity were determined. Results Both TCT and WPI groups ran >50% longer (2271 ± 185m and 2195 ± 265m respectively) than the Control group (1428 ± 139m) during the run to exhaustion test (P<0.05), TCT + WPI did not further improve exercise endurance (2068 ± 104m). WPIs increased the maximum in vitro activity of beta-hydroxyacyl-CoA in the soleus muscle (P<0.05 vs. Control) but not in the plantaris. Citrate synthase activity was not different between groups. Neither supplement had any effect on weight gain, adiposity, glucose tolerance or insulin sensitivity. Conclusion Ten weeks of both TCTs and WPIs increased exercise endurance by 50% in sedentary, diet-induced obese rats. These positive effects of TCTs and WPIs were independent of body weight, adiposity or glucose tolerance. PMID:27058737

The impact of supervised weight loss and intentional weight regain on sex hormone binding globulin and testosterone in premenopausal women.

PubMed

Aubuchon, Mira; Liu, Ying; Petroski, Gregory F; Thomas, Tom R; Polotsky, Alex J

2016-08-01

What is the impact of intentional weight loss and regain on serum androgens in women? We conducted an ancillary analysis of prospectively collected samples from a randomized controlled trial. The trial involved supervised 10% weight loss (8.5 kg on average) with diet and exercise over 4-6 months followed by supervised intentional regain of 50% of the lost weight (4.6 kg on average) over 4-6 months. Participants were randomized prior to the partial weight regain component to either continuation or cessation of endurance exercise. Analytic sample included 30 obese premenopausal women (mean age of 40 ± 5.9 years, mean baseline body mass index (BMI) of 32.9 ± 4.2 kg/m(2)) with metabolic syndrome. We evaluated sex hormone binding globulin (SHBG), total testosterone (T), free androgen index (FAI), and high molecular weight adiponectin (HMWAdp). Insulin, homeostasis model assessment (HOMA), and quantitative insulin sensitivity check index (QUICKI), and visceral adipose tissue (VAT) measured in the original trial were reanalyzed for the current analytic sample. Insulin, HOMA, and QUICKI improved with weight loss and were maintained despite weight regain. Log-transformed SHBG significantly increased from baseline to weight loss, and then significantly decreased with weight regain. LogFAI and logVAT decreased similarly and increased with weight loss followed by weight regain. No changes were found in logT and LogHMWAdp. There was no significant difference in any tested parameters by exercise between the groups. SHBG showed prominent sensitivity to body mass fluctuations, as reduction with controlled intentional weight regain showed an inverse relationship to VAT and occurred despite stable HMWAdp and sustained improvements with insulin resistance. FAI showed opposite changes to SHBG, while T did not change significantly with weight. Continued exercise during weight regain did not appear to impact these findings.

Functional high-intensity training improves pancreatic β-cell function in adults with type 2 diabetes.

PubMed

Nieuwoudt, Stephan; Fealy, Ciarán E; Foucher, Julie A; Scelsi, Amanda R; Malin, Steven K; Pagadala, Mangesh; Rocco, Michael; Burguera, Bartolome; Kirwan, John P

2017-09-01

Type 2 diabetes (T2D) is characterized by reductions in β-cell function and insulin secretion on the background of elevated insulin resistance. Aerobic exercise has been shown to improve β-cell function, despite a subset of T2D patients displaying "exercise resistance." Further investigations into the effectiveness of alternate forms of exercise on β-cell function in the T2D patient population are needed. We examined the effect of a novel, 6-wk CrossFit functional high-intensity training (F-HIT) intervention on β-cell function in 12 sedentary adults with clinically diagnosed T2D (54 ± 2 yr, 166 ± 16 mg/dl fasting glucose). Supervised training was completed 3 days/wk, comprising functional movements performed at a high intensity in a variety of 10- to 20-min sessions. All subjects completed an oral glucose tolerance test and anthropometric measures at baseline and following the intervention. The mean disposition index, a validated measure of β-cell function, was significantly increased (PRE: 8.4 ± 3.1, POST: 11.5 ± 3.5, P = 0.02) after the intervention. Insulin processing inefficiency in the β-cell, expressed as the fasting proinsulin-to-insulin ratio, was also reduced (PRE: 2.40 ± 0.37, POST: 1.78 ± 0.30, P = 0.04). Increased β-cell function during the early-phase response to glucose correlated significantly with reductions in abdominal body fat ( R 2 = 0.56, P = 0.005) and fasting plasma alkaline phosphatase ( R 2 = 0.55, P = 0.006). Mean total body-fat percentage decreased significantly (Δ: -1.17 0.30%, P = 0.003), whereas lean body mass was preserved (Δ: +0.05 ± 0.68 kg, P = 0.94). We conclude that F-HIT is an effective exercise strategy for improving β-cell function in adults with T2D. Copyright © 2017 the American Physiological Society.

Enzymatic capacities of skeletal muscle - Effects of different types of training

NASA Technical Reports Server (NTRS)

Booth, F. W.; Hugman, G. R.

1981-01-01

Long-term adaptation mechanisms to maintain homeostasis at increased levels of exertion such as those caused by regular exercise are described. Mitochondrial changes have been found to be a result of endurance exercises, while mitochondrial responses to other types of exercise are small. Further discussion is devoted to long-term changes in glucose transport, hexokinase, phosphofructokinase, pyruvate kinase, and the increased sensitivity of an endurance trained muscle to insulin. Less lactate has been found to be produced by the skeletal muscles at the same work rate after adaptation to endurance exercise training, and the capacity for the flux of the two-carbon acetyl chain through the citric acid cycle increases in skeletal muscles in response to endurance training. Finally, endurance training is noted to result in glycogen sparing and an increase in the capacity to utilize fatty acids.

Impact of exercise training without caloric restriction on inflammation, insulin resistance and visceral fat mass in obese adolescents.

PubMed

Mendelson, M; Michallet, A-S; Monneret, D; Perrin, C; Estève, F; Lombard, P R; Faure, P; Lévy, P; Favre-Juvin, A; Pépin, J-L; Wuyam, B; Flore, P

2015-08-01

Exercise training has been shown to improve cardiometabolic health in obese adolescents. Evaluate the impact of a 12-week exercise-training programme (without caloric restriction) on obese adolescents' cardiometabolic and vascular risk profiles. We measured systemic markers of oxidation, inflammation, metabolic variables and endothelial function in 20 obese adolescents (OB) (age: 14.5 ± 1.5 years; body mass index: 34.0 ± 4.7 kg m(-2) ) and 20 age- and gender-matched normal-weight adolescents (NW). Body composition was assessed by magnetic resonance imagery. Peak aerobic capacity and maximal fat oxidation were evaluated during specific incremental exercise tests. OB participated in a 12-week exercise-training programme. OB presented lower peak aerobic capacity (24.2 ± 5.9 vs. 39.8 ± 8.3 mL kg(-1)  min(-1) , P < 0.05) and maximal fat oxidation compared with NW (P < 0.05). OB displayed greater F2t-Isoprostanes (20.5 ± 6.7 vs. 13.4 ± 4.2 ng mmol(-1) creatinine), Interleukin-1 receptor antagonist (IL-1Ra) (1794.8 ± 532.2 vs. 835.1 ± 1027.4 pg mL(-1) ), Tumor Necrosis Factor-α (TNF-α) (2.1 ± 1.2 vs. 1.5 ± 1.0 pg mL(-1) ), Soluble Tumor Necrosis Factor-α Type II Receptor (sTNFαRII), leptin, insulin, homeostasis model assessment of insulin resistance, version 2 (HOMA2-IR), high-sensitive C-reactive protein, triglycerides and lower adiponectin and high-density lipoprotein cholesterol (all P < 0.05). After exercise training, despite lack of weight loss, VO2peak (mL.kg(-1) .min(-1) ) and maximal fat oxidation increased (P < 0.05). IL-1Ra and IFN-gamma-inducible protein 10 (IP-10) decreased (P < 0.05). Insulin and HOMA2-IR decreased (14.8 ± 1.5 vs. 10.2 ± 4.2 μUI mL(-1) and 1.9 ± 0.8 vs. 1.3 ± 0.6, respectively, P < 0.05). Change in visceral fat mass was inversely associated with change in maximal fat oxidation (r = -0.54; P = 0.024). The subgroup of participants that lost visceral fat mass showed greater improvements in triglycerides, insulin resistance and maximal fat oxidation. Our data confirms the role of exercise training on improving the inflammatory profile and insulin resistance of OB in the absence of weight loss. However, those who lost a greater amount of visceral fat mass showed greater benefits in terms of insulin profile, triglycerides and maximal fat oxidation. © 2014 The Authors. Pediatric Obesity © 2014 World Obesity.

Treadmill exercise alleviates diabetic cardiomyopathy by suppressing plasminogen activator inhibitor expression and enhancing eNOS in streptozotocin-induced male diabetic rats.

PubMed

Chengji, Wang; Xianjin, Fan

2018-04-01

To investigate the biological mechanism of the effect of different intensity exercises on diabetic cardiomyopathy. 87 raise specific pathogen SPF healthy 6-week-old male Sprague-Dawley rats, fed 6 weeks with high-fat diet for rats were used, and a diabetic model was established by intraperitoneal injection of streptozotocin - randomly selected 43 rats were divided into Diabetic control group (DCG, n  = 10), Diabetic exercise group 1 (DEG1, n  = 11), Diabetic exercise group 2 (DEG2, n  = 11) and Diabetic exercise group 3 (DEG3, n  = 11). The rats in DEG1 were forced to run on a motorized treadmill, the exercise load consisted of running at a speed of 10 m/min, the exercise load of the rats in DEG2 were running at a speed of 15 m/min, the exercise load of the rats in DEG3 were running at a speed of 20 m/min, for one hour once a day for 6 weeks. After 6 weeks of exercise intervention, glucose metabolism-related indexes in rats such as blood glucose (FBG), glycosylated serum protein (GSP) and insulin (FINS); cardiac fibrinolytic system parameters such as PAI-1 (plasminogen activator inhibitor 1), Von Willebrand factor (vWF), protein kinase C (PKC) and diacylglycerol (DAG); and serum level of NO, eNOS and T-NOS were measured. Compared with DCG, fasting blood glucose and GSP were decreased, while insulin sensitivity index and insulin level were increased in all rats of the three exercise groups. FBG decrease was statistically significant ( P  < 0.01), only GSP decrease was statistically significant ( P  < 0.05) in DEG1 and DEG2, PAI-1 in three exercise groups were significantly reduced ( P  < 0.05), plasma vWF levels in the three exercise groups were significantly lower than those in the DCG group ( P  < 0.01); PKC levels decreased dramatically in the three exercise groups and DAG levels decrease slightly ( P  < 0.05), but with no significant difference. Compared with DCG, the serum level of NO was significantly higher ( P  < 0.05), and eNOS level was significantly elevated ( P  < 0.05). T-NOS elevation was statistically significant in DEG1 ( P  < 0.05). Low- and moderate-intensity exercise can better control blood glucose level in diabetic rats; myocardial PAI-1 in DEG1, DEG2 and DEG3 rats decreased significantly ( P  < 0.05), serum NO increased ( P  < 0.05) and eNOS increased ( P  < 0.05) significantly. Therefore, it is inferred that exercise improves the biological mechanism of diabetic cardiomyopathy by affecting the levels of PAI-1 and eNOS, and there is a dependence on intensity. © 2018 The authors.

The influence of short-term endurance training on the insulin blood level, binding, and degradation of 125I-insulin by erythrocyte receptors in patients after myocardial infarction.

PubMed

Dylewicz, P; Przywarska, I; Szcześniak, L; Rychlewski, T; Bieńkowska, S; Długiewicz, I; Wilk, M

1999-01-01

This study was directed toward establishing whether and to what extent, short-term endurance training influences the insulin blood level, and the binding and degradation of 125I-insulin by erythrocyte receptors in patients undergoing rehabilitation after myocardial infarction. The study was conducted in a group of 60 patients who had had myocardial infarction within the past 1.5 to 3 months and who did not have arterial hypertension and diabetes mellitus. All the patients took a symptom-limited cardiopulmonary exercise test. Before and after the test, venous blood was collected to determine lactic acid and insulin blood levels as well as the binding and degradation of 125I-insulin. The study group was randomized into two subgroups. One subgroup entered into a 3-week in-patient rehabilitation course. The control group was discharged from the hospital and was given no recommendations for physical exercise. The same investigation was repeated 3 weeks later. In the patients (50%) with hyperinsulinemia (insulin resistance index, > 10 microIU/mL), which was detected during the first investigation, insulin blood level decreased from 23.9 +/- 4.4 to 15.0 +/- 1.9 microIU/mL (P < 0.05) after rehabilitation, whereas insulin binding increased from 0.67 +/- 0.05 to 0.85 +/- 0.08 pg 125I/10(11) erythrocytes (P < 0.05). In the control group, which included normal subjects and those with hyperinsulinemia, the results obtained during the first and second investigations showed no statistically significant changes when compared. The results suggest that a 3-week endurance training period during rehabilitation after myocardial infarction reduces insulin resistance in patients with hyperinsulinemia.

The effect of different volumes of high-intensity interval training on proinsulin in participants with the metabolic syndrome: a randomised trial.

PubMed

Ramos, Joyce S; Dalleck, Lance C; Borrani, Fabio; Mallard, Alistair R; Clark, Bronwyn; Keating, Shelley E; Fassett, Robert G; Coombes, Jeff S

2016-11-01

The continuous demand for insulin in the face of insulin resistance, coupled with the glucolipotoxic environment associated with the metabolic syndrome (MetS), adversely affects the quality of insulin produced and secreted by the pancreatic beta cells. This is depicted by increased circulating intact proinsulin concentration, which is associated with increased MetS severity and risk of cardiovascular (CV) mortality. High-intensity interval training (HIIT) has been shown to reduce insulin resistance and other CV disease risk factors to a greater degree than moderate-intensity continuous training (MICT). We therefore aimed to investigate the impact of MICT and different volumes of HIIT on circulating intact proinsulin concentration. This was a substudy of the 'Exercise in prevention of Metabolic Syndrome' (EX-MET) multicentre trial. Sixty-six individuals with MetS were randomised to 16 weeks of: (1) MICT (n = 21, 30 min at 60-70% peak heart rate [HRpeak], five times/week); (2) 4HIIT (n = 22, 4 × 4 min bouts at 85-95% HRpeak, interspersed with 3 min of active recovery at 50-70% HRpeak, three times/week); or (3) 1HIIT (n = 23, 1 × 4 min bout at 85-95% HRpeak, three times/week). A subanalysis investigated the differential impact of these training programmes on intact proinsulin concentration in MetS individuals with type 2 diabetes (MICT, n = 6; 4HIIT, n = 9; 1HIIT, n = 12) and without type 2 diabetes (MICT, n = 15; 4HIIT, n = 13; 1HIIT, n = 11). Intact proinsulin, insulin and C-peptide concentrations were measured in duplicate via ELISA, following a 12 h fast, before and after the exercise programme. Fasting intact proinsulin concentration was also expressed relative to insulin and C-peptide concentrations. Following the exercise training, there were no significant (p > 0.05) changes in fasting intact proinsulin concentration indices in all participants (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: MICT 19% decrease, 6% increase, 4% increase; 4HIIT 19% decrease, 8% decrease, 11% decrease; 1HIIT 34% increase, 49% increase, 36% increase). In participants who did not have type 2 diabetes, only 4HIIT significantly (p < 0.05) reduced fasting intact proinsulin concentration indices from pre to post intervention (pre- vs post-programme proinsulin, proinsulin:insulin, proinsulin:C-peptide: 4HIIT 32% decrease, 26% decrease, 32% decrease, p < 0.05; 1HIIT, 14% increase, 32% increase, 16% increase, p > 0.05; MICT 27% decrease, 17% decrease, 11% decrease), with a group × time interaction effect, indicating a greater reduction in intact proinsulin indices following 4HIIT compared with MICT and 1HIIT. There were no significant (p > 0.05) changes in intact proinsulin concentration indices in participants with type 2 diabetes. Higher-volume HIIT (4HIIT) improved insulin quality in MetS participants without type 2 diabetes. ClinicalTrials.gov NCT01676870 FUNDING: The study was funded by the Norwegian University of Science and Technology and from an unrestricted research grant from the Coca-Cola company. Funding for the collection of physical activity data was derived from a 'UQ New Staff Start Up' grant awarded to B. Clark.

Exercise-induced changes in insulin action are associated with ACE gene polymorphisms in older adults.

PubMed

Dengel, Donald R; Brown, Michael D; Ferrell, Robert E; Reynolds, Thomas H; Supiano, Mark A

2002-10-29

We evaluated the association between insulin resistance and the angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) gene polymorphism in a group of older hypertensive subjects (63 +/- 1 yr, n = 35) before and after a 6-mo aerobic exercise program (AEX). Insulin sensitivity index (S(I)), assessed by the frequently sampled intravenous glucose tolerance test, was significantly (P = 0.0001) increased following AEX. In addition, there was a significant (P = 0.001) interaction between AEX and ACE genotype. S(I) increased significantly (P < 0.05) more in those with the II (2.5 +/- 0.8 microU x 10(-4) x min(-1) x ml(-1)) ACE genotype compared with both the DD and ID (0.7 +/- 0.1 and 0.7 +/- 0.2 microU x 10(-4) x min(-1) x ml(-1), respectively) ACE genotypes. Similarly, there was a significant (P = 0.036) decrease in the acute insulin response to glucose (AIR(G)) and a significant (P = 0.05) interaction between AEX and ACE genotype. AIR(G) decreased significantly (P < 0.05) more in those with the II (-17.6 +/- 5.6 mU/ml) ACE genotype compared with both the DD and ID (-1.4 +/- 6.2 and -3.6 +/- 2.5 mU/ml) ACE genotypes. In conclusion, we demonstrated that those older hypertensives with the ACE II genotype have the greatest improvement in insulin action following AEX.

High intensity interval training is associated with greater impact on physical fitness, insulin sensitivity and muscle mitochondrial content in males with overweight/obesity, as opposed to continuous endurance training: a randomized controlled trial.

PubMed

De Strijcker, Dorien; Lapauw, Bruno; Ouwens, D Margriet; Van de Velde, Dominique; Hansen, Dominique; Petrovic, Mirko; Cuvelier, Claude; Tonoli, Cajsa; Calders, Patrick

2018-06-01

To evaluate the effect of high intensity training (HIT) on physical fitness, basal respiratory exchange ratio (bRER), insulin sensitivity and muscle histology in overweight/obese men compared to continuous aerobic training (CAT). 16 male participants with overweight/obesity (age: 42-57 years, body mass index: 28-36 kg/m2) were randomized to HIT (n=8) or CAT (n=8) for 10 weeks, twice a week. HIT was composed of 10 minutes high intensity, 10 minutes continuous aerobic, 10 minutes high intensity exercises. CAT was composed of three times 10 minutes continuous exercising. Changes in anthropometry, physical and metabolic fitness were evaluated. Muscle histology (mitochondria and lipid content) was evaluated by transmission electron microscopy (TEM). HIT showed a significant increase for peak VO2 (P=0.01), for insulin sensitivity (AUC glucose (P<0,001), AUC insulin (P<0,001), OGTT composite score (P=0.007)) and a significant decrease of bRER (P<0.001) compared to CAT. Muscle mitochondrial content was significantly increased after HIT at the subsarcolemmal (P=0.004 number and P=0.001 surface) as well as the intermyofibrillar site (P<0.001 number and P=0.001 surface). High intensity training elicits stronger beneficial effects on physical fitness, basal RER, insulin sensitivity, and muscle mitochondrial content, as compared to continuous aerobic training.

Metabolic effects of low cortisol during exercise in humans.

PubMed

Del Corral, P; Howley, E T; Hartsell, M; Ashraf, M; Younger, M S

1998-03-01

This study examined the physiological effect of reduced plasma cortisol (C) during prolonged exercise in humans. The effects of normal C (NC) were compared with metyrapone-induced low C (LC) on plasma substrate availability and the respiratory exchange ratio during 2 h of exercise at approximately 60% peak O2 consumption in nine subjects. The C responses were compared with preexercise (Pre) levels and with a rest day (Con). At rest, C was attenuated by approximately 70% for LC compared with NC. At rest, plasma glucose, lactate, glycerol, beta-hydroxybutyrate, alanine, branched-chain amino acids, insulin, glucagon, growth hormone, epinephrine, and norepinephrine were similar under LC and NC (P > 0.05). During exercise under NC, plasma C increased compared with Pre, whereas it remained unchanged during LC. During NC, plasma C was elevated at 90 min (compared with Con) and at 120 min (compared with Con and Pre). During exercise, plasma glucose decreased to the same extent and lactate was similar under both conditions, whereas plasma glycerol, beta-hydroxybutyrate, alanine, and branched-chain amino acids were higher (P < 0.01) under NC. Plasma insulin declined (P = 0.01) to a greater extent under LC, whereas growth hormone, epinephrine, and norepinephrine tended to be higher (0.05

The Effects of Physical Exercise on Fatty Liver Disease

PubMed Central

van der Windt, Dirk J.; Sud, Vikas; Zhang, Hongji; Tsung, Allan; Huang, Hai

2018-01-01

The increasing prevalence of obesity has made nonalcoholic fatty liver disease (NAFLD) the most common chronic liver disease. As a consequence, NAFLD and especially its inflammatory form nonalcoholic steatohepatitis (NASH) are the fastest increasing etiology of end-stage liver disease and hepatocellular carcinoma. Physical inactivity is related to the severity of fatty liver disease irrespective of body weight, supporting the hypothesis that increasing physical activity through exercise can improve fatty liver disease. This review summarizes the evidence for the effects of physical exercise on NAFLD and NASH. Several clinical trials have shown that both aerobic and resistance exercise reduce the hepatic fat content. From clinical and basic scientific studies, it is evident that exercise affects fatty liver disease through various pathways. Improved peripheral insulin resistance reduces the excess delivery of free fatty acids and glucose for free fatty acid synthesis to the liver. In the liver, exercise increases fatty acid oxidation, decreases fatty acid synthesis, and prevents mitochondrial and hepatocellular damage through a reduction of the release of damage-associated molecular patterns. In conclusion, physical exercise is a proven therapeutic strategy to improve fatty liver disease. PMID:29212576

Effects of an acute bout of resistance exercise on fiber-type specific to GLUT4 and IGF-1R expression.

PubMed

Gallagher, Philip M; Touchberry, Chad D; Teson, Kelli; McCabe, Everlee; Tehel, Michelle; Wacker, Michael J

2013-05-01

The effects of resistance exercise on fiber-type-specific expression of insulin-like growth factor I receptor (IGF-1R) and glucose transporter 4 (GLUT4) was determined in 6 healthy males. The expression of both genes increased in Type I fibers (p < 0.05), but only GLUT4 increased (p < 0.05) in Type II fibers. These data demonstrates that an acute bout of resistance exercise can up-regulate mechanisms of glucose uptake in slow and fast-twitch fibers, but the IGF signaling axis may not be as effective in fast-twitch fibers.

Exercise Training and Calorie Restriction Influence the Metabolic Parameters in Ovariectomized Female Rats

PubMed Central

Pósa, Anikó; Kupai, Krisztina; Szalai, Zita; Veszelka, Médea; Török, Szilvia; Varga, Csaba

2015-01-01

The estrogen deficiency after menopause leads to overweight or obesity, and physical exercise is one of the important modulators of this body weight gain. Female Wistar rats underwent ovariectomy surgery (OVX) or sham operation (SO). OVX and SO groups were randomized into new groups based on the voluntary physical activity (with or without running) and the type of diet for 12 weeks. Rats were fed standard chow (CTRL), high triglyceride diet (HT), or restricted diet (CR). The metabolic syndrome was assessed by measuring the body weight gain, the glucose sensitivity, and the levels of insulin, triglyceride, leptin, and aspartate aminotransferase transaminase (AST) and alanine aminotransferase (ALT). The exercise training combined with the CR resulted in improvements in the glucose tolerance and the insulin sensitivity. Plasma TG, AST, and ALT levels were significantly higher in OVX rats fed with HT but these high values were suppressed by exercise and CR. Compared to SO animals, estrogen deprivation with HT caused a significant increase in leptin level. Our data provide evidence that CR combined with voluntary physical exercise can be a very effective strategy to prevent the development of a metabolic syndrome induced by high calorie diet. PMID:25874022

Oxidative stress and metabolism at rest and during exercise in persons with Down syndrome.

PubMed

Flore, Patrice; Bricout, Véronique-A; van Biesen, Debbie; Guinot, Michel; Laporte, François; Pépin, Jean-Louis; Eberhard, Yves; Favre-Juvin, Anne; Wuyam, Bernard; van de Vliet, Peter; Faure, Patrice

2008-02-01

Down syndrome (DS) is a risk factor for metabolic syndrome and cardiovascular disease. The greater oxidative stress described in DS can increase this risk owing to its potential deleterious effects on insulin sensitivity. We hypothesized that metabolic syndrome or its markers, at rest and during exercise, are more pronounced in young adults with DS. The study design is that of a controlled study. Thirteen physically active young adults with DS, after overnight polysomnography, plasma-lipid profile, and insulin-resistance [Homeostasis Model Assessment Insulin Resistance (HOMA-IR)] assessments, underwent a submaximal progressive treadmill exercise (10 min at 30 and 50%, and 20 min at 75% of V O2max), allowing for maximal fat-oxidation rate and blood-oxidative stress determinations. They were compared with 15 healthy control participants (C). V O2max of DS participants was lower than that of C (60.8+/-2.4 versus 44.4+/-3.3 ml/kg/min; P<0.001) but was close to the predicted value (95+/-6%). In DS participants, as expected, oxidative stress was greater than in C (+15%; P<0.001) at rest and all through the exercise protocol. Although a greater fat mass (DS: 19.9+/-1.3%; C: 13.5+/-0.9%; P<0.001), and a lower insulin sensitivity (HOMA-IR in DS: 1.09+/-0.16; in C: 0.64+/-0.13; P<0.05) was observed for DS participants, a metabolic syndrome could not be shown. Maximal fat-oxidation rate was lower in DS participants (394.2+/-69.9 versus 486.1+/-134.8 mg/min in C; P<0.01), but it was in the normal range. Despite greater oxidative stress and lower insulin sensitivity, the DS group involved in our study did not display clear metabolic abnormalities. The young age and lifestyle of this group might, partially, have accounted for this apparently healthy metabolic status.

Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults

PubMed Central

Solomon, Thomas P.J.; Sistrun, Sakita N.; Krishnan, Raj K.; Del Aguila, Luis F.; Marchetti, Christine M.; O'Carroll, Susan M.; O'Leary, Valerie B.; Kirwan, John P.

2013-01-01

Older, obese, and sedentary individuals are at high risk of developing diabetes and cardiovascular disease. Exercise training improves metabolic anomalies associated with such diseases, but the effects of caloric restriction in addition to exercise in such a high risk group are not known. Changes in body composition and metabolism during a lifestyle intervention were investigated in twenty three older, obese men and women (aged 66 ± 1 years, BMI 33.2 ± 1.4 kg.m−2) with impaired glucose tolerance. All volunteers undertook twelve weeks of aerobic exercise training (5 days per week for 60 min @ 75% VO2max) with either normal caloric intake (eucaloric group, 1901 ± 277 kcal.day−1, n = 12) or a reduced-calorie diet (hypocaloric group, 1307 ± 70 kcal.day−1, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic fitness (VO2max), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P < 0.05). Improvements in body composition, leptin and basal fat oxidation were greater in the hypocaloric group. Following the intervention there was a correlation between the increase in basal fat oxidation and the decrease in IMCL (r = −0.53, P = 0.04). In addition, basal fat oxidation was associated with circulating leptin after (r = 0.65, P = 0.0007), but not before the intervention (r = 0.05, P = 0.84). In conclusion, these data show that exercise training improves resting substrate oxidation and creates a metabolic milieu that appears to promote lipid utilization in skeletal muscle, thus facilitating a reversal of insulin resistance. We also demonstrate that leptin sensitivity is improved, but that such a trend may rely on reducing caloric intake in addition to exercise training. PMID:18323464

Swim training restores glucagon-like peptide-1 insulinotropic action in pancreatic islets from monosodium glutamate-obese rats.

PubMed

Svidnicki, P V; de Carvalho Leite, N; Venturelli, A C; Camargo, R L; Vicari, M R; de Almeida, M C; Artoni, R F; Nogaroto, V; Grassiolli, S

2013-09-01

Glucagon-like peptide-1 (GLP-1) is an important modulator of insulin secretion by endocrine pancreas. In the present study, we investigated the effect of swim training on GLP-1 insulinotropic action in pancreatic islets from monosodium glutamate (MSG)-obese rats. Obesity was induced by neonatal MSG administration. MSG-obese and control (CON) exercised rats swam for 30 min (3 times week(-1) ) for 10 weeks. Pancreatic islets were isolated by colagenase technique and incubated with low (5.6 mM) or high (16.7 mM) glucose concentrations in the presence or absence of GLP-1 (10 nM). In addition, GLP-1 gene expression in ileum was quantified in fasting and glucose conditions. Exercise reduced obesity and hyperinsulinemia in MSG-obese rats. Swim training also inhibited glucose-induced insulin secretion in islets from both groups. Islets from MSG-obese rats maintained GLP-1 insulinotropic response in low glucose concentration. In contrast, in the presence of high glucose concentration, GLP-1 insulinotropic action was absent in islets from MSG-obese rats. Islets from MSG-exercised rats showed reduced GLP-1 insulinotropic action in the presence of low glucose. However, in high glucose concentration swim training restored GLP-1 insulinotropic response in islets from MSG-obese rats. In all groups, glucose intake increased GLP-1 immunoreactivity and gene expression in ileum cells in relation to fasting conditions. Swim training reduced these parameters only in ileum cells from CON-exercised rats. Neither MSG treatment nor exercise affected GLP-1 expression in the ileum. Exercise avoids insulin hypersecretion restoring GLP-1's insulinotropic action in pancreatic islets from MSG-obese rats. © 2013 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

Modified lingguizhugan decoction incorporated with dietary restriction and exercise ameliorates hyperglycemia, hyperlipidemia and hypertension in a rat model of the metabolic syndrome.

PubMed

Yao, Limei; Wei, Jingjing; Shi, Si; Guo, Kunbin; Wang, Xiangyu; Wang, Qi; Chen, Dingsheng; Li, Weirong

2017-02-28

Modified Lingguizhugan Decoction (MLD) came from famous Chinese medicine Linggui Zhugan Decoction. The MLD is used for the treatment of metabolic syndrome in the clinical setting. Our study focuses on the comprehensive treatment of MLD incorporated with dietary restriction and exercise in a rat model of the metabolic syndrome (MS). Rats were divided into five groups: control group (Cont), high-fat diet group (HFD), high-fat diet incorporated with dietary restriction group (HFD-DR), exercise incorporated with dietary restriction group (HFD-DR-Ex) and MLD incorporated with dietary restriction and exercise group (HFD-DR-Ex-MLD). Treatments were conducted for 1 week after feeding high-fat diet for 12 weeks. The effects of treatments on high fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance in rats of MS were examined. In addition, the tumor necrosis factor-α (TNF-α), leptin and protein kinase B (PKB) in rats serum and liver were also examined by enzyme-linked immunosorbent assay (ELISA). After a week's intervention by dietary restriction, dietary restriction incorporated with exercise or MLD, compared with HFD rats, the relative weight of liver and fat, levels of triglyceride, total cholesterol, low-density lipoprotein, free fatty acid, aspartate aminotransferase, glutamic-pyruvic transaminase and alkaline phosphatase, insulin, were significantly decreased (p < 0.05 or 0.01). This treatment also inhibited abnormal increases of TNF-α, leptin and PKB in serum and liver. MLD incorporated with dietary restriction and exercise treatment exhibit effects in alleviating high-fat diet-induced obesity, hyperglycemia, hyperlipidemia, hypertension, hepatic injury and insulin resistance, which are possibly due to the down-regulation of TNF-α, leptin and PKB.

High, but not low, exercise volume shifts the balance of renin-angiotensin system toward ACE2/Mas receptor axis in skeletal muscle in obese rats.

PubMed

Frantz, Eliete Dalla Corte; Giori, Isabele Gomes; Machado, Marcus Vinícius; Magliano, D'Angelo Carlo; Freitas, Fernanda Marques; Andrade, Mariana Sodré Boêta; Vieira, Aline Bomfim; Nóbrega, Antonio Claudio Lucas; Tibiriçá, Eduardo

2017-10-01

Metabolic syndrome is a cluster of metabolic risk factors that is linked to central obesity, elevated blood pressure, insulin resistance (IR), and dyslipidemia, where the renin-angiotensin system (RAS) may provide a link among them. This study aimed to evaluate volume exercise effects comparing low vs. high volume of chronic aerobic exercise on RAS axes in skeletal muscle in a diet-induced obesity (DIO) rat model. For this, male Wistar-Kyoto rats were fed a standard chow (SC) diet or a high-fat (HF) diet for 32 wk. Animals receiving the HF diet were randomly divided into low exercise volume (LEV, 150 min/wk) and high exercise volume (HEV, 300 min/wk) at the 20th week. After 12 wk of aerobic treadmill training, the body mass and composition, blood pressure, glucose and lipid metabolism, RAS axes, insulin signaling, and inflammatory pathway were performed. HEV slowed the body mass gain, reduced intra-abdominal fat pad and leptin levels, improved total and peripheral body composition and inflammatory cytokine, reduced angiotensin II type 1 receptor expression, and increased Mas receptor protein expression compared with the HF animals. Sedentary groups (SC and HF) presented lower time to exhaustion and maximal velocity compared with the LEV and HEV groups. Both exercise training groups showed reduced resting systolic blood pressure and heart rate, improved glucose tolerance, IR, insulin signaling, and lipid profile. We conclude that the HEV, but not LEV, shifted the balance of RAS toward the ACE2/Mas receptor axis in skeletal muscle, presenting protective effects against the DIO model. Copyright © 2017 the American Physiological Society.

Type 1 Diabetes and Sports Participation: Strategies for Training and Competing Safely.

ERIC Educational Resources Information Center

Draznin, Martin B.

2000-01-01

Athletes with type 1 diabetes require frequent blood glucose checks throughout the day and intensive diabetes management to balance insulin, carbohydrate intake, and the effects of exercise. Effective care begins with a targeted preparticipation examination. Decreasing insulin dosage may be necessary for heavier exercise programs. Analysis of…

Modification of insulin sensitivity and glycemic control by activity and exercise.

PubMed

Roberts, Christian K; Little, Jonathan P; Thyfault, John P

2013-10-01

Type 2 diabetes has progressed into a major contributor to preventable death, and developing optimal therapeutic strategies to prevent future type 2 diabetes and its primary clinical manifestation of cardiovascular disease is a major public health challenge. This article will provide a brief overview of the role of activity and exercise in modulating insulin sensitivity and will outline the effect of physical activity, high-intensity interval training, and resistance training on insulin sensitivity and glycemic control.

Effects of performing morning versus afternoon exercise on glycemic control and hypoglycemia frequency in type 1 diabetes patients on sensor-augmented insulin pump therapy.

PubMed

Gomez, Ana Maria; Gomez, Claudia; Aschner, Pablo; Veloza, Angelica; Muñoz, Oscar; Rubio, Claudia; Vallejo, Santiago

2015-05-01

Although physical exercise (PE) is recommended for individuals with type 1 diabetes (DM1), participation in exercise is challenging because it increases the risk of severe hypoglycemia and the available therapeutic options to prevent it frequently result in hyperglycemia. There is no clear recommendation about the best timing for exercise. The aim of this study was to compare the risk of hypoglycemia after morning or afternoon exercise sessions up to 36 hours postworkout. This randomized crossover study enrolled subjects with DM1, older than 18 years of age, on sensor-augmented insulin pump (SAP) therapy. Participants underwent 2 moderate-intensity exercise sessions; 1 in the morning and 1 in the afternoon, separated by a 7 to 14 day wash-out period. Continuous glucose monitoring (CGM) data were collected 24 hours before, during and 36 hours after each session. Thirty-five subjects (mean age 30.31 ± 12.66 years) participated in the study. The rate of hypoglycemia was significantly lower following morning versus afternoon exercise sessions (5.6 vs 10.7 events per patient, incidence rate ratio, 0.52; 95% CI, 0.43-0.63; P < .0001). Most hypoglycemic events occurred 15-24 hours after the session. On days following morning exercise sessions, there were 20% more CGM readings in near-euglycemic range (70-200 mg/dL) than on days prior to morning exercise (P = .003). Morning exercise confers a lower risk of late-onset hypoglycemia than afternoon exercise and improves metabolic control on the subsequent day. © 2015 Diabetes Technology Society.

Hormonal control of hepatic glycogen metabolism in food-deprived, continuously swimming coho salmon Oncorhynchus kisutch

USGS Publications Warehouse

Vijayan, M.M.; Maule, A.G.; Schreck, C.B.; Moon, T.W.

1993-01-01

The plasma cortisol concentration and liver cytosolic glucocorticoid receptor activities of continuously swimming, food-deprived coho salmon (Oncorhynchus kisutch) did not differ from those of resting, fed fish. Plasma glucose concentration was significantly higher in the exercising, starved fish, but there were no significant differences in either hepatic glycogen concentration or hepatic activities of glycogen phosphorylase, glycogen synthase, pyruvate kinase, or lactate dehydrogenase between the two groups. Total glucose production by hepatocytes did not differ significantly between the two groups; glycogen breakdown accounted for all the glucose produced in the resting, fed fish whereas it explained only 59% of the glucose production in the exercised animals. Epinephrine and glucagon stimulation of glucose production by hepatocytes was decreased in the exercised fish without significantly affecting hepatocyte glycogen breakdown in either group. Insulin prevented glycogen breakdown and enhanced glycogen deposition in exercised fish. The results indicate that food-deprived, continuously swimming coho salmon conserve glycogen by decreasing the responsiveness of hepatocytes to catabolic hormones and by increasing the responsiveness to insulin (anabolic hormone).

Exercise-induced circulating extracellular vesicles protect against cardiac ischemia-reperfusion injury.

PubMed

Bei, Yihua; Xu, Tianzhao; Lv, Dongchao; Yu, Pujiao; Xu, Jiahong; Che, Lin; Das, Avash; Tigges, John; Toxavidis, Vassilios; Ghiran, Ionita; Shah, Ravi; Li, Yongqin; Zhang, Yuhui; Das, Saumya; Xiao, Junjie

2017-07-01

Extracellular vesicles (EVs) serve an important function as mediators of intercellular communication. Exercise is protective for the heart, although the signaling mechanisms that mediate this cardioprotection have not been fully elucidated. Here using nano-flow cytometry, we found a rapid increase in plasma EVs in human subjects undergoing exercise stress testing. We subsequently identified that serum EVs were increased by ~1.85-fold in mice after 3-week swimming. Intramyocardial injection of equivalent quantities of EVs from exercised mice and non-exercised controls provided similar protective effects against acute ischemia/reperfusion (I/R) injury in mice. However, injection of exercise-induced EVs in a quantity equivalent to the increase seen with exercise (1.85 swim group) significantly enhanced the protective effect. Similarly, treatment with exercise-induced increased EVs provided additional anti-apoptotic effect in H 2 O 2 -treated H9C2 cardiomyocytes mediated by the activation of ERK1/2 and HSP27 signaling. Finally, by treating H9C2 cells with insulin-like growth factor-1 to mimic exercise stimulus in vitro, we found an increased release of EVs from cardiomyocytes associated with ALIX and RAB35 activation. Collectively, our results show that exercise-induced increase in circulating EVs enhances the protective effects of endogenous EVs against cardiac I/R injury. Exercise-derived EVs might serve as a potent therapy for myocardial injury in the future.

High-Intensity Interval Training and Isocaloric Moderate-Intensity Continuous Training Result in Similar Improvements in Body Composition and Fitness in Obese Individuals.

PubMed

Martins, Catia; Kazakova, Irina; Ludviksen, Marit; Mehus, Ingar; Wisloff, Ulrik; Kulseng, Bard; Morgan, Linda; King, Neil

2016-06-01

This study aimed to determine the effects of 12 weeks of isocaloric programs of high-intensity intermittent training (HIIT) or moderate-intensity continuous training (MICT) or a short-duration HIIT (1/2HIIT) inducing only half the energy deficit on a cycle ergometer, on body weight and composition, cardiovascular fitness, resting metabolism rate (RMR), respiratory exchange ratio (RER), nonexercise physical activity (PA) levels and fasting and postprandial insulin response in sedentary obese individuals. Forty-six sedentary obese individuals (30 women), with a mean BMI of 33.3 ± 2.9 kg/m2 and a mean age of 34.4 ± 8.8 years were randomly assigned to one of the three training groups: HIIT (n = 16), MICT (n = 14) or 1/2HIIT (n = 16) and exercise was performed 3 times/week for 12 weeks. Overall, there was a significant reduction in body weight, waist (p < .001) and hip (p < .01) circumference,, trunk and leg fat mass (FM; p < .01) and an increase in trunk and leg fat free mass (FFM; p < .01) and cardiovascular fitness (VO2max in ml/kg/min; p < .001) with exercise. However, no significant differences were observed between groups. There was no significant change in RMR, RER, nonexercise PA levels, fasting insulin or insulin sensitivity with exercise or between groups. There was a tendency for a reduction in AUC insulin with exercise (p = .069), but no differences between groups. These results indicate that isocaloric training protocols of HIIT or MICT (or 1/2HIIT inducing only half the energy deficit) exert similar metabolic and cardiovascular improvements in sedentary obese individuals.

Exercise counteracts fatty liver disease in rats fed on fructose-rich diet

PubMed Central

2010-01-01

Background This study aimed to analyze the effects of exercise at the aerobic/anaerobic transition on the markers of non-alcoholic fatty liver disease (NAFLD), insulin sensitivity and the blood chemistry of rats kept on a fructose-rich diet. Methods We separated 48 Wistar rats into two groups according to diet: a control group (balanced diet AIN-93 G) and a fructose-rich diet group (60% fructose). The animals were tested for maximal lactate-steady state (MLSS) in order to identify the aerobic/anaerobic metabolic transition during swimming exercises at 28 and 90 days of age. One third of the animals of each group were submitted to swimming training at an intensity equivalent to the individual MLSS for 1 hours/day, 5 days/week from 28 to 120 days (early protocol). Another third were submitted to the training from 90 to 120 days (late protocol), and the others remained sedentary. The main assays performed included an insulin tolerance test (ITT) and tests of serum alanine aminotransferase [ALT] and aspartate aminotransferase [AST] activities, serum triglyceride concentrations [TG] and liver total lipid concentrations. Results The fructose-fed rats showed decreased insulin sensitivity, and the late-exercise training protocol counteracted this alteration. There was no difference between the groups in levels of serum ALT, whereas AST and liver lipids increased in the fructose-fed sedentary group when compared with the other groups. Serum triglycerides concentrations were higher in the fructose-fed trained groups when compared with the corresponding control group. Conclusions The late-training protocol was effective in restoring insulin sensitivity to acceptable standards. Considering the markers here evaluated, both training protocols were successful in preventing the emergence of non-alcoholic fatty liver status disease. PMID:20946638

The Effects of Physical Exercise and Cognitive Training on Memory and Neurotrophic Factors.

PubMed

Heisz, Jennifer J; Clark, Ilana B; Bonin, Katija; Paolucci, Emily M; Michalski, Bernadeta; Becker, Suzanna; Fahnestock, Margaret

2017-11-01

This study examined the combined effect of physical exercise and cognitive training on memory and neurotrophic factors in healthy, young adults. Ninety-five participants completed 6 weeks of exercise training, combined exercise and cognitive training, or no training (control). Both the exercise and combined training groups improved performance on a high-interference memory task, whereas the control group did not. In contrast, neither training group improved on general recognition performance, suggesting that exercise training selectively increases high-interference memory that may be linked to hippocampal function. Individuals who experienced greater fitness improvements from the exercise training (i.e., high responders to exercise) also had greater increases in the serum neurotrophic factors brain-derived neurotrophic factor and insulin-like growth factor-1. These high responders to exercise also had better high-interference memory performance as a result of the combined exercise and cognitive training compared with exercise alone, suggesting that potential synergistic effects might depend on the availability of neurotrophic factors. These findings are especially important, as memory benefits accrued from a relatively short intervention in high-functioning young adults.

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

PubMed

Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

Managing insulin therapy during exercise in type 1 diabetes mellitus.

PubMed

Toni, Sonia; Reali, Maria Francesca; Barni, Federica; Lenzi, Lorenzo; Festini, Filippo

2006-01-01

Exercise is integral to the life of T1DM subjects. Several factors influence the metabolic response to exercise in these patients. Despite physical and psychological benefits of exercise, its hypo- and hyperglycemic effects may cause discouragement from participation in sports and games. To use existing evidence from literature to provide practical indications for the management of insulin therapy in subjects with T1DM who practice sports or physical activities. Bibliographic research was performed on PubMed and the main Systematic Review and Guidelines database were also searched. Existing guidelines are useful but the exact adjustments of insulin dose must be made on an individual basis and these adjustments can be made only by "trial and error" approach. These clinical indications may be a starting point from which health care providers can find practical advices for each patient.

Effects of exercise with or without blueberries in the diet on cardio-metabolic risk factors: An exploratory pilot study in healthy subjects

PubMed Central

Nyberg, Sofia; Gerring, Edvard; Gjellan, Solveig; Vergara, Marta; Lindström, Torbjörn

2013-01-01

Background. The improvement of insulin sensitivity by exercise has been shown to be inhibited by supplementation of vitamins acting as antioxidants. Objective. To examine effects of exercise with or without blueberries, containing natural antioxidants, on cardio-metabolic risk factors. Methods. Fifteen healthy men and 17 women, 27.6 ± 6.5 years old, were recruited, and 26 completed a randomized cross-over trial with 4 weeks of exercise by running/jogging 5 km five times/week and 4 weeks of minimal physical activity. Participants were also randomized to consume 150 g of blueberries, or not, on exercise days. Laboratory variables were measured before and after a 5 km running-race at maximal speed at the beginning and end of each period, i.e. there were four maximal running-races and eight samplings in total for each participant. Results. Insulin and triglyceride levels were reduced while HDL-cholesterol increased by exercise compared with minimal physical activity. Participants randomized to consume blueberries showed an increase in fasting glucose levels compared with controls, during the exercise period (blueberries: from 5.12 ± 0.49 mmol/l to 5.32 ± 0.29 mmol/l; controls: from 5.24 ± 0.27 mmol/l to 5.17 ± 0.23 mmol/l, P = 0.04 for difference in change). Triglyceride levels fell in the control group (from 1.1 ± 0.49 mmol/l to 0.93 ± 0.31 mmol/l, P = 0.02), while HDL-cholesterol increased in the blueberry group (from 1.51 ± 0.29 mmol/l to 1.64 ± 0.33 mmol/l, P = 0.006). Conclusions. Ingestion of blueberries induced differential effects on cardio-metabolic risk factors, including increased levels of both fasting glucose and HDL-cholesterol. However, since it is possible that indirect effects on food intake were induced, other than consumption of blueberries, further studies are needed to confirm the findings. PMID:23977864

Effects of exercise with or without blueberries in the diet on cardio-metabolic risk factors: an exploratory pilot study in healthy subjects.

PubMed

Nyberg, Sofia; Gerring, Edvard; Gjellan, Solveig; Vergara, Marta; Lindström, Torbjörn; Nystrom, Fredrik H

2013-11-01

The improvement of insulin sensitivity by exercise has been shown to be inhibited by supplementation of vitamins acting as antioxidants. To examine effects of exercise with or without blueberries, containing natural antioxidants, on cardio-metabolic risk factors. Fifteen healthy men and 17 women, 27.6 ± 6.5 years old, were recruited, and 26 completed a randomized cross-over trial with 4 weeks of exercise by running/jogging 5 km five times/week and 4 weeks of minimal physical activity. Participants were also randomized to consume 150 g of blueberries, or not, on exercise days. Laboratory variables were measured before and after a 5 km running-race at maximal speed at the beginning and end of each period, i.e. there were four maximal running-races and eight samplings in total for each participant. Insulin and triglyceride levels were reduced while HDL-cholesterol increased by exercise compared with minimal physical activity. Participants randomized to consume blueberries showed an increase in fasting glucose levels compared with controls, during the exercise period (blueberries: from 5.12 ± 0.49 mmol/l to 5.32 ± 0.29 mmol/l; controls: from 5.24 ± 0.27 mmol/l to 5.17 ± 0.23 mmol/l, P = 0.04 for difference in change). Triglyceride levels fell in the control group (from 1.1 ± 0.49 mmol/l to 0.93 ± 0.31 mmol/l, P = 0.02), while HDL-cholesterol increased in the blueberry group (from 1.51 ± 0.29 mmol/l to 1.64 ± 0.33 mmol/l, P = 0.006). Ingestion of blueberries induced differential effects on cardio-metabolic risk factors, including increased levels of both fasting glucose and HDL-cholesterol. However, since it is possible that indirect effects on food intake were induced, other than consumption of blueberries, further studies are needed to confirm the findings.

Evaluation of cardiovascular risk-lowering health benefits accruing from laboratory-based, community-based and exercise-referral exercise programmes.

PubMed

Webb, R; Thompson, J E S; Ruffino, J-S; Davies, N A; Watkeys, L; Hooper, S; Jones, P M; Walters, G; Clayton, D; Thomas, A W; Morris, K; Llewellyn, D H; Ward, M; Wyatt-Williams, J; McDonnell, B J

2016-01-01

To evaluate the ability of community-based exercise programmes to facilitate public participation in exercise and hence improved cardiovascular health, we assessed the respective impacts of: a continuously monitored exercise programme based within our university (study 1); a Valleys Regional Park-facilitated community-based outdoor exercise programme (study 2); a Wales National Exercise Referral Scheme-delivered exercise-referral programme (study 3). Biomolecular (monocytic PPARγ target gene expression), vascular haemodynamic (central/peripheral blood pressure, arterial stiffness), clinical (insulin sensitivity, blood lipids) and anthropometric (body mass index, waist circumference, heart rate) parameters were investigated using RT-PCR, applanation tonometry, chemical analysis and standard anthropometric techniques. In studies 1-3, 22/28, 32/65 and 11/14 participants adhered to their respective exercise programmes, and underwent significant increases in physical activity levels. Importantly, beneficial effects similar to those seen in our previous studies (eg, modulations in expression of monocytic PPARγ target genes, decreases in blood pressure/arterial stiffness, improvements in blood lipids/insulin sensitivity) were observed (albeit to slightly differing extents) only in participants who adhered to their respective exercise programmes. While study 1 achieved more intense exercise and more pronounced beneficial effects, significant cardiovascular risk-lowering health benefits related to biomolecular markers, blood pressure, arterial stiffness and blood lipids were achieved via community/referral-based delivery modes in studies 2 and 3. Because cardiovascular health benefits were observed in all 3 studies, we conclude that the majority of benefits previously reported in laboratory-based studies can also be achieved in community-based/exercise-referral settings. These findings may be of use in guiding policymakers with regard to introduction and/or continued implementation of community/referral-based exercise programmes.

Strategies for reducing body fat mass: effects of liposuction and exercise on cardiovascular risk factors and adiposity

PubMed Central

Benatti, Fabiana Braga; Lira, Fábio Santos; Oyama, Lila Missae; do Nascimento, Cláudia Maria da Penha Oller; Lancha, Antonio Herbert

2011-01-01

Liposuction is the most popular aesthetic surgery performed in Brazil and worldwide. Evidence showing that adipose tissue is a metabolically active tissue has led to the suggestion that liposuction could be a viable method for improving metabolic profile through the immediate loss of adipose tissue. However, the immediate liposuction-induced increase in the proportion of visceral to subcutaneous adipose tissue could be detrimental to metabolism, because a high proportion of visceral to subcutaneous adipose tissue is associated with risk factors for cardiovascular disease. The results of studies investigating the effects of liposuction on the metabolic profile are inconsistent, however, with most studies reporting either no change or improvements in one or more cardiovascular risk factors. In addition, animal studies have demonstrated a compensatory growth of intact adipose tissue in response to lipectomy, although studies with humans have reported inconsistent results. Exercise training improves insulin sensitivity, inflammatory balance, lipid oxidation, and adipose tissue distribution; increases or preserves the fat-free mass; and increases total energy expenditure. Thus, liposuction and exercise appear to directly affect metabolism in similar ways, which suggests a possible interaction between these two strategies. To our knowledge, no studies have reported the associated effects of liposuction and exercise in humans. Nonetheless, one could suggest that exercise training associated with liposuction could attenuate or even block the possible compensatory fat deposition in intact depots or regrowth of the fat mass and exert an additive or even a synergistic effect to liposuction on improving insulin sensitivity and the inflammatory balance, resulting in an improvement of cardiovascular risk factors. Consequently, one could suggest that liposuction and exercise appear to be safe and effective strategies for either the treatment of metabolic disorders or aesthetic purposes. PMID:21779146

Effects of β-Hydroxy-β-methylbutyrate Free Acid Ingestion and Resistance Exercise on the Acute Endocrine Response

PubMed Central

Townsend, Jeremy R.; Hoffman, Jay R.; Gonzalez, Adam M.; Jajtner, Adam R.; Boone, Carleigh H.; Robinson, Edward H.; Mangine, Gerald T.; Wells, Adam J.; Fragala, Maren S.; Fukuda, David H.; Stout, Jeffrey R.

2015-01-01

Objective. To examine the endocrine response to a bout of heavy resistance exercise following acute β-hydroxy-β-methylbutyrate free acid (HMB-FA) ingestion. Design. Twenty resistance trained men were randomized and consumed either 1 g of HMB-FA (BetaTor) or placebo (PL) 30 min prior to performing an acute heavy resistance exercise protocol. Blood was obtained before (PRE), immediately after (IP), and 30 min after exercise (30P). Circulating concentrations of testosterone, growth hormone (GH), insulin-like growth factor (IGF-1), and insulin were assayed. Data were analyzed with a repeated measures ANOVA and area under the curve (AUC) was analyzed by the trapezoidal rule. Results. The resistance exercise protocol resulted in significant elevations from PRE in testosterone (P < 0.01), GH (P < 0.01), and insulin (P = 0.05) at IP, with GH (P < 0.01) and insulin (P < 0.01) remaining elevated at 30P. A significant interaction was noted between groups in the plasma GH response at IP, which was significantly higher following HMB-FA compared to PL (P < 0.01). AUC analysis revealed an elevated GH and IGF-1 response in the HMB-FA group compared to PL. Conclusion. HMB-FA prior to resistance exercise augments the GH response to high volume resistance exercise compared to PL. These findings provide further support for the potential anabolic benefits associated with HMB supplementation. PMID:25792982

The Effects of Physical Training on Blood Lipid Profiles in Adolescents with Insulin-Dependent Diabetes Mellitus.

ERIC Educational Resources Information Center

Campaigne, B. N.; And Others

1985-01-01

Fourteen adolescents with insulin-dependent diabetes mellitus (IDDM) participated in a 12-week exercise program to determine whether such training would bring about changes in blood lipid and lipoprotein profiles. The findings support the beneficial effects of regular exercise for individuals with IDDM. (MT)

Exercise reverses metabolic syndrome in high-fat diet-induced obese rats.

PubMed

Touati, Sabeur; Meziri, Fayçal; Devaux, Sylvie; Berthelot, Alain; Touyz, Rhian M; Laurant, Pascal

2011-03-01

Chronic consumption of a high-fat diet induces obesity. We investigated whether exercise would reverse the cardiometabolic disorders associated with obesity without it being necessary to change from a high- to normal-fat diet. Sprague-Dawley rats were placed on a high-fat (HFD) or control diet (CD) for 12 wk. HFD rats were then divided into four groups: sedentary HFD (HFD-S), exercise trained (motor treadmill for 12 wk) HFD (HFD-Ex), modified diet (HFD to CD; HF/CD-S), and exercise trained with modified diet (HF/CD-Ex). Cardiovascular risk parameters associated with metabolic syndrome were measured, and contents of aortic Akt, phospho-Akt at Ser (473), total endothelial nitric oxide synthase (eNOS), and phospho-eNOS at Ser (1177) were determined by Western blotting. Chronic consumption of HFD induced a metabolic syndrome. Exercise and dietary modifications reduced adiposity, improved glucose and insulin levels and plasma lipid profile, and exerted an antihypertensive effect. Exercise was more effective than dietary modification in improving plasma levels of thiobarbituric acid-reacting substance and in correcting the endothelium-dependent relaxation to acetylcholine and insulin. Furthermore, independent of the diet used, exercise increased Akt and eNOS phosphorylation. Metabolic syndrome induced by HFD is reversed by exercise and diet modification. It is demonstrated that exercise training induces these beneficial effects without the requirement for dietary modification, and these beneficial effects may be mediated by shear stress-induced Akt/eNOS pathway activation. Thus, exercise may be an effective strategy to reverse almost all the atherosclerotic risk factors linked to obesity, particularly in the vasculature.

Muscle glycogen storage after different amounts of carbohydrate ingestion.

PubMed

Ivy, J L; Lee, M C; Brozinick, J T; Reed, M J

1988-11-01

The purpose of this study was to determine whether the rate of muscle glycogen storage could be enhanced during the initial 4-h period postexercise by substantially increasing the amount of the carbohydrate consumed. Eight subjects cycled for 2 h on three separate occasions to deplete their muscle glycogen stores. Immediately and 2 h after exercise they consumed either 0 (P), 1.5 (L), or 3.0 g glucose/kg body wt (H) from a 50% glucose polymer solution. Blood samples were drawn from an antecubital vein before exercise, during exercise, and throughout recovery. Muscle biopsies were taken from the vastus lateralis immediately, 2 h, and 4 h after exercise. Blood glucose and insulin declined significantly during exercise in each of the three treatments. They remained below the preexercise concentrations during recovery in the P treatment but increased significantly above the preexercise concentrations during the L and H treatments. By the end of the 4 h-recovery period, blood glucose and insulin were still significantly above the preexercise concentrations in both treatments. Muscle glycogen storage was significantly increased above the basal rate (P, 0.5 mumol.g wet wt-1.h-1) after ingestion of either glucose polymer supplement. The rates of muscle glycogen storage, however, were not different between the L and H treatments during the first 2 h (L, 5.2 +/- 0.9 vs. H, 5.8 +/- 0.7 mumol.g wet wt-1.h-1) or the second 2 h of recovery (L, 4.0 +/- 0.9 vs. H, 4.5 +/- 0.6 mumol.g wet wt-1. h-1).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes

PubMed Central

Waling, Maria; Isaksson, Andreas; Tellström, Anna; Lundin-Olsson, Lillemor; Brage, Søren; Ryberg, Mats; Svensson, Michael; Olsson, Tommy

2017-01-01

Background Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed. Methods Thirty-two patients with type 2 diabetes (age 59±8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX). Results For the within group analyses, fat mass decreased by 5.7 kg (IQR: −6.6, −4.1; p<0.001) in the PD group and by 6.7 kg (−8.2, −5.3; p<0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p<0.001) and PD-EX (p<0.001) groups. HbA1c decreased by 0.9% (−1.2, −0.6; p<0.001) in the PD group and 1.1% (−1.7, −0.7; p<0.01) in the PD-EX group. Leptin decreased by 62 % (p<0.001) in the PD group and 42 % (p<0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p<0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (−3.6, −1.3) in the PD group and by 1.2 kg (−1.3, 1.0) in the PD-EX group (p<0.05 for the difference between intervention groups). Conclusions A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness. PMID:27235022

Factors Associated with Nocturnal Hypoglycemia in At-Risk Adolescents and Young Adults with Type 1 Diabetes

PubMed Central

Wilson, Darrell M.; Calhoun, Peter M.; Maahs, David M.; Chase, H. Peter; Messer, Laurel; Buckingham, Bruce A.; Aye, Tandy; Clinton, Paula K.; Hramiak, Irene; Kollman, Craig

2015-01-01

Abstract Background: Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk. Materials and Methods: Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15–45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose. Results: Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia. Conclusions: Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night. PMID:25761202

Factors associated with nocturnal hypoglycemia in at-risk adolescents and young adults with type 1 diabetes.

PubMed

Wilson, Darrell M; Calhoun, Peter M; Maahs, David M; Chase, H Peter; Messer, Laurel; Buckingham, Bruce A; Aye, Tandy; Clinton, Paula K; Hramiak, Irene; Kollman, Craig; Beck, Roy W

2015-06-01

Hypoglycemia remains an impediment to good glycemic control, with nocturnal hypoglycemia being particularly dangerous. Information on major contributors to nocturnal hypoglycemia remains critical for understanding and mitigating risk. Continuous glucose monitoring (CGM) data for 855 nights were studied, generated by 45 subjects 15-45 years of age with hemoglobin A1c (HbA1c) levels of ≤8.0% who participated in a larger randomized study. Factors assessed for potential association with nocturnal hypoglycemia (CGM measurement of <60 mg/dL for ≥30 min) included bedtime blood glucose (BG), exercise intensity, bedtime snack, insulin on board, day of the week, previous daytime hypoglycemia, age, gender, HbA1c level, diabetes duration, daily basal insulin, and daily insulin dose. Hypoglycemia occurred during 221 of 885 (25%) nights and was more frequent with younger age (P<0.001), lower HbA1c levels (P=0.006), medium/high-intensity exercise during the preceding day (P=0.003), and the occurrence of antecedent daytime hypoglycemia (P=0.001). There was a trend for lower bedtime BG levels to be associated with more frequent nocturnal hypoglycemia (P=0.10). Bedtime snack, before bedtime insulin bolus, weekend versus weekday, gender, and daily basal and bolus insulin were not associated with nocturnal hypoglycemia. Awareness that HbA1c level, exercise, bedtime BG level, and daytime hypoglycemia are all modifiable factors associated with nocturnal hypoglycemia may help patients and providers decrease the risk of hypoglycemia at night. Risk for nocturnal hypoglycemia increased in a linear fashion across the range of variables, with no clear-cut thresholds to guide clinicians or patients for any particular night.

Impact of metformin treatment and swimming exercise on visfatin levels in high-fat-induced obesity rats.

PubMed

Gao, Ya; Wang, Changjiang; Pan, Tianrong; Luo, Li

2014-02-01

Visfatin is a recently discovered adipocytokine that contributes to glucose and obesity-related conditions. Until now, its responses to the insulin-sensitizing agent metformin and to exercise are largely unknown. We aim to investigate the impact of metformin treatment and/or swimming exercise on serum visfatin and visfatin levels in subcutaneous adipose tissue (SAT), peri-renal adipose tissue (PAT) and skeletal muscle (SM) of high-fat-induced obesity rats. Sprague-Dawley rats were fed a normal diet or a high-fat diet for 16 weeks to develop obesity model. The high-fat-induced obesity model rats were then randomized to metformin (MET), swimming exercise (SWI), or adjunctive therapy of metformin and swimming exercise (MAS), besides high-fat obesity control group and a normal control group, all with 10 rats per group. Zoometric and glycemic parameters, lipid profile, and serum visfatin levels were assessed at baseline and after 6 weeks of therapy. Visfatin levels in SAT, PAT and SM were determined by Western Blot. Metformin and swimming exercise improved lipid profile, and increased insulin sensitivity and body weight reduction were observed. Both metformin and swimming exercise down-regulated visfatin levels in SAT and PAT, while the adjunctive therapy conferred greater benefits, but no changes of visfatin levels were observed in SM. Our results indicate that visfatin down-regulation in SAT and PAT may be one of the mechanisms by which metformin and swimming exercise inhibit obesity.

The effect of acute pre-exercise dark chocolate consumption on plasma antioxidant status, oxidative stress and immunoendocrine responses to prolonged exercise.

PubMed

Davison, Glen; Callister, Robin; Williamson, Gary; Cooper, Karen A; Gleeson, Michael

2012-02-01

Acute antioxidant supplementation may modulate oxidative stress and some immune perturbations that typically occur following prolonged exercise. The aims of the present study were to examine the effects of acutely consuming dark chocolate (high polyphenol content) on plasma antioxidant capacity, markers of oxidative stress and immunoendocrine responses to prolonged exercise. Fourteen healthy men cycled for 2.5 h at ~60% maximal oxygen uptake 2 h after consuming 100 g dark chocolate (DC), an isomacronutrient control bar (CC) or neither (BL) in a randomised-counterbalanced design. DC enhanced pre-exercise antioxidant status (P = 0.003) and reduced by trend (P = 0.088) 1 h post-exercise plasma free [F₂-isoprostane] compared with CC (also, [F₂-isoprostane] increased post-exercise in CC and BL but not DC trials). Plasma insulin concentration was significantly higher pre-exercise (P = 0.012) and 1 h post-exercise (P = 0.026) in the DC compared with the CC trial. There was a better maintenance of plasma glucose concentration on the DC trial (2-way ANOVA trial × time interaction P = 0.001), which decreased post-exercise in all trials but was significantly higher 1 h post-exercise (P = 0.039) in the DC trial. There were no between trial differences in the temporal responses (trial × time interactions all P > 0.05) of hypothalamic-pituitary-adrenal axis stress hormones, plasma interleukin-6, the magnitude of leukocytosis and neutrophilia and changes in neutrophil function. Acute DC consumption may affect insulin, glucose, antioxidant status and oxidative stress responses, but has minimal effects on immunoendocrine responses, to prolonged exercise.

The ASPIRE study: design and methods of an in-clinic crossover trial on the efficacy of automatic insulin pump suspension in exercise-induced hypoglycemia.

PubMed

Brazg, Ronald L; Bailey, Timothy S; Garg, Satish; Buckingham, Bruce A; Slover, Robert H; Klonoff, David C; Nguyen, Xuan; Shin, John; Welsh, John B; Lee, Scott W

2011-11-01

The Paradigm®Veo™ System includes a low glucose suspend (LGS) feature which suspends insulin delivery when a prespecified glucose threshold setting is reached by the associated continuous glucose monitoring (CGM) sensor. The ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) study is a multicenter, in-clinic, randomized, crossover study to examine the efficacy of LGS in exercise-induced hypoglycemia. Insulin-pump users underwent two separate exercise sessions, one with the LGS feature set to suspend insulin (LGS-on) when the CGM-detected glucose concentration was ≤ 70 mg/dl and one with the LGS feature off. Exercise sessions were conducted after an overnight fast and with initial plasma glucose level as measured by the YSI 2300 STAT Plus glucose analyzer (YSI) of 100-140 mg/dl. Subjects exercised until their YSI value fell to ≤ 85 mg/dl; subsequent YSI values <70 mg/dl were recorded for up to 4 h to measure the duration and nadir of hypoglycemia. The protocol required that subjects with YSI values <50 or >300 mg/dl were rescued with carbohydrates or insulin, respectively, based on the provider's recommendation. The primary end point was comparison of duration and severity of hypoglycemia between LGS-on and LGS-off sessions. Secondary end points included areas under the glucose concentration curve, CGM sensor accuracy, and last YSI glucose. Device- and procedure-related adverse events and serious adverse events were recorded. Fifty adults and teenagers (17-58 years) with type 1 diabetes were randomized. Study completion is expected in November 2011. © 2011 Diabetes Technology Society.

A new table for prevention of hypoglycaemia during physical activity in type 1 diabetic patients.

PubMed

Grimm, J J; Ybarra, J; Berné, C; Muchnick, S; Golay, A

2004-11-01

The ability to adjust both insulin and nutrition to allow safe participation in physical activity and high performance has recently been recognized as an important management strategy in these patients. In particular, the important role played by the patient in self-monitoring blood glucose during physical activity and then using these data to improve performance and decrease hypoglycaemias is now fully accepted. The primary objective of this study is to compare different therapeutic options in exercising Type 1 diabetic patients (n=67) with or without CHO compensation and/or with or without insulin dosage reduction in order to prevent hypoglycaemias during and after exercise. Sixty-seven type 1 diabetic patients were aggregated into four treatment categories according to four strategies to prevent hypoglycaemia episodes, with or without carbohydrate compensation and/or with or without insulin dosage reduction. The protocol included 7 different disciplines and 9 subgroups according to 3 different durations (<20 min., 20-60 min., > 60 min.) and 3 intensity degrees (<60% of Maximal Heart Rate, 60-75% and > 75%). Our study shows that by replacing adequately the carbohydrates during the practice of physical exercise it is possible to prevent almost all hypoglycaemia episodes, independently of the insulin dosage adjustments. Furthermore, the amount of extra-carbohydrates correlates well with the number of hypoglycaemia while the decrease in insulin dosage does not. Adequate carbohydrate replacement during and after exercise seems to be the most important measure to prevent hypoglycaemia. However, the insulin dosage adjustment does not play such an important role. A decrease from 20 to 30% seems reasonable only for a long duration exercise (> 60 min.). Finally, a new user-friendly table for prevention of hypoglycaemia is proposed for physical activity of different intensity and duration.

Effect of post-exercise caffeine and green coffee bean extract consumption on blood glucose and insulin concentrations.

PubMed

Beam, Jason R; Gibson, Ann L; Kerksick, Chad M; Conn, Carole A; White, Ailish C; Mermier, Christine M

2015-02-01

The aim of this study was to investigate the effects of ingesting caffeine and green coffee bean extract on blood glucose and insulin concentrations during a post-exercise oral glucose tolerance test. Ten male cyclists (age: 26 ± 5 y; height: 179.9 ± 5.4 cm; weight: 77.6 ± 13.3 kg; body mass index: 24 ± 4.3 kg/m(2); VO2 peak: 55.9 ± 8.4 mL·kg·min(-1)) participated in this study. In a randomized order, each participant completed three 30-min bouts of cycling at 60% of peak power output. Immediately after exercise, each participant consumed 75 g of dextrose with either 5 mg/kg body weight of caffeine, 10 mg/kg of green coffee bean extract (5 mg/kg chlorogenic acid), or placebo. Venous blood samples were collected immediately before and after exercise during completion of the oral glucose tolerance test. No significant time × treatment effects for blood glucose and insulin were found. Two-h glucose and insulin area under the curve values, respectively, for the caffeine (658 ± 74 mmol/L and 30,005 ± 13,304 pmol/L), green coffee bean extract (637 ± 100 mmol/L and 31,965 ± 23,586 pmol/L), and placebo (661 ± 77 mmol/L and 27,020 ± 12,339 pmol/L) trials were not significantly different (P > 0.05). Caffeine and green coffee bean extract did not significantly alter postexercise blood glucose and insulin concentrations when compared with a placebo. More human research is needed to determine the impact of these combined nutritional treatments and exercise on changes in blood glucose and insulin. Copyright © 2015 Elsevier Inc. All rights reserved.

Individually and Combined Water-Based Exercise With Ginger Supplement, on Systemic Inflammation and Metabolic Syndrome Indices, Among the Obese Women With Breast Neoplasms.

PubMed

Karimi, Niloofar; Dabidi Roshan, Valiollah; Fathi Bayatiyani, Zohreh

2015-12-01

Breast neoplasms has known as the most common cancer among the women worldwide, and relationship between obesity, metabolic syndrome, inflammation and cancer has been recognized since many years ago. The aim of this study was to determine the individual and concomitant effect of 6-weeks water-based exercise and oral ginger supplement on markers that have related to metabolic syndrome and systemic inflammation in obese women with breast neoplasms. Forty women whose have diagnosed with breast neoplasms have volunteered to participate in the study. Subjects have randomly assigned into four groups; placebo, exercise training, ginger supplement and exercise training+ ginger supplement groups. Subjects in the ginger supplement group and the exercise training+ ginger supplement group have orally received 4 capsules, 7 days a week and for 6 weeks. The water-based exercise training program have collected at a progressive intensity and time, have ranged from 50% to 75% of heart rate reserve, in a pool, 4 times a week for 6 weeks. Fasting blood sampling has collected at the pretest and post-test. The ginger supplementation and the water-base exercise have resulted in a reduction of hs-CRP, IL-10, insulin, glucose, insulin resistance, LDL-C, TG; but an increase in HDL-C and HDL-C/LDL-C. The water-base exercise and ginger supplement group have significantly shown larger positive effect in all outcomes, in comparison with the water-base exercise or ginger supplement alone groups. Findings have suggested that obese breast neoplasms survivors have commonly shown metabolic syndrome and elevated inflammation, which placed them at an increased risk for cardiovascular diseases. Moreover, data has indicated a protective effect of the nondrug strategies, such as water-base exercise and ginger supplementation have played an important role in pathogenesis of inflammatory and metabolic responses, among diagnosed breast neoplasms.

The role of FOXO and PPAR transcription factors in diet-mediated inhibition of PDC activation and carbohydrate oxidation during exercise in humans and the role of pharmacological activation of PDC in overriding these changes.

PubMed

Constantin-Teodosiu, Dumitru; Constantin, Despina; Stephens, Francis; Laithwaite, David; Greenhaff, Paul L

2012-05-01

High-fat feeding inhibits pyruvate dehydrogenase complex (PDC)-controlled carbohydrate (CHO) oxidation, which contributes to muscle insulin resistance. We aimed to reveal molecular changes underpinning this process in resting and exercising humans. We also tested whether pharmacological activation of PDC overrides these diet-induced changes. Healthy males consumed a control diet (CD) and on two further occasions an isocaloric high-fat diet (HFD). After each diet, subjects cycled for 60 min after intravenous infusion with saline (CD and HFD) or dichloroacetate (HFD+DCA). Quadriceps muscle biopsies obtained before and after 10 and 60 min of exercise were used to estimate CHO use, PDC activation, and mRNAs associated with insulin, fat, and CHO signaling. Compared with CD, HFD increased resting pyruvate dehydrogenase kinase 2 (PDK2), PDK4, forkhead box class O transcription factor 1 (FOXO1), and peroxisome proliferator-activated receptor transcription factor α (PPARα) mRNA and reduced PDC activation. Exercise increased PDC activation and whole-body CHO use in HFD, but to a lower extent than in CD. Meanwhile PDK4 and FOXO1, but not PPARα or PDK2, mRNA remained elevated. HFD+DCA activated PDC throughout and restored whole-body CHO use during exercise. FOXO1 appears to play a role in HFD-mediated muscle PDK4 upregulation and inhibition of PDC and CHO oxidation in humans. Also, pharmacological activation of PDC restores HFD-mediated inhibition of CHO oxidation during exercise.

Effect of moderate- and high-intensity acute exercise on appetite in obese individuals.

PubMed

Martins, Catia; Stensvold, Dorthe; Finlayson, Graham; Holst, Jens; Wisloff, Ulrik; Kulseng, Bård; Morgan, Linda; King, Neil A

2015-01-01

The effect of acute exercise, and exercise intensity, on appetite control in obese individuals requires further study. The aim of this study was to compare the effects of acute isocaloric bouts (250 kcal) of high-intensity intermittent cycling (HIIC) and moderate-intensity continuous cycling (MICC) or short-duration HIIC (S-HIIC) (125 kcal) and a resting control condition on the appetite hormone responses, subjective feelings of appetite, energy intake (EI), and food reward in overweight/obese individuals. This study is a randomized crossover study on 12 overweight/obese volunteers. Participants were assigned to the control, MICC, HIIC, and S-HIIC conditions, 1 wk apart, in a counterbalanced order. Exercise was performed 1 h after a standard breakfast. An ad libitum test lunch was served 3 h after breakfast. Fasting/postprandial plasma samples of insulin, acylated ghrelin, polypeptide YY3-36, and glucagon-like peptide 1 and subjective feelings of appetite were measured every 30 min for 3 h. Nutrient and taste preferences were measured at the beginning and end of each condition using the Leeds Food Preference Questionnaire. Insulin levels were significantly reduced, and glucagon-like peptide 1 levels significantly increased during all exercise bouts compared with those during rest. Acylated ghrelin plasma levels were lower in the MICC and HIIC, but not in S-HIIC, compared with those in control. There were no significant differences for polypeptide YY3-36 plasma levels, hunger or fullness ratings, EI, or food reward. Our findings suggest that, in overweight/obese individuals, isocaloric bouts of moderate- or high-intensity exercise lead to a similar appetite response. This strengthens previous findings in normal-weight individuals that acute exercise, even at high intensity, does not induce any known physiological adaptation that would lead to increased EI.

Fasting hyperglycaemia blunts the reversal of impaired glucose tolerance after exercise training in obese older adults.

PubMed

Malin, S K; Kirwan, J P

2012-09-01

Lifestyle modification, consisting of exercise and weight loss, delays the progression from prediabetes to type 2 diabetes (T2D). However, no study has determined the efficacy of exercise training on glucose metabolism in the different prediabetes subtypes. Seventy-six older (65.1 ± 0.6 years) obese adults with impaired fasting glucose (IFG; n = 12), impaired glucose tolerance (IGT; n = 9) and combined glucose intolerance (IFG + IGT = CGI; n = 22) were compared with normal glucose tolerant (NGT; n = 15) and T2D (n = 18) groups after 12 weeks of exercise training (60 min/day for 5 days/week at ~85% HR(max)). An oral glucose tolerance test was used to assess glucose levels. Insulin sensitivity (IS; euglycaemic hyperinsulinaemic clamp at 40 mU/m(2)/min), β-cell function (glucose-stimulated insulin secretion corrected for IS), body composition (hydrostatic weighing/computed tomography scan) and cardiovascular fitness (treadmill VO(2) max) were also assessed. Exercise training reduced weight and increased cardiovascular fitness (p < 0.05). Exercise training lowered fasting glucose levels in IFG, CGI and T2D (p < 0.05) and 2-h glucose levels in IGT, CGI and T2D (p < 0.05). However, 2-h glucose levels were not normalized in adults with CGI compared with IGT (p < 0.05). β-Cell function improved similarly across groups (p < 0.05). Although not statistically significant, IS increased approximately 40% in IFG and IGT, but only 17% in CGI. The magnitude of improvement in glucose metabolism after 12 weeks of exercise training is not uniform across the prediabetes subtypes. Given the high risk of progressing to T2D, adults with CGI may require more aggressive therapies to prevent diabetes. © 2012 Blackwell Publishing Ltd.

Postprandial plasma incretin hormones in exercise-trained versus untrained subjects.

PubMed

Weiss, Edward P; Royer, Nathaniel K; Fisher, Jonathan S; Holloszy, John O; Fontana, Luigi

2014-06-01

After food ingestion, the incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are secreted by the intestines into circulation where they act on the pancreas to promote insulin secretion. We evaluated the hypothesis that low postprandial plasma insulin levels in lean exercise-trained individuals are associated with low concentrations of incretin hormones. A cross-sectional study was performed to compare postprandial incretin hormone levels in lean endurance exercise-trained individuals (EX; n = 14, ≥40 yr) and age- and sex-matched, nonobese, sedentary control subjects (CON, n = 14). The main outcome measures were GLP-1, GIP, insulin, and glucose incremental areas under the curve (AUC) as measured in plasma samples collected during a 2-h,75-g oral glucose tolerance test (OGTT). The EX group had lower body fat percentage (14.6% ± 1.1% vs 23.3% ± 1.7%, P = 0.0002) and higher maximal oxygen uptake (53 ± 2 vs 34 ± 2, P < 0.0001) than CON. Glucose AUC did not differ between groups (P = 0.20). Insulin AUC was lower in EX (2.5 ± 0.5 vs 4.2 ± 1.2 μU·mL·1000 min, P = 0.02). No differences were observed between groups (EX and CON, respectively) for GLP-1 AUC (3.5 ± 0.7 vs 4.1 ± 1.1 pmol·min·100 L, P = 0.61) or GIP AUC (19.2 ± 1.4 vs 18.0 ± 1.4 pg·min·1000 mL; P = 0.56). In CON, insulin AUC was correlated with AUC for GLP-1 (r = 0.53, P = 0.05) and GIP (r = 0.71, P = 0.004), but no such correlations were observed in EX (both P ≥ 0.67). Low postprandial insulin levels in lean exercise-trained individuals are not attributable to lower incretin hormone concentrations. However, exercise may decrease the dependency of postprandial insulin levels on incretin hormones.

Resistance training increases skeletal muscle oxidative capacity and net intramuscular triglyceride breakdown in type I and II fibres of sedentary males.

PubMed

Shepherd, S O; Cocks, M; Tipton, K D; Witard, O C; Ranasinghe, A M; Barker, T A; Wagenmakers, A J M; Shaw, C S

2014-06-01

Recent in vitro and in vivo experimental observations suggest that improvements in insulin sensitivity following endurance training are mechanistically linked to increases in muscle oxidative capacity, intramuscular triglyceride (IMTG) utilization during endurance exercise and increases in the content of the lipid droplet-associated perilipin 2 (PLIN2) and perilipin 5 (PLIN5). This study investigated the hypothesis that similar adaptations may also underlie the resistance training (RT)-induced improvements in insulin sensitivity. Thirteen sedentary men (20 ± 1 years old; body mass index 24.8 ± 0.8 kg m(-2)) performed 6 weeks of whole-body RT (three times per week), and changes in peak O2 uptake (in millilitres per minute per kilogram) and insulin sensitivity were assessed. Muscle biopsies (n = 8) were obtained before and after 60 min steady-state cycling at ~65% peak O2 uptake. Immunofluorescence microscopy was used to assess changes in oxidative capacity (measured as cytochrome c oxidase protein content), IMTG and PLIN2 and PLIN5 protein content. Resistance training increased peak O2 uptake (by 8 ± 3%), COX protein content (by 46 ± 13 and 61 ± 13% in type I and II fibres, respectively) and the Matsuda insulin sensitivity index (by 47 ± 6%; all P < 0.05). In type I fibres, IMTG (by 52 ± 11%; P < 0.05) and PLIN2 content (by 107 ± 19%; P < 0.05) were increased and PLIN5 content tended to increase (by 54 ± 22%; P = 0.054) post-training. In type II fibres, PLIN2 content increased (by 57 ± 20%; P < 0.05) and IMTG (by 46 ± 17%; P = 0.1) and PLIN5 content (by 44 ± 24%; P = 0.054) tended to increase post-training. Breakdown of IMTG during moderate-intensity exercise was greater in both type I and type II fibres (by 43 ± 5 and 37 ± 5%, respectively; P < 0.05) post-RT. The results confirm the hypothesis that RT enhances muscle oxidative capacity and increases IMTG breakdown and the content of PLIN2 and PLIN5 in both type I and type II fibres during endurance-type exercise. © 2014 The Authors. Experimental Physiology © 2014 The Physiological Society.

Lifestyle and metabolic approaches to maximizing erectile and vascular health.

PubMed

Meldrum, D R; Gambone, J C; Morris, M A; Esposito, K; Giugliano, D; Ignarro, L J

2012-01-01

Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.

Resistance to Aerobic Exercise Training Causes Metabolic Dysfunction and Reveals Novel Exercise-Regulated Signaling Networks

PubMed Central

Lessard, Sarah J.; Rivas, Donato A.; Alves-Wagner, Ana B.; Hirshman, Michael F.; Gallagher, Iain J.; Constantin-Teodosiu, Dumitru; Atkins, Ryan; Greenhaff, Paul L.; Qi, Nathan R.; Gustafsson, Thomas; Fielding, Roger A.; Timmons, James A.; Britton, Steven L.; Koch, Lauren G.; Goodyear, Laurie J.

2013-01-01

Low aerobic exercise capacity is a risk factor for diabetes and a strong predictor of mortality, yet some individuals are “exercise-resistant” and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease risk, we used selective breeding for 15 generations to develop rat models of low and high aerobic response to training. Before exercise training, rats selected as low and high responders had similar exercise capacities. However, after 8 weeks of treadmill training, low responders failed to improve their exercise capacity, whereas high responders improved by 54%. Remarkably, low responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise-resistant phenotype segregates with disease risk. Low responders had impaired exercise-induced angiogenesis in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low responders. Low responders had increased stress/inflammatory signaling and altered transforming growth factor-β signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system, we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease. PMID:23610057

Aerobic exercise training conserves insulin sensitivity for 1 yr following weight loss in overweight women.

PubMed

Fisher, Gordon; Hunter, Gary R; Gower, Barbara A

2012-02-01

The objectives of this study were to 1) identify the independent effects of exercise (aerobic or resistance training) and weight loss on whole body insulin sensitivity and 2) determine if aerobic or resistance training would be more successful for maintaining improved whole body insulin sensitivity 1 yr following weight loss. Subjects were 97 healthy, premenopausal women, body mass index (BMI) 27-30 kg/m(2). Following randomized assignment to one of three groups, diet only, diet + aerobic, or diet + resistance training until a BMI <25 kg/m(2) was achieved, body composition, fat distribution, and whole body insulin sensitivity were determined at baseline, in the weight reduced state, and at 1-yr follow up. The whole body insulin sensitivity index (S(I)) was determined using a frequently sampled intravenous glucose tolerance test. Results of repeated-measures ANOVA indicated a significant improvement in S(I) following weight loss. However, there were no group or group×time interactions. At 1-yr follow up, there were no significant time or group interactions for S(I;) however, there was a significant group×time interaction for S(I). Post hoc analysis revealed that women in the aerobic training group showed a significant increased S(I) from weight reduced to 1-yr follow up (P < 0.05), which was independent of intra-abdominal adipose tissue and %fat. No significant differences in S(I) from weight reduced to 1-yr follow up were observed for diet only or diet + resistance groups. Additionally, multiple linear regression analysis revealed that change in whole body insulin sensitivity from baseline to 1-yr follow up was independently associated with the change in Vo(2max) from baseline to 1-yr follow up (P < 0.05). These results suggest that long-term aerobic exercise training may conserve improvements in S(I) following weight loss and that maintaining cardiovascular fitness following weight loss may be important for maintaining improvements in S(I).

Lipid-induced metabolic dysfunction in skeletal muscle.

PubMed

Muoio, Deborah M; Koves, Timothy R

2007-01-01

Insulin resistance is a hallmark of type 2 diabetes and commonly observed in other energy-stressed settings such as obesity, starvation, inactivity and ageing. Dyslipidaemia and 'lipotoxicity'--tissue accumulation of lipid metabolites-are increasingly recognized as important drivers of insulin resistant states. Mounting evidence suggests that lipid-induced metabolic dysfunction in skeletal muscle is mediated in large part by stress-activated serine kinases that interfere with insulin signal transduction. However, the metabolic and molecular events that connect lipid oversupply to stress kinase activation and glucose intolerance are as yet unclear. Application of transcriptomics and targeted mass spectrometry-based metabolomics tools has led to our finding that insulin resistance is a condition in which muscle mitochondria are persistently burdened with a heavy lipid load. As a result, high rates of beta-oxidation outpace metabolic flux through the TCA cycle, leading to accumulation of incompletely oxidized acyl-carnitine intermediates. In contrast, exercise training enhances mitochondrial performance, favouring tighter coupling between beta-oxidation and the TCA cycle, and concomitantly restores insulin sensitivity in animals fed a chronic high fat diet. The exercise-activated transcriptional co-activator, PGC1alpha, plays a key role in co-ordinating metabolic flux through these two intersecting metabolic pathways, and its suppression by overfeeding may contribute to obesity-associated mitochondrial dysfunction. Our emerging model predicts that muscle insulin resistance arises from mitochondrial lipid stress and a resultant disconnect between beta-oxidation and TCA cycle activity. Understanding this 'disconnect' and its molecular basis may lead to new therapeutic targets for combating metabolic disease.

Do diabetes and obesity affect the metabolic response to exercise?

PubMed

Plomgaard, Peter; Weigert, Cora

2017-07-01

Exercise is recommended as therapeutic intervention for people at risk to develop type 2 diabetes to prevent or treat the disease. Recent studies on the influence of obesity and type 2 diabetes on the outcome of exercise programs are discussed. Poor glycemic control before an intervention can be a risk factor of reduced therapeutic benefit from exercise. But the acute metabolic response to exercise and the transcriptional profile of the working muscle is similar in healthy controls and type 2 diabetic patients, including but not limited to intact activation of skeletal muscle AMP-activated kinase signaling, glucose uptake and expression of peroxisome proliferator-activated receptor gamma coactivator 1α. The increase in plasma acylcarnitines during exercise is not influenced by type 2 diabetes or obesity. The hepatic response to exercise is dependent on the glucagon/insulin ratio and the exercise-induced increase in hepatokines such as fibroblast growth factor 21 and follistatin is impaired in type 2 diabetes and obesity, but consequences for the benefit from exercise are unknown yet. Severe metabolic dysregulation can reduce the benefit from exercise, but the intact response of key metabolic regulators in exercising skeletal muscle of diabetic patients demonstrates the effectiveness of exercise programs to treat the disease.

Effects of High Intensity Interval Training and Strength Training on Metabolic, Cardiovascular and Hormonal Outcomes in Women with Polycystic Ovary Syndrome: A Pilot Study.

PubMed

Almenning, Ida; Rieber-Mohn, Astrid; Lundgren, Kari Margrethe; Shetelig Løvvik, Tone; Garnæs, Kirsti Krohn; Moholdt, Trine

2015-01-01

Polycystic ovary syndrome is a common endocrinopathy in reproductive-age women, and associates with insulin resistance. Exercise is advocated in this disorder, but little knowledge exists on the optimal exercise regimes. We assessed the effects of high intensity interval training and strength training on metabolic, cardiovascular, and hormonal outcomes in women with polycystic ovary syndrome. Three-arm parallel randomized controlled trial. Thirty-one women with polycystic ovary syndrome (age 27.2 ± 5.5 years; body mass index 26.7 ± 6.0 kg/m2) were randomly assigned to high intensity interval training, strength training, or a control group. The exercise groups exercised three times weekly for 10 weeks. The main outcome measure was change in homeostatic assessment of insulin resistance (HOMA-IR). HOMA-IR improved significantly only after high intensity interval training, by -0.83 (95% confidence interval [CI], -1.45, -0.20), equal to 17%, with between-group difference (p = 0.014). After high intensity interval training, high-density lipoprotein cholesterol increased by 0.2 (95% CI, 0.02, 0.5) mmol/L, with between group difference (p = 0.04). Endothelial function, measured as flow-mediated dilatation of the brachial artery, increased significantly after high intensity interval training, by 2.0 (95% CI, 0.1, 4.0) %, between-group difference (p = 0.08). Fat percentage decreased significantly after both exercise regimes, without changes in body weight. After strength training, anti-Müllarian hormone was significantly reduced, by -14.8 (95% CI, -21.2, -8.4) pmol/L, between-group difference (p = 0.04). There were no significant changes in high-sensitivity C-reactive protein, adiponectin or leptin in any group. High intensity interval training for ten weeks improved insulin resistance, without weight loss, in women with polycystic ovary syndrome. Body composition improved significantly after both strength training and high intensity interval training. This pilot study indicates that exercise training can improve the cardiometabolic profile in polycystic ovary syndrome in the absence of weight loss. ClinicalTrial.gov NCT01919281.

Efficacy and safety of statins and exercise combination therapy compared to statin monotherapy in patients with dyslipidaemia: A systematic review and meta-analysis.

PubMed

Gui, Ya-Jun; Liao, Cai-Xiu; Liu, Qiong; Guo, Yuan; Yang, Tao; Chen, Jing-Yuan; Wang, Ya-Ting; Hu, Jia-Hui; Xu, Dan-Yan

2017-06-01

Background Statin treatment in association with physical exercise can substantially reduce mortality in dyslipidaemic individuals. However, the available data to compare the efficacy and safety of statins and exercise combination therapy with statin monotherapy are limited. Design Systematic review and meta-analysis. Methods We systematically searched PubMed, Embase and the Cochrane Library from database inception until December 2016. We included randomised and non-randomised studies that compared the efficacy and safety of statins and exercise combination therapy with statin monotherapy in patients with dyslipidaemia. Standardised mean differences were calculated and pooled by means of fixed effects models. The risk of bias and heterogeneity among trials was also assessed. Seven articles were assessed in terms of the efficacy of therapy and 13 from the viewpoint of therapeutic safety. Results In terms of efficacy, statins and exercise combination decreased the incidence of diabetes mellitus, improved insulin sensitivity and inflammation, but caused no change in lipid profile compared to statins alone. In terms of safety, statins and exercise combination increased peak oxygen uptake (standardised mean difference 1.01, 95% confidence interval 0.46 to 1.57) compared to statins alone. In contrast to statin-induced myopathy, chronic exercise training prior to statin treatment could counteract statin-induced adverse effects in skeletal muscle. Conclusion Statins and exercise combination therapy is more effective than statin monotherapy in terms of insulin sensitivity, inflammation and exercise capacity. The small number of studies warrants the need for more randomised controlled trials evaluating the efficacy and safety of combination therapy.

High-intensity interval training without weight loss improves exercise but not basal or insulin-induced metabolism in overweight/obese African American women.

PubMed

Arad, Avigdor D; DiMenna, Fred J; Thomas, Naketa; Tamis-Holland, Jacqueline; Weil, Richard; Geliebter, Allan; Albu, Jeanine B

2015-08-15

The purpose of this randomized controlled clinical trial was to determine the effect of a 14-week high-intensity interval training (HIIT) intervention with weight stability on metabolic flexibility, insulin sensitivity, and cardiorespiratory fitness in sedentary, premenopausal, nondiabetic, overweight/obese African American women. Twenty-eight subjects were allocated to one of two groups: HIIT, which performed three sessions per week of four high-intensity cycling intervals, or a control group (CON), which maintained their normal level of physical activity. Diet was controlled for all subjects to ensure weight stability. Pre- and postintervention (pre/post), subjects completed an incremental cycling test to limit of tolerance and, following a 10-day high-fat controlled feeding period, a euglycemic-hyperinsulinemic clamp to determine insulin sensitivity and substrate oxidation. Nine members of HIIT (age, 29 ± 4 yr; body mass, 90.1 ± 13.8 kg) and eleven members of CON (age, 30 ± 7 yr; body mass, 85.5 ± 10.7 kg) completed the study. HIIT experienced an increased limit of tolerance (post, 1,124 ± 202 s; pre, 987 ± 146 s; P < 0.05), gas exchange threshold (post, 1.29 ± 0.34 liters/min; pre, 0.97 ± 0.23 liters/min; P < 0.05), and fat oxidation at the same absolute submaximal work rate compared with CON (P < 0.05 for group-by-time interaction in all cases). However, changes in peak oxygen consumption (V̇o2peak), insulin sensitivity, free fatty acid suppression during insulin stimulation, and metabolic flexibility were not different in HIIT compared with CON. High-intensity interval training with weight stability increased exercise fat oxidation and tolerance in subjects at risk for diabetic progression, but did not improve insulin sensitivity or fat oxidation in the postabsorptive or insulin-stimulated state. Copyright © 2015 the American Physiological Society.

The Role of Physical Exercise to Improve the Browning of White Adipose Tissue via POMC Neurons.

PubMed

Rodrigues, Kellen C da Cruz; Pereira, Rodrigo M; de Campos, Thaís D P; de Moura, Rodrigo F; da Silva, Adelino S R; Cintra, Dennys E; Ropelle, Eduardo R; Pauli, José R; de Araújo, Michel B; de Moura, Leandro P

2018-01-01

Obesity is a public health issue that affects more than 600 million adults worldwide. The disease is characterized by fat accumulation, mainly in the abdominal area. The human body is mainly composed of two types of adipose tissue: white adipose tissue (WAT) and brown adipose tissue (BAT); however, the browning process generates a different type of brown fat-like adipocyte in WAT, which similar to BAT has thermogenic capacity by activating UCP-1. The hypothalamic arcuate nucleus plays an important role in WAT browning via POMC neurons, which are influenced by synergistic insulin and leptin signaling. On the other hand, stimulation of AgRP neurons suppresses WAT browning. The hypothalamic inflammatory process that occurs in obesity impairs insulin and leptin signaling in this tissue and, consequently, can decrease WAT browning. In addition, practicing physical exercise may be a great strategy for triggering the browning process since it reduces hypothalamic inflammation and increases POMC neurons gene expression. Moreover, physical exercise stimulates irisin gene expression, which has an important impact on thermogenesis, which in turn culminates in increased gene expression of proteins such as UCP-1 and Cidea, which are related to WAT browning. Furthermore, thermogenetic activation of WAT leads to increased energy expenditure, favoring obesity treatment. Therefore, this mini-review aimed to highlight the most recent studies that link the control of hypothalamic activity with the browning metabolism of adipose tissue in response to physical exercise.

Four-month course of soluble milk proteins interacts with exercise to improve muscle strength and delay fatigue in elderly participants.

PubMed

Gryson, Céline; Ratel, Sébastien; Rance, Mélanie; Penando, Stéphane; Bonhomme, Cécile; Le Ruyet, Pascale; Duclos, Martine; Boirie, Yves; Walrand, Stéphane

2014-12-01

The benefit of protein supplementation on the adaptive response of muscle to exercise training in older people is controversial. To investigate the independent and combined effects of a multicomponent exercise program with and without a milk-based nutritional supplement on muscle strength and mass, lower-extremity fatigue, and metabolic markers. A sample of 48 healthy sedentary men aged 60.8 ± 0.4 years were randomly assigned to a 16-week multicomponent exercise training program with a milk-based supplement containing, besides proteins [total milk proteins 4 or 10 g/day or soluble milk proteins rich in leucine (PRO) 10 g/day], carbohydrates and fat. Body composition, muscle mass and strength, and time to task failure, an index of muscle fatigue, were measured. Blood lipid, fibrinogen, creatine phosphokinase, glucose, insulin, C-reactive protein, interleukin-6, tumor necrosis factor-α soluble receptors, and endothelial markers were assessed. Body fat mass was reduced after the 4-month training program in groups receiving 10 g/day of protein supplementation (P < .01). The training program sustained with the daily 10 g/day PRO was associated with a significant increase in dominant fat free mass (+5.4%, P < .01) and in appendicular muscle mass (+4.5%, P < .01). Blood cholesterol was decreased in the trained group receiving 10 g/day PRO. The index of insulin resistance (homeostasis model assessment-insulin resistance) and blood creatine phosphokinase were reduced in the groups receiving 10 g/day PRO, irrespective of exercise. The inflammatory and endothelial markers were not different between the groups. Training caused a significant improvement (+10.6% to 19.4%, P < .01) in the maximal oxygen uptake. Increased maximum voluntary contraction force was seen in the trained groups receiving 10 g/day of proteins (about 3%, P < .05). Time to task failure was improved in the trained participants receiving a 10 g/day supplementation with PRO (P < .01). Soluble milk proteins rich in leucine improved time to muscle failure and increase in skeletal muscle mass and strength after prolonged multicomponent exercise training in healthy older men. Copyright © 2014 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

Does oral glutamine improve insulin sensitivity in adolescents with type 1 diabetes?

PubMed

Torres-Santiago, Lournaris; Mauras, Nelly; Hossain, Jobayer; Weltman, Arthur L; Darmaun, Dominique

2017-02-01

The decline in insulin sensitivity (S I ) associated with puberty increases the difficulty of achieving glycemic control in adolescents with type 1 diabetes (T1D). The aim of this study was to determine whether glutamine supplementation affects blood glucose by enhancing S I in adolescents with T1D. Thirteen adolescents with T1D (HbA1C 8.2 ± 0.1%) were admitted to perform afternoon exercise (four 15-min treadmill/5-min rest cycles of exercise) on two occasions within a 4-wk period. They were randomized to receive a drink containing either glutamine (0.25 g/kg) or placebo before exercise, at bedtime, and early morning in a double-blind, crossover design. Blood glucose was monitored overnight, and a hyperinsulinemic-euglycemic clamp was performed the following morning. Blood glucose concentration dropped comparably during exercise on both days. However, the total number of nocturnal hypoglycemic events (17 versus 7, P = 0.045) and the cumulative probability of overnight hypoglycemia (50% versus 33%, P = 0.02) were higher on the glutamine day than on the placebo day. During clamp, glucose infusion rate was not affected by glutamine supplementation (7.7 ± 1 mg • kg -1 • min -1 versus 7.0 ± 1; glutamine versus placebo; P = 0.4). Oral glutamine supplementation decreases blood glucose in adolescents with T1D after exercise. Insulin sensitivity, however, was unaltered during the euglycemic clamp. Although the mechanisms involved remain to be elucidated, studies to explore the potential use of glutamine to improve blood glucose control are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

Regular exercise coupled to diet regimen accelerates reduction of hepatic steatosis and associated pathological conditions in nonalcoholic fatty liver disease.

PubMed

Oh, Sechang; Tanaka, Kiyoji; Tsujimoto, Takehiko; So, Rina; Shida, Takashi; Shoda, Junichi

2014-06-01

A diet regimen focusing on weight loss is still the most efficient treatment for nonalcoholic fatty liver disease (NAFLD). Recently, specific benefits of exercise against NAFLD independent of weight loss have been reported. Hence, combining exercise with diet-induced weight loss can be expected to have an additive benefit for NAFLD management. We evaluated the effectiveness of diet in conjunction with exercise (DE) compared with that of diet alone (D) on hepatic steatosis and its underlying pathophysiology. Data obtained from 72 obese, middle-aged men with NAFLD who completed a 3-month program of DE or D in 2011 and 2012 were analyzed. Subjects went through a comprehensive parameters analysis for the pathophysiology of NAFLD. Subjects in the DE group, compared with those in the D group, elicited additive effects on the degree of hepatic steatosis (-82.6% vs. -60.0%) and body weight (-13.3% vs. -8.9%) accompanied by an improvement in serum marker levels: inflammation, ferritin (-16.1% vs. -2.1%); oxidative stress, lipid peroxidation (-31.8% vs. +4.8%); adipokine imbalance, adiponectin, and leptin (+27.4% vs. +2.6% and -74.4% vs. -30.2%). Consequently, subjects in the DE group achieved further attenuation of insulin resistance [homeostatsis model assessment of insulin resistance (HOMA-IR) (-63.6% vs. -40.0%)]. These observed additive benefits in the DE group were closely associated with the increased volume of physical activity. The addition of exercise to a diet regimen potentiates the benefits in NAFLD management through further improvement of hepatic steatosis, inflammatory and oxidative stress levels, and adipokine imbalance, thereby attenuating insulin resistance independent of detectable weight loss.

Resistance Exercise Attenuates High-Fructose, High-Fat-Induced Postprandial Lipemia

PubMed Central

Wilburn, Jessie R; Bourquin, Jeffrey; Wysong, Andrea; Melby, Christopher L

2015-01-01

INTRODUCTION Meals rich in both fructose and fat are commonly consumed by many Americans, especially young men, which can produce a significant postprandial lipemic response. Increasing evidence suggests that aerobic exercise can attenuate the postprandial increase in plasma triacylglycerols (TAGs) in response to a high-fat or a high-fructose meal. However, it is unknown if resistance exercise can dampen the postprandial lipemic response to a meal rich in both fructose and fat. METHODS Eight apparently healthy men (Mean ± SEM; age = 27 ± 2 years) participated in a crossover study to examine the effects of acute resistance exercise on next-day postprandial lipemia resulting from a high-fructose, high-fat meal. Participants completed three separate two-day conditions in a random order: (1) EX-COMP: a full-body weightlifting workout with the provision of additional kilocalories to compensate for the estimated net energy cost of exercise on day 1, followed by the consumption of a high-fructose, high-fat liquid test meal the next morning (day 2) (~600 kcal) and the determination of the plasma glucose, lactate, insulin, and TAG responses during a six-hour postprandial period; (2) EX-DEF: same condition as EX-COMP but without exercise energy compensation on day 1; and (3) CON: no exercise control. RESULTS The six-hour postprandial plasma insulin and lactate responses did not differ between conditions. However, the postprandial plasma TAG concentrations were 16.5% and 24.4% lower for EX-COMP (551.0 ± 80.5 mg/dL × 360 minutes) and EX-DEF (499.4 ± 73.5 mg/dL × 360 minutes), respectively, compared to CON (660.2 ± 95.0 mg/dL × 360 minutes) (P < 0.05). CONCLUSIONS A single resistance exercise bout, performed ~15 hours prior to a high-fructose, high-fat meal, attenuated the postprandial TAG response, as compared to a no-exercise control condition, in healthy, resistance-trained men. PMID:26508874

Resistance Exercise Attenuates High-Fructose, High-Fat-Induced Postprandial Lipemia.

PubMed

Wilburn, Jessie R; Bourquin, Jeffrey; Wysong, Andrea; Melby, Christopher L

2015-01-01

Meals rich in both fructose and fat are commonly consumed by many Americans, especially young men, which can produce a significant postprandial lipemic response. Increasing evidence suggests that aerobic exercise can attenuate the postprandial increase in plasma triacylglycerols (TAGs) in response to a high-fat or a high-fructose meal. However, it is unknown if resistance exercise can dampen the postprandial lipemic response to a meal rich in both fructose and fat. Eight apparently healthy men (Mean ± SEM; age = 27 ± 2 years) participated in a crossover study to examine the effects of acute resistance exercise on next-day postprandial lipemia resulting from a high-fructose, high-fat meal. Participants completed three separate two-day conditions in a random order: (1) EX-COMP: a full-body weightlifting workout with the provision of additional kilocalories to compensate for the estimated net energy cost of exercise on day 1, followed by the consumption of a high-fructose, high-fat liquid test meal the next morning (day 2) (~600 kcal) and the determination of the plasma glucose, lactate, insulin, and TAG responses during a six-hour postprandial period; (2) EX-DEF: same condition as EX-COMP but without exercise energy compensation on day 1; and (3) CON: no exercise control. The six-hour postprandial plasma insulin and lactate responses did not differ between conditions. However, the postprandial plasma TAG concentrations were 16.5% and 24.4% lower for EX-COMP (551.0 ± 80.5 mg/dL × 360 minutes) and EX-DEF (499.4 ± 73.5 mg/dL × 360 minutes), respectively, compared to CON (660.2 ± 95.0 mg/dL × 360 minutes) (P < 0.05). A single resistance exercise bout, performed ~15 hours prior to a high-fructose, high-fat meal, attenuated the postprandial TAG response, as compared to a no-exercise control condition, in healthy, resistance-trained men.

Impaired pituitary hormonal response to exhaustive exercise in overtrained endurance athletes.

PubMed

Urhausen, A; Gabriel, H H; Kindermann, W

1998-03-01

The aim of the present prospective longitudinal study was to investigate the hormonal response in overtrained athletes at rest and during exercise consisting of a short-term exhaustive endurance test on a cycle ergometer at an intensity 10% above the individual anaerobic threshold. Over a period of 19+/-1 months, 17 male endurance athletes (cyclists and triathletes; age 23.4+/-1.6 yr; VO2max. 61.2+/-1.8 mL x min(-1) x kg(-1); means+/-SEM) were examined five times on two separate days under standardized conditions. Short-term overtraining states (OT, N=15) were primarily induced by an increase of frequency of high-intensive bouts of exercise or competitions without increase of the total amount of training. OT was compared with normal training states intraindividually (NS, N=62). During OT, the time to exhaustion of the exercise test was significantly decreased by 27% on average. At rest and during exercise, the concentrations in plasma and the nocturnal excretion in urine of free epinephrine and norepinephrine were not significantly changed during OT. At physical rest, the concentrations of (free) testosterone, cortisol, luteinizing hormone, follicle-stimulating hormone, adrenocorticotropic hormone, growth hormone, and insulin during OT were comparable with those during NS. A significantly (P < 0.025) lower maximal exercise-induced increase of the adrenocorticotropic hormone and growth hormone, as well as a trend for a decrease of cortisol (P=0.060) and insulin (P=0.036), was measured. The response of free catecholamines as well as the ergometric performance of an all-out 30-s test was unchanged. Serum urea, uric acid, ferritin, and activity of creatine kinase showed no differences between conditions. In conclusion, the results confirm the hypothesis of a hypothalamo-pituitary dysregulation during OT expressed by an impaired response of pituitary hormones to exhaustive short-endurance exercise.

Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans.

PubMed

Newsom, Sean A; Brozinick, Joseph T; Kiseljak-Vassiliades, Katja; Strauss, Allison N; Bacon, Samantha D; Kerege, Anna A; Bui, Hai Hoang; Sanders, Phil; Siddall, Parker; Wei, Tao; Thomas, Melissa; Kuo, Ming Shang; Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C; Perreault, Leigh; Bergman, Bryan C

2016-06-01

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D (P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH (P < 0.05), tended to be elevated in OB vs. ATH (P = 0.07), and was inversely related to insulin sensitivity among the entire cohort (r = -0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio. Copyright © 2016 the American Physiological Society.

Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans

PubMed Central

Newsom, Sean A.; Brozinick, Joseph T.; Kiseljak-Vassiliades, Katja; Strauss, Allison N.; Bacon, Samantha D.; Kerege, Anna A.; Bui, Hai Hoang; Sanders, Phil; Siddall, Parker; Wei, Tao; Thomas, Melissa; Kuo, Ming Shang; Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C.; Perreault, Leigh

2016-01-01

Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D (P < 0.05), with total PC and PE positively relating to insulin sensitivity (both P < 0.05). Skeletal muscle PC:PE ratio was elevated in T2D compared with OB and ATH (P < 0.05), tended to be elevated in OB vs. ATH (P = 0.07), and was inversely related to insulin sensitivity among the entire cohort (r = −0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio. PMID:27032901

[Immunometabolism of exercise and sedentary lifestyle].

PubMed

Moreno-Eutimio, Mario Adán; Acosta-Altamirano, Gustavo

2014-01-01

Sedentary lifestyle leads to the accumulation of visceral fat. This is accompanied by the infiltration of immune cells with pro-inflammatory characteristics in adipose tissue, causing an increased release of cytokines and generating a low-grade inflammatory state. It has been associated with the development of insulin resistance, atherosclerosis, neurodegeneration, and development of tumors. Exercise can be used as a treatment to improve symptoms of many of these conditions because it promotes an anti-inflammatory effect. In this review we analyze the pro-inflammatory factors present in obesity and the induction of antiinflammatory factors that occur with exercise.

Pre-exercise nutrition: the role of macronutrients, modified starches and supplements on metabolism and endurance performance.

PubMed

Ormsbee, Michael J; Bach, Christopher W; Baur, Daniel A

2014-04-29

Endurance athletes rarely compete in the fasted state, as this may compromise fuel stores. Thus, the timing and composition of the pre-exercise meal is a significant consideration for optimizing metabolism and subsequent endurance performance. Carbohydrate feedings prior to endurance exercise are common and have generally been shown to enhance performance, despite increasing insulin levels and reducing fat oxidation. These metabolic effects may be attenuated by consuming low glycemic index carbohydrates and/or modified starches before exercise. High fat meals seem to have beneficial metabolic effects (e.g., increasing fat oxidation and possibly sparing muscle glycogen). However, these effects do not necessarily translate into enhanced performance. Relatively little research has examined the effects of a pre-exercise high protein meal on subsequent performance, but there is some evidence to suggest enhanced pre-exercise glycogen synthesis and benefits to metabolism during exercise. Finally, various supplements (i.e., caffeine and beetroot juice) also warrant possible inclusion into pre-race nutrition for endurance athletes. Ultimately, further research is needed to optimize pre-exercise nutritional strategies for endurance performance.

Pre-Exercise Nutrition: The Role of Macronutrients, Modified Starches and Supplements on Metabolism and Endurance Performance

PubMed Central

Ormsbee, Michael J.; Bach, Christopher W.; Baur, Daniel A.

2014-01-01

Endurance athletes rarely compete in the fasted state, as this may compromise fuel stores. Thus, the timing and composition of the pre-exercise meal is a significant consideration for optimizing metabolism and subsequent endurance performance. Carbohydrate feedings prior to endurance exercise are common and have generally been shown to enhance performance, despite increasing insulin levels and reducing fat oxidation. These metabolic effects may be attenuated by consuming low glycemic index carbohydrates and/or modified starches before exercise. High fat meals seem to have beneficial metabolic effects (e.g., increasing fat oxidation and possibly sparing muscle glycogen). However, these effects do not necessarily translate into enhanced performance. Relatively little research has examined the effects of a pre-exercise high protein meal on subsequent performance, but there is some evidence to suggest enhanced pre-exercise glycogen synthesis and benefits to metabolism during exercise. Finally, various supplements (i.e., caffeine and beetroot juice) also warrant possible inclusion into pre-race nutrition for endurance athletes. Ultimately, further research is needed to optimize pre-exercise nutritional strategies for endurance performance. PMID:24787031

Elevated muscle TLR4 expression and metabolic endotoxemia in human aging.

PubMed

Ghosh, Sangeeta; Lertwattanarak, Raweewan; Garduño, Jose de Jesus; Galeana, Joaquin Joya; Li, Jinqi; Zamarripa, Frank; Lancaster, Jack L; Mohan, Sumathy; Hussey, Sophie; Musi, Nicolas

2015-02-01

Aging is associated with alterations in glucose metabolism and sarcopenia that jointly contribute to a higher risk of developing type 2 diabetes. Because aging is considered as a state of low-grade inflammation, in this study we examined whether older, healthy (lean, community-dwelling) participants have altered signaling flux through toll-like receptor 4 (TLR4), a key mediator of innate and adaptive immune responses. We also examined whether a 4-month aerobic exercise program would have an anti-inflammatory effect by reducing TLR4 expression and signaling. At baseline, muscle TLR4, nuclear factor κB p50 and nuclear factor κB p65 protein content, and c-Jun N-terminal kinase phosphorylation were significantly elevated in older versus young participants. The plasma concentration of the TLR4 agonist lipopolysaccharide and its binding protein also were significantly elevated in older participants, indicative of metabolic endotoxemia, which is a recently described phenomenon of increased plasma endotoxin level in metabolic disease. These alterations in older participants were accompanied by decreased insulin sensitivity, quadriceps muscle volume, and muscle strength. The exercise training program increased insulin sensitivity, without affecting quadriceps muscle volume or strength. Muscle TLR4, nuclear factor κB, and c-Jun N-terminal kinase, and plasma lipopolysaccharide and lipopolysaccharide binding protein were not changed by exercise. In conclusion, insulin resistance and sarcopenia of aging are associated with increased TLR4 expression/signaling, which may be secondary to metabolic endotoxemia. © The Author 2014. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Exercise effects on adipokines and the IGF axis in men with prostate cancer treated with androgen deprivation: A randomized study

PubMed Central

Mina, Daniel Santa; Connor, Michael K.; Alibhai, Shabbir M.H.; Toren, Paul; Guglietti, Crissa; Matthew, Andrew G.; Trachtenberg, John; Ritvo, Paul

2013-01-01

Background Androgen deprivation therapy (ADT) has significant deleterious effects on body composition that may be accompanied by unfavourable changes in adipokine levels. While exercise has been shown to improve a number of side effects associated with ADT for prostate cancer, no studies have assessed the effect of exercise on adiponectin and leptin levels, which have been shown to alter the mitogenic environment. Methods: Twenty-six men with prostate cancer treated with ADT were randomized to home-based aerobic exercise training or resistance exercise training for 24 weeks. Adiponectin, leptin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor binding protein 3 (IGFBP-3) were analyzed by ELISA (enzyme-linked immunosorbent assay), in addition to physical activity volume, peak aerobic capacity, and anthropometric measurements, at baseline, 3 months and 6 months. Results: Resistance exercise significantly reduced IGF-1 after 3 months (p = 0.019); however, this change was not maintained at 6 months. At 6 months, IGFBP-3 was significantly increased compared to baseline for the resistance training group (p = 0.044). In an exploratory analysis of all exercisers, favourable changes in body composition and aerobic fitness were correlated with favourable levels of leptin, and favourable leptin:adiponectin and IGF-1:IGFBP-3 ratios at 3 and 6 months. Conclusions: Home-based exercise is correlated with positive changes in adipokine levels and the IGF-axis that may be related to healthy changes in physical fitness and body composition. While the improvements of adipokine markers appear to be more apparent with resistance training compared to aerobic exercise, these findings must be considered cautiously and require replication from larger randomized controlled trials to clarify the role of exercise on adipokines and IGF-axis proteins for men with prostate cancer. PMID:24282459

Influence of acute exercise with and without carbohydrate replacement on postprandial lipid metabolism.

PubMed

Harrison, Michael; O'Gorman, Donal J; McCaffrey, Noel; Hamilton, Marc T; Zderic, Theodore W; Carson, Brian P; Moyna, Niall M

2009-03-01

Acute exercise, undertaken on the day before an oral fat tolerance test (OFTT), typically reduces postprandial triglycerides (TG) and increases high-density lipoprotein-cholesterol (HDL-C). However, the benefits of acute exercise may be overstated when studies do not account for compensatory changes in dietary intake. The objective of this study was to determine the influence of acute exercise, with and without carbohydrate (CHO) replacement, on postprandial lipid metabolism. Eight recreationally active young men underwent an OFTT on the morning after three experimental conditions: no exercise [control (Con)], prolonged exercise without CHO replacement (Ex-Def) and prolonged exercise with CHO replacement to restore CHO and energy balance (Ex-Bal). The exercise session in Ex-Def and Ex-Bal consisted of 90 min cycle ergometry at 70% peak oxygen uptake (Vo(2peak)) followed by 10 maximal 1-min sprints. CHO replacement was achieved using glucose solutions consumed at 0, 2, and 4 h postexercise. Muscle glycogen was 40 +/- 4% (P < 0.05) and 94 +/- 3% (P = 0.24) of Con values on the morning of the Ex-Def and Ex-Bal OFTT, respectively. Postprandial TG were 40 +/- 14% lower and postprandial HDL-C, free fatty acids, and 3-hydroxybutyrate were higher in Ex-Def compared with Con (P < 0.05). Most importantly, these exercise effects were not evident in Ex-Bal. Postprandial insulin and glucose and the homeostatic model assessment of insulin resistance (HOMA(IR)) were not significantly different across trials. There was no relation between the changes in postprandial TG and muscle glycogen across trials. In conclusion, the influence of acute exhaustive exercise on postprandial lipid metabolism is largely dependent on the associated CHO and energy deficit.

The effect of aerobic training on CXL5, tumor necrosis factor α and insulin resistance index (HOMA-IR) in sedentary obese women.

PubMed

Zehsaz, Farzad; Farhangi, Negin; Mirheidari, Lamia

2014-01-01

The purpose of the present study was to investigate the effects of a 12-week training program on serum CXC ligand 5, tumor necrosis factor α (TNF-α) and insulin resistance index in obese sedentary women. To this end, twenty-four obese sedentary women were evaluated before and after a 12-week exercise program including a brief warm-up, followed by ~45 min per session of aerobic exercise at an intensity of 60-75% of age-predicted maximum heart rate (~300 kcal/day), followed by a brief cool down, five times per week. After the exercise program, body weight, waist circumference, waist to hip ratio, percentage body fat mass, fasting glucose and insulin of participants were decreased. Furthermore, serum CXCL5 levels were significantly decreased from 2693.2 ±375.8 to 2290.2 ±345.9 pg/ml (p < 0.001) after the training program, which was accompanied with significantly decreased HOMA-IR (p < 0.001) and TNF-α (p < 0.001). Exercise training induced weight loss resulted in a significant reduction in serum CXCL5 concentrations and caused an improvement in insulin resistance in obese sedentary women.

Physical Exercise Promotes Recovery of Neurological Function after Ischemic Stroke in Rats

PubMed Central

Zheng, Hai-Qing; Zhang, Li-Ying; Luo, Jing; Li, Li-Li; Li, Menglin; Zhang, Qingjie; Hu, Xi-Quan

2014-01-01

Although physical exercise is an effective strategy for treatment of ischemic stroke, the underlying protective mechanisms are still not well understood. It has been recently demonstrated that neural progenitor cells play a vital role in the recovery of neurological function (NF) through differentiation into mature neurons. In the current study, we observed that physical exercise significantly reduced the infarct size and improved damaged neural functional recovery after an ischemic stroke. Furthermore, we found that the treatment not only exhibited a significant increase in the number of neural progenitor cells and neurons but also decreased the apoptotic cells in the peri-infarct region, compared to a control in the absence of exercise. Importantly, the insulin-like growth factor-1 (IGF-1)/Akt signaling pathway was dramatically activated in the peri-infarct region of rats after physical exercise training. Therefore, our findings suggest that physical exercise directly influences the NF recovery process by increasing neural progenitor cell count via activation of the IGF-1/Akt signaling pathway. PMID:24945308

Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3

PubMed Central

Hong, Sungguan; Zhou, Wenjun; Fang, Bin; Lu, Wenyun; Loro, Emanuele; Damle, Manashree; Ding, Guolian; Jager, Jennifer; Zhang, Sisi; Zhang, Yuxiang; Feng, Dan; Chu, Qingwei; Dill, Brian D; Molina, Henrik; Khurana, Tejvir S; Rabinowitz, Joshua D; Lazar, Mitchell A; Sun, Zheng

2017-01-01

Type 2 diabetes (T2D) and insulin resistance are associated with reduced glucose utilization in the muscle and poor exercise performance. Here we find that depletion of an epigenome modifier, histone deacetylase 3 (HDAC3), specifically in skeletal muscle causes severe systemic insulin resistance in mice, but markedly enhances exercise endurance and muscle fatigue resistance, despite reducing muscle force. This seemingly paradoxical phenotype is due to lower glucose utilization and greater lipid oxidation in HDAC3-depleted muscles, a fuel switch caused by the activation of anaplerotic reactions driven by AMP deaminase 3 (Ampd3) and branched-chain amino acid catabolism. These findings highlight the pivotal role of amino acid catabolism in muscle fatigue and T2D pathogenesis. Further, as genome occupancy of HDAC3 in skeletal muscle is controlled by the circadian clock, these results delineate an epigenomic regulatory mechanism through which the circadian clock governs skeletal muscle bioenergetics. These findings suggest that physical exercise at certain times of the day or pharmacological targeting of HDAC3 could potentially be harnessed to alter systemic fuel metabolism and exercise performance. PMID:27991918

Epinephrine and the metabolic syndrome.

PubMed

Ziegler, Michael G; Elayan, Hamzeh; Milic, Milos; Sun, Ping; Gharaibeh, Munir

2012-02-01

Epinephrine is the prototypical stress hormone. Its stimulation of all α and β adrenergic receptors elicits short-term systolic hypertension, hyperglycemia, and other aspects of the metabolic syndrome. Acute epinephrine infusion increases cardiac output and induces insulin resistance, but removal of the adrenal medulla has no consistent effect on blood pressure. Epinephrine is the most effective endogenous agonist at the β2 receptor. Transgenic mice that cannot make epinephrine and mice that lack the β2 receptor become hypertensive during exercise, presumably owing to the absence of β2-mediated vasodilatation. Epinephrine-deficient mice also have cardiac remodeling and poor cardiac responses to stress, but do not develop resting hypertension. Mice that cannot make epinephrine have a normal metabolism on a regular 14% fat diet but become hyperglycemic and insulin resistant when they eat a high fat diet. Vigorous exercise prevents diabetes in young mice and humans that overeat. However, exercise is a less effective treatment in older type 2 human diabetics and had no effect on glucose or insulin responses in older, diabetic mice. Sensitivity of the β2 receptor falls sharply with advancing age, and adrenal epinephrine release also decreases. However, treatment of older diabetic mice with a β2 adrenergic agonist improved insulin sensitivity, indicating that β2 subsensitivity can be overcome pharmacologically. Recent studies show that over the long term, epinephrine prevents hypertension during stress and improves glucose tolerance. The hyperglycemic influence of epinephrine is short-lived. Chronic administration of epinephrine and other β2 agonists improves cellular glucose uptake and metabolism. Overall, epinephrine counteracts the metabolic syndrome.

Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change.

PubMed

Rinnankoski-Tuikka, Rita; Hulmi, Juha J; Torvinen, Sira; Silvennoinen, Mika; Lehti, Maarit; Kivelä, Riikka; Reunanen, Hilkka; Kujala, Urho M; Kainulainen, Heikki

2014-08-01

The relation between lipid accumulation and influence of exercise on insulin sensitivity is not straightforward. A proper balance between lipid droplet synthesis, lipolysis, and oxidative metabolism would ensure low local intramyocellular fatty acid levels, thereby possibly protecting against lipotoxicity-associated insulin resistance. This study investigated whether the accumulation of triglycerides and lipid droplets in response to high availability of fatty acids after high-fat feeding would parallel the abundance of intramyocellular perilipin proteins, especially PLIN5. The effects on these variables after diet change or voluntary running exercise intervention in skeletal muscle were also investigated. During a 19-week experiment, C57BL/6J mice were studied in six different groups: low-fat diet sedentary, low-fat diet active, high-fat diet sedentary, high-fat diet active and two groups which were high-fat sedentary for nine weeks, after which divided into low-fat sedentary or low-fat active groups. Myocellular triglyceride concentration and perilipin protein expression levels were assessed. We show that, concurrently with impaired insulin sensitivity, the expression level of PLIN5 and muscular triglyceride concentration increased dramatically after high-fat diet. These adaptations were reversible after the diet change intervention with no additional effect of exercise. After high-fat diet, lipid droplets become larger providing more surface area for PLIN5. We suggest that PLIN5 is an important regulator of lipid droplet turnover in altered conditions of fatty acid supply and consumption. Imbalances in lipid droplet metabolism and turnover might lead to lipotoxicity-related insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of exercise induced hyperlactatemia on retinal blood flow during normo- and hyperglycemia.

PubMed

Garhöfer, Gerhard; Kopf, Andreas; Polska, Elzbieta; Malec, Magdalena; Dorner, Guido T; Wolzt, Michael; Schmetterer, Leopold

2004-05-01

Short term hyperglycemia has previously been shown to induce a blood flow increase in the retina. The mechanism behind this effect is poorly understood. We set out to investigate whether exercise-induced hyperlactatemia may alter the response of retinal blood flow to hyperglycemia. We performed a randomized, controlled two-way cross over study comprising 12 healthy subjects, performed a 6-minutes period of dynamic exercise during an euglcaemic or hyperglycaemic insulin clamp. Retinal blood flow was assessed by combined vessel size measurement with the Zeiss retinal vessel analyzer and measurement of red blood cell velocities using bi-directional laser Doppler velocimetry. Retinal and systemic hemodynamic parameters were measured before, immediately after and 10 and 20 minutes after isometric exercise. On the euglycemic study day retinal blood flow increased after dynamic exercise. The maximum increase in retinal blood flow was observed 10 minutes after the end of exercise when lactate plasma concentration peaked. Hyperglycemia increased retinal blood flow under basal conditions, but had no incremental effect during exercise induced hyperlactatemia. Our results indicate that both lactate and glucose induce an increase in retinal blood flow in healthy humans. This may indicate a common pathway between glucose and lactate induced blood flow changes in the human retina.

Effects of interval aerobic training combined with strength exercise on body composition, glycaemic and lipid profile and aerobic capacity of obese rats.

PubMed

Coll-Risco, Irene; Aparicio, Virginia A; Nebot, Elena; Camiletti-Moirón, Daniel; Martínez, Rosario; Kapravelou, Garyfallia; López-Jurado, María; Porres, Jesús M; Aranda, Pilar

2016-08-01

The purpose of this study was to investigate the effects of interval aerobic training combined with strength exercise in the same training session on body composition, and glycaemic and lipid profile in obese rats. Sixteen lean Zucker rats and sixteen obese Zucker rats were randomly divided into exercise and sedentary subgroups (4 groups, n = 8). Exercise consisted of interval aerobic training combined with strength exercise in the same training session. The animals trained 60 min/day, 5 days/week for 8 weeks. Body composition, lipid and glycaemic profiles and inflammatory markers were assessed. Results showed that fat mass was reduced in both lean and obese rats following the exercise training (effect size (95% confidence interval (CI)) = 1.8 (0.5-3.0)). Plasma low-density lipoprotein-cholesterol and fasting glucose were lower in the exercise compared to the sedentary groups (d = 2.0 (0.7-3.2) and 1.8 (0.5-3.0), respectively). Plasma insulin was reduced in exercise compared to sedentary groups (d = 2.1 (0.8-3.4)). Some exercise × phenotype interactions showed that the highest decreases in insulin, homeostatic model assessment-insulin resistance, fasting and postprandial glucose were observed in the obese + exercise group (all, P < 0.01). The findings of this study suggest that interval aerobic training combined with strength exercise would improve body composition, and lipid and glycaemic profiles, especially in obese rats.

Exercise and the Development of the Artificial Pancreas

PubMed Central

Riddell, Michael C.; Zaharieva, Dessi P.; Yavelberg, Loren; Cinar, Ali; Jamnik, Veronica K.

2015-01-01

Regular physical activity (PA) promotes numerous health benefits for people living with type 1 diabetes (T1D). However, PA also complicates blood glucose control. Factors affecting blood glucose fluctuations during PA include activity type, intensity and duration as well as the amount of insulin and food in the body at the time of the activity. To maintain equilibrium with blood glucose concentrations during PA, the rate of glucose appearance (Ra) to disappearance (Rd) in the bloodstream must be balanced. In nondiabetics, there is a rise in glucagon and a reduction in insulin release at the onset of mild to moderate aerobic PA. During intense aerobic -anaerobic work, insulin release first decreases and then rises rapidly in early recovery to offset a more dramatic increase in counterregulatory hormones and metabolites. An “exercise smart” artificial pancreas (AP) must be capable of sensing glucose and perhaps other physiological responses to various types and intensities of PA. The emergence of this new technology may benefit active persons with T1D who are prone to hypo and hyperglycemia. PMID:26428933

Muscle glycogen synthesis before and after exercise.

PubMed

Ivy, J L

1991-01-01

The importance of carbohydrates as a fuel source during endurance exercise has been known for 60 years. With the advent of the muscle biopsy needle in the 1960s, it was determined that the major source of carbohydrate during exercise was the muscle glycogen stores. It was demonstrated that the capacity to exercise at intensities between 65 to 75% VO2max was related to the pre-exercise level of muscle glycogen, i.e. the greater the muscle glycogen stores, the longer the exercise time to exhaustion. Because of the paramount importance of muscle glycogen during prolonged, intense exercise, a considerable amount of research has been conducted in an attempt to design the best regimen to elevate the muscle's glycogen stores prior to competition and to determine the most effective means of rapidly replenishing the muscle glycogen stores after exercise. The rate-limiting step in glycogen synthesis is the transfer of glucose from uridine diphosphate-glucose to an amylose chain. This reaction is catalysed by the enzyme glycogen synthase which can exist in a glucose-6-phosphate-dependent, inactive form (D-form) and a glucose-6-phosphate-independent, active form (I-form). The conversion of glycogen synthase from one form to the other is controlled by phosphorylation-dephosphorylation reactions. The muscle glycogen concentration can vary greatly depending on training status, exercise routines and diet. The pattern of muscle glycogen resynthesis following exercise-induced depletion is biphasic. Following the cessation of exercise and with adequate carbohydrate consumption, muscle glycogen is rapidly resynthesised to near pre-exercise levels within 24 hours. Muscle glycogen then increases very gradually to above-normal levels over the next few days. Contributing to the rapid phase of glycogen resynthesis is an increase in the percentage of glycogen synthase I, an increase in the muscle cell membrane permeability to glucose, and an increase in the muscle's sensitivity to insulin. The slow phase of glycogen synthesis appears to be under the control of an intermediate form of glycogen synthase that is highly sensitive to glucose-6-phosphate activation. Conversion of the enzyme to this intermediate form may be due to the muscle tissue being constantly exposed to an elevated plasma insulin concentration subsequent to several days of high carbohydrate consumption. For optimal training performance, muscle glycogen stores must be replenished on a daily basis. For the average endurance athlete, a daily carbohydrate consumption of 500 to 600g is required. This results in a maximum glycogen storage of 80 to 100 mumol/g wet weight.(ABSTRACT TRUNCATED AT 400 WORDS)

Contractile activity of human skeletal muscle cells prevents insulin resistance by inhibiting pro-inflammatory signalling pathways.

PubMed

Lambernd, S; Taube, A; Schober, A; Platzbecker, B; Görgens, S W; Schlich, R; Jeruschke, K; Weiss, J; Eckardt, K; Eckel, J

2012-04-01

Obesity is closely associated with muscle insulin resistance and is a major risk factor for the pathogenesis of type 2 diabetes. Regular physical activity not only prevents obesity, but also considerably improves insulin sensitivity and skeletal muscle metabolism. We sought to establish and characterise an in vitro model of human skeletal muscle contraction, with a view to directly studying the signalling pathways and mechanisms that are involved in the beneficial effects of muscle activity. Contracting human skeletal muscle cell cultures were established by applying electrical pulse stimulation. To induce insulin resistance, skeletal muscle cells were incubated with human adipocyte-derived conditioned medium, monocyte chemotactic protein (MCP)-1 and chemerin. Similarly to in exercising skeletal muscle in vivo, electrical pulse stimulation induced contractile activity in human skeletal muscle cells, combined with the formation of sarcomeres, activation of AMP-activated protein kinase (AMPK) and increased IL-6 secretion. Insulin-stimulated glucose uptake was substantially elevated in contracting cells compared with control. The incubation of skeletal muscle cells with adipocyte-conditioned media, chemerin and MCP-1 significantly reduced the insulin-stimulated phosphorylation of Akt. This effect was abrogated by concomitant pulse stimulation of the cells. Additionally, pro-inflammatory signalling by adipocyte-derived factors was completely prevented by electrical pulse stimulation of the myotubes. We showed that the effects of electrical pulse stimulation on skeletal muscle cells were similar to the effect of exercise on skeletal muscle in vivo in terms of enhanced AMPK activation and IL-6 secretion. In our model, muscle contractile activity eliminates insulin resistance by blocking pro-inflammatory signalling pathways. This novel model therefore provides a unique tool for investigating the molecular mechanisms that mediate the beneficial effects of muscle contraction.

Cost-effectiveness of an exercise program during pregnancy to prevent gestational diabetes: results of an economic evaluation alongside a randomised controlled trial.

PubMed

Oostdam, Nicolette; Bosmans, Judith; Wouters, Maurice G A J; Eekhoff, Elisabeth M W; van Mechelen, Willem; van Poppel, Mireille N M

2012-07-04

The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide. GDM and the risks associated with GDM lead to increased health care costs and losses in productivity. The objective of this study is to evaluate whether the FitFor2 exercise program during pregnancy is cost-effective from a societal perspective as compared to standard care. A randomised controlled trial (RCT) and simultaneous economic evaluation of the FitFor2 program were conducted. Pregnant women at risk for GDM were randomised to an exercise program to prevent high maternal blood glucose (n = 62) or to standard care (n = 59). The exercise program consisted of two sessions of aerobic and strengthening exercises per week. Clinical outcome measures were maternal fasting blood glucose levels, insulin sensitivity and infant birth weight. Quality of life was measured using the EuroQol 5-D and quality-adjusted life-years (QALYs) were calculated. Resource utilization and sick leave data were collected by questionnaires. Data were analysed according to the intention-to-treat principle. Missing data were imputed using multiple imputations. Bootstrapping techniques estimated the uncertainty surrounding the cost differences and incremental cost-effectiveness ratios. There were no statistically significant differences in any outcome measure. During pregnancy, total health care costs and costs of productivity losses were statistically non-significant (mean difference €1308; 95%CI €-229 - €3204). The cost-effectiveness analyses showed that the exercise program was not cost-effective in comparison to the control group for blood glucose levels, insulin sensitivity, infant birth weight or QALYs. The twice-weekly exercise program for pregnant women at risk for GDM evaluated in the present study was not cost-effective compared to standard care. Based on these results, implementation of this exercise program for the prevention of GDM cannot be recommended. NTR1139.

The Yale Fitness Intervention Trial in female cancer survivors: Cardiovascular and physiological outcomes.

PubMed

Knobf, M Tish; Jeon, Sangchoon; Smith, Barbara; Harris, Lyndsay; Thompson, Siobhan; Stacy, Mitchel R; Insogna, Karl; Sinusas, Albert J

Induced premature menopause and cardio-toxic therapy increase cardiovascular disease risk in female cancer survivors. To compare the effects of a 12 month aerobic-resistance fitness center intervention to home based physical activity on cardiovascular function and metabolic risk factors. Subjects (N = 154) who had completed primary and/or adjuvant chemotherapy (past 3 years) were randomized to a fitness center intervention or a home based group. The fitness center intervention was a structured thrice weekly aerobic (30 min brisk walking treadmill in target heart range) combined with resistance (30 min of lower body strength training) exercise program, supervised for the first 6 months. The home based group received national guidelines for 30 min moderate intensity exercise most days of the week. Fasting serum samples were collected at baseline, 6 and 12 months for insulin, glucose, lipids and hemoglobin A-1C. A graded exercise stress test was also performed at baseline and 6 months. The majority of subjects were white (85.7%), had breast cancer (83.1%) and the average age was 51.9 years. Subjects in the fitness center intervention had significantly improved time on treadmill (p = .039), improved heart rate recovery at 1 min (p = .028), greater MET minutes/week (p ≤ .0001), a trend for improved insulin resistance (p = .067) and stable insulin levels (p = .045) compared to the home based physical activity group. Exercise represents a potential cardiac risk reduction intervention for cancer survivors. CLINICAL TRIALS.GOV: NCT01102985. Copyright © 2017. Published by Elsevier Inc.

Exercise and Glycemic Control: Focus on Redox Homeostasis and Redox-Sensitive Protein Signaling

PubMed Central

Parker, Lewan; Shaw, Christopher S.; Stepto, Nigel K.; Levinger, Itamar

2017-01-01

Physical inactivity, excess energy consumption, and obesity are associated with elevated systemic oxidative stress and the sustained activation of redox-sensitive stress-activated protein kinase (SAPK) and mitogen-activated protein kinase signaling pathways. Sustained SAPK activation leads to aberrant insulin signaling, impaired glycemic control, and the development and progression of cardiometabolic disease. Paradoxically, acute exercise transiently increases oxidative stress and SAPK signaling, yet postexercise glycemic control and skeletal muscle function are enhanced. Furthermore, regular exercise leads to the upregulation of antioxidant defense, which likely assists in the mitigation of chronic oxidative stress-associated disease. In this review, we explore the complex spatiotemporal interplay between exercise, oxidative stress, and glycemic control, and highlight exercise-induced reactive oxygen species and redox-sensitive protein signaling as important regulators of glucose homeostasis. PMID:28529499

Effect of carbohydrate-electrolyte consumption on insulin, cortisol hormones and blood glucose after high-intensity exercise.

PubMed

Mor, Ahmet; Kayacan, Yildirim; Ipekoglu, Gokhan; Arslanoglu, Erkal

2018-04-21

This study aimed to examine the effect of CHO-E consumption after high-intensity exercise on insulin, cortisol hormones and blood glucose responses, which is important for performance and recovery in athletes. Sixteen volunteers, male athletes, participated into this study. Athletes were divided into two groups as experiment (CHO-E) and placebo (PLA). Blood was taken from the athletes three times as basal, post-exercise (PE) and 2 h after ingestion of supplement (PS). When inter-group comparisons, insulin was significantly higher in the CHO-E group than the PLA group at the PS phase (p < .05). Cortisol significantly decreased in the CHO-E group at the PS compared to the PE (p < .05). Carbohydrate-electrolyte consumption after high-intensity exercise, accelerates the recovery process by providing optimal recovery, and enable the metabolism to remain in the anabolic state by preventing it from entering in the catabolic process as well as provides hormonal balance in metabolism.

Acute exercise increases brain region-specific expression of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.

PubMed

Takimoto, Masaki; Hamada, Taku

2014-05-01

The brain is capable of oxidizing lactate and ketone bodies through monocarboxylate transporters (MCTs). We examined the protein expression of MCT1, MCT2, MCT4, glucose transporter 1 (GLUT1), and cytochrome-c oxidase subunit IV (COX IV) in the rat brain within 24 h after a single exercise session. Brain samples were obtained from sedentary controls and treadmill-exercised rats (20 m/min, 8% grade). Acute exercise resulted in an increase in lactate in the cortex, hippocampus, and hypothalamus, but not the brainstem, and an increase in β-hydroxybutyrate in the cortex alone. After a 2-h exercise session MCT1 increased in the cortex and hippocampus 5 h postexercise, and the effect lasted in the cortex for 24 h postexercise. MCT2 increased in the cortex and hypothalamus 5-24 h postexercise, whereas MCT2 increased in the hippocampus immediately after exercise, and remained elevated for 10 h postexercise. Regional upregulation of MCT2 after exercise was associated with increases in brain-derived neurotrophic factor and tyrosine-related kinase B proteins, but not insulin-like growth factor 1. MCT4 increased 5-10 h postexercise only in the hypothalamus, and was associated with increased hypoxia-inducible factor-1α expression. However, none of the MCT isoforms in the brainstem was affected by exercise. Whereas GLUT 1 in the cortex increased only at 18 h postexercise, COX IV in the hippocampus increased 10 h after exercise and remained elevated for 24 h postexercise. These results suggest that acute prolonged exercise induces the brain region-specific upregulation of MCT1, MCT2, MCT4, GLUT1, and COX IV proteins.

Effect of palatable hyperlipidic diet on lipid metabolism of sedentary and exercised rats.

PubMed

Estadella, Debora; Oyama, Lila M; Dâmaso, Ana R; Ribeiro, Eliane B; Oller Do Nascimento, Claudia M

2004-02-01

The present study was designed to examine 1) whether continuous feeding with a palatable hyperlipidic diet and cycling this diet with chow diet would affect lipid and carbohydrate metabolism in a similar way; and 2) whether the effect of chronic exercise on lipid and carbohydrate metabolism would be modified by these diet regimens. Male 25-d-old Wistar rats were assigned to one of six groups: sedentary rats fed with chow diet; exercised (swimming 90 min/d, 5 d/wk) rats fed with chow diet; sedentary rats fed with a palatable hyperlipidic diet; exercised rats fed with the palatable hyperlipidic diet; sedentary rats fed with food cycles (four cycles alternating the chow and hyperlipidic diets weekly); and exercised rats fed with food cycles. After 8 wk of treatment, the animals were killed 24 h after the last exercise session. The hyperlipidic diet and food cycles schedules caused similar increases in body weight gain, carcass lipogenesis rate and adiposity, lipid content of the liver and gastrocnemius muscle, and serum total lipid, triacylglycerol, insulin, and leptin levels. The exercise attenuated body weight gain, adipose tissue mass, and serum triacylglycerol, insulin, and leptin levels similarly in the hyperlipidic and food cycles groups. Carcass lipogenesis rate was not affected by exercise in any of the three groups. The data showed that the continuous intake of a hyperlipidic palatable diet for 8 wk and the alternation of the high-fat intake with periods of chow intake cause obesity and affected lipid metabolism in a similar way. Chronic exercise attenuated body weight gain and adiposity and improved serum lipid concentrations in both high-fat feeding regimens.

Effects of exercise at individual anaerobic threshold and maximal fat oxidation intensities on plasma levels of nesfatin-1 and metabolic health biomarkers.

PubMed

Mohebbi, Hamid; Nourshahi, Maryam; Ghasemikaram, Mansour; Safarimosavi, Saleh

2015-03-01

Exercise is recognized as an effective method of weight management and short-term appetite regulation tool. The effect of different exercise intensities on appetite regulation hormones in healthy overweight participants has not been intensively studied. The aim of this study was to examine the influence of exercise at individual anaerobic threshold (IAT) and maximal fat oxidation (Fatmax) intensities on the nesfatin-1 response and metabolic health biomarkers in overweight men. Nine healthy overweight males (age, 23.1 ± 1.1 years) volunteered in this study in a counterbalanced order. Blood samples were obtained before, immediately after, and following the first 45 min of recovery for measuring plasma variables. There was significant decrease in plasma levels of nesfatin-1 and leptin after exercise at the IAT intensity which remained lower than baseline following 45 min of recovery. However, nesfatin-1 and leptin levels did not change significantly in any time courses of Fatmax intensity (P > 0.09). Plasma interleukin-6 (IL-6) concentration increased during exercise in both intensities (P < 0.05), whereas changes in free fatty acids (FFAs) and epinephrine concentrations were significant only at the IAT. In addition, a significant correlation was found among nesfatin-1 levels with insulin (r = 0.39, P < 0.05) and glucose (r = 0.41, P < 0.05) at basal and in response to exercise. These results indicate that IAT has a greater exercise-induced appetite regulation effect compared with Fat(max). Based on these data, the intensity of exercise may have an important role in changes of nesfatin-1, leptin, FFA, and epinephrine concentrations even though this was not the case for IL-6 and insulin resistance.

Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review.

PubMed

Harrison, Anne L; Shields, Nora; Taylor, Nicholas F; Frawley, Helena C

2016-10-01

Does exercise improve postprandial glycaemic control in women diagnosed with gestational diabetes mellitus? A systematic review of randomised trials. Pregnant women diagnosed with gestational diabetes mellitus. Exercise, performed more than once a week, sufficient to achieve an aerobic effect or changes in muscle metabolism. Postprandial blood glucose, fasting blood glucose, glycated haemoglobin, requirement for insulin, adverse events and adherence. This systematic review identified eight randomised, controlled trials involving 588 participants; seven trials (544 participants) had data that were suitable for meta-analysis. Five trials scored ≥ 6 on the PEDro scale, indicating a relatively low risk of bias. Meta-analysis showed that exercise, as an adjunct to standard care, significantly improved postprandial glycaemic control (MD -0.33mmol/L, 95% CI -0.49 to -0.17) and lowered fasting blood glucose (MD -0.31 mmol/L, 95% CI -0.56 to -0.05) when compared with standard care alone, with no increase in adverse events. Effects of similar magnitude were found for aerobic and resistance exercise programs, if performed at a moderate intensity or greater, for 20 to 30minutes, three to four times per week. Meta-analysis did not show that exercise significantly reduced the requirement for insulin. All studies reported that complications or other adverse events were either similar or reduced with exercise. Aerobic or resistance exercise, performed at a moderate intensity at least three times per week, safely helps to control postprandial blood glucose levels and other measures of glycaemic control in women diagnosed with gestational diabetes mellitus. PROSPERO CRD42015019106. [Harrison AL, Shields N, Taylor NF, Frawley HC (2016) Exercise improves glycaemic control in women diagnosed with gestational diabetes mellitus: a systematic review.Journal of Physiotherapy62: 188-196]. Copyright © 2016 Australian Physiotherapy Association. Published by Elsevier B.V. All rights reserved.

Regulation of fuel metabolism during exercise in hypopituitarism with growth hormone-deficiency (GHD).

PubMed

Zueger, Thomas; Loher, Hannah; Egger, Andrea; Boesch, Chris; Christ, Emanuel

2016-08-01

Growth hormone (GH) has a strong lipolytic action and its secretion is increased during exercise. Data on fuel metabolism and its hormonal regulation during prolonged exercise in patients with growth hormone deficiency (GHD) is scarce. This study aimed at evaluating the hormonal and metabolic response during aerobic exercise in GHD patients. Ten patients with confirmed GHD and 10 healthy control individuals (CI) matched for age, sex, BMI, and waist performed a spiroergometric test to determine exercise capacity (VO2max). Throughout a subsequent 120-minute exercise on an ergometer at 50% of individual VO2max free fatty acids (FFA), glucose, GH, cortisol, catecholamines and insulin were measured. Additionally substrate oxidation assessed by indirect calorimetry was determined at begin and end of exercise. Exercise capacity was lower in GHD compared to CI (VO2max 35.5±7.4 vs 41.5±5.5ml/min∗kg, p=0.05). GH area under the curve (AUC-GH), peak-GH and peak-FFA were lower in GHD patients during exercise compared to CI (AUC-GH 100±93.2 vs 908.6±623.7ng∗min/ml, p<0.001; peak-GH 1.5±1.53 vs 12.57±9.36ng/ml, p<0.001, peak-FFA 1.01±0.43 vs 1.51±0.56mmol/l, p=0.036, respectively). There were no significant differences for insulin, cortisol, catecholamines and glucose. Fat oxidation at the end of exercise was higher in CI compared to GHD patients (295.7±73.9 vs 187.82±103.8kcal/h, p=0.025). A reduced availability of FFA during a 2-hour aerobic exercise and a reduced fat oxidation at the end of exercise may contribute to the decreased exercise capacity in GHD patients. Catecholamines and cortisol do not compensate for the lack of the lipolytic action of GH in patients with GHD. Copyright © 2016 Elsevier Ltd. All rights reserved.

Short-term endurance training after coronary artery bypass grafting improves insulin resistance parameters in patients with hypertension.

PubMed

Borowicz-Bieńkowska, Sławomira; Przywarska, Izabela; Dylewicz, Piotr; Pilaczyńska-Szcześniak, Łucja; Rychlewski, Tadeusz; Wilk, Małgorzata; Rózańska, Anna

2004-05-01

It has been shown that short-term exercise training improves insulin resistance parameters in patients with ischaemic heart disease. The effects of such a rehabilitation programme in patients with hypertension have not been well established. To assess whether short-term endurance training after coronary artery bypass grafting (CABG) may improve metabolic parameters and reduce blood pressure in patients with hypertension. The study group consisted of 30 male patients (15 with hypertension and 15 normotensive) aged 55+/-2.1 years who underwent CABG 1 to 6 months before the initiation of a 3-week endurance training. Glucose, insulin and C-peptide blood levels as well as binding and degradation of 125I-insulin by erythrocyte receptors were assessed before and after the training programme. The effects of training on blood pressure values were also evaluated. A significant improvement (p<0.01) in the insulin resistance parameters, i.e. binding and degradation of labelled insulin was noted only in patients with hypertension. This was accompanied by a significant (p<0.05) increase in the HDL-cholesterol level. In the subgroup with hypertension, both the exercise systolic and diastolic pressures decreased significantly (p<0.05 and p<0.01, respectively), and similar changes were noted in the resting systolic and diastolic blood pressures values (p<0.05). Rehabilitation after CABG based on the endurance training was especially effective in patients with hypertension in whom beneficial changes in some metabolic risk factors of ischaemic heart disease as well as the reduction in the blood pressure values were observed.

Cellular fibronectin response to supervised moderate aerobic training in patients with type 2 diabetes

PubMed Central

Alghadir, Ahmad H.; Gabr, Sami A.; Al-Eisa, Einas

2016-01-01

[Purpose] Physical activity is one of the most pivotal targets for the prevention and management of vascular complications, especially endothelial dysfunctions. Cellular fibronectin is an endothelium-derived protein involved in subendothelial matrix assembly. Its plasma levels reflect matrix alterations and vessel wall destruction in patients with type II diabetes. This study investigated the influence of 12 weeks of supervised aerobic training on cellular fibronectin and its relationship with insulin resistance and body weight in type II diabetic subjects. [Subjects and Methods] This study included 50 men with type II diabetes who had a mean age of 48.8 ± 14.6 years and were randomly divided into two groups: an aerobic exercise group (12 weeks, three 50 minutes sessions per week) and control group. To examine changes in cellular fibronectin, glycosylated hemoglobin, insulin resistance, fasting insulin, fasting blood sugar, and lipid profile, 5 ml of blood was taken from the brachial vein of patients before and 48 hours after completion of the exercise period and after 12 hours of fasting at rest. Data analysis was performed using the SPSS-16 software with the independent and paired t-tests. [Results] A significant decrease was observed in body mass index and body fat percentage in the experimental group. Compared with the control group, the aerobic exercise group showed a significant decrease in cellular fibronectin, glycosylated hemoglobin, insulin resistance, fasting insulin, fasting blood sugar, and lipid profile after 12 weeks of aerobic exercise. The change in cellular fibronectin showed positive significant correlation with body mass index, diabetic biomarkers, and physical activity level. [Conclusion] The results showed that supervised aerobic exercise as a stimulus can change the levels of cellular fibronectin as matrix metalloproteinase protein a long with improvement of insulin sensitivity and glycosylated hemoglobin in order to prevent cardiovascular diseases in men with diabetes PMID:27190433

Effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance of overweight women.

PubMed

Faramarzi, Mohammad; Banitalebi, Ebrahim; Nori, Saba; Farzin, Shiva; Taghavian, Zohreh

2016-04-01

Omentin, chemerin and vaspin are novel adipokines that are secreted from adipose tissue and improved insulin sensitive. The purpose of this study was to examine the effects of rhythmic aerobic exercise plus core stability training on serum omentin, chemerin and vaspin levels and insulin resistance (IR) of overweight women. Forty aged healthy women (age; 25-45 years old, waist circumference [WC]>88 cm; Body Mass Index (BMI)>25 kg/m2) were selected purposely and divided in two control (N.=16) and experimental (N.=19) groups. Five dropped out during the study. The experimental group trained 12 weeks (3 sessions per week, one hr/session). The exercise program consisted of rhythmic aerobic exercise (55-85% maximum heart rate) along with core stability training. Serum chemerin, omentin, vaspin and insulin concentration were assayed by commercially ELISA kit. IR was evaluated according to the Homeostasis Model Assessment of Insulin Resistance Index (HOMA-IR). Data were analyzed by dependent and independent t-test to compare pre-test and post-test in each group and to compare the amount of changes in experimental and control training groups after twelve weeks. The result showed that exercise training had significant effect on BMI (P=0.00), WC (P=0.00), body fat (P=0.05), chemerin (P=0.041) and vaspin (P=0.045). But, this training had non-significant effect on plasma omentin level (P=0.090), plasma glucose level (P=0.670), insulin (P=0.11) and IR (P=0.07). Despite the fact that this kind of intervention could be an effective treatment to improve some adipokine levels and was accompanied by decreased body fat and waist circumference. However, more intense training is required to significantly change IR and serum omentin level in overweight women.

Acute effects of physical exercise on the serum insulin-like growth factor system in women with fibromyalgia.

PubMed

Mannerkorpi, Kaisa; Landin-Wilhelmsen, Kerstin; Larsson, Anette; Cider, Åsa; Arodell, Olivia; Bjersing, Jan L

2017-01-25

Increased Serum insulin-like growth factor-1 (S-IGF-1) has been noted after physical activity in healthy subjects, while the acute release of S-IGF-1 in relation to exercise has not previously been studied in women with fibromyalgia (FM). S-IGF-1 and its binding protein (S-IGFBP-3) are mediated by growth hormone and have anabolic effects on the skeletal muscle. Aim of the study was to investigate acute release of IGF-1 after aerobic exercise in women with FM. The acute effect of physical exercise on S-IGF-1 and S-IGFBP-3 were studied in 22 women with FM and in 27 healthy controls during moderate and high-intensity cycling (i.e. ratings 12-13 and 15-17, on Borg's perceived exertion scale (RPE), respectively). Self-reported pain and fatigue were recorded. Differences within and between the two groups were analyzed. After 15 min of bicycling, S-IGF-1 and S-IGFBP-3 increased both within the group with FM and in the healthy controls (p < 0.01). The increases in S-IGF-1 did not significantly differ between the women with FM and the healthy control group (mean increase 11 ± 10 vs. 11 ± 15 ng/ml and 13 ± 10 vs. 19 ± 22 ng/ml) when bicycling at moderate or high intensity, respectively. Self-reported pain and fatigue during exercise, irrespective of intensity, were higher in women with FM compared with healthy controls (p < 0.001). Fifteen minutes bicycling at moderate intensity was sufficient to acutely mobilise S-IGF-1 in women with FM similarly to healthy controls in spite of higher score of fatigue and pain in women with FM. Hence, patients with FM were able to activate their skeletal muscle metabolism during a short, moderate bout of exercise and were not resistant to training effects. The result is important for encouraging clinical rehabilitation of patients with FM who commonly exercise at a moderate, rather than at a high-intensity level. ClinicalTrials.govNCT01592916 , May 4, 2012.

Intense Exercise Promotes Adult Hippocampal Neurogenesis But Not Spatial Discrimination

PubMed Central

So, Ji H.; Huang, Chao; Ge, Minyan; Cai, Guangyao; Zhang, Lanqiu; Lu, Yisheng; Mu, Yangling

2017-01-01

Hippocampal neurogenesis persists throughout adult life and plays an important role in learning and memory. Although the influence of physical exercise on neurogenesis has been intensively studied, there is controversy in regard to how the impact of exercise may vary with its regime. Less is known about how distinct exercise paradigms may differentially affect the learning behavior. Here we found that, chronic moderate treadmill running led to an increase of cell proliferation, survival, neuronal differentiation, and migration. In contrast, intense running only promoted neuronal differentiation and migration, which was accompanied with lower expressions of vascular endothelial growth factor, brain-derived neurotrophic factor, insulin-like growth factor 1, and erythropoietin. In addition, the intensely but not mildly exercised animals exhibited a lower mitochondrial activity in the dentate gyrus. Correspondingly, neurogenesis induced by moderate but not intense exercise was sufficient to improve the animal’s ability in spatial pattern separation. Our data indicate that the effect of exercise on spatial learning is intensity-dependent and may involve mechanisms other than a simple increase in the number of new neurons. PMID:28197080

Impact of long-term high-intensity interval and moderate-intensity continuous training on subclinical inflammation in overweight/obese adults.

PubMed

Gerosa-Neto, José; Antunes, Barbara M M; Campos, Eduardo Z; Rodrigues, Jhennyfer; Ferrari, Gustavo D; Rosa Neto, José C; Bueno, Carlos R; Lira, Fábio S

2016-12-01

Obesity is a risk factor able to trigger several inflammatory alterations and the imbalance between pro- and anti-inflammatory cytokine productions. Physical exercise is an important strategy for reduction of inflammatory established process. The aim of this study was to evaluate the effect of 16 weeks of three exercise training programs in the inflammatory profile and insulin resistance in overweight/obesity. Thirty two men and women (46.4±10.1 years; 162.0±9.1 cm; 82.0±13.6 kg) were divided into three groups for training on a treadmill: continuous at 70% maximum heart rate (HRmax) 5 times a week (CONT); 1×4 min (1-bout) and 4×4 min (high intensity interval training, HIIT) at 90% HRmax 3 times a week. Interleukin (IL) 6 and IL-10, tumor necrosis factor-alpha (TNF-α), insulin and adiponectin levels were analyzed by enzyme-linked immunosorbent assay, and homeostasis model assessment insulin resistance was calculated. After 16 weeks of training blood concentrations of IL-6 decreased in the HIIT group ( P =0.035), TNF-α decreased in the CONT ( P =0.037) and increased in HIIT ( P =0.001) and adiponectin decreased in the three training models. There was a trend towards decreased body weight and body mass index (BMI) after HIIT only ( P =0.059 and P =0.060, respectively). Despite the decrease of adiponectin and the increase of TNF-α in HIIT group, insulin sensitivity showed a trend for improvement ( P =0.08). HIIT program decreased IL-6 at rest and although not significant was the only who tended to decrease total body weight and BMI. Taken together, our data suggest that both HIIT as well as CONT exercises training program promotes changes in inflammatory profile in overweight/obesity, but dissimilar response is seen in TNF-α levels.

Improvements in insulin sensitivity after aerobic exercise and weight loss in older women with a history of gestational diabetes and type 2 diabetes mellitus.

PubMed

Ryan, Alice S

2016-05-01

To determine whether a hypocaloric diet alone (WL) or with exercise training (AEX + WL) is effective in improving body composition, fitness, glucose utilization and CVD risk factors in sedentary women with a history of gestational diabetes (GDM) and with type 2 diabetes (T2DM). Longitudinal clinical investigation of 25 overweight/obese (BMI: 32 ± 1 kg/m(2)) women (59 ± 1 yrs) with a GDM history (n = 20) or T2DM (n = 5). Women completed 6 months WL (n = 10) or AEX+WL (n = 15) with VO2max, body composition, and glucose tolerance testing. Insulin sensitivity was measured during the last 30 min of 2 h hyperinsulinemic-euglycemic clamps (40 mU·m(-2.)min(-1)) before and after interventions. Body weight decreased ~7% after WL and AEX+WL (p < 0.001), with an 11-12% decrease in fat mass (p < 0.0001). Visceral fat and subcutaneous abdominal fat decreased 27 and 10% after WL (p < 0.01) and 14 and 11% after AEX + WL (p < 0.05). VO2max increased 16% after AEX + WL (p < 0.001) and did not change after WL. Glucose AUC decreased 14 and 13% after WL (p < 0.05) and AEX + WL (p < 0.01) with a 42% decrease in insulin AUC after AEX + WL (p < 0.01). Glucose utilization increased 25% (p = 0.05) with AEX + WL and 7% with WL. A six-month aerobic exercise program combined with moderate weight loss reduces body weight, visceral and subcutaneous abdominal fat, and improves insulin sensitivity in older women who had previously been diagnosed with GDM and those with T2DM. These findings should encourage women with a history of GDM to engage in an active lifestyle and reduce caloric intake to lower the risk for the development of T2DM.

Improvements in Insulin Sensitivity after Aerobic Exercise and Weight Loss in Older Women with a History of Gestational Diabetes and Type 2 Diabetes Mellitus

PubMed Central

Ryan, Alice S.

2016-01-01

Purpose To determine whether a hypocaloric diet alone (WL) or with exercise training (AEX+WL) is effective in improving body composition, fitness, glucose utilization and CVD risk factors in sedentary women with a history of gestational diabetes (GDM) and with type 2 diabetes (T2DM). Materials and Methods Longitudinal clinical investigation of 25 overweight/obese (BMI:32±1 kg/m2) women (59±1 yrs) with a GDM history (n=20) or T2DM (n=5). Women completed 6 months WL (n=10) or AEX+WL (n=15) with VO2max, body composition, and glucose tolerance testing. Insulin sensitivity was measured during the last 30 min of 2-hour hyperinsulinemic-euglycemic clamps (40 mU·m−2·min−1) before and after interventions. Results Body weight decreased ~7% after WL and AEX+WL (P<0.001), with an 11–12% decrease in fat mass (P<0.0001). Visceral fat and subcutaneous abdominal fat decreased 27 and 10% after WL (P<0.01) and 14 and 11% after AEX+WL (P<0.05). VO2max increased 16% after AEX+WL (P<0.001) and did not change after WL. Glucose AUC decreased 14 and 13% after WL (P<0.05) and AEX+WL (P<0.01) with a 42% decrease in insulin AUC after AEX+WL (P<0.01). Glucose utilization increased 25% (P=0.05) with AEX+WL and 7% with WL. Conclusions A six-month aerobic exercise program combined with moderate weight loss reduces body weight, visceral and subcutaneous abdominal fat, and improves insulin sensitivity in older women who had previously been diagnosed with GDM and those with T2DM. These findings should encourage women with a history of GDM to engage in an active lifestyle and reduce caloric intake to lower the risk for the development of T2DM. PMID:26925596

Inorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Release.

PubMed

Roberts, Lee D; Ashmore, Tom; McNally, Ben D; Murfitt, Steven A; Fernandez, Bernadette O; Feelisch, Martin; Lindsay, Ross; Siervo, Mario; Williams, Elizabeth A; Murray, Andrew J; Griffin, Julian L

2017-03-01

Exercise is an effective intervention for the prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals that contribute to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance, and performance. The transcriptional regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers, an effect reversed in insulin resistance and diabetes. We found that nitrate induces PGC1α expression and a switch toward type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1α-dependent myokine FNDC5/irisin and β-aminoisobutyric acid from myotubes and muscle in rats and humans. Both exercise and nitrate stimulated PGC1α-mediated γ-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans; thus, GABA may function as an exercise/PGC1α-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health. © 2017 by the American Diabetes Association.

Diet and exercise regimens to improve breast carcinoma prognosis.

PubMed

Stoll, B A

1996-12-15

Clinical studies agree that obesity worsens the prognosis of breast carcinoma in both pre- and postmenopausal women. There is considerable evidence that free estrogen levels are raised in obese women, especially in those with abdominal (visceral) obesity and hyperinsulinemic insulin resistance. It has been postulated that estrogen may synergize with the concomitants of hyperinsulinemia in stimulating breast carcinoma growth. Reduction of estrogen and insulin levels may slow this growth. A current clinical trial in the U.S. is examining the effect of dietary fat reduction on recurrence and survival rates after primary treatment of early stage breast carcinoma in postmenopausal women. Recent research suggests that a high fiber/fat ratio in the diet and regular physical exercise may help to reduce estrogen and insulin levels. Regular exercise may also help to maintain long term weight loss. A second-generation trial is proposed of a high fiber, low fat diet associated with regular physical exercise in women with early breast carcinoma. Changes in circulating levels of estrogen and insulin will be monitored in relation to timing of tumor recurrence and second primary breast carcinoma rates. Weight and fat distribution will be monitored in relation to measurements of dietary compliance. Breast carcinoma patients wishing to change their lifestyle are likely to benefit from a higher dietary fiber/fat ratio combined with regular physical exercise. If the trial shows an improved prognosis from intervention correlated with changes in biomarkers, a similar trial model could be used to identify specific fiber supplements, micronutrients, and exercise regimens that may improve survival rates in patients with breast carcinoma.

Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.

PubMed

García-Hermoso, A; Ceballos-Ceballos, R J M; Poblete-Aro, C E; Hackney, A C; Mota, J; Ramírez-Vélez, R

2017-04-01

Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. Exercise was associated with a significant increase in adiponectin (WMD=0.882 μg ml -1 , 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.

Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men.

PubMed

Veldhuis, Johannes D; Olson, Thomas P; Takahashi, Paul Y; Miles, John M; Joyner, Michael J; Yang, Rebecca J; Wigham, Jean

2015-09-01

Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6h. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1h, followed by negative feedback 3-5h later. The dynamic GH excursion was strongly (R(2)=0.634) influenced by (i) insulin negatively (P=0.011), (ii) power positively (P=0.0008), and (iii) E2 positively (P=0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P=0.0039) and power positively (P=0.0034) (R(2)=0.454). Under rest/saline, power (P=0.031) and total abdominal fat (P=0.012) (R(2)=0.267) were the dominant correlates of GH excursions. In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

A Methodology to Compare Insulin Dosing Recommendations in Real-Life Settings.

PubMed

Groat, Danielle; Grando, Maria A; Thompson, Bithika; Neto, Pedro; Soni, Hiral; Boyle, Mary E; Bailey, Marilyn; Cook, Curtiss B

2017-11-01

We propose a methodology to analyze complex real-life glucose data in insulin pump users. Patients with type 1 diabetes (T1D) on insulin pumps were recruited from an academic endocrinology practice. Glucose data, insulin bolus (IB) amounts, and self-reported alcohol consumption and exercise events were collected for 30 days. Rules were developed to retrospectively compare IB recommendations from the insulin pump bolus calculator (IPBC) against recommendations from a proposed decision aid (PDA) and for assessing the PDA's recommendation for exercise and alcohol. Data from 15 participants were analyzed. When considering instances where glucose was below target, the PDA recommended a smaller dose in 14%, but a larger dose in 13% and an equivalent IB in 73%. For glucose levels at target, the PDA suggested an equivalent IB in 58% compared to the subject's IPBC, but higher doses in 20% and lower in 22%. In events where postprandial glucose was higher than target, the PDA suggested higher doses in 25%, lower doses in 13%, and equivalent doses in 62%. In 64% of all alcohol events the PDA would have provided appropriate advice. In 75% of exercise events, the PDA appropriately advised an IB, a carbohydrate snack, or neither. This study provides a methodology to systematically analyze real-life data generated by insulin pumps and allowed a preliminary analysis of the performance of the PDA for insulin dosing. Further testing of the methodological approach in a broader diabetes population and prospective testing of the PDA are needed.

Diabetes and physical activity in school.

PubMed

Kollipara, Sobha; Warren-Boulton, Elizabeth

2004-05-01

Physical activity and exercise are critical components of diabetes management. Everyone can benefit from regular exercise, but it is even more important for a student with diabetes. In addition to maintaining cardiovascular fitness and controlling weight, physical activity can help to lower blood glucose levels and increase insulin sensitivity. With the nearly epidemic incidence of childhood obesity and type 2 diabetes in youth, physical education should be part of the school day for all children. Students with diabetes should participate fully in physical education classes and team sports. To maintain blood glucose levels within their target ranges during exercise, students with type 1 diabetes will make adjustments in their insulin and food intake. To prevent hypoglycemia, they also will need to check their blood glucose levels more frequently while engaging in physical activity. Physical education instructors and sports coaches must be able to recognize and assist with the treatment of hypoglycemia. A quick-acting source of glucose and the student's glucose meter should always be available, along with water. The student's Diabetes Medical Management Plan, nursing care plan, 504 Plan, IEP, or other education plan should include specific instructions.

Insulin Sensitivity and Plasma Glucose Response to Aerobic Exercise in Pregnant Women at Risk for Gestational Diabetes Mellitus.

PubMed

Embaby, Heba; Elsayed, Enas; Fawzy, Mohamed

2016-09-01

Gestational diabetes mellitus (GDM) is one of the common complications that occur during pregnancy. Early intervention is essential to prevent the development of the disease in the non-pregnant state but also helpful in preventing the occurrence of GDM. The aim of the study was to assess the effect of aerobic exercises on insulin sensitivity and fasting plasma glucose level in pregnant women with risk for gestational diabetes mellitus. Forty multigravidae women between 20-24 weeks of gestation with risk for GDM were randomly selected (age range was 25-35 years), body mass index ranged from 30-35 kg/m 2 . Women were divided into two equal groups: intervention group (A), which followed an aerobic exercise program in the form of walking on treadmill, three times weekly until the end of 37 weeks of gestation in addition to diet control. Control group (B) which received diet control with usual care given by obstetricians and midwives. Evaluation of the women in both groups was carried out before and after treatment program through assessment of fasting blood glucose and insulin levels. There was a highly statistically significance decrease in fasting blood glucose level, fasting insulin level in both groups where the p value was 0.0001 favoring group (A). Moderate intensity of aerobic exercises were effective in reducing fasting blood glucose level and fasting insulin level in pregnant women with risk for gestational diabetes mellitus.

Effect of Opuntia humifusa Supplementation and Acute Exercise on Insulin Sensitivity and Associations with PPAR-γ and PGC-1α Protein Expression in Skeletal Muscle of Rats

PubMed Central

Kang, Junyong; Lee, Junghun; Kwon, Daekeun; Song, Youngju

2013-01-01

This study examined whether Opuntia humifusa (O. humifusa), which is a member of the Cactaceae family, supplementation and acute swimming exercise affect insulin sensitivity and associations with PPAR-γ and PGC-1α protein expression in rats. Thirty-two rats were randomly divided into four groups (HS: high fat diet sedentary group, n = 8; HE: high fat diet acute exercise group, n = 8; OS: 5% O. humifusa supplemented high fat diet sedentary group, n = 8; OE: 5% O. humifusa supplemented high fat diet acute exercise group, n = 8). Rats in the HE and OE swam for 120 min. before being sacrificed. Our results indicated that serum glucose level, fasting insulin level and homeostasis model assessment of insulin resistance (HOMA-IR) in OS were significantly lower compared to those of the HS (p < 0.01, p < 0.05, p < 0.05). In addition, PPAR-γ protein expression in the OS and OE was significantly higher than that of the HS and HE, respectively (p < 0.05, p < 0.01). PGC-1α and GLUT-4 protein expressions in the OS were significantly higher compared to those of the HS (p < 0.05, p < 0.05). From these results, O. humifusa supplementation might play an important role for improving insulin sensitivity through elevation of PPAR-γ, PGC-1α, and GLUT-4 protein expression in rat skeletal muscle. PMID:23538842

Primary care physician perspectives on basal insulin initiation and maintenance in patients with type 2 diabetes mellitus.

PubMed

Kalirai, Samaneh; Stephenson, Judith; Perez-Nieves, Magaly; Grabner, Michael; Hadjiyianni, Irene; Geremakis, Caroline; Pollom, Roy Daniel; Reed, Beverly; Fisher, Lawrence

2018-04-01

To describe primary care physicians' (PCPs) perceptions of patient reactions and concerns about insulin initiation and identify opportunities for increased support. Cross-sectional, online survey of PCPs prescribing basal insulin to adults with type 2 diabetes mellitus (T2DM). PCPs were identified from administrative claims of a large commercial health plan and descriptive results of PCP responses were reported. PCPs (N=100) treated an average of 17 patients receiving insulin during a typical week. More than 85% of insulin initiation recommendations originated with PCPs. Most offered glucose monitoring instructions (96%) and advice on diet, exercise, and diabetes management (96%); 35% provided insulin titration algorithms; 93% reported that patients often or always took their insulin daily within 3 months of initiation; 31% of PCPs reported monthly office contacts with patients for the first 3 months; 16% reported no outreach efforts; fewer than 20% connected patients with support groups. When starting basal insulin, PCPs reported patients feeling personal failure regarding their diabetes treatment (33% often/always) and lacking confidence in their ability to manage insulin therapy (38% often/always). Study results identify additional opportunities for assisting patients in making the transition to insulin, including more frequent direct outreach to monitor insulin usage. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Exercise Training at Maximal Fat Oxidation Intensity for Older Women with Type 2 Diabetes.

PubMed

Tan, Sijie; Du, Ping; Zhao, Wanting; Pang, Jiaqi; Wang, Jianxiong

2018-05-01

The purpose of this study was to investigate the pleiotropic effects of 12 weeks of supervised exercise training at maximal fat oxidation (FATmax) intensity on body composition, lipid profile, glycemic control, insulin sensitivity and serum adipokine levels in older women with type 2 diabetes. Thirty-one women with type 2 diabetes, aged 60 to 69 years, were randomly allocated into exercise and control groups. Body composition, lipid profile, blood glucose, insulin resistance and serum leptin and adiponectin concentrations were measured before and after the intervention. Exercise group (n=16) walked at individualized FATmax intensities for 1 h/day for 3 days/week over 12 weeks. No dietary intervention was introduced during the experimental period. Maximal fat oxidation rate was 0.37±0.10 g/min, and occurred at 37.3±7.3% of the estimated VO 2 max. Within the exercise group, significant improvements were observed for most of the measured variables compared to non-exercising controls; in particular, the FATmax program reduced body fat% (p<0.001), visceral fat% (p<0.001), and insulin resistance (p<0.001). There was no significant change in daily energy intake for all participants during the intervention period. These results suggest that individualized FATmax training is an effective exercise training intensity for managing type 2 diabetes in older women. © Georg Thieme Verlag KG Stuttgart · New York.

Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance.

PubMed

Haus, Jacob M; Solomon, Thomas P J; Marchetti, Christine M; Edmison, John M; González, Frank; Kirwan, John P

2010-01-01

The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; approximately 1800 kcal; n = 11) or hypocaloric (HYPO; approximately 1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass(-1) per minute(-1)) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m(2) . min(-1)) euglycemic (5.0 mm) clamp with [3-(3)H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 +/- 0.8, 2.0 +/- 0.5, and 2.6 +/- 0.4; HYPO, 3.8 +/- 0.5, 1.2 +/- 0.3, and 2.3 +/- 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: -42 +/- 22%; HYPO: -50 +/- 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: -15 +/- 24% vs. HYPO: -58 +/- 19%, P = 0.02). Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention.

Randomized Face-to-Face vs. Home Exercise Interventions in Pregnant Women with Gestational Diabetes

PubMed Central

DOWNS, Danielle Symons; DINALLO, Jennifer M.; BIRCH, Leann L.; PAUL, Ian M.; ULBRECHT, Jan S.

2017-01-01

Objectives Evaluate effects of a theoretically-based, semi-intensive (Face-to-Face; F2F) exercise intervention and minimum-contact (Home) exercise intervention to the standard care (Control) on exercise, its motivational determinants, blood glucose levels, and insulin use of pregnant women with gestational diabetes mellitus (GDM). Design Randomized control trial with two intervention arms and control (standard care). Method Participants (N=65) were randomized to a Control (standard prenatal care/GDM dietary counseling), Home (standard care + phone education/support + home exercise), or F2F (standard care + on-site education/support + guided exercise with instructor on 2 days/week) group from ~20 weeks gestation to delivery. Assessments of exercise and motivational determinants were obtained at baseline (20-weeks gestation) and follow-up (32-weeks gestation). Blood glucose levels (fasting/postprandial mg/dL) and insulin use were extrapolated from medical records. Results At the 32-week follow-up, the F2F group had significantly higher exercise min, pedometer steps/day, and motivational determinants (attitude, subjective norm, perceived control, intention) than controls (p’s < .05) and significantly higher exercise min and subjective norm than the Home group (p’s < .05); these effect sizes were medium-large (η2 = .11–.23). There was a medium effect (η2 = .13) on postprandial blood glucose at 36-weeks gestation with the F2F group having lower values than controls. Although not significant, the F2F group started insulin later (33 weeks gestation) than the Home (27 weeks) and Control (31 weeks) groups. Conclusion A theoretically-based, F2F exercise intervention has multiple health benefits and may be the necessary approach for promoting exercise motivation and behavior among GDM women. PMID:28428728

Randomized Face-to-Face vs. Home Exercise Interventions in Pregnant Women with Gestational Diabetes.

PubMed

Downs, Danielle Symons; Dinallo, Jennifer M; Birch, Leann L; Paul, Ian M; Ulbrecht, Jan S

2017-05-01

Evaluate effects of a theoretically-based, semi-intensive (Face-to-Face; F2F) exercise intervention and minimum-contact (Home) exercise intervention to the standard care (Control) on exercise, its motivational determinants, blood glucose levels, and insulin use of pregnant women with gestational diabetes mellitus (GDM). Randomized control trial with two intervention arms and control (standard care). Participants ( N =65) were randomized to a Control (standard prenatal care/GDM dietary counseling), Home (standard care + phone education/support + home exercise), or F2F (standard care + on-site education/support + guided exercise with instructor on 2 days/week) group from ~20 weeks gestation to delivery. Assessments of exercise and motivational determinants were obtained at baseline (20-weeks gestation) and follow-up (32-weeks gestation). Blood glucose levels (fasting/postprandial mg/dL) and insulin use were extrapolated from medical records. At the 32-week follow-up, the F2F group had significantly higher exercise min, pedometer steps/day, and motivational determinants (attitude, subjective norm, perceived control, intention) than controls ( p 's < .05) and significantly higher exercise min and subjective norm than the Home group ( p 's < .05); these effect sizes were medium-large (η 2 = .11-.23). There was a medium effect (η 2 = .13) on postprandial blood glucose at 36-weeks gestation with the F2F group having lower values than controls. Although not significant, the F2F group started insulin later (33 weeks gestation) than the Home (27 weeks) and Control (31 weeks) groups. A theoretically-based, F2F exercise intervention has multiple health benefits and may be the necessary approach for promoting exercise motivation and behavior among GDM women.

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans.

PubMed

Koves, Timothy R; Sparks, Lauren M; Kovalik, J P; Mosedale, Merrie; Arumugam, Ramamani; DeBalsi, Karen L; Everingham, Karen; Thorne, Leigh; Phielix, Esther; Meex, Ruth C; Kien, C Lawrence; Hesselink, Matthijs K C; Schrauwen, Patrick; Muoio, Deborah M

2013-02-01

Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1α in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects. These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance.

PPARγ coactivator-1α contributes to exercise-induced regulation of intramuscular lipid droplet programming in mice and humans

PubMed Central

Koves, Timothy R.; Sparks, Lauren M.; Kovalik, J. P.; Mosedale, Merrie; Arumugam, Ramamani; DeBalsi, Karen L.; Everingham, Karen; Thorne, Leigh; Phielix, Esther; Meex, Ruth C.; Kien, C. Lawrence; Hesselink, Matthijs K. C.; Schrauwen, Patrick; Muoio, Deborah M.

2013-01-01

Intramuscular accumulation of triacylglycerol, in the form of lipid droplets (LD), has gained widespread attention as a hallmark of metabolic disease and insulin resistance. Paradoxically, LDs also amass in muscles of highly trained endurance athletes who are exquisitely insulin sensitive. Understanding the molecular mechanisms that mediate the expansion and appropriate metabolic control of LDs in the context of habitual physical activity could lead to new therapeutic opportunities. Herein, we show that acute exercise elicits robust upregulation of a broad program of genes involved in regulating LD assembly, morphology, localization, and mobilization. Prominent among these was perilipin-5, a scaffolding protein that affects the spatial and metabolic interactions between LD and their surrounding mitochondrial reticulum. Studies in transgenic mice and primary human skeletal myocytes established a key role for the exercise-responsive transcriptional coactivator PGC-1α in coordinating intramuscular LD programming with mitochondrial remodeling. Moreover, translational studies comparing physically active versus inactive humans identified a remarkably strong association between expression of intramuscular LD genes and enhanced insulin action in exercise-trained subjects. These results reveal an intimate molecular connection between intramuscular LD biology and mitochondrial metabolism that could prove relevant to the etiology and treatment of insulin resistance and other disorders of lipid imbalance. PMID:23175776

Preferential reductions in intermuscular and visceral adipose tissue with exercise-induced weight loss compared with calorie restriction

PubMed Central

Murphy, Joan C.; McDaniel, Jennifer L.; Mora, Katherine; Villareal, Dennis T.; Fontana, Luigi

2012-01-01

Intermuscular adipose tissue (IMAT) and visceral adipose tissue (VAT) are associated with insulin resistance. We sought to determine whether exercise-induced weight loss (EX) results in greater reductions in IMAT and VAT compared with similar weight loss induced by calorie restriction (CR) and whether these changes are associated with improvements in glucoregulation. Sedentary men and women (50–60 yr; body mass index of 23.5–29.9 kg/m2) were randomized to 1 yr of CR (n = 17), EX (n = 16), or a control group (CON; n = 6). Bilateral thigh IMAT and VAT volumes were quantified using multi-slice magnetic resonance imaging. Insulin sensitivity index (ISI) was determined from oral glucose tolerance test glucose and insulin levels. Weight loss was comparable (P = 0.25) in the CR (−10.8 ± 1.4%) and EX groups (−8.3 ± 1.5%) and greater than in the control group (−2.0 ± 2.4%; P < 0.05). IMAT and VAT reductions were larger in the CR and EX groups than in the CON group (P ≤ 0.05). After controlling for differences in total fat mass change between the CR and EX groups, IMAT and VAT reductions were nearly twofold greater (P ≤ 0.05) in the EX group than in the CR group (IMAT: −45 ±5 vs. −25 ± 5 ml; VAT: −490 ± 64 vs. −267 ± 61 ml). In the EX group, the reductions in IMAT were correlated with increases in ISI (r = −0.71; P = 0.003), whereas in the CR group, VAT reductions were correlated with increases in ISI (r = −0.64; P = 0.006). In conclusion, calorie restriction and exercise-induced weight loss both decrease IMAT and VAT volumes. However, exercise appears to result in preferential reductions in these fat depots. PMID:22016371

Benefits of a Paleolithic diet with and without supervised exercise on fat mass, insulin sensitivity, and glycemic control: a randomized controlled trial in individuals with type 2 diabetes.

PubMed

Otten, Julia; Stomby, Andreas; Waling, Maria; Isaksson, Andreas; Tellström, Anna; Lundin-Olsson, Lillemor; Brage, Søren; Ryberg, Mats; Svensson, Michael; Olsson, Tommy

2017-01-01

Means to reduce future risk for cardiovascular disease in subjects with type 2 diabetes are urgently needed. Thirty-two patients with type 2 diabetes (age 59 ± 8 years) followed a Paleolithic diet for 12 weeks. Participants were randomized to either standard care exercise recommendations (PD) or 1-h supervised exercise sessions (aerobic exercise and resistance training) three times per week (PD-EX). For the within group analyses, fat mass decreased by 5.7 kg (IQR: -6.6, -4.1; p < 0.001) in the PD group and by 6.7 kg (-8.2, -5.3; p < 0.001) in the PD-EX group. Insulin sensitivity (HOMA-IR) improved by 45% in the PD (p < 0.001) and PD-EX (p < 0.001) groups. HbA 1c decreased by 0.9% (-1.2, -0.6; p < 0.001) in the PD group and 1.1% (-1.7, -0.7; p < 0.01) in the PD-EX group. Leptin decreased by 62% (p < 0.001) in the PD group and 42% (p < 0.001) in the PD-EX group. Maximum oxygen uptake increased by 0.2 L/min (0.0, 0.3) in the PD-EX group, and remained unchanged in the PD group (p < 0.01 for the difference between intervention groups). Male participants decreased lean mass by 2.6 kg (-3.6, -1.3) in the PD group and by 1.2 kg (-1.3, 1.0) in the PD-EX group (p < 0.05 for the difference between intervention groups). A Paleolithic diet improves fat mass and metabolic balance including insulin sensitivity, glycemic control, and leptin in subjects with type 2 diabetes. Supervised exercise training may not enhance the effects on these outcomes, but preserves lean mass in men and increases cardiovascular fitness. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Hypoglycaemia in patients with type 1 and type 2 diabetes mellitus on insulin therapy. Results of the global HAT study in Argentina].

PubMed

Costa Gil, José E; Linari, María A; Pugnaloni, Natalia; Zambon, Fabio G; Pérez Manghi, Federico; Rezzónico, Mariana

2017-01-01

We describe the results of the HAT study in 433 Argentinean patients with type 1 diabetes (T1D) and 823 with type 2 diabetes (T2D). HAT was an international non-interventional study assessing severe and non-severe hypoglycaemia in patients with T1D and T2D under insulin treatment through a two-part self-assessment questionnaire (retrospective and prospective). The annual incidence of at least one hypoglycaemic episode was 46 episode/patient/year in T1D and 14.2 in T2D (retrospective), 96.5 and 24.6 episode/patient/year in T1D and T2D, respectively (prospective). Hypoglycaemia affected quality of life (on a scale of 0-10 for fear of hypoglycaemia: 60% in T1D and 37.6% in T2D scored 5 to 10), daily life, occupational or academic performance (2.1% with T1D and 3.2% with T2D did not attend to their work after hypoglycaemia), and induced an increased use of health resources (T1D: 66.1% increased glucose monitoring, 60.5% food intake, 51% consultations, 3.5% hospital admissions; 60.5% reduced insulin and 20.9% exercises; T2D increased 46.2% glucose monitoring, 43.8% consultations, 38.6% food intake, 24.1% reduced and 13.9% skipped the insulin dose and 14.3% suspended exercises). Greater numbers of episodes were recorded in the prospective period. An instrument to assess hypoglycaemia in clinical practice and strategies to reduce their risk are required. It is also important to ask about the episodes and reinforce the education of patients and close relatives on hypoglycaemia prevention and treatment.

Insulin resistance syndrome in children.

PubMed

Ten, Svetlana; Maclaren, Noel

2004-06-01

The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer's disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation's homes and schools.

Parity and increased risk of insulin resistance in postmenopausal women: the 2010 Korean National Health and Nutrition Examination Survey.

PubMed

Kim, Jin Hwi; Lee, Sung Jong

2017-07-01

The objective of this study was to assess the association between parity and insulin resistance in nondiabetic, postmenopausal women. This cross-sectional study was conducted using data from the 2010 Korean National Health and Nutrition Examination Survey administered by the Korean Ministry of Health and Welfare. A total of 1,243 nondiabetic postmenopausal women were included in this study and subdivided into three groups according to parity (1-2, 3-4, and ≥5 live births). Insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The relationship between parity and insulin resistance was investigated using analysis of covariance. HOMA-IR showed a positive relationship with parity. Mean HOMA-IR (geometric mean and 95% CI) increased according to increasing parity group (1-2, 3-4, and ≥5 live births) after adjustment for age, smoking, alcohol consumption, exercise, education, income, and body mass index as follows: 2.1 (2.0-2.2) < 2.2 (2.1-2.3) < 2.5 (2.2-2.8) (P = 0.040 and P for trend = 0.012). In addition, this positive association was more apparent when insulin resistance was accompanied by obesity. The mean parity of the obese and insulin-resistant group was significantly higher than that of the nonobese insulin-sensitive group (3.6 ± 0.1 vs 3.2 ± 0.1, P = 0.047). Our study provides the first evidence that parity is significantly associated with insulin resistance in nondiabetic postmenopausal women. Further prospective longitudinal studies are needed to confirm the impact of parity on insulin resistance.

FTO rs9939609 Does Not Interact with Physical Exercise but Influences Basal Insulin Metabolism in Brazilian Overweight and Obese Adolescents

PubMed Central

Leite, Neiva; Furtado-Alle, Lupe; Teixeira, Mayza Dalcin; de Souza, Ricardo Lehtonen Rodrigues; da Silva, Larissa Rosa; Pizzi, Juliana; Lopes, Maria de Fátima Aguiar; Titski, Ana Cláudia Kapp

2018-01-01

Purpose The rs9939609 SNP (T > A) in FTO gene is associated with obesity and type 2 diabetes. The present study aimed at verifying whether this SNP influenced biochemical outcomes of children and adolescents who are overweight/obese submitted to a program of physical exercise and also if there was influence on basal levels of these biochemical variables. Methods The sample was composed by 432 children and adolescents grouped in three ways (obese, overweight, and normal weight); of these, 135 children and adoloescents who are obese and overweight were submitted to a physical exercise program for 12 weeks. All were genotyped by TaqMan SNP genotyping assay. Results The children and adolescents who are overweight/obese and carriers of AA genotype had higher levels of insulin (p=0.03) and HOMA (p=0.007) and lower levels of glucose (p=0.003), but the SNP did not modulate the response to physical exercise. Conclusions In our study, the rs9939609 AA genotype was associated with parameters related to insulin metabolism but did not interact with physical exercise. PMID:29854435

Exercise increases TBC1D1 phosphorylation in human skeletal muscle

PubMed Central

Jessen, Niels; An, Ding; Lihn, Aina S.; Nygren, Jonas; Hirshman, Michael F.; Thorell, Anders

2011-01-01

Exercise and weight loss are cornerstones in the treatment and prevention of type 2 diabetes, and both interventions function to increase insulin sensitivity and glucose uptake into skeletal muscle. Studies in rodents demonstrate that the underlying mechanism for glucose uptake in muscle involves site-specific phosphorylation of the Rab-GTPase-activating proteins AS160 (TBC1D4) and TBC1D1. Multiple kinases, including Akt and AMPK, phosphorylate TBC1D1 and AS160 on distinct residues, regulating their activity and allowing for GLUT4 translocation. In contrast to extensive rodent-based studies, the regulation of AS160 and TBC1D1 in human skeletal muscle is not well understood. In this study, we determined the effects of dietary intervention and a single bout of exercise on TBC1D1 and AS160 site-specific phosphorylation in human skeletal muscle. Ten obese (BMI 33.4 ± 2.4, M-value 4.3 ± 0.5) subjects were studied at baseline and after a 2-wk dietary intervention. Muscle biopsies were obtained from the subjects in the resting (basal) state and immediately following a 30-min exercise bout (70% V̇o2 max). Muscle lysates were analyzed for AMPK activity and Akt phosphorylation and for TBC1D1 and AS160 phosphorylation on known or putative AMPK and Akt sites as follows: AS160 Ser711 (AMPK), TBC1D1 Ser231 (AMPK), TBC1D1 Ser660 (AMPK), TBC1D1 Ser700 (AMPK), and TBC1D1 Thr590 (Akt). The diet intervention that consisted of a major shift in the macronutrient composition resulted in a 4.2 ± 0.4 kg weight loss (P < 0.001) and a significant increase in insulin sensitivity (M value 5.6 ± 0.6), but surprisingly, there was no effect on expression or phosphorylation of any of the muscle-signaling proteins. Exercise increased muscle AMPKα2 activity but did not increase Akt phosphorylation. Exercise increased phosphorylation on AS160 Ser711, TBC1D1 Ser231, and TBC1D1 Ser660 but had no effect on TBC1D1 Ser700. Exercise did not increase TBC1D1 Thr590 phosphorylation or TBC1D1/AS160 PAS phosphorylation, consistent with the lack of Akt activation. These data demonstrate that a single bout of exercise regulates TBC1D1 and AS160 phosphorylation on multiple sites in human skeletal muscle. PMID:21505148

Effect of creatine supplementation and resistance-exercise training on muscle insulin-like growth factor in young adults.

PubMed

Burke, Darren G; Candow, Darren G; Chilibeck, Philip D; MacNeil, Lauren G; Roy, Brian D; Tarnopolsky, Mark A; Ziegenfuss, Tim

2008-08-01

The purpose of this study was to compare changes in muscle insulin-like growth factor-I (IGF-I) content resulting from resistance-exercise training (RET) and creatine supplementation (CR). Male (n=24) and female (n=18) participants with minimal resistance-exercise-training experience (=1 year) who were participating in at least 30 min of structured physical activity (i.e., walking, jogging, cycling) 3-5 x/wk volunteered for the study. Participants were randomly assigned in blocks (gender) to supplement with creatine (CR: 0.25 g/kg lean-tissue mass for 7 days; 0.06 g/kg lean-tissue mass for 49 days; n=22, 12 males, 10 female) or isocaloric placebo (PL: n=20, 12 male, 8 female) and engage in a whole-body RET program for 8 wk. Eighteen participants were classified as vegetarian (lacto-ovo or vegan; CR: 5 male, 5 female; PL: 3 male, 5 female). Muscle biopsies (vastus lateralis) were taken before and after the intervention and analyzed for IGF-I using standard immunohistochemical procedures. Stained muscle cross-sections were examined microscopically and IGF-I content quantified using image-analysis software. Results showed that RET increased intramuscular IGF-I content by 67%, with greater accumulation from CR (+78%) than PL (+54%; p=.06). There were no differences in IGF-I between vegetarians and nonvegetarians. These findings indicate that creatine supplementation during resistance-exercise training increases intramuscular IGF-I concentration in healthy men and women, independent of habitual dietary routine.

Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats

PubMed Central

Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara EF; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia CM; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M

2016-01-01

This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. PMID:26490345

Beneficial effects of previous exercise training on renal changes in streptozotocin-induced diabetic female rats.

PubMed

Amaral, Liliany S de Brito; Silva, Fernanda A; Correia, Vicente B; Andrade, Clara E F; Dutra, Bárbara A; Oliveira, Márcio V; de Magalhães, Amélia C M; Volpini, Rildo A; Seguro, Antonio C; Coimbra, Terezila M; Soares, Telma de J

2016-02-01

This study evaluated the effects of aerobic exercise performed both previously and after the induction of diabetes mellitus on changes of renal function and structure in streptozotocin-induced diabetic rats. Female wistar rats were divided into five groups: sedentary control (C + Se); trained control (C + Ex); sedentary diabetic (D + Se); trained diabetic (D + Ex) and previously trained diabetic (D + PEx). The previous exercise consisted of treadmill running for four weeks before the induction of diabetes mellitus. After induction of diabetes mellitus with streptozotocin, the D + PEx, D + Ex and C + Ex groups were submitted to eight weeks of aerobic exercise. At the end of the training protocol, we evaluate the serum glucose, insulin and 17β-estradiol levels, renal function and structure, proteinuria, and fibronectin, collagen IV and transforming growth factor beta 1 (TGF-β1) renal expressions. Induction of diabetes mellitus reduced the insulin and did not alter 17β-estradiol levels, and exercise did not affect any of these parameters. Previous exercise training attenuated the loss of body weight, the blood glucose, the increase of glomerular filtration rate and prevented the proteinuria in the D + PEx group compared to D + Se group. Previous exercise also reduced glomerular hypertrophy, tubular and glomerular injury, as well as the expressions of fibronectin and collagen IV. These expressions were associated with reduced expression of TGF-β1. In conclusion, our study shows that regular aerobic exercise especially performed previously to induction of diabetes mellitus improved metabolic control and has renoprotective action on the diabetic kidney. © 2016 by the Society for Experimental Biology and Medicine.

Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast muscles of hypophysectomized rats

NASA Technical Reports Server (NTRS)

Grossman, E. J.; Grindeland, R. E.; Roy, R. R.; Talmadge, R. J.; Evans, J.; Edgerton, V. R.

1997-01-01

The effects of growth hormone (GH) or insulin-like growth factor I (IGF-I) with or without exercise (ladder climbing) in countering the effects of unweighting on fast muscles of hypophysectomized rats during 10 days of hindlimb suspension were determined. Compared with untreated suspended rats, muscle weights were 16-29% larger in GH-treated and 5-15% larger in IGF-I-treated suspended rats. Exercise alone had no effect on muscle weights. Compared with ambulatory control, the medial gastrocnemius weight in suspended, exercised rats was larger after GH treatment and maintained with IGF-I treatment. The combination of GH or IGF-I plus exercise in suspended rats resulted in an increase in size of each predominant fiber type, i.e., types I, I + IIa and IIa + IIx, in the medial gastrocnemius compared with untreated suspended rats. Normal ambulation or exercise during suspension increased the proportion of fibers expressing embryonic myosin heavy chain in hypophysectomized rats. The phenotype of the medial gastrocnemius was minimally affected by GH, IGF-I, and/or exercise. These results show that there is an IGF-I, as well as a GH, and exercise interactive effect in maintaining medial gastrocnemius fiber size in suspended hypophysectomized rats.

Molecular Mechanisms Underlying Cardiac Adaptation to Exercise

PubMed Central

Vega, Rick B.; Konhilas, John P.; Kelly, Daniel P.; Leinwand, Leslie A.

2017-01-01

Exercise elicits coordinated multi-organ responses including skeletal muscle, vasculature, heart and lung. In the short term, the output of the heart increases to meet the demand of strenuous exercise. Long term exercise instigates remodeling of the heart including growth and adaptive molecular and cellular re-programming. Signaling pathways such as the insulin-like growth factor 1/PI3K/Akt pathway mediate many of these responses. Exercise-induced, or physiologic, cardiac growth contrasts with growth elicited by pathological stimuli such as hypertension. Comparing the molecular and cellular underpinnings of physiologic and pathologic cardiac growth has unveiled phenotype-specific signaling pathways and transcriptional regulatory programs. Studies suggest that exercise pathways likely antagonize pathological pathways, and exercise training is often recommended for patients with chronic stable heart failure or following myocardial infarction. Herein, we summarize the current understanding of the structural and functional cardiac responses to exercise as well as signaling pathways and downstream effector molecules responsible for these adaptations. PMID:28467921

Nutrition and exercise in the management of liver cirrhosis

PubMed Central

Toshikuni, Nobuyuki; Arisawa, Tomiyasu; Tsutsumi, Mikihiro

2014-01-01

Liver cirrhosis (LC) patients often have protein-energy malnutrition (PEM) and decreased physical activity. These conditions often lead to sarcopenia, which is the loss of skeletal muscle volume and increased muscle weakness. Recent studies have demonstrated that PEM and sarcopenia are predictors for poor survival in LC patients. Nutrition and exercise management can improve PEM and sarcopenia in those patients. Nutrition management includes sufficient dietary intake and improved nutrient metabolism. With the current high prevalence of obesity, the number of obese LC patients has increased, and restriction of excessive caloric intake without the exacerbation of impaired nutrient metabolism is required for such patients. Branched chain amino acids are good candidates for supplemental nutrients for both obese and non-obese LC patients. Exercise management can increase skeletal muscle volume and strength and improve insulin resistance; however, nutritional status and LC complications should be assessed before an exercise management regimen is implemented in LC patients. The establishment of optimal exercise regimens for LC patients is currently required. In this review, we describe nutritional status and its clinical impact on the outcomes of LC patients and discuss general nutrition and exercise management in LC patients. PMID:24966599

Paradoxical post-exercise responses of acylated ghrelin and leptin during a simulated night shift.

PubMed

Morris, Christopher J; Fullick, Sarah; Gregson, Warren; Clarke, Neil; Doran, Dominic; MacLaren, Don; Atkinson, Greg

2010-05-01

Approximately 10% of employees undertake night work, which is a significant predictor of weight gain, possibly because responses to activity and eating are altered at night. It is known that the appetite-related hormone, acylated ghrelin, is suppressed after an acute bout of exercise during the day, but no researcher has explored whether evening exercise alters acylated ghrelin and other appetite-related outcomes during a subsequent night shift. Six healthy men (mean +/- SD: age 30 +/- 8 yrs, body mass index 23.1 +/- 1.1 kg/m(2)) completed two crossover trials (control and exercise) in random order. Participants fasted from 10:00 h, consumed a test meal at 18:00 h, and then cycled at 50% peak oxygen uptake or rested between 19:00-20:00 h. Participants then completed light activities during a simulated night shift which ended at 05:00 h. Two small isocaloric meals were consumed at 22:00 and 02:00 h. Venous blood samples were drawn via cannulation at 1 h intervals between 19:00-05:00 h for the determination of acylated ghrelin, leptin, insulin, glucose, triglyceride, and non-esterified fatty acids concentrations. Perceived hunger and wrist actimetry were also recorded. During the simulated night shift, mean +/- SD acylated ghrelin concentration was 86.5 +/- 40.8 pg/ml following exercise compared with 71.7 +/- 37.7 pg/ml without prior exercise (p = 0.015). Throughout the night shift, leptin concentration was 263 +/- 242 pg/ml following exercise compared with 187 +/- 221 pg/ml without prior exercise (p = 0.017). Mean levels of insulin, triglyceride, non-esterified fatty acids, and wrist actimetry level were also higher during the night shift that followed exercise (p < 0.05). These data indicate that prior exercise increases acylated ghrelin and leptin concentrations during a subsequent simulated night shift. These findings differ from the known effects of exercise on acylated ghrelin and leptin during the day, and therefore have implications for energy balance during night work.

The anaerobic threshold: over-valued or under-utilized? A novel concept to enhance lipid optimization!

PubMed

Connolly, Declan A J

2012-09-01

The purpose of this article is to assess the value of the anaerobic threshold for use in clinical populations with the intent to improve exercise adaptations and outcomes. The anaerobic threshold is generally poorly understood, improperly used, and poorly measured. It is rarely used in clinical settings and often reserved for athletic performance testing. Increased exercise participation within both clinical and other less healthy populations has increased our attention to optimizing exercise outcomes. Of particular interest is the optimization of lipid metabolism during exercise in order to improve numerous conditions such as blood lipid profile, insulin sensitivity and secretion, and weight loss. Numerous authors report on the benefits of appropriate exercise intensity in optimizing outcomes even though regulation of intensity has proved difficult for many. Despite limited use, selected exercise physiology markers have considerable merit in exercise-intensity regulation. The anaerobic threshold, and other markers such as heart rate, may well provide a simple and valuable mechanism for regulating exercising intensity. The use of the anaerobic threshold and accurate target heart rate to regulate exercise intensity is a valuable approach that is under-utilized across populations. The measurement of the anaerobic threshold can be simplified to allow clients to use nonlaboratory measures, for example heart rate, in order to self-regulate exercise intensity and improve outcomes.

Ghrelin and PYY levels in adolescents with severe obesity: effects of weight loss induced by long-term exercise training and modified food habits.

PubMed

Gueugnon, Carine; Mougin, Fabienne; Nguyen, Nhu Uyen; Bouhaddi, Malika; Nicolet-Guénat, Marie; Dumoulin, Gilles

2012-05-01

This study investigated (a) changes in ghrelin and peptide YY (PYY) concentrations during a weight reduction programme and (b) baseline ghrelin and PYY levels as predictors of weight loss in 32 severely obese adolescents (BMI z score = 4.1). Subjects spent an academic year in an institution for childhood obesity. Fasting ghrelin and PYY, leptin, insulin levels and insulin resistance were measured at baseline (month 0) and during the programme (months 3, 6, 9). In addition, 15 normal-weight teenagers served as reference for the baseline assessments. At baseline, obese teenagers had lower ghrelin and PYY concentrations than normal-weight adolescents (P < 0.05). Moreover, they showed significantly higher leptin, insulin levels and homeostasis model assessment (HOMA) (P < 0.0001). During the lifestyle modification, there was a significant decrease in body weight among obese teenagers, associated with an increase in ghrelin (apparent from month 6; P < 0.05), a decrease in leptin (from month 3; P < 0.05) and a decrease in insulin and HOMA (from month 3; P < 0.0001), without any significant change in PYY. Anthropometrical changes were correlated neither with baseline ghrelin levels nor with changes in ghrelin and PYY after the lifestyle modification. However, higher baseline PYY tended to correlate with greater anthropometrical changes (P < 0.1). In adolescents with severe obesity, a long-term combination of supervised aerobic exercises and a balanced diet led to weight reduction and increased ghrelin concentrations, without any change in PYY concentrations. Moreover, baseline PYY concentrations might be considered as predictors of weight loss.

Prior exercise alters the difference between arterialised and venous glycaemia: implications for blood sampling procedures.

PubMed

Edinburgh, Robert M; Hengist, Aaron; Smith, Harry A; Betts, James A; Thompson, Dylan; Walhin, Jean-Philippe; Gonzalez, Javier T

2017-05-01

Oral glucose tolerance and insulin sensitivity are common measures, but are determined using various blood sampling methods, employed under many different experimental conditions. This study established whether measures of oral glucose tolerance and oral glucose-derived insulin sensitivity (insulin sensitivity indices; ISI) differ when calculated from venous v. arterialised blood. Critically, we also established whether any differences between sampling methods are consistent across distinct metabolic conditions (after rest v. after exercise). A total of ten healthy men completed two trials in a randomised order, each consisting of a 120-min oral glucose tolerance test (OGTT), either at rest or post-exercise. Blood was sampled simultaneously from a heated hand (arterialised) and an antecubital vein of the contralateral arm (venous). Under both conditions, glucose time-averaged AUC was greater from arterialised compared with venous plasma but importantly, this difference was larger after rest relative to after exercise (0·99 (sd 0·46) v. 0·56 (sd 0·24) mmol/l, respectively; P<0·01). OGTT-derived ISIMatsuda and ISICederholm were lower when calculated from arterialised relative to venous plasma and the arterialised-venous difference was greater after rest v. after exercise (ISIMatsuda: 1·97 (sd 0·81) v. 1·35 (sd 0·57) arbitrary units (au), respectively; ISICederholm : 14·76 (sd 7·83) v. 8·70 (sd 3·95) au, respectively; both P<0·01). Venous blood provides lower postprandial glucose concentrations and higher estimates of insulin sensitivity, compared with arterialised blood. Most importantly, these differences between blood sampling methods are not consistent after rest v. post-exercise, preventing standardised venous-to-arterialised corrections from being readily applied.

Effects of aerobic exercise training on serum sex hormone binding globulin, body fat index, and metabolic syndrome factors in obese postmenopausal women.

PubMed

Kim, Jong-Won; Kim, Do-Yeon

2012-12-01

The percentage of obese postmenopausal women with metabolic syndrome is rising, and physical factors associated with the metabolic syndrome prevalence or incidence are also rising, including high body mass index (BMI), visceral fat area (VFA), low plasma sex hormone-binding globulin (SHBG) levels, and low cardiorespiratory fitness. Therefore, we investigated the influence of aerobic exercise on SHBG, body fat index (BFI), and metabolic syndrome factors in obese postmenopausal Korean women. Thirty healthy postmenopausal, women aged 53.46 ± 2.4 years and with over 32% body fat, were randomly assigned to an aerobic exercise group (EX; n=15) or to a "nonexercise" control (Con; n=15) group. The primary outcome measurements were serum SHBG, lipid profiles, insulin levels, and metabolic syndrome factors. Secondary outcome measurements were body composition, VFA, blood pressure (BP), and homeostasis model assessment of insulin resistance (HOMA-IR). Posttraining body weight and BFI (P<0.05), total cholesterol, glucose, and insulin levels (P<0.01), BP, and HOMA-IR (P<0.001) decreased, whereas SHBG (P<0.001) and metabolic syndrome factors (P<0.01) improved in the exercise group but not in the control group. SHBG levels also showed a significant positive correlation with high-density lipoprotein cholesterol (HDL-C) and significant negative correlations withglucose, diastolic blood pressure, fat mass, BMI, and percent body fat (P<0.05). Our findings indicate that aerobic exercise improves body composition, SHBG, insulin levels, and metabolic syndrome factors. These findings suggest that in obesepostmenopausal Korean women, 16 weeks of aerobic exercise is effective for preventing the metabolic syndrome caused by obesity.

Resistance exercise-induced increases in putative anabolic hormones do not enhance muscle protein synthesis or intracellular signalling in young men.

PubMed

West, Daniel W D; Kujbida, Gregory W; Moore, Daniel R; Atherton, Philip; Burd, Nicholas A; Padzik, Jan P; De Lisio, Michael; Tang, Jason E; Parise, Gianni; Rennie, Michael J; Baker, Steven K; Phillips, Stuart M

2009-11-01

We aimed to determine whether exercise-induced elevations in systemic concentration of testosterone, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) enhanced post-exercise myofibrillar protein synthesis (MPS) and phosphorylation of signalling proteins important in regulating mRNA translation. Eight young men (20 +/- 1.1 years, BMI = 26 +/- 3.5 kg m(-2)) completed two exercise protocols designed to maintain basal hormone concentrations (low hormone, LH) or elicit increases in endogenous hormones (high hormone, HH). In the LH protocol, participants performed a bout of unilateral resistance exercise with the elbow flexors. The HH protocol consisted of the same elbow flexor exercise with the contralateral arm followed immediately by high-volume leg resistance exercise. Participants consumed 25 g of protein after arm exercise to maximize MPS. Muscle biopsies and blood samples were taken as appropriate. There were no changes in serum testosterone, GH or IGF-1 after the LH protocol, whereas there were marked elevations after HH (testosterone, P < 0.001; GH, P < 0.001; IGF-1, P < 0.05). Exercise stimulated a rise in MPS in the biceps brachii (rest = 0.040 +/- 0.007, LH = 0.071 +/- 0.008, HH = 0.064 +/- 0.014% h(-1); P < 0.05) with no effect of elevated hormones (P = 0.72). Phosphorylation of the 70 kDa S6 protein kinase (p70S6K) also increased post-exercise (P < 0.05) with no differences between conditions. We conclude that the transient increases in endogenous purportedly anabolic hormones do not enhance fed-state anabolic signalling or MPS following resistance exercise. Local mechanisms are likely to be of predominant importance for the post-exercise increase in MPS.

The effect of endurance exercise on both skeletal muscle and systemic oxidative stress in previously sedentary obese men

PubMed Central

Samjoo, I A; Safdar, A; Hamadeh, M J; Raha, S; Tarnopolsky, M A

2013-01-01

Background: Obesity is associated with low-grade systemic inflammation, in part because of secretion of proinflammatory cytokines, resulting into peripheral insulin resistance (IR). Increased oxidative stress is proposed to link adiposity and chronic inflammation. The effects of endurance exercise in modulating these outcomes in insulin-resistant obese adults remain unclear. We investigated the effect of endurance exercise on markers of oxidative damage (4-hydroxy-2-nonenal (4-HNE), protein carbonyls (PCs)) and antioxidant enzymes (superoxide dismutase (SOD), catalase) in skeletal muscle; urinary markers of oxidative stress (8-hydroxy-2-deoxyguanosine (8-OHdG), 8-isoprostane); and plasma cytokines (C-reactive protein (CRP), interleukin-6 (IL-6), leptin, adiponectin). Methods: Age- and fitness-matched sedentary obese and lean men (n=9 per group) underwent 3 months of moderate-intensity endurance cycling training with a vastus lateralis biopsy, 24-h urine sample and venous blood samples taken before and after the intervention. Results: Obese subjects had increased levels of oxidative damage: 4-HNE (+37% P⩽0.03) and PC (+63% P⩽0.02); evidence of increased adaptive response to oxidative stress because of elevated levels of copper/zinc SOD (Cu/ZnSOD) protein content (+84% P⩽0.01); increased markers of inflammation: CRP (+737% P⩽0.0001) and IL-6 (+85% P⩽0.03), and these correlated with increased markers of obesity; and increased leptin (+262% P⩽0.0001) with lower adiponectin (−27% P⩽0.01) levels vs lean controls. Training reduced 4-HNE (−10% P⩽0.04), PC (−21% P⩽0.05), 8-isoprostane (−26% P⩽0.02) and leptin levels (−33% P⩽0.01); had a tendency to decrease IL-6 levels (−21% P=0.07) and IR (−17% P=0.10); and increased manganese SOD (MnSOD) levels (+47% P⩽0.01). Conclusion: Endurance exercise reduced skeletal muscle-specific and systemic oxidative damage while improving IR and cytokine profile associated with obesity, independent of weight loss. Hence, exercise is a useful therapeutic modality to reduce risk factors associated with the pathogenesis of IR in obesity. PMID:24042701

A comparison of methods for analyzing glucose and insulin areas under the curve following nine months of exercise in overweight adults.

PubMed

Potteiger, J A; Jacobsen, D J; Donnelly, J E

2002-01-01

We examined three methods for calculating the area under the curve (AUC) following an oral glucose tolerance test (OGTT) in overweight adults prior to and after 9 months of exercise. Subjects (n=27) were randomly assigned to a control (CON, n=9) or intervention (INT, n=18) group. INT performed supervised exercise 5 days per week, 45 min per session, at 65% of heart rate reserve. OGTTs were administered pre- and post-training. Blood was collected during a 75 g OGTT and analyzed for glucose (GLU) and insulin (INS) concentrations. AUCs were calculated using the incremental, positive incremental, and total AUC methods and the difference scores for pre- and post-training were determined. No differences were observed among the methods for glucose AUC for either group. Significant differences were observed for INT insulin AUC with total AUC (1525+/-3291 microU/1/180 min) significantly greater than incremental AUC (1112+/-3229 microU/1/180 min) or positive incremental AUC (1085+/-3195 microU/I/180 min). Total insulin AUC was significantly reduced following training for INT, while incremental and positive incremental insulin AUCs showed no change. These data suggest that the method of used to calculate AUC may affect the interpretation of whether or not an intervention was effective.

Acute Exercise and Insulin Sensitivity in Boys: A Time-Course Study.

PubMed

Cockcroft, Emma J; Williams, Craig A; Weaver, Hayley; O'Connor, Amy; Jackman, Sarah R; Armstrong, Neil; Barker, Alan R

2017-11-01

This study examined the time course of adaptions in insulin sensitivity (IS) in adolescent boys after acute high-intensity interval exercise (HIIE) and moderate-intensity exercise (MIE). Eight boys (15.1±0.4 y) completed three 3-day experimental trials in a randomised order: 1) 8×1 min cycling at 90% peak power with 75 s recovery (HIIE); 2) cycling at 90% of gas exchange threshold for a duration to match work during HIIE (MIE); and 3) rest (CON). Plasma [glucose] and [insulin] were measured before (PRE-Ex), 24 and 48 h post (24 h-POST, 48 h-POST) in a fasted state, and 40 min (POST-Ex) and 24 h (24 h-POST) post in response to an oral glucose tolerance test (OGTT). IS was estimated using the Cederholm (OGTT) and HOMA (fasted) indices. There was no change to HOMA at 24 h or 48 h-POST (all P> 0.05). IS from the OGTT was higher POST-EX for HIIE compared to CON (17.4%, P =0.010, ES=1.06), and a non-significant increase in IS after MIE compared to CON (9.0%, P =0.14, ES=0.59). At 24 h-POST, IS was higher following both HIIE and MIE compared to CON (HIIE: P =0.019, 13.2%, ES=0.88; MIE: 9.7%, P =0.024, ES=0.65). In conclusion, improvements to IS after a single bout of HIIE and MIE persist up to 24 h after exercise when assessed by OGTT. © Georg Thieme Verlag KG Stuttgart · New York.

Glycolytic and mitochondrial metabolism in pancreatic islets from MSG-treated obese rats subjected to swimming training.

PubMed

Leite, Nayara de Carvalho; Ferreira, Thiago Rentz; Rickli, Sarah; Borck, Patricia Cristine; Mathias, Paulo Cezar de Freitas; Emilio, Henriette Rosa de Oliveira; Grassiolli, Sabrina

2013-01-01

Obese rats obtained by neonatal monosodium glutamate (MSG) administration present insulin hypersecretion. The metabolic mechanism by which glucose catabolism is coupled to insulin secretion in the pancreatic β-cells from MSG-treated rats is understood. The purpose of this study was to evaluate glucose metabolism in pancreatic islets from MSG-treated rats subjected to swimming training. MSG-treated and control (CON) rats swam for 30 minutes (3 times/week) over a period of 10 weeks. Pancreatic islets were isolated and incubated with glucose in the presence of glycolytic or mitochondrial inhibitors. Swimming training attenuated fat pad accumulation, avoiding changes in the plasma levels of lipids, glucose and insulin in MSG-treated rats. Adipocyte and islet hypertrophy observed in MSG-treated rats were attenuated by exercise. Pancreatic islets from MSG-treated obese rats also showed insulin hypersecretion, greater glucose transporter 2 (GLUT2) expression, increased glycolytic flux and reduced mitochondrial complex III activity. Swimming training attenuated islet hypertrophy and normalised GLUT2 expression, contributing to a reduction in the glucose responsiveness of pancreatic islets from MSG-treated rats without altering glycolytic flux. However, physical training increased the activity of mitochondrial complex III in pancreatic islets from MSG-treated rats without a subsequent increase in glucose-induced insulin secretion. Copyright © 2013 S. Karger AG, Basel.

Dissociation of muscle insulin sensitivity from exercise endurance in mice by HDAC3 depletion.

PubMed

Hong, Sungguan; Zhou, Wenjun; Fang, Bin; Lu, Wenyun; Loro, Emanuele; Damle, Manashree; Ding, Guolian; Jager, Jennifer; Zhang, Sisi; Zhang, Yuxiang; Feng, Dan; Chu, Qingwei; Dill, Brian D; Molina, Henrik; Khurana, Tejvir S; Rabinowitz, Joshua D; Lazar, Mitchell A; Sun, Zheng

2017-02-01

Type 2 diabetes and insulin resistance are associated with reduced glucose utilization in the muscle and poor exercise performance. Here we find that depletion of the epigenome modifier histone deacetylase 3 (HDAC3) specifically in skeletal muscle causes severe systemic insulin resistance in mice but markedly enhances endurance and resistance to muscle fatigue, despite reducing muscle force. This seemingly paradoxical phenotype is due to lower glucose utilization and greater lipid oxidation in HDAC3-depleted muscles, a fuel switch caused by the activation of anaplerotic reactions driven by AMP deaminase 3 (Ampd3) and catabolism of branched-chain amino acids. These findings highlight the pivotal role of amino acid catabolism in muscle fatigue and type 2 diabetes pathogenesis. Further, as genome occupancy of HDAC3 in skeletal muscle is controlled by the circadian clock, these results delineate an epigenomic regulatory mechanism through which the circadian clock governs skeletal muscle bioenergetics. These findings suggest that physical exercise at certain times of the day or pharmacological targeting of HDAC3 could potentially be harnessed to alter systemic fuel metabolism and exercise performance.

Neurobiological markers of exercise-related brain plasticity in older adults

PubMed Central

Voss, Michelle W.; Erickson, Kirk I.; Prakash, Ruchika Shaurya; Chaddock, Laura; Kim, Jennifer S.; Alves, Heloisa; Szabo, Amanda; White, Siobhan M.; Wójcicki, Thomas R.; Mailey, Emily L.; Olson, Erin A.; Gothe, Neha; Potter, Vicki V.; Martin, Stephen A.; Pence, Brandt D.; Cook, Marc D.; Woods, Jeffrey A.; McAuley, Edward; Kramer, Arthur F.

2012-01-01

The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age = 66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF. PMID:23123199

The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity.

PubMed

Barnard, Neal D; Scialli, Anthony R; Turner-McGrievy, Gabrielle; Lanou, Amy J; Glass, Jolie

2005-09-01

This study investigated the effect of a low-fat, plant-based diet on body weight, metabolism, and insulin sensitivity, while controlling for exercise in free-living individuals. In an outpatient setting, 64 overweight, postmenopausal women were randomly assigned to a low-fat, vegan diet or a control diet based on National Cholesterol Education Program guidelines, without energy intake limits, and were asked to maintain exercise unchanged. Dietary intake, body weight and composition, resting metabolic rate, thermic effect of food, and insulin sensitivity were measured at baseline and 14 weeks. Mean +/- standard deviation intervention-group body weight decreased 5.8 +/- 3.2 kg, compared with 3.8 +/- 2.8 kg in the control group (P = .012). In a regression model of predictors of weight change, including diet group and changes in energy intake, thermic effect of food, resting metabolic rate, and reported energy expenditure, significant effects were found for diet group (P < .05), thermic effect of food (P < .05), and resting metabolic rate (P < .001). An index of insulin sensitivity increased from 4.6 +/- 2.9 to 5.7 +/- 3.9 (P = .017) in the intervention group, but the difference between groups was not significant (P = .17). Adoption of a low-fat, vegan diet was associated with significant weight loss in overweight postmenopausal women, despite the absence of prescribed limits on portion size or energy intake.

[Effects of a structured exercise programme on cardiovascular risk programmes in post-menopausal women. CLIDERICA study].

PubMed

Saucedo Rodrigo, Pedro; Abellán Alemán, José; Gómez Jara, Purificación; Leal Hernández, Mariano; Ortega Toro, Enrique; Colado, Juan Carlos; Colado Sánchez, Juan Carlos; Sáinz de Baranda Andújar, Pilar

2008-07-01

To analyse the influence of a physical exercise programme of strength/stamina on cardiovascular risk factors in low-risk post-menopausal women. Six-month randomised clinical trial with post-menopausal women. Three health centres in the autonomous community of Murcia, Spain. Sixty-three post-menopausal women aged 45 to 59 at low cardiovascular risk. INTERVENTIONS AND MAIN MEASUREMENTS: They were split into 2 groups: a) control: 23 people with no specific intervention, and b) 40 people with an intervention of strength/stamina exercise with protocol for in water and on land. At their initial and final visits, everyone in the 2 groups had anamnesis, physical examination, and general analyses, including Apo A, Apo B, insulin, serum creatinine, creatinine clearance, creatinine in urine, albuminuria, ultrasensitive PCR, and HOMA index. The insulin levels increased in the control group by 2.02 mU/L and dropped in the experimental group by 0.13 mU/L (P=.021). At the start of the study, creatinine in the control group was 0.83+/-0.12 mg/dL; and at the end, 0.91+/-0.02 mg/dL. In the intervention group it was 0.84+/-0.12 mg/dL at the start and 0.90+/-0.13 mg/dL at the end (NS). Systolic blood pressure dropped in both groups, with a bigger drop in the exercise group (11.81 vs 0.17 mm Hg) (P=.0001). HDL-C values increased in the control group by 4.97 mg/dL; and in the experimental group, by 3.46 mg/dL (NS). A controlled programme of strength/stamina physical exercise reduces the cardiovascular risk of post-menopausal women.

Effect of 7 days of exercise on exogenous carbohydrate oxidation and insulin resistance in children with obesity.

PubMed

Chu, Lisa; Morrison, Katherine M; Riddell, Michael C; Raha, Sandeep; Timmons, Brian W

2018-07-01

The capacity to match carbohydrate (CHO) oxidation with CHO availability (deemed metabolic flexibility (MetFlex)) may be important for type 2 diabetes prevention. In adults, impaired MetFlex is associated with insulin resistance (IR), which can be improved with as little as 7 days of exercise. Whether this occurs similarly in children is unknown. We hypothesized that 7 consecutive days of exercise would improve MetFlex and IR in children with obesity. Twelve children (8 boys, 4 girls) completed 2 study visits before (PRE) and 2 study visits after (POST) exercise training. At visit 1, fasting blood was collected, and anthropometry and maximal oxygen uptake were assessed. At visit 2, a 13 C-enriched CHO drink was ingested before exercise (3 × 20 min) at ∼59% maximal oxygen uptake. Exogenous CHO oxidative efficiency, used as a surrogate measurement of MetFlex, was calculated from breath samples. During training, participants alternated between continuous and high-intensity interval cycling sessions at home under supervision. In spite of good training adherence, there was no improvement in MetFlex (PRE: 20.7% ± 1.8%, POST: 18.9% ± 4.9%, p = 0.22) or homeostasis model assessment of insulin resistance (PRE: 8.7 ± 4.6, POST: 8.1 ± 6.0, p = 0.51). Future research should investigate exercise volume, sex, and pubertal effects on the early responsiveness of MetFlex to exercise therapy.

Orally administered H-Dmt-Tic-Lys-NH-CH2-Ph (MZ-2), a potent mu/delta-opioid receptor antagonist, regulates obese-related factors in mice.

PubMed

Marczak, Ewa D; Jinsmaa, Yunden; Myers, Page H; Blankenship, Terry; Wilson, Ralph; Balboni, Gianfranco; Salvadori, Severo; Lazarus, Lawrence H

2009-08-15

Orally active dual mu-/delta-opioid receptor antagonist, H-Dmt-Tic-Lys-NH-CH(2)-Ph (MZ-2) was applied to study body weight gain, fat content, bone mineral density, serum insulin, cholesterol and glucose levels in female ob/ob (B6.V-Lep/J homozygous) and lean wild mice with or without voluntary exercise on wheels for three weeks, and during a two week post-treatment period under the same conditions. MZ-2 (10mg/kg/day, p.o.) exhibited the following actions: (1) reduced body weight gain in sedentary obese mice that persisted beyond the treatment period without effect on lean mice; (2) stimulated voluntary running on exercise wheels of both groups of mice; (3) decreased fat content, enhanced bone mineral density (BMD), and decreased serum insulin and glucose levels in obese mice; and (4) MZ-2 (30 microM) increased BMD in human osteoblast cells (MG-63) comparable to naltrexone, while morphine inhibited mineral nodule formation. Thus, MZ-2 has potential application in the clinical management of obesity, insulin and glucose levels, and the amelioration of osteoporosis.

Exercise Promotes Healthy Aging of Skeletal Muscle

PubMed Central

Cartee, Gregory D.; Hepple, Russell T.; Bamman, Marcas M.; Zierath, Juleen R.

2016-01-01

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics, and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes “healthy aging” by inducing modifications in skeletal muscle. PMID:27304505

Muscle-Specific Overexpression of PGC-1α Does Not Augment Metabolic Improvements in Response to Exercise and Caloric Restriction

PubMed Central

Wong, Kari E.; Mikus, Catherine R.; Slentz, Dorothy H.; Seiler, Sarah E.; DeBalsi, Karen L.; Ilkayeva, Olga R.; Crain, Karen I.; Kinter, Michael T.; Kien, C. Lawrence; Stevens, Robert D.

2015-01-01

This study used mice with muscle-specific overexpression of PGC-1α, a transcriptional coactivator that promotes mitochondrial biogenesis, to determine whether increased oxidative potential facilitates metabolic improvements in response to lifestyle modification. MCK-PGC1α mice and nontransgenic (NT) littermates were fed a high-fat diet (HFD) for 10 weeks, followed by stepwise exposures to voluntary wheel running (HFD+Ex) and then 25% caloric restriction with exercise (Ex/CR), each for an additional 10 weeks with continued HFD. Running and CR improved weight and glucose control similarly in MCK-PGC1α and NT mice. Sedentary MCK-PGC1α mice were more susceptible to diet-induced glucose intolerance, and insulin action measured in isolated skeletal muscles remained lower in the transgenic compared with the NT group, even after Ex/CR. Comprehensive profiling of >200 metabolites and lipid intermediates revealed dramatic group-specific responses to the intervention but did not produce a lead candidate that tracked with changes in glucose tolerance irrespective of genotype. Instead, principal components analysis identified a chemically diverse metabolite cluster that correlated with multiple measures of insulin responsiveness. These findings challenge the notion that increased oxidative capacity defends whole-body energy homeostasis and suggest that the interplay between mitochondrial performance, lipotoxicity, and insulin action is more complex than previously proposed. PMID:25422105

Effects of exercise on insulin resistance and body composition in overweight and obese women with and without polycystic ovary syndrome.

PubMed

Hutchison, Samantha K; Stepto, Nigel K; Harrison, Cheryce L; Moran, Lisa J; Strauss, Boyd J; Teede, Helena J

2011-01-01

Polycystic ovary syndrome (PCOS) is an insulin-resistant (IR) state. Visceral fat (VF) is independently associated with IR. The objectives of the study were to explore mechanisms underpinning IR by assessing the effect of exercise training on IR and body composition in overweight PCOS and non-PCOS women. This was a prospective exercise intervention study. The study was conducted at an academic medical center. Participants included 20 overweight PCOS and 14 overweight non-PCOS women. The intervention included 12 wk of intensified aerobic exercise (3 h/wk). IR on euglycemic hyperinsulinemic clamp, body composition including abdominal visceral and sc fat distribution by computer tomography and lipids was measured. PCOS subjects were more IR (P = 0.02) and had more VF (P = 0.04 age adjusted) than non-PCOS women. In PCOS women, IR correlated with VF (r = -0.78, P < 0.01). With exercise training, both groups maintained weight but within PCOS, VF (-12.0 cm(2), P = 0.03) and within non-PCOS abdominal sc fat (-40.2 cm(2), P = 0.02) decreased. Despite exercise-induced improvement in IR within PCOS (+27.9 mg · m(-2) · min(-1), P = 0.03), no relationship with decreased VF (r = -0.08, P = 0.84) and no differential changes in IR and VF between groups were noted. Triglycerides decreased within PCOS (-0.27 mmol/liter, P = 0.02) and decreased differentially between groups (P < 0.01). Higher IR was related to increased VF in PCOS, suggesting an etiological role for VF in intrinsic IR in PCOS; however, changes with exercise intervention did not support a causal relationship. Triglycerides were modulated more by exercise training in PCOS than non-PCOS women. Within-group exercise-induced reductions in cardiometabolic risk factors including IR, triglycerides, and VF in PCOS were observed without significant weight loss and if confirmed in future controlled trials, suggest weight loss should not be the sole focus of exercise programs.

Regular voluntary exercise cures stress-induced impairment of cognitive function and cell proliferation accompanied by increases in cerebral IGF-1 and GST activity in mice.

PubMed

Nakajima, Sanae; Ohsawa, Ikuroh; Ohta, Shigeo; Ohno, Makoto; Mikami, Toshio

2010-08-25

Chronic stress impairs cognitive function and hippocampal neurogenesis. This impairment is attributed to increases in oxidative stress, which result in the accumulation of lipid peroxide. On the other hand, voluntary exercise enhances cognitive function, hippocampal neurogenesis, and antioxidant capacity in normal animals. However, the effects of voluntary exercise on cognitive function, neurogenesis, and antioxidants in stressed mice are unclear. This study was designed to investigate whether voluntary exercise cures stress-induced impairment of cognitive function accompanied by improvement of hippocampal neurogenesis and increases in antioxidant capacity. Stressed mice were exposed to chronic restraint stress (CRS), which consisted of 12h immobilization daily and feeding in a small cage, for 8 weeks. Exercised mice were allowed free access to a running wheel during their exposure to CRS. At the 6th week, cognitive function was examined using the Morris water maze (MWM) test. Daily voluntary exercise restored stress-induced impairment of cognitive function and the hippocampal cell proliferation of newborn cells but not cell survival. Voluntary exercise increased insulin-like growth factor 1 (IGF-1) protein and mRNA expression in the cerebral cortex and liver, respectively. In addition, CRS resulted in a significant increase in the number of 4-hydrosynonenal (4-HNE)-positive cells in the hippocampal dentate gyrus; whereas, voluntary exercise inhibited it and enhanced glutathione s-transferases (GST) activity in the brain. These findings suggest that voluntary exercise attenuated the stress-induced impairment of cognitive function accompanied by improvement of cell proliferation in the dentate gyrus. This exercise-induced improvement was attributed to exercise-induced enhancement of IGF-1 protein and GST activity in the brain. Copyright 2010 Elsevier B.V. All rights reserved.

The Effects of Exercise on Food Intake and Hunger: Relationship with Acylated Ghrelin and Leptin

PubMed Central

Vatansever-Ozen, Serife; Tiryaki-Sonmez, Gul; Bugdayci, Guler; Ozen, Guclu

2011-01-01

This study investigated the effects of a long bout of aerobic exercise on hunger and energy intake and circulating levels of leptin and acylated ghrelin. Ten healthy male subjects undertook two, 4 h trials in a randomized crossover design. In the exercise trial subjects ran for 105 min at 50% of maximal oxygen uptake and the last 15 min at 70% of maximal oxygen uptake followed by a 120 min rest period. In the control trial, subjects rested for 4 h. Subjects consumed a buffet test meal at 180 min during each trial. Hunger ratings, acylated ghrelin, leptin, glucose and insulin concentrations were measured at 0, 1, 2, 3 and 4 h. No differences were found at baseline values for hunger, acylated ghrelin, leptin, insulin and glucose for both trials (p > 0.05). The estimated energy expenditure of the exercise trial was 1550 ± 136 kcal. Exercise did not change subsequent absolute energy intake, but produced a significant decrease (p < 0.05) in relative energy intake. A two-way ANOVA revealed a significant (p < 0. 05) interaction effect for hunger and acylated ghrelin. In conclusion, this exercise regimen had a positive effect on reducing appetite which is related to reduced acylated ghrelin responses over time. This finding lends support for a role of exercise in weight management. Key points Physical exercise is a strategy used to counteract obesity, since it lowers the energetic balance by increasing energy expenditure. However, because any energy expended in exercise elevates the intensity of hunger and drives food consumption, it is pertinent to ask how effective exercise could be in helping people to lose weight or to prevent weight gain. The effects of exercise on hunger sensations and food intake are fairly controversial and depend on the intensity and duration of exercise. 120 min prolonged treadmill exercise with mix intensity, temporarily decreased hunger sensations, acylated ghrelin and relative energy intake. Variations in exercise intensity should theoretically be a useful means of weight loss. PMID:24149873

Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs

PubMed Central

Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min

2018-01-01

Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPARγ and lipid synthetic genes, as well as enhancing PPARα and lipid β-oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes. PMID:29743883

Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs.

PubMed

Zhang, Qiang; Xu, Lingyan; Xia, Jie; Wang, Dongmei; Qian, Min; Ding, Shuzhe

2018-01-01

Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPAR γ and lipid synthetic genes, as well as enhancing PPAR α and lipid β -oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes.

[Physical activity and exercise training in the prevention and therapy of type 2 diabetes mellitus].

PubMed

Francesconi, Claudia; Lackinger, Christian; Weitgasser, Raimund; Haber, Paul; Niebauer, Josef

2016-04-01

Lifestyle in general (nutrition, exercise, smoking habits), besides the genetic predisposition, is known to be a strong predictor for the development of diabetes. Exercise in particular is not only useful in improving glycaemia by lowering insulin resistance and positively affect insulin secretion, but to reduce cardiovascular risk.To gain substantial health benefits a minimum of 150 min of moderate or vigorous intense aerobic physical activity and muscle strengthening activities per week are needed. The positive effect of training correlates directly with the amount of fitness gained and lasts only as long as the fitness level is sustained. The effect of exercise is independent of age and gender. It is reversible and reproducible.Based on the large evidence of exercise referral and prescription the Austrian Diabetes Associations aims to implement the position of a "physical activity adviser" in multi-professional diabetes care.

Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls.

PubMed

Morrison, John A; Glueck, Charles J; Wang, Ping

2010-05-01

We evaluated the associations of teenage insulin and adolescent diet with 10-year weight gain in an analysis sample of black and white girls matched for pubertal stage, body mass index (BMI) (or fat mass), and insulin at ages 9 to 10 years. We hypothesized that preteen insulin and insulin resistance would interact with dietary factors to positively predict increases in BMI. Furthermore, we hypothesized that increased insulin and insulin resistance, interacting with higher caloric intake during adolescence, would lead to greater increments in BMI in black girls than in white girls. Prospective 10-year follow-up was performed on 215 pairs of black and white schoolgirls matched at baseline by BMI (or fat mass), insulin, and pubertal stage, with repeated measures of body habitus, insulin, and dietary intake. When matched for BMI, black girls had higher fat-free mass and white girls had higher fat mass at ages 9 to 10 years. Black-white differences in caloric intake were not significant at ages 9 to 10 years, but black girls consumed more calories at age 19 years. Black girls consumed a greater percentage of calories from fat throughout. At age 19 years, black girls had higher BMI, fat mass index, and insulin. When matched at ages 9 to 10 years for fat mass, black girls were heavier, had higher BMI, and had greater fat-free mass. By ages 18 to 19 years, black girls continued to have higher BMI, but had accrued higher fat mass and a higher percentage of body fat. By stepwise multiple regression, 10-year increases in BMI were predicted by ages 9 to 10 years BMI, 10-year change in insulin, and a 3-way interaction between ages 9 to 10 years insulin, adolescent caloric intake, and race (higher in black girls) (all Ps < .0001). Insulin at ages 9 to 10 years interacts with caloric intake to increase BMI by age 19 years. There appear to be intrinsic black-white metabolic differences that lead to greater gains in fat during adolescence in black girls. Evaluating BMI and insulin at ages 9 to 10 years could identify girls (particularly black) who would optimally benefit from dietary and exercise interventions to avoid obesity.

The effect of acute dark chocolate consumption on carbohydrate metabolism and performance during rest and exercise.

PubMed

Stellingwerff, Trent; Godin, Jean-Philippe; Chou, Chieh J; Grathwohl, Dominik; Ross, Alastair B; Cooper, Karen A; Williamson, Gary; Actis-Goretta, Lucas

2014-02-01

Consumption of cocoa-enriched dark chocolate (DC) has been shown to alter glucose and insulin concentration during rest and exercise compared with cocoa-depleted control (CON). However, the impact of DC consumption on exercise metabolism and performance is uncertain. Therefore, we investigated carbohydrate metabolism via stable isotope tracer techniques during exercise after subjects ingested either DC or CON. Sixteen overnight-fasted male cyclists performed a single-blinded, randomized, crossover design trial, after consuming either DC or CON at 2 h prior to 2.5 h of steady-state (SS) exercise (∼45% peak oxygen uptake). This was followed by an ∼15-min time-trial (TT) and 60 min of recovery. [6,6-(2)H2]Glucose and [U-(13)C]glucose were infused during SS to assess glucose rate of appearance (Ra) and disappearance (Rd). After DC consumption, plasma (-)-glucose and insulin concentrations were significantly (p < 0.001) elevated throughout vs. CON. During SS, there was no difference in [6,6-(2)H2]glucose Ra between treatments, but towards the end of SS (last 60 min) there was a ∼16% decrease in Rd in DC vs. CON (p < 0.05). Accordingly, after DC there was an ∼18% significant decrease in plasma glucose oxidation (trial effect; p = 0.032), and an ∼15% increase in tracer-derived muscle glycogen utilization (p = 0.045) late during SS exercise. The higher blood glucose concentrations during exercise and recovery after DC consumption coincided with high concentrations of epicatechin and (or) theobromine. In summary, DC consumption altered muscle carbohydrate partitioning, between muscle glucose uptake and glycogen oxidation, but did not effect cycling TT performance.

Effect of different exercise protocols on metabolic profiles and fatty acid metabolism in skeletal muscle in high-fat diet-fed rats.

PubMed

Shen, Youqing; Xu, Xiangfeng; Yue, Kai; Xu, Guodong

2015-05-01

To evaluate the efficacy of mild-intensity endurance, high-intensity interval, and concurrent exercise on preventing high-fat diet-induced obesity. Male rats were divided into five groups, control diet/sedentary group, high-fat diet/sedentary, high-fat diet/endurance exercise, high-fat diet/interval exercise (HI), and high-fat diet/concurrent exercise. All exercise groups were made to exercise for 10 weeks, with matched running distances. Body weight, fat content, blood metabolites, quantitative insulin sensitivity check index (QUICKI), and adipocyte and liver lipid droplet size were assessed, and the expression of fatty acid metabolism-related genes was quantified. All exercise protocols reduced body weight, adiposity, serum triglycerides, and fasting glucose and also improved QUICKI to some extent. However, only HI prevented obesity and its associated pathologies completely. The expression of stearoyl-coenzyme A desaturase-1 was elevated in all rats fed a high-fat diet whereas carnitine palmitoyltransferase 1 (CPT1) expression was increased with exercise. Rev-erbα expression was elevated only in the HI group, which also had the highest level of CPT1 expression. The HI-induced increase in Rev-erbα and CPT1 expression was associated with the complete prevention of diet-induced obesity. Moreover, the increased caloric expenditure achieved with this protocol was preferential over other exercise regimens, and might be used to improve lipid metabolism. © 2015 The Obesity Society.

Treatment of Diabetes and Long-Term Survival After Insulin and Glucokinase Gene Therapy

PubMed Central

Callejas, David; Mann, Christopher J.; Ayuso, Eduard; Lage, Ricardo; Grifoll, Iris; Roca, Carles; Andaluz, Anna; Ruiz-de Gopegui, Rafael; Montané, Joel; Muñoz, Sergio; Ferre, Tura; Haurigot, Virginia; Zhou, Shangzhen; Ruberte, Jesús; Mingozzi, Federico; High, Katherine A.; Garcia, Felix; Bosch, Fatima

2013-01-01

Diabetes is associated with severe secondary complications, largely caused by poor glycemic control. Treatment with exogenous insulin fails to prevent these complications completely, leading to significant morbidity and mortality. We previously demonstrated that it is possible to generate a “glucose sensor” in skeletal muscle through coexpression of glucokinase and insulin, increasing glucose uptake and correcting hyperglycemia in diabetic mice. Here, we demonstrate long-term efficacy of this approach in a large animal model of diabetes. A one-time intramuscular administration of adeno-associated viral vectors of serotype 1 encoding for glucokinase and insulin in diabetic dogs resulted in normalization of fasting glycemia, accelerated disposal of glucose after oral challenge, and no episodes of hypoglycemia during exercise for >4 years after gene transfer. This was associated with recovery of body weight, reduced glycosylated plasma proteins levels, and long-term survival without secondary complications. Conversely, exogenous insulin or gene transfer for insulin or glucokinase alone failed to achieve complete correction of diabetes, indicating that the synergistic action of insulin and glucokinase is needed for full therapeutic effect. This study provides the first proof-of-concept in a large animal model for a gene transfer approach to treat diabetes. PMID:23378612

Free Fatty Acid-Induced Hepatic Insulin Resistance is Attenuated Following Lifestyle Intervention in Obese Individuals with Impaired Glucose Tolerance

PubMed Central

Haus, Jacob M.; Solomon, Thomas P. J.; Marchetti, Christine M.; Edmison, John M.; González, Frank; Kirwan, John P.

2010-01-01

Objective: The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Research Design and Methods: Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; ∼1800 kcal; n = 11) or hypocaloric (HYPO; ∼1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass−1 per minute−1) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m2 · min−1) euglycemic (5.0 mm) clamp with [3-3H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). Results: At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 ± 0.8, 2.0 ± 0.5, and 2.6 ± 0.4; HYPO, 3.8 ± 0.5, 1.2 ± 0.3, and 2.3 ± 0.4, respectively). After the intervention the HYPO group lost more body weight (P < 0.05) and fat mass (P < 0.05). However, both lifestyle interventions reduced hepatic insulin resistance during basal (P = 0.005) and INS (P = 0.001) conditions, and insulin-mediated suppression of HGP during INS was equally improved in both groups (EU: −42 ± 22%; HYPO: −50 ± 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: −15 ± 24% vs. HYPO: −58 ± 19%, P = 0.02). Conclusions: Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention. PMID:19906790

Combination of Recreational Soccer and Caloric Restricted Diet Reduces Markers of Protein Catabolism and Cardiovascular Risk in Patients with Type 2 Diabetes.

PubMed

Vieira de Sousa, M; Fukui, R; Krustrup, P; Dagogo-Jack, S; Rossi da Silva, M E

2017-01-01

Moderate calorie-restricted diets and exercise training prevent loss of lean mass and cardiovascular risk. Because adherence to routine exercise recommendation is generally poor, we utilized recreational soccer training as a novel therapeutic exercise intervention in type 2 diabetes (T2D) patients. We compared the effects of acute and chronic soccer training plus calorie-restricted diet on protein catabolism and cardiovascular risk markers in T2D. Fifty-one T2D patients (61.1±6.4 years, 29 females: 22 males) were randomly allocated to the soccer+diet-group (SDG) or to the diet-group (DG). The 40-min soccer sessions were held 3 times per week for 12 weeks. Nineteen participants attended 100% of scheduled soccer sessions, and none suffered any injuries. The SDG group showed higher levels of growth hormone (GH), free fatty acids and ammonia compared with DG. After 12 weeks, insulin-like growth factor binding protein (IGFPB)-3 and glucose levels were lower in SDG, whereas insulin-like growth factor (IGF)-1/ IGFBP-3 ratio increased in both groups. After the last training session, an increase in IGF-1/IGFBP-3 and attenuation in ammonia levels were suggestive of lower muscle protein catabolism. Recreational soccer training was popular and safe, and was associated with decreased plasma glucose and IGFBP-3 levels, decreased ammoniagenesis, and increased lipolytic activity and IGF-1/IGFBP-3 ratio, all indicative of attenuated catabolism.

Managing Activity in Patients Who Have Diabetes. Practical Ways to Incorporate Exercise into Lifestyle.

ERIC Educational Resources Information Center

Taunton, Jack E.; McCargar, Linda

1995-01-01

Diabetes control involves the appropriate balance of exercise, diet, and medication. Regular exercise has many benefits for people with diabetes. Physicians can educate patients about ways to regulate and monitor blood glucose before, during, and after workouts. Patients need to understand the effects of exercise and diet on insulin requirements.…

Effect of exercise intensity on abdominal fat loss during calorie restriction in overweight and obese postmenopausal women: a randomized, controlled trial1234

PubMed Central

Nicklas, Barbara J; Wang, Xuewen; You, Tongjian; Lyles, Mary F; Demons, Jamehl; Easter, Linda; Berry, Michael J; Lenchik, Leon; Carr, J Jeffrey

2009-01-01

Background: Exercise intensity may affect the selective loss of abdominal adipose tissue. Objective: This study showed whether aerobic exercise intensity affects the loss of abdominal fat and improvement in cardiovascular disease risk factors under conditions of equal energy deficit in women with abdominal obesity. Design: This was a randomized trial in 112 overweight and obese [body mass index (in kg/m2): 25–40; waist circumference >88 cm], postmenopausal women assigned to one of three 20-wk interventions of equal energy deficit: calorie restriction (CR only), CR plus moderate-intensity aerobic exercise (CR + moderate-intensity), or CR plus vigorous-intensity exercise (CR + vigorous-intensity). The diet was a controlled program of underfeeding during which meals were provided at individual calorie levels (≈400 kcal/d). Exercise (3 d/wk) involved treadmill walking at an intensity of 45–50% (moderate-intensity) or 70–75% (vigorous-intensity) of heart rate reserve. The primary outcome was abdominal visceral fat volume. Results: Average weight loss for the 95 women who completed the study was 12.1 kg (±4.5 kg) and was not significantly different across groups. Maximal oxygen uptake (O2max) increased more in the CR + vigorous-intensity group than in either of the other groups (P < 0.05). The CR-only group lost relatively more lean mass than did either exercise group (P < 0.05). All groups showed similar decreases in abdominal visceral fat (≈25%; P < 0.001 for all). However, changes in visceral fat were inversely related to increases in O2max (P < 0.01). Changes in lipids, fasting glucose or insulin, and 2-h glucose and insulin areas during the oral-glucose-tolerance test were similar across treatment groups. Conclusion: With a similar amount of total weight loss, lean mass is preserved, but there is not a preferential loss of abdominal fat when either moderate- or vigorous-intensity aerobic exercise is performed during caloric restriction. This trial was registered at clinicaltrials.gov as NCT00664729. PMID:19211823

Management of diabetes mellitus in children and adolescents: engaging in physical activity.

PubMed

Nadella, Silpa; Indyk, Justin A; Kamboj, Manmohan K

2017-07-01

Regular physical activity is an important component in the management of both type 1 and type 2 diabetes mellitus (T1DM and T2DM), as it has the potential to improve glycemic control, delay cardiovascular complications, and increase overall well-being. Unfortunately, many children and adolescents with diabetes do not partake in regular exercise and physical activity for multiple reasons. This review identifies the barriers to participation from the aspect of the patient, caregiver, and the healthcare provider. The management of physical activity of children and adolescents with diabetes mellitus is unique and requires an understanding of exercise physiology and how it differs in these children and adolescents from those without the condition. These individuals are at risk for important and potentially life threatening complications including, but not limited to, severe or delayed nocturnal hypoglycemia. It is essential to identify these risks as well as, monitor and manage adjustments to carbohydrate intake and insulin dosing through basal-bolus regimen or insulin pump adjustments appropriately before, during, and after the exercise activity. This review discusses these issues and also outlines differences in management between patients with T1DM and T2DM.

Child and Adolescent Athletes with Diabetes.

ERIC Educational Resources Information Center

Blackett, Piers R.

1988-01-01

Exercise may be a useful element in teaching diabetic children to control the disease. Controlling glucose levels during exercise requires close regulation of diet and insulin. Practical and medical aspects of exercise for diabetics are discussed, as well as its physical benefits, such as a strengthened heart. (JL)

Acute regulation of IGF-I by alterations in post-exercise macronutrients

USDA-ARS?s Scientific Manuscript database

This investigation sought to examine the contributions of exercise and nutrient replenishment on in vivo regulation of the insulin-like growth factor-I (IGF-I) axis components. Eight college-aged males completed three high-intensity interval training (HIIT) protocols followed by three post-exercise ...

The associations between increasing degrees of homeostatic model assessment for insulin resistance and muscular strengthening activities among euglycaemic US adults.

PubMed

Boyer, William R; Johnson, Tammie M; Fitzhugh, Eugene C; Richardson, Michael R; Churilla, James R

2015-11-01

To examine the associations between the homeostatic model assessment for insulin resistance and self-reported muscular strengthening activity in a nationally representative sample of euglycaemic US adults. Sample included euglycaemic adults (⩾20 years of age (n = 2009)) from the 1999 to 2004 National Health and Nutrition Examination Survey. Homeostatic model assessment for insulin resistance was categorized into quartiles and was the primary independent variable of interest. No reported muscular strengthening activity was the dependent variable. Following adjustment for covariates, those with homeostatic model assessment for insulin resistance values in fourth (odds ratio: 2.04, 95% confidence interval: 1.35-3.06, p < 0.001) quartile were found to have significantly greater odds of reporting no muscular strengthening activity. Following further adjustment for non-muscular strengthening activity specific aerobic leisure-time physical activity, results remained significant for the fourth (odds ratio: 2.30, 95% confidence interval: 1.50-3.52, p < 0.001) quartile. A significant trend was seen across quartiles of homeostatic model assessment for insulin resistance for increasing prevalence of no muscular strengthening activity (p < 0.001). Having a higher homeostatic model assessment for insulin resistance value is associated with greater odds of reporting no muscular strengthening activity among euglycaemic US adults. This implies that subjects with an increasing degree of insulin resistance are more likely to not engage in muscular strengthening activity, an exercise modality that has been shown to reduce the risk of several cardiometabolic diseases and improve glycaemic status. © The Author(s) 2015.

Increased recovery rates of phosphocreatine and inorganic phosphate after isometric contraction in oxidative muscle fibers and elevated hepatic insulin resistance in homozygous carriers of the A-allele of FTO rs9939609.

PubMed

Grunnet, Louise G; Brøns, Charlotte; Jacobsen, Stine; Nilsson, Emma; Astrup, Arne; Hansen, Torben; Pedersen, Oluf; Poulsen, Pernille; Quistorff, Bjørn; Vaag, Allan

2009-02-01

Recent studies identified the rs9939609 A-allele of the FTO (fat mass and obesity associated) gene as being associated with obesity and type 2 diabetes. We studied the role of the A-allele in the regulation of peripheral organ functions involved in the pathogenesis of obesity and type 2 diabetes. Forty-six young men underwent a hyperinsulinemic euglycemic clamp with excision of skeletal muscle biopsies, an iv glucose tolerance test, 31phosphorous magnetic resonance spectroscopy, and 24-h whole body metabolism was measured in a respiratory chamber. The FTO rs9939609 A-allele was associated with elevated fasting blood glucose and plasma insulin, hepatic insulin resistance, and shorter recovery half-times of phosphocreatine and inorganic phosphate after exercise in a primarily type I muscle. These relationships--except for fasting insulin--remained significant after correction for body fat percentage. The risk allele was not associated with fat distribution, peripheral insulin sensitivity, insulin secretion, 24-h energy expenditure, or glucose and fat oxidation. The FTO genotype did not influence the mRNA expression of FTO or a set of key nuclear or mitochondrially encoded genes in skeletal muscle during rest. Increased energy efficiency--and potentially increased mitochondrial coupling--as suggested by faster recovery rates of phosphocreatine and inorganic phosphate in oxidative muscle fibers may contribute to the increased risk of obesity and type 2 diabetes in homozygous carriers of the FTO A-risk allele. Hepatic insulin resistance may represent the key metabolic defect responsible for mild elevations of fasting blood glucose associated with the FTO phenotype.

Co-ingestion of carbohydrate and whey protein increases fasted rates of muscle protein synthesis immediately after resistance exercise in rats

PubMed Central

Wang, Wanyi; Ding, Zhenping; Solares, Geoffrey J.; Choi, Soon-Mi; Wang, Bo; Yoon, Aram; Farrar, Roger P.; Ivy, John L.

2017-01-01

The objective of the study was to investigate whether co-ingestion of carbohydrate and protein as compared with protein alone augments muscle protein synthesis (MPS) during early exercise recovery. Two months old rats performed 10 repetitions of ladder climbing with 75% of body weight attached to their tails. Placebo (PLA), whey protein (WP), or whey protein plus carbohydrate (CP) was then given to rats by gavage. An additional group of sedentary rats (SED) was used as controls. Blood samples were collected immediately and at either 1 or 2 h after exercise. The flexor hallucis longus muscle was excised at 1 or 2 h post exercise for analysis of MPS and related signaling proteins. MPS was significantly increased by CP compared with PLA (p<0.05), and approached significance compared with WP at 1 h post exercise (p = 0.08). CP yielded a greater phosphorylation of mTOR compared with SED and PLA at 1 h post exercise and SED and WP at 2 h post exercise. CP also increased phosphorylation of p70S6K compared with SED at 1 and 2 h post exercise. 4E-BP1 phosphorylation was inhibited by PLA at 1 h but elevated by WP and CP at 2 h post exercise relative to SED. The phosphorylation of AMPK was elevated by exercise at 1 h post exercise, and this elevated level was sustained only in the WP group at 2 h. The phosphorylation of Akt, GSK3, and eIF2Bε were unchanged by treatments. Plasma insulin was transiently increased by CP at 1 h post exercise. In conclusion, post-exercise CP supplementation increases MPS post exercise relative to PLA and possibly WP, which may have been mediated by greater activation of the mTOR signaling pathway. PMID:28296942

Mechanisms of insulin resistance in obesity

PubMed Central

Ye, Jianping

2014-01-01

Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

Insulin-like growth factor-I, physical activity, and control of cellular anabolism.

PubMed

Nindl, Bradley C

2010-01-01

The underlying mechanisms responsible for mediating the beneficial outcomes of exercise undoubtedly are many, but the insulin-like growth factor-I (IGF-I) system is emerging as an important and central hormonal axis that plays a significant role concerning cellular anabolism. This introductory article summarizes the intent and the content for papers presented as part of a 2008 American College of Sports Medicine national symposium entitled "Insulin-like Growth Factor-I, Physical Activity, and Control of Cellular Anabolism." The individual authors and their papers are as follows: Jan Frystyk authoring "The relationship between exercise and the growth hormone/insulin-like growth factor-I axis," Greg Adams authoring "IGF-I signaling in skeletal muscle and the potential for cytokine interactions," and Brad Nindl authoring "Insulin-like growth factor-I as a biomarker of health, fitness, and training status." These papers focus on 1) different assay methodologies for IGF-I within the paradigm of exercise studies, 2) research demonstrating that intracellular signaling components associated with several proinflammatory cytokines have the potential to interact with anabolic signaling processes in skeletal muscle, and 3) an overview of IGF-I as a biomarker related to exercise training, muscle and bone remodeling, body composition, cognition, and cancer. When summed in total, the contribution that these papers will make will undoubtedly involve bringing attention to the vast regulatory complexity of the IGF-I system and will hopefully convince the reader that the IGF-I system warrants further detailed scientific inquiry to resolve many unanswered questions and paradoxical experimental findings. The IGF-I system remains one of the most intriguing and captivating marvels of human physiology that seems central in mediating numerous adaptations from physical activity.

Effects of exercise on energy-regulating hormones and appetite in men and women

PubMed Central

Hagobian, Todd A.; Sharoff, Carrie G.; Stephens, Brooke R.; Wade, George N.; Silva, J. Enrique; Chipkin, Stuart R.; Braun, Barry

2009-01-01

When previously sedentary men and women follow exercise training programs with ad libitum feeding, men lose body fat, but women do not. The purpose of this study was to evaluate whether this observation could be related to sex differences in the way energy-regulating hormones and appetite perception respond to exercise. Eighteen (9 men, 9 women) overweight/obese individuals completed four bouts of exercise with energy added to the baseline diet to maintain energy balance (BAL), and four bouts without energy added to induce energy deficit (DEF). Concentrations of acylated ghrelin, insulin, and leptin, as well as appetite ratings were measured in response to a meal after a no-exercise baseline and both exercise conditions. In men, acylated ghrelin area under the curve (AUC) was not different between conditions. In women, acylated ghrelin AUC was higher after DEF (+32%) and BAL (+25%), and the change from baseline was higher than men (P < 0.05). In men, insulin AUC was reduced (−17%) after DEF (P < 0.05), but not BAL. In women, insulin AUC was lower (P < 0.05) after DEF (−28%) and BAL (−15%). Leptin concentrations were not different across conditions in either sex. In men, but not in women, appetite was inhibited after BAL relative to DEF. The results indicate that, in women, exercise altered energy-regulating hormones in a direction expected to stimulate energy intake, regardless of energy status. In men, the response to exercise was abolished when energy balance was maintained. The data are consistent with the paradigm that mechanisms to maintain body fat are more effective in women. PMID:19073905

Exercise and coronary heart disease risk markers in South Asian and European men.

PubMed

Arjunan, Saravana Pillai; Bishop, Nicolette Claire; Reischak-Oliveira, Alvaro; Stensel, David John

2013-07-01

South Asians have a higher-than-average risk of CHD. The reasons for this are unclear, but physical inactivity and/or poor responsiveness to exercise may play a role. This study compared the effect of prior exercise on postprandial triacylglycerol (TAG), glucose, insulin, interleukin-6, and soluble intercellular adhesion molecule-1 concentrations in South Asian and European men. Ten healthy South Asian men (i.e., nine Indian men and one Pakistani man) and 10 healthy European men age 20 to 28 yr completed two 2-d trials (exercise and control) in a randomized crossover design. On the afternoon of day 1 of the exercise trial, participants ran on a treadmill for 60 min at approximately 70% of maximal oxygen uptake. Participants rested on day 1 of the control trial. On day 2 of both trials, participants rested and consumed high-fat (57% of energy content) test meals for breakfast (0 h) and lunch (4 h). Fourteen venous blood samples were collected from a cannula between 0 and 9 h for metabolic measurements. Three-way ANOVA identified higher (P < 0.05) postprandial TAG and insulin concentrations in South Asian versus European men. Exercise lowered postprandial TAG and interleukin-6 and elevated soluble intercellular adhesion molecule-1 concentrations. An interaction effect indicated a greater decrease (22% vs 10%) in TAG area under the concentration versus time curve after exercise in South Asian than in European men. Postprandial TAG and insulin responses to high-fat meals were elevated in these South Asian men, but acute exercise was equally, if not more, effective for reducing postprandial lipemia in South Asian than in European men.

Exercise Promotes Healthy Aging of Skeletal Muscle.

PubMed

Cartee, Gregory D; Hepple, Russell T; Bamman, Marcas M; Zierath, Juleen R

2016-06-14

Primary aging is the progressive and inevitable process of bodily deterioration during adulthood. In skeletal muscle, primary aging causes defective mitochondrial energetics and reduced muscle mass. Secondary aging refers to additional deleterious structural and functional age-related changes caused by diseases and lifestyle factors. Secondary aging can exacerbate deficits in mitochondrial function and muscle mass, concomitant with the development of skeletal muscle insulin resistance. Exercise opposes deleterious effects of secondary aging by preventing the decline in mitochondrial respiration, mitigating aging-related loss of muscle mass and enhancing insulin sensitivity. This review focuses on mechanisms by which exercise promotes "healthy aging" by inducing modifications in skeletal muscle. Copyright © 2016 Elsevier Inc. All rights reserved.

No effect of acute beetroot juice ingestion on oxygen consumption, glucose kinetics, or skeletal muscle metabolism during submaximal exercise in males.

PubMed

Betteridge, Scott; Bescós, Raúl; Martorell, Miquel; Pons, Antoni; Garnham, Andrew P; Stathis, Christos C; McConell, Glenn K

2016-02-15

Beetroot juice, which is rich in nitrate (NO3 (-)), has been shown in some studies to decrease oxygen consumption (V̇o2) for a given exercise workload, i.e., increasing efficiency and exercise tolerance. Few studies have examined the effect of beetroot juice or nitrate supplementation on exercise metabolism. Eight healthy recreationally active males participated in three trials involving ingestion of either beetroot juice (Beet; ∼8 mmol NO3 (-)), Placebo (nitrate-depleted Beet), or Beet + mouthwash (Beet+MW), all of which were performed in a randomized single-blind crossover design. Two-and-a-half hours later, participants cycled for 60 min on an ergometer at 65% of V̇o2 peak. [6,6-(2)H]glucose was infused to determine glucose kinetics, blood samples obtained throughout exercise, and skeletal muscle biopsies that were obtained pre- and postexercise. Plasma nitrite [NO2 (-)] increased significantly (∼130%) with Beet, and this was attenuated in MW+Beet. Beet and Beet+MW had no significant effect on oxygen consumption, blood glucose, blood lactate, plasma nonesterified fatty acids, or plasma insulin during exercise. Beet and Beet+MW also had no significant effect on the increase in glucose disposal during exercise. In addition, Beet and Beet+MW had no significant effect on the decrease in muscle glycogen and phosphocreatine and the increase in muscle creatine, lactate, and phosphorylated acetyl CoA carboxylase during exercise. In conclusion, at the dose used, acute ingestion of beetroot juice had little effect on skeletal muscle metabolism during exercise. Copyright © 2016 the American Physiological Society.

Lack of increase of serum adiponectin concentrations with a moderate weight loss during six months on a high-caloric diet in military service among a young male Finnish population.

PubMed

Mousavinasab, Firoozeh; Tähtinen, Tuula; Jokelainen, Jari; Koskela, Pentti; Vanhala, Mauno; Oikarinen, Jorma; Keinänen-Kiukaanniemi, Sirkka

2005-02-01

An increase of insulin resistance and a worsening of lipid profile during 6 mo of military service in young male Finnish population has previously been shown by us. The present study demonstrates unfavorable changes of serum adiponectin concentrations and their association with weight loss in these particular circumstances. Adiponectin in a range of 4.3-21.2 microg/mL was present in the serum samples and had a significant negative correlation with weight, body mass index, waist to hip ratio, and insulin. Fasting serum lipids and plasma insulin significantly increased and serum adiponectin levels significantly decreased during the military service. Even the subjects with a 5-10% decrease in body weight showed the same result. In cases with more than 10% weight reduction and a significant decrease of fasting insulin concentration, the total and low density lipoprotein cholesterol significantly increased and adiponectin concentration tended to decreased. Only in severely obese cases (BMI >/= 30 kg/m2) with more than 10% decrease in body mass index adiponectin levels tended to increase, although not statistically significantly. This study shows that serum adiponectin concentrations decreased during a 6 mo high-caloric diet in military service, and even a moderate weight reduction induced by high-energy expenditure in exercise during service did not increase its levels.

Acute effects of physical exercise in type 2 diabetes: A review

PubMed Central

Asano, Ricardo Yukio; Sales, Marcelo Magalhães; Browne, Rodrigo Alberto Vieira; Moraes, José Fernando Vila Nova; Coelho Júnior, Hélio José; Moraes, Milton Rocha; Simões, Herbert Gustavo

2014-01-01

The literature has shown the efficiency of exercise in the control of type 2 diabetes (T2D), being suggested as one of the best kinds of non-pharmacological treatments for its population. Thus, the scientific production related to this phenomenon has growing exponentially. However, despite its advances, still there is a lack of studies that have carried out a review on the acute effects of physical exercise on metabolic and hemodynamic markers and possible control mechanisms of these indicators in individuals with T2D, not to mention that in a related way, these themes have been very little studied today. Therefore, the aim of this study was to organize and analyze the current scientific production about the acute effects of physical exercise on metabolic and hemodynamic markers and possible control mechanisms of these indicators in T2D individuals. For such, a research with the following keywords was performed: -exercise; diabetes and post-exercise hypotension; diabetes and excess post-exercise oxygen consumption; diabetes and acute effects in PUBMED, SCIELO and HIGHWIRE databases. From the analyzed studies, it is possible to conclude that, a single exercise session can promote an increase in the bioavailability of nitric oxide and elicit decreases in postexercise blood pressure. Furthermore, the metabolic stress from physical exercise can increase the oxidation of carbohydrate during the exercise and keep it, in high levels, the post exercise consumption of O², this phenomenon increases the rate of fat oxidation during recovery periods after exercise, improves glucose tolerance and insulin sensitivity and reduces glycemia between 2-72 h, which seems to be dependent on the exercise intensity and duration of the effort. PMID:25317243

Low-intensity aerobic exercise training: inhibition of skeletal muscle atrophy in high-fat-diet-induced ovariectomized rats.

PubMed

Kim, Hye Jin; Lee, Won Jun

2017-09-30

Postmenopausal women are highly susceptible to diseases, such as obesity, type 2 diabetes, osteoporosis, or skeletal muscle atrophy and many people recognize the need for regular physical activity. Aerobic exercise training is known to improve the oxidative capacity and insulin sensitivity of skeletal muscles. This study aimed to investigate the role of low-intensity aerobic exercise training on skeletal muscle protein degradation or synthesis in the plantaris muscles of high-fat-fed ovariectomized rats. Ovariectomized female rats were divided into two groups: a high-fat diet-sedentary group (HFD), and a high-fat diet-aerobic exercise group (HFD+EX). The exercise group exercised aerobically on a treadmill 5 days/week for 8 weeks. The rats progressively ran 30 min/day at 15 m/min, up to 40 min/day at 18 m/min, 0% slope, in the last 4 weeks. Although aerobic exercise led to significantly increased AMP-activated protein kinase (AMPK) phosphorylation at Thr172, phosphorylation of the mammalian target of rapamycin (mTOR) substrate Thr389 S6K1 level did not decrease. Additionally, even though Akt activity did not increase at Ser473, the atrogin-1 level significantly decreased in the exercise group compared to the non-exercise group. Immunohistochemical staining revealed that high-fat-induced TSC2 protein expression was eliminated in response to aerobic exercise. These results suggest that aerobic exercise can inhibit skeletal muscle protein degradation, but it cannot increase protein synthesis in the plantaris muscle of high-fat-fed ovariectomized rats. Our findings have implications in understanding skeletal muscle mass maintenance with low intensity aerobic exercise in post-menopausal women. ©2017 The Korean Society for Exercise Nutrition

Energy-matched moderate and high intensity exercise training improves nonalcoholic fatty liver disease risk independent of changes in body mass or abdominal adiposity - A randomized trial.

PubMed

Winn, Nathan C; Liu, Ying; Rector, R Scott; Parks, Elizabeth J; Ibdah, Jamal A; Kanaley, Jill A

2018-01-01

Exercise training is commonly prescribed for individuals diagnosed with nonalcoholic fatty liver disease (NAFLD); however, consensus regarding the volume and intensity of exercise for optimal benefits is lacking. Thus, we determined whether high intensity interval exercise training (HIIT) produced greater reductions in intrahepatic lipid (IHL) content and NAFLD risk factors compared with energy-matched moderate intensity continuous exercise training (MICT) in obese adults with liver steatosis. Eighteen obese adults were randomized to either 4weeks of HIIT (4min 80% VO 2 peak/3min, 50% VO 2 peak) or MICT (55% VO 2 peak, ~60min), matched for energy expenditure (~400kcal/session) and compared to five non-exercising age-matched control subjects. IHL was measured by 1 H-MRS and frequent blood samples were analyzed for glucose, insulin, c-peptide, and NEFA levels during a liquid meal test (180min) to characterize metabolic phenotype. Baseline body weight, visceral abdominal adiposity, and fasting insulin concentrations were greater in the MICT vs HIIT group (P<0.05), while IHL was tightly matched between MICT and HIIT subjects (P>0.05), albeit higher than control subjects (P<0.01). Visceral abdominal adiposity, body mass, liver aminotransferases (ALT, AST), and hepatic apoptotic/inflammatory markers (cytokeratin 18 and fetuin a) were not reduced with either exercise training intervention (P>0.05). Both HIIT and MICT lowered IHL (HIIT, -37.0±12.4%; MICT, -20.1±6.6%, P<0.05); however, the reduction in IHL was not statistically different between exercise intensities (P=0.25). Furthermore, exercise training decreased postprandial insulin, c-peptide, and lipid peroxidation levels (iAUC, P<0.05). Collectively, these findings indicate that energy-matched high intensity and moderate intensity exercise are effective at decreasing IHL and NAFLD risk that is not contingent upon reductions in abdominal adiposity or body mass. Copyright © 2017 Elsevier Inc. All rights reserved.

The role of exercise in cardiovascular rehabilitation: a review.

PubMed

Koutroumpi, Matina; Pitsavos, Christos; Stefanadis, Christodoulos

2008-02-01

The epidemiological literature supports an inverse association and a dose-response gradient between exercise training and both cardiovascular disease in general and coronary artery disease in particular. An overwhelming number of studies has supported similar findings for hypertension, dyslipidaemia, obesity, diabetes, inflammatory and coagulation markers related to cardiovascular disease and cardiac heart failure. Findings are highly suggestive that endurance type exercise training, of moderate intensity most days of the week can lower blood pressure in patients with hypertension, can decrease triglyceride levels and increase HDL cholesterol levels in patients with dyslipidaemia, reduces body weight when combined with diet, improves insulin sensitivity, modifies the inflammatory process and finally can improve stroke volume and reduce cardiomegaly in patients with cardiac heart failure.

Comparing minimally supervised home-based and closely supervised gym-based exercise programs in weight reduction and insulin resistance after bariatric surgery: A randomized clinical trial.

PubMed

Kaviani, Sara; Dadgostar, Haleh; Mazaherinezhad, Ali; Adib, Hanie; Solaymani-Dodaran, Masoud; Soheilipour, Fahimeh; Hakiminezhad, Mahdi

2017-01-01

Background: Effectiveness of various exercise protocols in weight reduction after bariatric surgery has not been sufficiently explored in the literature. Thus, in the present study, we aimed at comparing the effect of minimally supervised home-based and closely supervised gym-based exercise programs on weight reduction and insulin resistance after bariatric surgery. Methods: Females undergoing gastric bypass surgery were invited to participate in an exercise program and were randomly allocated into 2 groups using a random number generator in Excel. They were either offered a minimally supervised home-based (MSHB) or closely supervised gym-based (CSGB) exercise program. The CSGB protocol constitutes 2 weekly training sessions under ACSM guidelines. In the MSHB protocol, the participants received a notebook containing a list of recommended aerobic and resistance exercises, a log to record their activity, and a schedule of follow-up phone calls and clinic visits. Both groups received a pedometer. We measured their weight, BMI, lipid profile, FBS, and insulin level at baseline and at 20 weeks after the exercises, the results of which were compared using t test or Mann-Whitney U test at the end of the study. All the processes were observed by 1 senior resident in sport medicine. Results: A total of 80 patients were recruited who were all able to complete our study (MSHB= 38 and CSGB= 42). The baseline comparison revealed that the 2 groups were similar. The mean change (reduction) in BMI was slightly better in CSGB (8.61 95% CI 7.76-9.45) compared with the MSHB (5.18 95% CI 3.91-6.46); p< 0.01. However, the 2 groups did not have a statistically significant difference in the amount of change in the other factors including FBS and Homa.ir. Conclusion: As we expected a non-inferiority result, our results showed that both MSHB and CSGB exercise methods are somewhat equally effective in improving lipid profile and insulin resistance in the 2 groups, but a slightly better effect on BMI was observed in CSGB group. With considerably lower costs of minimally supervised home- based exercise programs, both methods should be considered when there is lack of adequate funding.

Metabolic consequences of physical inactivity.

PubMed

Biolo, Gianni; Ciocchi, Beniamino; Stulle, Manuela; Piccoli, Arianna; Lorenzon, Stefania; Dal Mas, Viviana; Barazzoni, Rocco; Zanetti, Michela; Guarnieri, Gianfranco

2005-01-01

Physical inactivity is associated with alteration of normal physiologic processes leading to muscle atrophy, reduced exercise capacity, insulin resistance, and altered energy balance. Bed rest studies in human beings using stable isotopes of amino acids indicate that muscle unloading decreases the turnover rates of muscle and whole-body proteins, with a prevailing inhibition of protein synthesis. In the fasting state, muscle and whole-body nitrogen loss was not accelerated during bed rest. In experimental postprandial states, the amino acid-mediated stimulation of protein synthesis was impaired, whereas the ability of combined insulin and glucose infusion to decrease whole-body proteolysis was not affected by muscle inactivity. Thus, an impaired ability of protein/amino acid feeding to stimulate body protein synthesis is the major catabolic mechanism for the effect of bed rest on protein metabolism. This suggests that a protein intake level greater than normal could be required to achieve the same postprandial anabolic effect during muscle inactivity. Metabolic adaptation to muscle inactivity also involves development of resistance to the glucoregulatory action of insulin, decreased energy requirements, and increased insulin and leptin secretion. These alterations may lead to the development of the metabolic syndrome that is defined as the association of hyperinsulinemia, dyslipidemia, hypertension, hyperglycemia, and abdominal obesity. This cluster of metabolic abnormalities is a risk factor for coronary artery disease and stroke. Evidence indicates that exercise training programs may counteract all of these abnormalities both in healthy sedentary subjects and in patients affected by a variety of chronic disease states.

Changes in gut hormone levels and negative energy balance during aerobic exercise in obese young males.

PubMed

Ueda, Shin-ya; Yoshikawa, Takahiro; Katsura, Yoshihiro; Usui, Tatsuya; Nakao, Hayato; Fujimoto, Shigeo

2009-04-01

We examined whether changes in gut hormone levels due to a single bout of aerobic exercise differ between obese young males and normal controls, and attempted to determine the involvement of hormonal changes during exercise in the regulation of energy balance (EB) in these obese subjects. Seven obese and seven age-matched subjects of normal weight participated in exercise and rest sessions. Subjects consumed a standardized breakfast that was followed by constant cycling exercise at 50% VO(2max) or rest for 60 min. At lunch, a test meal was presented, and energy intake (EI) and relative energy intake (REI) were calculated. Blood samples were obtained at 30 min intervals during both sessions for measurement of glucose, insulin, glucagon, ghrelin, peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). Plasma levels of PYY and GLP-1 were increased by exercise, whereas plasma ghrelin levels were unaffected by exercise. The areas under the curve (AUC) of the time courses of PYY and GLP-1 levels did not significantly differ between the two groups. In contrast, EI and REI were decreased by exercise in both groups, and energy deficit was significantly larger in obese subjects than in normal controls. The present findings suggest that short-term EB during a single exercise session might be regulated not by increased amounts of these gut hormones per se.

Improving Metabolic Health in Obese Male Mice via Diet and Exercise Restores Embryo Development and Fetal Growth

PubMed Central

McPherson, Nicole O.; Bakos, Hassan W.; Owens, Julie A.; Setchell, Brian P.; Lane, Michelle

2013-01-01

Paternal obesity is now clearly associated with or causal of impaired embryo and fetal development and reduced pregnancy rates in humans and rodents. This appears to be a result of reduced blastocyst potential. Whether these adverse embryo and fetal outcomes can be ameliorated by interventions to reduce paternal obesity has not been established. Here, male mice fed a high fat diet (HFD) to induce obesity were used, to determine if early embryo and fetal development is improved by interventions of diet (CD) and/or exercise to reduce adiposity and improve metabolism. Exercise and to a lesser extent CD in obese males improved embryo development rates, with increased cell to cell contacts in the compacting embryo measured by E-cadherin in exercise interventions and subsequently, increased blastocyst trophectoderm (TE), inner cell mass (ICM) and epiblast cell numbers. Implantation rates and fetal development from resulting blastocysts were also improved by exercise in obese males. Additionally, all interventions to obese males increased fetal weight, with CD alone and exercise alone, also increasing fetal crown-rump length. Measures of embryo and fetal development correlated with paternal measures of glycaemia, insulin action and serum lipids regardless of paternal adiposity or intervention, suggesting a link between paternal metabolic health and subsequent embryo and fetal development. This is the first study to show that improvements to metabolic health of obese males through diet and exercise can improve embryo and fetal development, suggesting such interventions are likely to improve offspring health. PMID:23977045

CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity.

PubMed

Cappel, David A; Lantier, Louise; Palmisano, Brian T; Wasserman, David H; Stafford, John M

2015-01-01

Pharmacological approaches to reduce obesity have not resulted in dramatic reductions in the risk of coronary heart disease (CHD). Exercise, in contrast, reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer Protein (CETP) is a lipid transfer protein that shuttles lipids between serum lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in humans. Mice naturally lack CETP, but we previously reported that transgenic expression of CETP increases muscle glycolysis in fasting and protects against insulin resistance with high-fat diet (HFD) feeding in female but not male mice. Since glycolysis provides an important energy source for working muscle, we aimed to define if CETP expression protects against the decline in exercise capacity associated with obesity. We measured exercise capacity in female mice that were fed a chow diet and then switched to a HFD. There was no difference in exercise capacity between lean, chow-fed CETP female mice and their non-transgenic littermates. Female CETP transgenic mice were relatively protected against the decline in exercise capacity caused by obesity compared to WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly two-fold increase in run distance compared to WT. After an additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria were isolated. We found that improved exercise capacity in CETP mice corresponded with increased muscle mitochondrial oxidative capacity, and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). These results suggest that CETP can protect against the obesity-induced impairment in exercise capacity and may be a target to improve exercise capacity in the context of obesity.

CETP Expression Protects Female Mice from Obesity-Induced Decline in Exercise Capacity

PubMed Central

Cappel, David A.; Lantier, Louise; Palmisano, Brian T.; Wasserman, David H.; Stafford, John M.

2015-01-01

Pharmacological approaches to reduce obesity have not resulted in dramatic reductions in the risk of coronary heart disease (CHD). Exercise, in contrast, reduces CHD risk even in the setting of obesity. Cholesteryl Ester Transfer Protein (CETP) is a lipid transfer protein that shuttles lipids between serum lipoproteins and tissues. There are sexual-dimorphisms in the effects of CETP in humans. Mice naturally lack CETP, but we previously reported that transgenic expression of CETP increases muscle glycolysis in fasting and protects against insulin resistance with high-fat diet (HFD) feeding in female but not male mice. Since glycolysis provides an important energy source for working muscle, we aimed to define if CETP expression protects against the decline in exercise capacity associated with obesity. We measured exercise capacity in female mice that were fed a chow diet and then switched to a HFD. There was no difference in exercise capacity between lean, chow-fed CETP female mice and their non-transgenic littermates. Female CETP transgenic mice were relatively protected against the decline in exercise capacity caused by obesity compared to WT. Despite gaining similar fat mass after 6 weeks of HFD-feeding, female CETP mice showed a nearly two-fold increase in run distance compared to WT. After an additional 6 weeks of HFD-feeding, mice were subjected to a final exercise bout and muscle mitochondria were isolated. We found that improved exercise capacity in CETP mice corresponded with increased muscle mitochondrial oxidative capacity, and increased expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). These results suggest that CETP can protect against the obesity-induced impairment in exercise capacity and may be a target to improve exercise capacity in the context of obesity. PMID:26313355

Paradoxical post-exercise responses of acylated ghrelin and leptin during a simulated night-shift

PubMed Central

Morris, Chris; Fullick, Sarah; Gregson, Warren; Clarke, Neil; Doran, Dominic; MacLaren, Don; Atkinson, Greg

2009-01-01

Approximately 10% of employees undertake night-work which is a significant predictor of weight-gain, possibly because responses to activity and eating are altered at night. It is known that the appetite-related hormone, acylated ghrelin is suppressed after an acute bout of exercise during the day, but no researcher has explored whether evening exercise alters acylated ghrelin and other appetite-related outcomes during a subsequent night-shift. Six healthy men (mean±SD: age 30±8 yrs, body mass index 23.1±1.1 kg/m2) completed two crossover trials (control and exercise) in a random order. Participants fasted from 10:00 h, consumed a test meal at 18:00 h and then cycled at 50% peak oxygen uptake or rested between 19:00-20:00 h. Participants then completed light activities during a simulated night-shift which ended at 05:00 h. Two small isocaloric meals were consumed at 22:00 and 02:00 h. Venous blood samples were drawn via cannulation at 1-h intervals between 19:00-05:00 h for the determination of acylated ghrelin, leptin, insulin, glucose, triglyceride and non-esterified fatty acids concentrations. Perceived hunger and wrist actimetry were also recorded. During the night-shift, mean±SD acylated ghrelin concentration was 86.5±40.8 pg/ml following exercise compared with 71.7±37.7 pg/ml without prior exercise (P=0.015). Throughout the night-shift, leptin concentration was 263±242 pg/ml following exercise compared with 187±221 pg/ml without prior exercise (P=0.017). Mean levels of insulin, triglyceride, non-esterified fatty acids and wrist actimetry were also higher during the night-shift that followed exercise (P<0.05). These data indicate that prior exercise increases acylated ghrelin and leptin concentrations during a subsequent simulated night-shift. These findings differ from the known effects of exercise on acylated ghrelin and leptin during the day, and therefore have implications for energy balance during night-work. PMID:20524803

Aging Reduces the Activation of the mTORC1 Pathway after Resistance Exercise and Protein Intake in Human Skeletal Muscle: Potential Role of REDD1 and Impaired Anabolic Sensitivity.

PubMed

Francaux, Marc; Demeulder, Bénédicte; Naslain, Damien; Fortin, Raphael; Lutz, Olivier; Caty, Gilles; Deldicque, Louise

2016-01-15

This study was designed to better understand the molecular mechanisms involved in the anabolic resistance observed in elderly people. Nine young (22 ± 0.1 years) and 10 older (69 ± 1.7 years) volunteers performed a one-leg extension exercise consisting of 10 × 10 repetitions at 70% of their 3-RM, immediately after which they ingested 30 g of whey protein. Muscle biopsies were taken from the vastus lateralis at rest in the fasted state and 30 min after protein ingestion in the non-exercised (Pro) and exercised (Pro+ex) legs. Plasma insulin levels were determined at the same time points. No age difference was measured in fasting insulin levels but the older subjects had a 50% higher concentration than the young subjects in the fed state (p < 0.05). While no difference was observed in the fasted state, in response to exercise and protein ingestion, the phosphorylation state of PKB (p < 0.05 in Pro and Pro+ex) and S6K1 (p = 0.059 in Pro; p = 0.066 in Pro+ex) was lower in the older subjects compared with the young subjects. After Pro+ex, REDD1 expression tended to be higher (p = 0.087) in the older group while AMPK phosphorylation was not modified by any condition. In conclusion, we show that the activation of the mTORC1 pathway is reduced in skeletal muscle of older subjects after resistance exercise and protein ingestion compared with young subjects, which could be partially due to an increased expression of REDD1 and an impaired anabolic sensitivity.

Metabolic Disturbance in PCOS: Clinical and Molecular Effects on Skeletal Muscle Tissue

PubMed Central

Silva Dantas, Wagner; Gualano, Bruno; Patrocínio Rocha, Michele; Roberto Grimaldi Barcellos, Cristiano; dos Reis Vieira Yance, Viviane; Miguel Marcondes, José Antonio

2013-01-01

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome. PMID:23844380

Metabolic disturbance in PCOS: clinical and molecular effects on skeletal muscle tissue.

PubMed

Dantas, Wagner Silva; Gualano, Bruno; Rocha, Michele Patrocínio; Barcellos, Cristiano Roberto Grimaldi; dos Reis Vieira Yance, Viviane; Marcondes, José Antonio Miguel

2013-01-01

Polycystic ovary syndrome is a complex hormonal disorder affecting the reproductive and metabolic systems with signs and symptoms related to anovulation, infertility, menstrual irregularity and hirsutism. Skeletal muscle plays a vital role in the peripheral glucose uptake. Since PCOS is associated with defects in the activation and pancreatic dysfunction of β-cell insulin, it is important to understand the molecular mechanisms of insulin resistance in PCOS. Studies of muscle tissue in patients with PCOS reveal defects in insulin signaling. Muscle biopsies performed during euglycemic hyperinsulinemic clamp showed a significant reduction in glucose uptake, and insulin-mediated IRS-2 increased significantly in skeletal muscle. It is recognized that the etiology of insulin resistance in PCOS is likely to be as complicated as in type 2 diabetes and it has an important role in metabolic and reproductive phenotypes of this syndrome. Thus, further evidence regarding the effect of nonpharmacological approaches (e.g., physical exercise) in skeletal muscle of women with PCOS is required for a better therapeutic approach in the management of various metabolic and reproductive problems caused by this syndrome.

Despite higher body fat content, Ecuadorian subjects with Laron syndrome have less insulin resistance and lower incidence of diabetes than their relatives.

PubMed

Guevara-Aguirre, Jaime; Procel, Patricio; Guevara, Carolina; Guevara-Aguirre, Marco; Rosado, Verónica; Teran, Enrique

2016-06-01

In the present pandemics of obesity and insulin resistant diabetes mellitus (DM), the specific contribution of etiological factors such as shifts in nutritional and exercise patterns, genetic and hormonal, is subject of ongoing research. Among the hormonal factors implicated, we selected obesity-driven insulin resistance for further evaluation. It is known that growth hormone (GH) has profound effects on carbohydrate metabolism. In consequence, we compared the effects of the lack of the counter-regulatory effects of GH, in a group of subjects with GH receptor deficiency (GHRD) due to a mutated GH receptor vs. that of their normal relatives. It was found that, despite their obesity, subjects with GHRD, have diminished incidence of diabetes, lower glucose and insulin concentrations, and lower values of indexes indicative of insulin resistance such as HOMA-IR. The GHRD subjects were also capable of appropriately handling glucose or mixed meal loads despite diminished insulin secretion. These observations allow us to suggest that the association of obesity with increased risk for diabetes appears to be dependent on intact growth hormone signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of acute lipid overload on skeletal muscle insulin resistance, metabolic flexibility, and mitochondrial performance

PubMed Central

Coen, Paul M.; DiStefano, Giovanna; Chacon, Alexander C.; Helbling, Nicole L.; Desimone, Marisa E.; Stafanovic-Racic, Maja; Hames, Kazanna C.; Despines, Alex A.; Toledo, Frederico G. S.; Goodpaster, Bret H.

2014-01-01

We hypothesized that acute lipid-induced insulin resistance would be attenuated in high-oxidative muscle of lean trained (LT) endurance athletes due to their enhanced metabolic flexibility and mitochondrial capacity. Lean sedentary (LS), obese sedentary (OS), and LT participants completed two hyperinsulinemic euglycemic clamp studies with and without (glycerol control) the coinfusion of Intralipid. Metabolic flexibility was measured by indirect calorimetry as the oxidation of fatty acids and glucose during fasted and insulin-stimulated conditions, the latter with and without lipid oversupply. Muscle biopsies were obtained for mitochondrial and insulin-signaling studies. During hyperinsulinemia without lipid, glucose infusion rate (GIR) was lowest in OS due to lower rates of nonoxidative glucose disposal (NOGD), whereas state 4 respiration was increased in all groups. Lipid infusion reduced GIR similarly in all subjects and reduced state 4 respiration. However, in LT subjects, fat oxidation was higher with lipid oversupply, and although glucose oxidation was reduced, NOGD was better preserved compared with LS and OS subjects. Mitochondrial performance was positively associated with better NOGD and insulin sensitivity in both conditions. We conclude that enhanced mitochondrial performance with exercise is related to better metabolic flexibility and insulin sensitivity in response to lipid overload. PMID:25352435

Transient enhancement of GLUT-4 levels in rat epitrochlearis muscle after exercise training

PubMed Central

Reynolds, Thomas H.; Brozinick, Joseph T.; Larkin, Lisa M.; Cushman, Samuel W.

2009-01-01

The purpose of the present study was to examine the effect of detraining on the glucose transport system after short-term swim training (5 days), long-term swim training (5 wk), and treadmill run training (5 wk). Skeletal muscles were isolated from female Wistar rats at 24 or 48 h posttraining. SST produces a 48% increase in GLUT-4 mRNA, a 30% increase in GLUT-4 protein, and a 60% increase in insulin-stimulated glucose transport activity at 24 h posttraining but not at 48 h posttraining. Similar to SST, long-term swim training produces a 60% increase in GLUT-4 mRNA and a 30% increase in GLUT-4 protein content at 24 h posttraining but not at 48 h posttraining. Finally, treadmill run training produces a transient 35% increase in GLUT-4 protein content that is completely reversed at 48 h after the last bout of exercise. These results demonstrate that the increase in GLUT-4 mRNA and GLUT-4 protein occurs during the first week of exercise training and is rapidly lost after training cessation. We believe that the transient enhancement in GLUT-4 protein after exercise training is due to a short GLUT-4 half-life, a process that is primarily regulated by pretranslational mechanisms. PMID:10846041

Transient enhancement of GLUT-4 levels in rat epitrochlearis muscle after exercise training.

PubMed

Reynolds, T H; Brozinick, J T; Larkin, L M; Cushman, S W

2000-06-01

The purpose of the present study was to examine the effect of detraining on the glucose transport system after short-term swim training (5 days), long-term swim training (5 wk), and treadmill run training (5 wk). Skeletal muscles were isolated from female Wistar rats at 24 or 48 h posttraining. SST produces a 48% increase in GLUT-4 mRNA, a 30% increase in GLUT-4 protein, and a 60% increase in insulin-stimulated glucose transport activity at 24 h posttraining but not at 48 h posttraining. Similar to SST, long-term swim training produces a 60% increase in GLUT-4 mRNA and a 30% increase in GLUT-4 protein content at 24 h posttraining but not at 48 h posttraining. Finally, treadmill run training produces a transient 35% increase in GLUT-4 protein content that is completely reversed at 48 h after the last bout of exercise. These results demonstrate that the increase in GLUT-4 mRNA and GLUT-4 protein occurs during the first week of exercise training and is rapidly lost after training cessation. We believe that the transient enhancement in GLUT-4 protein after exercise training is due to a short GLUT-4 half-life, a process that is primarily regulated by pretranslational mechanisms.

Liver and Muscle Contribute Differently to the Plasma Acylcarnitine Pool During Fasting and Exercise in Humans.

PubMed

Xu, G; Hansen, J S; Zhao, X J; Chen, S; Hoene, M; Wang, X L; Clemmesen, J O; Secher, N H; Häring, H U; Pedersen, B K; Lehmann, R; Weigert, Cora; Plomgaard, Peter

2016-12-01

Plasma acylcarnitine levels are elevated by physiological conditions such as fasting and exercise but also in states of insulin resistance and obesity. To elucidate the contribution of liver and skeletal muscle to plasma acylcarnitines in the fasting state and during exercise in humans. In 2 independent studies, young healthy males were fasted overnight and performed an acute bout of exercise to investigate either acylcarnitines in skeletal muscle biopsies and arterial-to-venous plasma differences over the exercising and resting leg (n = 9) or the flux over the hepato-splanchnic bed (n = 10). In the fasting state, a pronounced release of C2- and C3-carnitines from the hepato-splanchnic bed and an uptake of free carnitine by the legs were detected. Exercise further increased the release of C3-carnitine from the hepato-splanchnic bed and the uptake of free carnitine in the exercising leg. In plasma and in the exercising muscle, exercise induced an increase of most acylcarnitines followed by a rapid decline to preexercise values during recovery. In contrast, free carnitine was decreased in the exercising muscle and quickly restored thereafter. C8-, C10-, C10:1-, C12-, and C12:1-carnitines were released from the exercising leg and simultaneously; C6, C8, C10, C10:1, C14, and C16:1 were taken up by the hepato-splanchnic. These data provide novel insight to the organo-specific release/uptake of acylcarnitines. The liver is a major contributor to systemic short chain acylcarnitines, whereas the muscle tissue releases mostly medium chain acylcarnitines during exercise, indicating that other tissues are contributing to the systemic increase in long chain acylcarnitines.

Vegetarian diet-induced increase in linoleic acid in serum phospholipids is associated with improved insulin sensitivity in subjects with type 2 diabetes.

PubMed

Kahleova, H; Matoulek, M; Bratova, M; Malinska, H; Kazdova, L; Hill, M; Pelikanova, T

2013-06-17

Fatty acids are important cellular constituents that may affect many metabolic processes relevant for the development of diabetes and its complications. We showed previously that vegetarian diet leads to greater increase in metabolic clearance rate of glucose (MCR) than conventional hypocaloric diet. The aim of this secondary analysis was to explore the role of changes in fatty acid composition of serum phospholipids in diet- and exercise-induced changes in MCR in subjects with type 2 diabetes (T2D). Subjects with T2D (n=74) were randomly assigned into a vegetarian group (VG, n=37) following vegetarian diet or a control group (CG, n=37) following a conventional diet. Both diets were calorie restricted (-500 kcal day(-1)). Participants were examined at baseline, 12 weeks of diet intervention and 24 weeks (subsequent 12 weeks of diet were combined with aerobic exercise). The fatty acid composition of serum phospholipids was measured by gas liquid chromatography. MCR was measured by hyperinsulinemic isoglycemic clamp. Visceral fat (VF) was measured by magnetic resonance imaging. Linoleic acid (LA; 18:2n6) increased in VG (P=0.04), whereas it decreased in CG (P=0.04) in response to dietary interventions. It did not change significantly after the addition of exercise in either group (group × time P<0.001). In VG, changes in 18:2n6 correlated positively with changes in MCR (r=+0.22; P=0.04) and negatively with changes in VF (r=-0.43; P=0.01). After adjustment for changes in body mass index, the association between 18:2n6 and MCR was no longer significant. The addition of exercise resulted in greater changes of phospholipid fatty acids composition in VG than in CG. We demonstrated that the insulin-sensitizing effect of a vegetarian diet might be related to the increased proportion of LA in serum phospholipids.

Effects of long-term resveratrol-induced SIRT1 activation on insulin and apoptotic signalling in aged skeletal muscle.

PubMed

Sin, Thomas K; Yu, Angus P; Yung, Benjamin Y; Yip, Shea P; Chan, Lawrence W; Wong, Cesar S; Rudd, John A; Siu, Parco M

2015-12-01

Activation of Foxo1 is known to promote apoptosis and disturbances to insulin signalling. However, their modulating roles in aged skeletal muscle are not clear. The present study tested the hypothesis that long-term (i.e. 8 month) resveratrol supplementation would improve physical traits including exercise capacity and basal voluntary activity of aged mice and modulate insulin/apoptotic signalling in aged skeletal muscle. This study also examined whether these resveratrol-associated alterations would involve orchestration of the SIRT1-Foxo1 signalling axis. Two-month-old SAMP8 mice were randomly assigned to young, aged and aged with resveratrol treatment (AR) groups. The AR mice were supplemented with 4.9 mg(-1) kg(-1) day(-1) resveratrol for 8 months. All animals were subject to endurance capacity test and voluntary motor behaviour assessment. The lateral gastrocnemius muscle tissues were harvested for further analyses. Long-term resveratrol treatment significantly alleviated the age-associated reductions in exercise capacity and voluntary motor behaviour. The protein content, but not the deacetylase activity of SIRT1 was increased with concomitant elevations of p300 acetylase and acetylation of Foxo1 in aged muscle. The aged muscle also manifested signs of impaired insulin signalling including attenuated phosphorylation of Akt, activity of pyruvate dehydrogenase and membrane trafficking of GLUT4 and elevated levels of phosphorylated IRS1 and iNOS and apoptotic activation measured as Bim, p53 and apoptotic DNA fragmentation. Intriguingly, all these age-related adverse changes were mitigated with the activation of SIRT1 deacetylase activity after long-term resveratrol treatment. These data suggest that modulation of the SIRT1-Foxo1 axis by long-term resveratrol treatment enhances physical traits and alleviates the unfavourable changes in insulin and apoptotic signalling in aged muscle.

Using financial incentives to promote physical activity in American Indian adolescents: A randomized controlled trial

PubMed Central

Chadwick, Jennifer Q.; Cannady, Tamela K.; Branam, Dannielle E.; Wharton, David F.; Tullier, Mary A.; Thompson, David M.; Copeland, Kenneth C.

2018-01-01

American Indians (AI) have high prevalence of diabetes in youth and may benefit from increasing physical activity as a strategy to improve metabolic health. We tested whether financial incentives would elicit greater frequency and/or duration of exercise in AI youth at high risk for developing diabetes. Overweight/obese AI boys and girls, 11–20 years old, were instructed to exercise on 3 days/week for 48 weeks at a tribal wellness center. The program was divided into three, 16-week-long phases to test different financial incentive strategies. Within each phase participants were randomly assigned to one of two groups that received different payments for exercise. Phase 1 was designed to test whether the size of the incentive would affect exercise frequency. In Phase 1, the number of exercise sessions did not differ between the group receiving a modest fixed-value payment per exercise session and the group receiving enhanced incentives to exercise more frequently (26 ± 3 versus 28 ± 2 sessions, respectively, p = 0.568). In Phase 2, the provision of an enhanced financial incentive to increase exercise duration resulted longer sessions, as the incentivized and standard payment groups exercised 38 ± 2 versus 29 ± 1 minutes per session (p = 0.002), respectively. In Phase 3, the effect of reducing the incentives on maintenance of exercise behaviors was inconclusive due to high participant withdrawal. Aerobic fitness increased 10% during Phase 1 but was unchanged thereafter. Insulin sensitivity and body composition were unchanged during the study. In conclusion, enhanced financial incentives increased the duration of exercise sessions, but had minimal effects on exercise participation. These results indicate that financial incentives hold promise in motivating previously sedentary, overweight/obese adolescents to exercise longer, but motivating them to sustain an exercise program remains the major challenge. Trial Registration: ClinicalTrials.gov NCT01848353. PMID:29856832

Genes, Diet and Type 2 Diabetes Mellitus: A Review

PubMed Central

Dedoussis, George V.Z.; Kaliora, Andriana C.; Panagiotakos, Demosthenes B.

2007-01-01

Diabetes mellitus is widely recognized as one of the leading causes of death and disability. While insulin insensitivity is an early phenomenon partly related to obesity, pancreatic β-cell function declines gradually over time even before the onset of clinical hyperglycemia. Several mechanisms have been proposed to be responsible for insulin resistance, including increased non-esterified fatty acids, inflammatory cytokines, adipokines, and mitochondrial dysfunction, as well as glucotoxicity, lipotoxicity, and amyloid formation for β-cell dysfunction. Moreover, the disease has a strong genetic component, although only a handful of genes have been identified so far. Diabetic management includes diet, exercise and combinations of antihyperglycemic drug treatment with lipid-lowering, antihypertensive, and antiplatelet therapy. Since many persons with type 2 diabetes are insulin resistant and overweight, nutrition therapy often begins with lifestyle strategies to reduce energy intake and increase energy expenditure through physical activity. These strategies should be implemented as soon as diabetes or impaired glucose homoeostasis (pre-diabetes) is diagnosed. PMID:17565412