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Sample records for affect glucose tolerance

  1. Ceylon cinnamon does not affect postprandial plasma glucose or insulin in subjects with impaired glucose tolerance.

    PubMed

    Wickenberg, Jennie; Lindstedt, Sandra; Berntorp, Kerstin; Nilsson, Jan; Hlebowicz, Joanna

    2012-06-01

    Previous studies on healthy subjects have shown that the intake of 6 g Cinnamomum cassia reduces postprandial glucose and that the intake of 3 g C. cassia reduces insulin response, without affecting postprandial glucose concentrations. Coumarin, which may damage the liver, is present in C. cassia, but not in Cinnamomum zeylanicum. The aim of the present study was to study the effect of C. zeylanicum on postprandial concentrations of plasma glucose, insulin, glycaemic index (GI) and insulinaemic index (GII) in subjects with impaired glucose tolerance (IGT). A total of ten subjects with IGT were assessed in a crossover trial. A standard 75 g oral glucose tolerance test (OGTT) was administered together with placebo or C. zeylanicum capsules. Finger-prick capillary blood samples were taken for glucose measurements and venous blood for insulin measurements, before and at 15, 30, 45, 60, 90, 120, 150 and 180 min after the start of the OGTT. The ingestion of 6 g C. zeylanicum had no significant effect on glucose level, insulin response, GI or GII. Ingestion of C. zeylanicum does not affect postprandial plasma glucose or insulin levels in human subjects. The Federal Institute for Risk Assessment in Europe has suggested the replacement of C. cassia by C. zeylanicum or the use of aqueous extracts of C. cassia to lower coumarin exposure. However, the positive effects seen with C. cassia in subjects with poor glycaemic control would then be lost.

  2. Dosing obese cats based on body weight spuriously affects some measures of glucose tolerance.

    PubMed

    Reeve-Johnson, M K; Rand, J S; Anderson, S T; Appleton, D J; Morton, J M; Vankan, D

    2016-10-01

    The primary objective was to investigate whether dosing glucose by body weight results in spurious effects on measures of glucose tolerance in obese cats because volume of distribution does not increase linearly with body weight. Healthy research cats (n = 16; 6 castrated males, 10 spayed females) were used. A retrospective study was performed using glucose concentration data from glucose tolerance and insulin sensitivity tests before and after cats were fed ad libitum for 9 to 12 mo to promote weight gain. The higher dose of glucose (0.5 vs 0.3 g/kg body weight) in the glucose tolerance tests increased 2-min glucose concentrations (P < 0.001), and there was a positive correlation between 2-min and 2-h glucose (r = 0.65, P = 0.006). Two-min (P = 0.016 and 0.019, respectively), and 2-h (P = 0.057 and 0.003, respectively) glucose concentrations, and glucose half-life (T1/2; P = 0.034 and <0.001 respectively) were positively associated with body weight and body condition score. Glucose dose should be decreased by 0.05 g for every kg above ideal body weight. Alternatively, for every unit of body condition score above 5 on a 9-point scale, observed 2-h glucose concentration should be adjusted down by 0.1 mmol/L. Dosing glucose based on body weight spuriously increases glucose concentrations at 2 h in obese cats and could lead to cats being incorrectly classified as having impaired glucose tolerance. This has important implications for clinical studies assessing the effect of interventions on glucose tolerance when lean and obese cats are compared. PMID:27572923

  3. Glucose Tolerance and Hyperkinesis.

    ERIC Educational Resources Information Center

    Langseth, Lillian; Dowd, Judith

    Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

  4. Monitoring breath during oral glucose tolerance tests.

    PubMed

    Ghimenti, S; Tabucchi, S; Lomonaco, T; Di Francesco, F; Fuoco, R; Onor, M; Lenzi, S; Trivella, M G

    2013-03-01

    The evolution of breath composition during oral glucose tolerance tests (OGTTs) was analysed by thermal desorption/gas chromatography/mass spectrometry in 16 subjects and correlated to blood glucose levels. The glucose tolerance tests classified five of the subjects as diabetics, eight as affected by impaired glucose tolerance and three as normoglycaemic. Acetone levels were generally higher in diabetics (average concentration values: diabetics, 300 ± 40 ppbv; impaired glucose tolerance, 350 ± 30 ppbv; normoglycaemic, 230 ± 20 ppbv) but the large inter-individual variability did not allow us to identify the three groups by this parameter alone. The exhalation of 3-hydroxy-butan-2-one and butane-2,3-dione, likely due to the metabolization of glucose by bacteria in the mouth, was also observed. Future work will involve the extension of the analyses to other volatile compounds by attempting to improve the level of discrimination between the various classes of subjects. PMID:23446273

  5. Glucose tolerance test - non-pregnant

    MedlinePlus

    Oral glucose tolerance test - non-pregnant; OGTT - non-pregnant; Diabetes - glucose tolerance test ... The most common glucose tolerance test is the oral glucose tolerance test (OGTT). Before the test begins, a sample of blood will be taken. You will then ...

  6. Impaired Glucose Tolerance or Newly Diagnosed Diabetes Mellitus Diagnosed during Admission Adversely Affects Prognosis after Myocardial Infarction: An Observational Study

    PubMed Central

    George, Anish; Bhatia, Raghav T.; Buchanan, Gill L.; Whiteside, Anne; Moisey, Robert S.; Beer, Stephen F.; Chattopadhyay, Sudipta; Sathyapalan, Thozhukat; John, Joseph

    2015-01-01

    Objective To investigate the prognostic effect of newly diagnosed diabetes mellitus (NDM) and impaired glucose tolerance (IGT) post myocardial infarction (MI). Research Design and Methods Retrospective cohort study of 768 patients without preexisting diabetes mellitus post-MI at one centre in Yorkshire between November 2005 and October 2008. Patients were categorised as normal glucose tolerance (NGT n = 337), IGT (n = 279) and NDM (n = 152) on pre- discharge oral glucose tolerance test (OGTT). Primary end-point was the first occurrence of major adverse cardiovascular events (MACE) including cardiovascular death, non-fatal MI, severe heart failure (HF) or non-haemorrhagic stroke. Secondary end-points were all cause mortality and individual components of MACE. Results Prevalence of NGT, impaired fasting glucose (IFG), IGT and NDM changed from 90%, 6%, 0% and 4% on fasting plasma glucose (FPG) to 43%, 1%, 36% and 20% respectively after OGTT. 102 deaths from all causes (79 as first events of which 46 were cardiovascular), 95 non fatal MI, 18 HF and 9 non haemorrhagic strokes occurred during 47.2 ± 9.4 months follow up. Event free survival was lower in IGT and NDM groups. IGT (HR 1.54, 95% CI: 1.06–2.24, p = 0.024) and NDM (HR 2.15, 95% CI: 1.42–3.24, p = 0.003) independently predicted MACE free survival. IGT and NDM also independently predicted incidence of MACE. NDM but not IGT increased the risk of secondary end-points. Conclusion Presence of IGT and NDM in patients presenting post-MI, identified using OGTT, is associated with increased incidence of MACE and is associated with adverse outcomes despite adequate secondary prevention. PMID:26571120

  7. Lower Maternal Body Condition During Pregnancy Affects Skeletal Muscle Structure and Glut-4 Protein Levels But Not Glucose Tolerance in Mature Adult Sheep

    PubMed Central

    Costello, Paula M.; Hollis, Lisa J.; Cripps, Roselle L.; Bearpark, Natasha; Patel, Harnish P.; Sayer, Avan Aihie; Cooper, Cyrus; Hanson, Mark A.; Ozanne, Susan E.

    2013-01-01

    Suboptimal maternal nutrition and body composition are implicated in metabolic disease risk in adult offspring. We hypothesized that modest disruption of glucose homeostasis previously observed in young adult sheep offspring from ewes of a lower body condition score (BCS) would deteriorate with age, due to changes in skeletal muscle structure and insulin signaling mechanisms. Ewes were fed to achieve a lower (LBCS, n = 10) or higher (HBCS, n = 14) BCS before and during pregnancy. Baseline plasma glucose, glucose tolerance and basal glucose uptake into isolated muscle strips were similar in male offspring at 210 ± 4 weeks. Vastus total myofiber density (HBCS, 343 ± 15; LBCS, 294 ± 14 fibers/mm2, P < .05) and fast myofiber density (HBCS, 226 ± 10; LBCS 194 ± 10 fibers/mm2, P < .05), capillary to myofiber ratio (HBCS, 1.5 ± 0.1; LBCS 1.2 ± 0.1 capillary:myofiber, P < .05) were lower in LBCS offspring. Vastus protein levels of Akt1 were lower (83% ± 7% of HBCS, P < .05), and total glucose transporter 4 was increased (157% ± 6% of HBCS, P < .001) in LBCS offspring, Despite the reduction in total myofiber density in LBCS offspring, glucose tolerance was normal in mature adult life. However, such adaptations may lead to complications in metabolic control in an overabundant postnatal nutrient environment. PMID:23420826

  8. Okara ameliorates glucose tolerance in GK rats.

    PubMed

    Hosokawa, Masaya; Katsukawa, Michiko; Tanaka, Hiroshi; Fukuda, Hitomi; Okuno, Sonomi; Tsuda, Kinsuke; Iritani, Nobuko

    2016-05-01

    Okara, a food by-product from the production of tofu and soy milk, is rich in three beneficial components: insoluble dietary fiber, β-conglycinin, and isoflavones. Although isoflavones and β-conglycinin have recently been shown to improve glucose tolerance, the effects of okara have not yet been elucidated. Therefore, we herein investigated the effects of okara on glucose tolerance in Goto-Kakizaki (GK) rats, a representative animal model of Japanese type 2 diabetes. Male GK rats were fed a 10% lard diet with or without 5% dry okara powder for 2 weeks and an oral glucose tolerance test was performed. Rats were then fed each diet for another week and sacrificed. The expression of genes that are the master regulators of glucose metabolism in adipose tissue was subsequently examined. No significant differences were observed in body weight gain or food intake between the two groups of GK rats. In the oral glucose tolerance test, increases in plasma glucose levels were suppressed by the okara diet. The mRNA expression levels of PPARγ, adiponectin, and GLUT4, which up-regulate the effects of insulin, were increased in epididymal adipose tissue by the okara diet. These results suggest that okara provides a useful means for treating type 2 diabetes. PMID:27257347

  9. Age as independent determinant of glucose tolerance.

    PubMed

    Shimokata, H; Muller, D C; Fleg, J L; Sorkin, J; Ziemba, A W; Andres, R

    1991-01-01

    It has been proposed that the decline in glucose tolerance with age is not a primary aging effect but is secondary to a combination of other age-associated characteristics, i.e., disease, medication, obesity, central and upper-body fat deposition, and inactivity. To test this hypothesis, we first eliminated from analysis the Baltimore Longitudinal Study of Aging participants with identifiable diseases or medications known to influence glucose tolerance. Seven hundred forty-three men and women, aged 17-92 yr, remained for analysis. As indices of fatness, body mass index and percent body fat were determined. As indices of body fat distribution, waist-hip ratio and subscapular triceps skin-fold ratio were calculated. As indices of fitness, physical activity level, determined by detailed questionnaire, and maximum 02 consumption were calculated. We tested whether the effect of age on glucose tolerance remains when data were adjusted for fatness, fitness, and fat distribution; 2-h glucose values were 6.61, 6.78, and 7.83 mM for young (17-39 yr), middle-aged (40-59 yr), and old (60-92 yr) men and 6.22, 6.22, and 7.28 mM for the three groups of women, respectively. The differences between the young and middle-aged groups were not significant, but the old groups had significantly higher values than young or middle-aged groups. Fatness, fitness, and fat distribution can account for the decline in glucose tolerance from the young adult to the middle-aged years. However, age remains a significant determinant of the further decline in glucose tolerance of healthy old subjects.

  10. Zinc dosing and glucose tolerance in humans

    SciTech Connect

    Greenley, S.; Taylor, M.

    1986-03-05

    Animal data suggest the existence of a physiologic relationship between glucoregulatory hormones and zinc metabolism. In order to investigate this proposed relationship in humans, they examined the effect of moderately elevated plasma zinc levels on blood glucose clearance. Eight women (24-37 yrs) served as subjects for the study. Fasted volunteers were tested under two experimental conditions (a) ingestion of 50 g D-glucose (b) ingestion of 25 mg zinc followed 60 min later by ingestion of 50 g D-glucose. Five ml venous blood was drawn into trace-metal-free, fluoride-containing vacutainer tubes prior to and 15, 30, 45, 60, 90, and 120 min after glucose ingestion. Plasma was analyzed for glucose and zinc; glycemic responses were quantified by computing areas under the curves and times to peak concentration. Their human data indicate varied glycemic responses to the acute elevation of plasma zinc: 4 subjects showed little apparent effect; 3 subjects marginally increased either the area under the curve or time to peak and 1 subject (classified as suspect diabetic in the non-zinc condition) showed marked improvement in glycemic response following zinc ingestion. Their preliminary results suggest that blood glucose clearance may be affected in some individuals by the acute elevation of plasma zinc.

  11. Unpredictable feeding impairs glucose tolerance in growing lambs.

    PubMed

    Jaquiery, Anne L; Oliver, Mark H; Landon-Lane, Nina; Matthews, Samuel J; Harding, Jane E; Bloomfield, Frank H

    2013-01-01

    Irregular eating is associated with insulin resistance and metabolic disease in adults but may affect young, growing children differently. We investigated the metabolic effects of unpredictable feeding in female juvenile lambs randomly assigned to receive, for six weeks, maintenance feed given twice daily in equal portions (Control Group, C; n = 24) or the same weekly feed amount in aliquots of variable size at unpredictable times (Unpredictable Group, U; n = 21). Intravenous glucose tolerance tests (IVGTT), insulin tolerance tests (ITT), and measurement of diurnal plasma cortisol concentrations were performed pre and post the dietary intervention. Groups were compared using t test and RM ANOVA. Weight gain was similar in both groups (C 18 ± 2%; U 16 ± 2% of initial body weight). Glucose area under the curve (AUC) was unchanged in C (AUC pre 818 ± 34, post 801 ± 33 mmol.min.l(-1)), but increased by 20% in U (pre 830 ± 25, post 1010 ± 19 mmol.min.l(-1); p<0.0001), with an inadequate insulin response to glucose load (log(AUC insulin first 40 minutes) post intervention C 1.49 ± 0.04 vs U 1.36 ± 0.04 ng.min.ml(-1); p = 0.03). Insulin tolerance and diurnal variation of plasma cortisol concentrations were not different between groups. Unpredictable feeding impairs insulin response to glucose in growing lambs despite high quality food and normal weight gain. Irregular eating warrants investigation as a potentially remediable risk factor for disordered glucose metabolism.

  12. Effect of Intravenous Glucose Tolerance Test on Bone Turnover Markers in Adults with Normal Glucose Tolerance

    PubMed Central

    Xiang, Shou-Kui; Wan, Jing-Bo; Jiang, Xiao-Hong; Zhu, Yong-Hua; Ma, Jin-Hong; Hua, Fei

    2016-01-01

    Background It is well known that enteral nutrients result in acute suppression of bone turnover markers (BTMs), and incretin hormones are believed to play a significant role in this physiological skeletal response. However, there is limited research exploring the impact of parenteral nutrients on BTMs. Our aim was to assess the influence of intravenous glucose on BTMs in adults with normal glucose tolerance (NGT). Material/Methods We conducted 1-h intravenous glucose tolerance test (IVGTT) in 24 subjects with NGT. Blood samples were collected before and 5, 10, 15, 20, 30, 60 min after administration of glucose, then serum levels of bone formation marker procollagen type I N-terminal propeptide (P1NP) and resorption marker C-terminal cross-linking telopeptides of collagen type I (CTX) were measured. Results During IVGTT, the fasting CTX level fell gradually and reached a nadir of 80.4% of the basal value at 60 min. Conversely, the fasting P1NP level decreased mildly and reached a nadir of 90.6% of the basal value at 15 min, then gradually increased and reached 96.6% at 60 min. The CTX-to-P1NP ratio increased slightly and reached a peak of 104.3% of the basal value at 10 min, then fell gradually and reached a nadir of 83% at 60 min. Conclusions Our study indicates that intravenous glucose results in an acute suppression of BTMs in the absence of incretin hormones. The mechanism responsible for this needs further investigation. PMID:27447783

  13. Altered glucose tolerance in women with deliberate self-harm.

    PubMed

    Westling, Sofie; Ahrén, Bo; Sunnqvist, Charlotta; Träskman-Bendz, Lil

    2009-07-01

    Disturbances in glucose metabolism are of importance for violent behaviour in men, but studies in women are lacking. We used the 5h-oral glucose tolerance test (OGTT) in this study of 17 female psychiatric patients, selected for violent behaviour directed against themselves (deliberate self-harm) and 17 healthy controls matched for age and BMI. Following OGTT, patients had higher glucose levels at 30 min (p=0.007) and increased glucagon area under the curve (p=0.011). Since a co-morbid eating disorder might affect results, we as a post-hoc analysis subgrouped the patients and found that the increased glucagon levels only were present in patients with an eating disorder. In contrast, those without an eating disorder showed a significantly lower p-glucose nadir (p=0.015) and unaltered glucagon levels compared to controls. There were no significant differences in insulin and C-peptide levels between patients and controls. We conclude that deliberate self-harm in women may be associated with alterations in carbohydrate metabolism in certain groups. Eating disorder is a confounding factor.

  14. Impaired Glucose Tolerance in Healthy Men Treated with St. John's Wort.

    PubMed

    Stage, Tore Bjerregaard; Damkier, Per; Christensen, Mette Marie Hougaard; Nielsen, Lene Buch-Krogh; Højlund, Kurt; Brøsen, Kim

    2016-03-01

    The purpose of this study was to examine whether the over-the-counter herbal medicinal plant St. John's wort affects glucose tolerance in healthy men. To do this, we included 10 healthy men who were examined by a 2-hr oral glucose tolerance test on three occasions: A: baseline; B: after 21 days of treatment with St. John's wort; and C: at least 6 weeks after the last capsule of St. John's wort was ingested. Plasma glucose, serum insulin and C-peptide levels were measured during an oral glucose tolerance test and used for estimation of area under the concentration-time curve (AUC) as well as indices of insulin sensitivity and insulin secretion. We found that treatment with St. John's wort increased total and incremental glucose AUC and 2-hr plasma glucose levels. Surprisingly, this effect was sustained and even further increased 6 weeks after the last capsule of St. John's wort was taken. No effect on indices of insulin sensitivity was seen, but indices of insulin secretion were reduced even after adjustment for insulin sensitivity. In conclusion, this study indicates that long-term treatment with St. John's wort may impair glucose tolerance by reducing insulin secretion in young, healthy men. The unregulated use of this over-the-counter drug might be a risk factor for impaired glucose tolerance and type 2 diabetes.

  15. Sleep restriction acutely impairs glucose tolerance in rats.

    PubMed

    Jha, Pawan K; Foppen, Ewout; Kalsbeek, Andries; Challet, Etienne

    2016-06-01

    Chronic sleep curtailment in humans has been related to impairment of glucose metabolism. To better understand the underlying mechanisms, the purpose of the present study was to investigate the effect of acute sleep deprivation on glucose tolerance in rats. A group of rats was challenged by 4-h sleep deprivation in the early rest period, leading to prolonged (16 h) wakefulness. Another group of rats was allowed to sleep during the first 4 h of the light period and sleep deprived in the next 4 h. During treatment, food was withdrawn to avoid a postmeal rise in plasma glucose. An intravenous glucose tolerance test (IVGTT) was performed immediately after the sleep deprivation period. Sleep deprivation at both times of the day similarly impaired glucose tolerance and reduced the early-phase insulin responses to a glucose challenge. Basal concentrations of plasma glucose, insulin, and corticosterone remained unchanged after sleep deprivation. Throughout IVGTTs, plasma corticosterone concentrations were not different between the control and sleep-deprived group. Together, these results demonstrate that independent of time of day and sleep pressure, short sleep deprivation during the resting phase favors glucose intolerance in rats by attenuating the first-phase insulin response to a glucose load. In conclusion, this study highlights the acute adverse effects of only a short sleep restriction on glucose homeostasis. PMID:27354542

  16. Impact of Glucose Tolerance Status, Sex, and Body Size on Glucose Absorption Patterns During OGTTs

    PubMed Central

    Færch, Kristine; Pacini, Giovanni; Nolan, John J.; Hansen, Torben; Tura, Andrea; Vistisen, Dorte

    2013-01-01

    OBJECTIVE We studied whether patterns of glucose absorption during oral glucose tolerance tests (OGTTs) were abnormal in individuals with impaired glucose regulation and whether they were related to sex and body size (height and fat-free mass). We also examined how well differences in insulin sensitivity and β-cell function measured by gold-standard tests were reflected in the corresponding OGTT-derived estimates. RESEARCH DESIGN AND METHODS With validated methods, various aspects of glucose absorption were estimated from 12-point, 3-h, 75-g OGTTs in 66 individuals with normal glucose tolerance (NGT), isolated impaired fasting glucose (i-IFG), or isolated impaired glucose tolerance (i-IGT). Insulin sensitivity and β-cell function were measured with the euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance tests, respectively. Surrogate markers of both conditions were calculated from OGTTs. RESULTS More rapid glucose absorption (P ≤ 0.036) and reduced late glucose absorption (P ≤ 0.039) were observed in the i-IFG group relative to NGT and i-IGT groups. Women with i-IGT had a lower early glucose absorption than did men with i-IGT (P = 0.041); however, this difference did not persist when differences in body size were taken into account (P > 0.28). Faster glucose absorption was related to higher fasting (P = 0.001) and lower 2-h (P = 0.001) glucose levels and to greater height and fat-free mass (P < 0.001). All OGTT-derived measures of insulin sensitivity, but only one of three measures of β-cell function, reflected the differences for these parameters between those with normal and impaired glucose regulation as measured by gold-standard tests. CONCLUSIONS Glucose absorption patterns during an OGTT are significantly related to plasma glucose levels and body size, which should be taken into account when estimating β-cell function from OGTTs in epidemiological studies. PMID:24062321

  17. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series.

    PubMed

    Tonoike, Mie; Kishimoto, Miyako; Yamamoto, Mayumi; Yano, Tetsu; Noda, Mitsuhiko

    2016-01-01

    Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM) in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases). Furthermore, the standard deviation (SD) and mean amplitude of glycemic excursions (MAGE) were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women. PMID:26949348

  18. Diagnostic value of fasting capillary glucose, fructosamine and glycosylated haemoglobin in detecting diabetes and other glucose tolerance abnormalities compared to oral glucose tolerance test.

    PubMed

    Herdzik, E; Safranow, K; Ciechanowski, K

    2002-04-01

    New diagnostic criteria for diabetes mellitus recommend lowering of the fasting plasma glucose to 7.0 mmol/l. In contrast to recommendations of the American Diabetes Association (ADA), WHO recommends using the oral glucose tolerance test (OGTT) in clinical practice. In this study. based on OGTT results and WHO 1998 criteria, we determined if measuring fasting capillary glycaemia (FCG) along with fructosamine and/or glycosylated haemoglobin allows the detection of glucose tolerance abnormalities better than FCG alone. OGTT was performed in 538 patients. Serum fructosamine was determined in 480 of the patients, and glycosylated haemoglobin in 234 of the patients. According to WHO 1998 criteria, the patients were divided into groups due to glucose tolerance abnormalities. Fructosamine correlated stronger with 2-h post-load glucose concentrations than with FCG. HbAlc correlated stronger with FCG than with 2-h post-load glucose. Combined use of fructosamine and FCG predicted 2-h post-load glucose better than combined use of FCG and HbA1c. Receiver operating characteristic curve analyses showed that FCG was the best criterion in discriminating diabetes. Combined use of FCG and fructosamine slightly improved the ability to discriminate glucose tolerance abnormalities from normal glucose tolerance. FCG is the most effective predictor of 2-h post-load glucose and the best criterion for discriminating diabetes and other glucose tolerance abnormalities from normal glucose tolerance. Fructosamine is a potentially useful post-load glycaemia index. OGTT is irreplaceable in identification of patients with high post-load glycaemia.

  19. Fetal growth and impaired glucose tolerance in men and women.

    PubMed

    Phipps, K; Barker, D J; Hales, C N; Fall, C H; Osmond, C; Clark, P M

    1993-03-01

    A follow-up study was carried out to determine whether reduced fetal growth is associated with the development of impaired glucose tolerance in men and women aged 50 years. Standard oral glucose tolerance tests were carried out on 140 men and 126 women born in Preston (Lancashire, UK) between 1935 and 1943, whose size at birth had been measured in detail. Those subjects found to have impaired glucose tolerance or non-insulin-dependent diabetes mellitus had lower birthweight, a smaller head circumference and were thinner at birth. They also had a higher ratio of placental weight to birthweight. The prevalence of impaired glucose tolerance or diabetes fell from 27% in subjects who weighed 2.50 kg (5.5 pounds) or less at birth to 6% in those who weighed more than 3.41 kg (7.5 pounds) (p < 0.002 after adjusting for body mass index). Plasma glucose concentrations taken at 2-h in the glucose tolerance test fell progressively as birthweight increased (p < 0.004), as did 2-h plasma insulin concentrations (p < 0.001). The trends with birthweight were independent of duration of gestation and must therefore be related to reduced rates of fetal growth. These findings confirm the association between impaired glucose tolerance in adult life and low birthweight previously reported in Hertfordshire (UK), and demonstrate it in women as well as men. It is suggested that the association reflects the long-term effects of reduced growth of the endocrine pancreas and other tissues in utero. This may be a consequence of maternal undernutrition. PMID:8462770

  20. Effects of endogenous GLP-1 and GIP on glucose tolerance after Roux-en-Y gastric bypass surgery.

    PubMed

    Svane, Maria S; Bojsen-Møller, Kirstine N; Nielsen, Signe; Jørgensen, Nils B; Dirksen, Carsten; Bendtsen, Flemming; Kristiansen, Viggo B; Hartmann, Bolette; Holst, Jens J; Madsbad, Sten

    2016-04-01

    Exaggerated secretion of glucagon-like peptide 1 (GLP-1) is important for postprandial glucose tolerance after Roux-en-Y gastric bypass (RYGB), whereas the role of glucose-dependent insulinotropic polypeptide (GIP) remains to be resolved. We aimed to explore the relative importance of endogenously secreted GLP-1 and GIP on glucose tolerance and β-cell function after RYGB. We used DPP-4 inhibition to enhance concentrations of intact GIP and GLP-1 and the GLP-1 receptor antagonist exendin-(9-39) (Ex-9) for specific blockage of GLP-1 actions. Twelve glucose-tolerant patients were studied after RYGB in a randomized, placebo-controlled, 4-day crossover study with standard mixed-meal tests and concurrent administration of placebo, oral sitagliptin, Ex-9 infusion, or combined Ex-9-sitagliptin. GLP-1 receptor antagonism increased glucose excursions, clearly attenuated β-cell function, and aggravated postprandial hyperglucagonemia compared with placebo, whereas sitagliptin had no effect despite two- to threefold increased concentrations of intact GLP-1 and GIP. Similarly, sitagliptin did not affect glucose tolerance or β-cell function during GLP-1R blockage. This study confirms the importance of GLP-1 for glucose tolerance after RYGB via increased insulin and attenuated glucagon secretion in the postprandial state, whereas amplification of the GIP signal (or other DPP-4-sensitive glucose-lowering mechanisms) did not appear to contribute to the improved glucose tolerance seen after RYGB. PMID:26786780

  1. The effect of the interaction between glucose tolerance and breakfasts varying in carbohydrate and fibre on mood and cognition.

    PubMed

    Nabb, Samantha L; Benton, David

    2006-01-01

    As a glucose containing drink has been reported to improve memory, and missing breakfast has been reported to adversely influence memory late in the morning, meals designed to differ in their ability to release glucose into the blood stream were contrasted. Using a factorial design, breakfasts containing 15, 30 or 50 g of carbohydrate and 1.5, 6 or 13 g of fibre were compared. The glucose tolerance of participants proved to be an important factor. Those with better tolerance reported better mood. Those eating breakfasts containing greater amounts of carbohydrate reported feeling tired rather than energetic. The amount of carbohydrate did not negatively affect memory in those with better glucose tolerance, however, the consumption of more carbohydrate resulted in more forgetting in those with poorer glucose tolerance. The effect with reactions times differed from memory in that a greater intake of carbohydrate resulted in faster responses later in the morning. PMID:17176639

  2. Regulatory focus affects physician risk tolerance.

    PubMed

    Veazie, Peter J; McIntosh, Scott; Chapman, Benjamin P; Dolan, James G

    2014-01-01

    Risk tolerance is a source of variation in physician decision-making. This variation, if independent of clinical concerns, can result in mistaken utilization of health services. To address such problems, it will be helpful to identify nonclinical factors of risk tolerance, particularly those amendable to intervention-regulatory focus theory suggests such a factor. This study tested whether regulatory focus affects risk tolerance among primary care physicians. Twenty-seven primary care physicians were assigned to promotion-focused or prevention-focused manipulations and compared on the Risk Taking Attitudes in Medical Decision Making scale using a randomization test. Results provide evidence that physicians assigned to the promotion-focus manipulation adopted an attitude of greater risk tolerance than the physicians assigned to the prevention-focused manipulation (p = 0.01). The Cohen's d statistic was conventionally large at 0.92. Results imply that situational regulatory focus in primary care physicians affects risk tolerance and may thereby be a nonclinical source of practice variation. Results also provide marginal evidence that chronic regulatory focus is associated with risk tolerance (p = 0.05), but the mechanism remains unclear. Research and intervention targeting physician risk tolerance may benefit by considering situational regulatory focus as an explanatory factor.

  3. ARA290 Improves Insulin Release and Glucose Tolerance in Type 2 Diabetic Goto-Kakizaki Rats

    PubMed Central

    Muller, Carole; Yassin, Kamal; Li, Luo-Sheng; Palmblad, Magnus; Efendic, Suad; Berggren, Per-Olof; Cerami, Anthony; Brines, Michael; Östenson, Claes-Göran

    2015-01-01

    Effects of ARA290 on glucose homeostasis were studied in type 2 diabetic Goto-Kakizaki (GK) rats. In GK rats receiving ARA290 daily for up to 4 wks, plasma glucose concentrations were lower after 3 and 4 wks, and hemoglobin A1c (Hb A1c) was reduced by ~20% without changes in whole body and hepatic insulin sensitivity. Glucose-stimulated insulin secretion was increased in islets from ARA290-treated rats. Additionally, in response to glucose, carbachol and KCl, islet cytoplasmic free Ca2+ concentrations, [Ca2+]i, were higher and the frequency of [Ca2+]i oscillations enhanced compared with placebo. ARA290 also improved stimulus–secretion coupling for glucose in GK rat islets, as shown by an improved glucose oxidation rate, ATP production and acutely enhanced glucose-stimulated insulin secretion. ARA290 also exerted an effect distal to the ATP-sensitive potassium (KATP) channel on the insulin exocytotic pathway, since the insulin response was improved following islet depolarization by KCl when KATP channels were kept open by diazoxide. Finally, inhibition of protein kinase A completely abolished effects of ARA290 on insulin secretion. In conclusion, ARA290 improved glucose tolerance without affecting hematocrit in diabetic GK rats. This effect appears to be due to improved β-cell glucose metabolism and [Ca2+]i handling, and thereby enhanced glucose-induced insulin release. PMID:26736179

  4. Evaluation of a Self-Administered Oral Glucose Tolerance Test

    PubMed Central

    Bethel, M. Angelyn; Price, Hermione C.; Sourij, Harald; White, Sarah; Coleman, Ruth L.; Ring, Arne; Kennedy, Irene E.C.; Tucker, Lynne; Holman, Rury R.

    2013-01-01

    OBJECTIVE To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes. PMID:23321216

  5. Stable-label intravenous glucose tolerance test minimal model

    SciTech Connect

    Avogaro, A.; Bristow, J.D.; Bier, D.M.; Cobelli, C.; Toffolo, G. )

    1989-08-01

    The minimal model approach to estimating insulin sensitivity (Sl) and glucose effectiveness in promoting its own disposition at basal insulin (SG) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with (6,6-{sup 2}H{sub 2})glucose, (2-{sup 2}H)glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated S*l derived from the stable-label IVGTT was greater than Sl in each case except one, and the tracer-estimated SG* was less than SG in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of +/- 5% (range 3-9%) compared to average precisions of +/- 74% (range 7-309%) for SG and +/- 22% (range 3-72%) for Sl. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women.

  6. Measurement of glucose homeostasis in vivo: glucose and insulin tolerance tests.

    PubMed

    Beguinot, Francesco; Nigro, Cecilia

    2012-01-01

    The feasibility of investigating glucose tolerance and insulin action and secretion in vivo in mouse models has provided major insights into both type 2 diabetes pathogenesis and the identification of novel strategies to treat this common disorder. When initial studies provide evidence for altered levels of insulin and/or glucose in the animal blood, a number of well-characterized tests can be adopted to estimate glucose homeostasis and insulin action and secretion in vivo. These tests include model assessments, glucose and insulin sensitivity studies, and glucose clamps. None of them can be considered appropriate under all circumstances and there is significant variation in their complexity, technical ease, and invasiveness. Thus, while the euglycaemic hyperinsulinemic clamp represents the gold standard for measuring in vivo insulin action, less labor-intensive as well as invasive techinques are usually considered as the initial approach to evaluate glucose homeostasis. This section focuses on glucose and insulin tolerance tests. The clamp technique is described in Chapter 15.

  7. Maternal Arsenic Exposure and Impaired Glucose Tolerance during Pregnancy

    PubMed Central

    Ettinger, Adrienne S.; Zota, Ami R.; Amarasiriwardena, Chitra J.; Hopkins, Marianne R.; Schwartz, Joel; Hu, Howard; Wright, Robert O.

    2009-01-01

    Background Accumulating evidence has shown an increased risk of type 2 diabetes in general populations exposed to arsenic, but little is known about exposures during pregnancy and the association with gestational diabetes (GD). Objectives We studied 532 women living proximate to the Tar Creek Superfund Site to investigate whether arsenic exposure is associated with impaired glucose tolerance during pregnancy. Methods Blood glucose was measured between 24 and 28 weeks gestation after a 1-hr oral glucose tolerance test (GTT) as part of routine prenatal care. Blood and hair were collected at delivery and analyzed for arsenic using inductively coupled plasma mass spectrometry with dynamic reaction cell. Results Arsenic concentrations ranged from 0.2 to 24.1 μg/L (ppb) (mean ± SD, 1.7 ±1.5) and 1.1 to 724.4 ng/g (ppb) (mean ± SD, 27.4 ± 61.6) in blood and hair, respectively. One-hour glucose levels ranged from 40 to 284 mg/dL (mean ± SD, 108.7 ± 29.5); impaired glucose tolerance was observed in 11.9% of women when using standard screening criterion (> 140 mg/dL). Adjusting for age, Native-American race, prepregnancy body mass index, Medicaid use, and marital status, women in the highest quartile of blood arsenic exposure had 2.8 higher odds of impaired GTT than women in the lowest quartile of exposure (95% confidence interval, 1.1–6.9) (p-trend = 0.008). Conclusions Among this population of pregnant women, arsenic exposure was associated with increased risk of impaired GTT at 24–28 weeks gestation and therefore may be associated with increased risk of GD. PMID:19654913

  8. Dietary Patterns and Glucose Tolerance Abnormalities in Chinese Adults

    PubMed Central

    He, Yuna; Ma, Guansheng; Zhai, Fengying; Li, Yanping; Hu, Yisong; Feskens, Edith J.M.; Yang, Xiaoguang

    2009-01-01

    OBJECTIVE To investigate the association of the dietary pattern with the presence of newly diagnosed glucose tolerance abnormalities among Chinese adults. RESEARCH DESIGN AND METHODS A total of 20,210 adults aged 45–69 years from the 2002 China National Nutrition and Health Survey were included. Information on dietary intake was collected using a validated food frequency questionnaire. Factor analysis and cluster analysis were used to identify the food factors and dietary pattern clusters. RESULTS Four dietary pattern clusters were identified (“Green Water,” “Yellow Earth,” “Western Adopter,” and “New Affluence”). The prevalence of glucose tolerance abnormalities ranged from 3.9% in the Green Water to 8.0% in the New Affluence. After adjustment for area, age, sex, current smoking, and physical activity, subjects in the Yellow Earth cluster (prevalence ratio 1.22 [95% CI 1.04–1.43]) and New Affluence cluster (2.05 [1.76–2.37]) had significantly higher prevalence rates compared with those for the Green Water cluster. After further adjustment for BMI and waist-to-height ratio, the elevated risk in the New Affluence remained statistically significant. CONCLUSIONS Dietary patterns and food factors are associated with the presence of glucose tolerance abnormalities in China, even independent of obesity. A New Affluence diet is an important modifiable risk factor, which needs attention from the prevention point of view. PMID:19675202

  9. Kidney Function, β-Cell Function and Glucose Tolerance in Older Men

    PubMed Central

    Jia, Ting; Risérus, Ulf; Xu, Hong; Lindholm, Bengt; Ärnlöv, Johan; Sjögren, Per; Cederholm, Tommy; Larsson, Tobias E.; Ikizler, Talat Alp

    2015-01-01

    Context: Kidney dysfunction induces insulin resistance, but it is unknown if β cell function is affected. Objective: To investigate insulin release (β cell function) and glucose tolerance following a standardized oral glucose tolerance test (OGTT) across kidney function strata. Setting and Design: Community-based cohort study from the Uppsala Longitudinal Study of Adult Men (ULSAM). Participants and Main Outcome Measure: Included were 1015 nondiabetic Swedish men aged 70–71 years. All participants underwent OGTT and euglycaemic hyperinsulinaemic clamp (HEGC) tests, allowing determination of insulin sensitivity, β cell function, and glucose tolerance. Kidney function was estimated by cystatin C-algorithms. Mixed models were used to identify determinants of insulin secretion after the hyperglycemic load. Results: As many as 466 (46%) of participants presented moderate-advanced kidney disease. Insulin sensitivity (by HEGC) decreased across decreasing kidney function quartiles. After the OGTT challenge, however, β cell function indices (area under the curve for insulin release, the estimated first phase insulin release, and the insulinogenic index) were incrementally higher. Neither the oral disposition index nor the 2-h postload glucose tolerance differed across the kidney function strata. Mixed models showed that dynamic insulin release during the OGTT was inversely associated with kidney function, despite the correction for each individual's insulin sensitivity or its risk factors. Conclusions: In older men, β cell function after a hyperglycemic load appropriately compensated the loss in insulin sensitivity that accompanies kidney dysfunction. As a result, the net balance between insulin sensitivity and β cell function was preserved. PMID:25429626

  10. How High Glucose Levels Affect Tendon Homeostasis.

    PubMed

    Snedeker, Jess G

    2016-01-01

    Among the many factors playing a role in tendon disease, unregulated biochemical reactions between glucose and the collagen extracellular matrix are coming increasingly into focus. We have shown that formation of advanced glycation end-products that cross-link the collagen extracellular matrix can drastically affect cellular level mechanical properties of the matrix, and in turn affect cell-level biomechanical stimuli during physiological loading of the tissue. We suggest that these may adversely affect tendon cell response to matrix damage, as well as the quality of the consequent repair. If such mechanical feedback loops are altered, the ability of tendon cells to maintain tissue in a functional, healthy state may be compromised. Although key foundational elements of biochemical, biomechanical, and biological understanding are now in place, the full extent of how these aspects interact, including the precise mechanisms by which advanced glycation end-products pathologically disrupt connective tissue homeostasis and damage repair, are only beginning to be adequately appreciated. PMID:27535261

  11. Diagnosis of prediabetes in cats: glucose concentration cut points for impaired fasting glucose and impaired glucose tolerance.

    PubMed

    Reeve-Johnson, M K; Rand, J S; Vankan, D; Anderson, S T; Marshall, R; Morton, J M

    2016-10-01

    Diabetes is typically diagnosed in cats once clinical signs are evident. Diagnostic criteria for prediabetes in cats have not been defined. The objective of the study was to establish methodology and cut points for fasting and 2-h blood glucose concentrations in healthy client-owned senior cats (≥8 yr) using ear/paw samples and a portable glucose meter calibrated for feline blood. Of the 78 cats, 27 were ideal (body condition score [BCS] 4 or 5 of 9), 31 overweight (BCS 6 or 7), and 20 obese (BCS 8 or 9); 19 were Burmese and 59 non-Burmese. After an 18-24-h fast and an ear/paw blood glucose measurement using a portable glucose meter, glucose (0.5 g/kg bodyweight) was administered intravenous and blood glucose measured at 2 min and 2 h. Cut points for fasting and 2-h glucose concentrations were defined as the upper limits of 95% reference intervals using cats with BCS 4 or 5. The upper cut point for fasting glucose was 6.5 mmol/L. Of the overweight and obese cats, 1 (BCS 7) was above this cut point indicating evidence of impaired fasting glucose. The cut point for 2-h glucose was 9.8 mmol/L. A total of 7 cats (4 with BCS 8 or 9 including 1 Burmese; 3 with BCS 6 or 7, non-Burmese) were above this cut point and thus had evidence of impaired glucose tolerance. In conclusion, the methodology and cutpoints for diagnosis of prediabetes are defined for use in healthy cats 8 yr and older with a range of BCSs. PMID:27565231

  12. Effects of ambient temperature on glucose tolerance and insulin sensitivity test outcomes in normal and obese C57 male mice.

    PubMed

    Dudele, Anete; Rasmussen, Gitte Marie; Mayntz, David; Malte, Hans; Lund, Sten; Wang, Tobias

    2015-05-01

    Mice are commonly used as animal models to study human metabolic diseases, but experiments are typically performed at room temperature, which is far below their thermoneutral zone and is associated with elevated heart rate, food intake, and energy expenditure. We set out to study how ambient temperature affects glucose tolerance and insulin sensitivity in control and obese male mice. Adult male C57BL/6J mice were housed at room temperature (23°C) for 6 weeks and fed either control or high fat diet. They were then fasted for 6 h before glucose or insulin tolerance tests were performed at 15, 20, 25, or 30°C. To ensure that behavioral thermoregulation did not counterbalance the afflicted ambient temperatures, oxygen consumption was determined on mice with the same thermoregulatory opportunities as during the tests. Decreasing ambient temperatures increased oxygen consumption and body mass loss during fasting in both groups. Mice fed high fat diet had improved glucose tolerance at 30°C and increased levels of fasting insulin followed by successive decrease of fasting glucose. However, differences between control and high-fat diet mice were present at all temperatures. Ambient temperature did not affect glucose tolerance in control group and insulin tolerance in either of the groups. Ambient temperature affects glucose metabolism in mice and this effect is phenotype specific.

  13. Regulation of Glucose Tolerance and Sympathetic Activity by MC4R Signaling in the Lateral Hypothalamus

    PubMed Central

    Morgan, Donald A.; McDaniel, Latisha N.; Yin, Terry; Khan, Michael; Jiang, Jingwei; Acevedo, Michael R.; Walsh, Susan A.; Ponto, Laura L. Boles; Norris, Andrew W.; Lutter, Michael; Rahmouni, Kamal

    2015-01-01

    Melanocortin 4 receptor (MC4R) signaling mediates diverse physiological functions, including energy balance, glucose homeostasis, and autonomic activity. Although the lateral hypothalamic area (LHA) is known to express MC4Rs and to receive input from leptin-responsive arcuate proopiomelanocortin neurons, the physiological functions of MC4Rs in the LHA are incompletely understood. We report that MC4RLHA signaling regulates glucose tolerance and sympathetic nerve activity. Restoring expression of MC4Rs specifically in the LHA improves glucose intolerance in obese MC4R-null mice without affecting body weight or circulating insulin levels. Fluorodeoxyglucose-mediated tracing of whole-body glucose uptake identifies the interscapular brown adipose tissue (iBAT) as a primary source where glucose uptake is increased in MC4RLHA mice. Direct multifiber sympathetic nerve recording further reveals that sympathetic traffic to iBAT is significantly increased in MC4RLHA mice, which accompanies a significant elevation of Glut4 expression in iBAT. Finally, bilateral iBAT denervation prevents the glucoregulatory effect of MC4RLHA signaling. These results identify a novel role for MC4RLHA signaling in the control of sympathetic nerve activity and glucose tolerance independent of energy balance. PMID:25605803

  14. Gut microbiota and diet in patients with different glucose tolerance

    PubMed Central

    Egshatyan, Lilit; Kashtanova, Daria; Popenko, Anna; Tkacheva, Olga; Tyakht, Alexander; Alexeev, Dmitry; Karamnova, Natalia; Kostryukova, Elena; Babenko, Vladislav; Vakhitova, Maria; Boytsov, Sergey

    2015-01-01

    Type 2 diabetes (T2D) is a serious disease. The gut microbiota (GM) has recently been identified as a new potential risk factor in addition to well-known diabetes risk factors. To investigate the GM composition in association with the dietary patterns in patients with different glucose tolerance, we analyzed 92 patients: with normal glucose tolerance (n=48), prediabetes (preD, n=24), and T2D (n=20). Metagenomic analysis was performed using 16S rRNA sequencing. The diet has been studied by a frequency method with a quantitative evaluation of food intake using a computer program. Microbiota in the samples was predominantly represented by Firmicutes, in a less degree by Bacteroidetes. Blautia was a dominant genus in all samples. The representation of Blautia, Serratia was lower in preD than in T2D patients, and even lower in those with normal glucose tolerance. After the clustering of the samples into groups according to the percentage of protein, fat, carbohydrates in the diet, the representation of the Bacteroides turned to be lower and Prevotella abundance turned to be higher in carbohydrate cluster. There were more patients with insulin resistance, T2D in the fat–protein cluster. Using the Calinski–Harabasz index identified the samples with more similar diets. It was discovered that half of the patients with a high-fat diet had normal tolerance, the others had T2D. The regression analysis showed that these T2D patients also had a higher representation of Blautia. Our study provides the further evidence concerning the structural modulation of the GM in the T2DM pathogenesis depending on the dietary patterns. PMID:26555712

  15. Characterization of the intravenous glucose tolerance test and the combined glucose-insulin test in donkeys.

    PubMed

    Mendoza, F J; Aguilera-Aguilera, R; Gonzalez-De Cara, C A; Toribio, R E; Estepa, J C; Perez-Ecija, A

    2015-12-01

    Glucose-insulin dynamic challenges such as the intravenous glucose tolerance test (IVGTT) and combined glucose-insulin test (CGIT) have not been described in donkeys. The objectives of this study were (1) to characterize the IVGTT and CGIT in healthy adult donkeys, and (2) to establish normal glucose-insulin proxies. Sixteen donkeys were used and body morphometric variables obtained each. For the IVGTT, glucose (300 mg/kg) was given IV. For the CGIT, glucose (150 mg/kg) followed by recombinant insulin (0.1 IU/kg) were administered IV. Blood samples for glucose and insulin determinations were collected over 300 min. In the IVGTT the positive phase lasted 160.9 ± 13.3 min, glucose concentration peaked at 323.1 ± 9.2 mg/dL and declined at a rate of 1.28 ± 0.15 mg/dL/min. The glucose area under the curve (AUC) was 21.4 ± 1.9 × 10(3) mg/dL/min and the insulin AUC was 7.2 ± 0.9 × 10(3) µIU/mL/min. The positive phase of the CGIT curve lasted 44 ± 3 min, with a glucose clearance rate of 2.01 ± 0.18 mg/dL/min. The negative phase lasted 255.9 ± 3 min, decreasing glucose concentration at rate of -0.63 ± 0.06 mg/dL/min, and reaching a nadir (33.1 ± 3.6 mg/dL) at 118.3 ± 6.3 min. The glucose and insulin AUC values were 15.2 ± 0.9 × 10(3) mg/dL/min and 13.2 ± 0.9 × 10(3) µIU/mL/min. This is the first study characterizing CGIT and IVGTT, and glucose-insulin proxies in healthy adult donkeys. Distinct glucose dynamics, when compared with horses, support the use of species-specific protocols to assess endocrine function.

  16. Dry period plane of energy: Effects on glucose tolerance in transition dairy cows.

    PubMed

    Mann, S; Leal Yepes, F A; Duplessis, M; Wakshlag, J J; Overton, T R; Cummings, B P; Nydam, D V

    2016-01-01

    Overfeeding energy in the dry period can affect glucose metabolism and the energy balance of transition dairy cows with potential detrimental effects on the ability to successfully adapt to early lactation. The objectives of this study were to investigate the effect of different dry cow feeding strategies on glucose tolerance and on resting concentrations of blood glucose, glucagon, insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate (BHB) in the peripartum period. Cows entering second or greater lactation were enrolled at dry-off (57 d before expected parturition) into 1 of 3 treatment groups following a randomized block design: cows that received a total mixed ration (TMR) formulated to meet but not exceed energy requirements during the dry period (n=28, controlled energy); cows that received a TMR supplying approximately 150% of energy requirements during the dry period (n=28, high energy); and cows that were fed the same diet as the controlled energy group for the first 28 d, after which the TMR was formulated to supply approximately 125% of energy requirements until calving (n=28, intermediate energy). Intravenous glucose tolerance tests (IVGTT) with rapid administration of 0.25 g of glucose/kg of body weight were performed 28 and 10d before expected parturition, as well as at 4 and 21 d after calving. Area under the curve for insulin and glucose, maximal concentration and time to half-maximal concentration of insulin and glucose, and clearance rates were calculated. Insulin resistance (IR) indices were calculated from baseline samples obtained during IVGTT and Spearman rank correlations determined between IVGTT parameters and IR indices. Treatment did not affect IVGTT parameters at any of the 4 time points. Correlation between IR indices and IVGTT parameters was generally poor. Overfeeding cows energy in excess of predicted requirements by approximately 50% during the entire dry period resulted in decreased postpartum basal plasma glucose and

  17. Dry period plane of energy: Effects on glucose tolerance in transition dairy cows.

    PubMed

    Mann, S; Leal Yepes, F A; Duplessis, M; Wakshlag, J J; Overton, T R; Cummings, B P; Nydam, D V

    2016-01-01

    Overfeeding energy in the dry period can affect glucose metabolism and the energy balance of transition dairy cows with potential detrimental effects on the ability to successfully adapt to early lactation. The objectives of this study were to investigate the effect of different dry cow feeding strategies on glucose tolerance and on resting concentrations of blood glucose, glucagon, insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate (BHB) in the peripartum period. Cows entering second or greater lactation were enrolled at dry-off (57 d before expected parturition) into 1 of 3 treatment groups following a randomized block design: cows that received a total mixed ration (TMR) formulated to meet but not exceed energy requirements during the dry period (n=28, controlled energy); cows that received a TMR supplying approximately 150% of energy requirements during the dry period (n=28, high energy); and cows that were fed the same diet as the controlled energy group for the first 28 d, after which the TMR was formulated to supply approximately 125% of energy requirements until calving (n=28, intermediate energy). Intravenous glucose tolerance tests (IVGTT) with rapid administration of 0.25 g of glucose/kg of body weight were performed 28 and 10d before expected parturition, as well as at 4 and 21 d after calving. Area under the curve for insulin and glucose, maximal concentration and time to half-maximal concentration of insulin and glucose, and clearance rates were calculated. Insulin resistance (IR) indices were calculated from baseline samples obtained during IVGTT and Spearman rank correlations determined between IVGTT parameters and IR indices. Treatment did not affect IVGTT parameters at any of the 4 time points. Correlation between IR indices and IVGTT parameters was generally poor. Overfeeding cows energy in excess of predicted requirements by approximately 50% during the entire dry period resulted in decreased postpartum basal plasma glucose and

  18. Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet

    SciTech Connect

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-11-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat Western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. -- Highlights: ► Nrf2 deficiency improves glucose tolerance in mice fed a high-fat diet. ► The anti-diabetic hormone, Fgf21, is highly expressed in livers of Nrf2-null mice. ► The absence of Nrf2 increases the insulin-regulated Igfbp-1 mRNA in liver.

  19. Featured Article: Inhibition of diabetic cataract by glucose tolerance factor extracted from yeast.

    PubMed

    Mirsky, Nitsa; Cohen, Revital; Eliaz, Anat; Dovrat, Ahuva

    2016-04-01

    Diabetes leads to many complications; among them is the development of cataract. Hyperglycemia brings to increased polyol concentration in the lens, to glycation of lens proteins, and to elevated level of ROS (Reactive Oxygen Species) causing oxidative stress. The glucose tolerance factor (GTF) was found by several groups to decrease hyperglycemia and oxidative stress both in diabetic animals and humans. The aim of our study was to explore the damages induced by high glucose to the eye lens and to assess the protective effects of GTF both in vivo and in vitro The in vivo study included control healthy rats, streptozotocin (STZ) diabetic untreated rats, and STZ diabetic rats orally treated with 15 doses of GTF. The diabetic untreated rats developed cataracts, whereas the development of cataract was totally or partially prevented in GTF treated animals. In vitro studies were done on bovine lenses incubated for 14 days. Half of the lenses were incubated in normal glucose conditions, and half in high glucose conditions (450 mg%). To one group of the normal or high glucose condition GTF was added. The optical quality of all the lenses was measured daily by an automated scanning laser system. The control lenses, whether with or without GTF addition, did not show any reduction in their quality. High glucose conditions induced optical damage to the lenses. Addition of GTF to high glucose conditions prevented this damage. High glucose conditions affected the activity of aldose reductase and sodium potassium ATPase in lens epithelial cell. Addition of GTF decreased the destructive changes induced by high glucose conditions. The amount of soluble cortical lens proteins was decreased and structural changes were detected in lenses incubated in high glucose medium. These changes could be prevented when GTF was added to high glucose medium. Our findings demonstrate the anticataractogenic potential of GTF. PMID:26825353

  20. Featured Article: Inhibition of diabetic cataract by glucose tolerance factor extracted from yeast

    PubMed Central

    Cohen, Revital; Eliaz, Anat; Dovrat, Ahuva

    2016-01-01

    Diabetes leads to many complications; among them is the development of cataract. Hyperglycemia brings to increased polyol concentration in the lens, to glycation of lens proteins, and to elevated level of ROS (Reactive Oxygen Species) causing oxidative stress. The glucose tolerance factor (GTF) was found by several groups to decrease hyperglycemia and oxidative stress both in diabetic animals and humans. The aim of our study was to explore the damages induced by high glucose to the eye lens and to assess the protective effects of GTF both in vivo and in vitro. The in vivo study included control healthy rats, streptozotocin (STZ) diabetic untreated rats, and STZ diabetic rats orally treated with 15 doses of GTF. The diabetic untreated rats developed cataracts, whereas the development of cataract was totally or partially prevented in GTF treated animals. In vitro studies were done on bovine lenses incubated for 14 days. Half of the lenses were incubated in normal glucose conditions, and half in high glucose conditions (450 mg%). To one group of the normal or high glucose condition GTF was added. The optical quality of all the lenses was measured daily by an automated scanning laser system. The control lenses, whether with or without GTF addition, did not show any reduction in their quality. High glucose conditions induced optical damage to the lenses. Addition of GTF to high glucose conditions prevented this damage. High glucose conditions affected the activity of aldose reductase and sodium potassium ATPase in lens epithelial cell. Addition of GTF decreased the destructive changes induced by high glucose conditions. The amount of soluble cortical lens proteins was decreased and structural changes were detected in lenses incubated in high glucose medium. These changes could be prevented when GTF was added to high glucose medium. Our findings demonstrate the anticataractogenic potential of GTF. PMID:26825353

  1. Nrf2 Deficiency Improves Glucose Tolerance in Mice Fed a High-Fat Diet

    PubMed Central

    Zhang, Yu-Kun Jennifer; Wu, Kai Connie; Liu, Jie; Klaassen, Curtis D.

    2012-01-01

    Nrf2, a master regulator of intracellular redox homeostasis, is indicated to participate in fatty acid metabolism in liver. However, its role in diet-induced obesity remains controversial. In the current study, genetically engineered Nrf2-null, wild-type (WT), and Nrf2-activated, Keap1-knockdown (K1-KD) mice were fed either a control or a high-fat western diet (HFD) for 12 weeks. The results indicate that the absence or enhancement of Nrf2 activity did not prevent diet-induced obesity, had limited effects on lipid metabolism, but affected blood glucose homeostasis. Whereas the Nrf2-null mice were resistant to HFD-induced glucose intolerance, the Nrf2-activated K1-KD mice exhibited prolonged elevation of circulating glucose during a glucose tolerance test even on the control diet. Feeding a HFD did not activate the Nrf2 signaling pathway in mouse livers. Fibroblast growth factor 21 (Fgf21) is a liver-derived anti-diabetic hormone that exerts glucose- and lipid-lowering effects. Fgf21 mRNA and protein were both elevated in livers of Nrf2-null mice, and Fgf21 protein was lower in K1-KD mice than WT mice. The inverse correlation between Nrf2 activity and hepatic expression of Fgf21 might explain the improved glucose tolerance in Nrf2-null mice. Furthermore, a more oxidative cellular environment in Nrf2-null mice could affect insulin signaling in liver. For example, mRNA of insulin-like growth factor binding protein 1, a gene repressed by insulin in hepatocytes, was markedly elevated in livers of Nrf2-null mice. In conclusion, genetic alteration of Nrf2 does not prevent diet-induced obesity in mice, but deficiency of Nrf2 improves glucose homeostasis, possibly through its effects on Fgf21 and/or insulin signaling. PMID:23017736

  2. Periodic 48 h feed withdrawal improves glucose tolerance in growing pigs by enhancing adipogenesis and lipogenesis

    PubMed Central

    2012-01-01

    Background Adipocyte numbers and peroxisome proliferators activated receptorγ (PPARγ) expression of retroperitoneal tissue increased while area under the curve (AUC) during the glucose tolerance test (GTT) was reduced in rats subjected to certain feed withdrawal (FW) regimens. Thus, using pigs as the experimental model, the hypothesis that FW regimens influence glucose tolerance by influencing fat cell function was evaluated with the objective of determining the effect of a single (FWx1; at age of 19 wk for 48 h) or periodic, multiple (FWx4; 24 h FW at 7 and 11 wk of age and 48 h FW at 15 and 19 wk of age) FW on AUC of glucose and insulin during the GTT relative to pigs that did not experience FW (Control). Methods Growth, body composition, adipocyte numbers, PPARγ expression, lipogenic potential as glucose uptake into fat of adipocytes of varying diameter in omental (OM) and subcutaneous (SQ) fat as affected by FW regimens were determined in pigs initiated into the study at 5 wk of age and fed the same diet, ad libitum. Results Blood glucose concentrations for prior to and 120 min post glucose meal tended to be lower (p = 0.105 and 0.097, respectively) in pigs in FW treatments. In OM fat; cell numbers, glucose Universal14C [U14C] incorporation into fat and rate of incorporation per 104 cells was greatest for cells with diameters of 90-119 μm. Pigs undergoing FWx4 tended to have greater (p = 0.0685; by 191%) number of adipocytes, increased (p = 0.0234) glucose U14C incorporation into adipocytes and greater (p = 0.0872) rate of glucose uptake into cells of 119-150 μm diameter than of cells from control or FWx1 pigs. Subcutaneous adipocyte numbers in 22-60 and 61-90 μm diameter ranges from pigs in FWx1 tended to be greater (p = 0.08 and 0.06, respectively) than for those in FWx4 treatment, yet PPARγ expression and total cell number were not affected by treatment. Conclusions Results suggest that FW regimens influence fat cell function or lipogenesis rather

  3. Transgenic mice with muscle-specific insulin resistance develop increased adiposity, impaired glucose tolerance, and dyslipidemia.

    PubMed

    Moller, D E; Chang, P Y; Yaspelkis, B B; Flier, J S; Wallberg-Henriksson, H; Ivy, J L

    1996-06-01

    Impaired skeletal muscle insulin receptor function is a feature of common forms of insulin resistance, including obesity and noninsulin-dependent diabetes mellitus. However, the extent to which this defect accounts for impaired muscle glucose disposal or altered in vivo glucose homeostasis remains to be established. We recently showed that transgenic mice that overexpress dominant-negative insulin receptors specifically in striated muscle have a severe defect in muscle insulin receptor-mediated signaling and modest hyperinsulinemia. Here we performed hindlimb perfusion studies to determine the impact of this defect on muscle glucose uptake and metabolism. Maximal rates of insulin-stimulated muscle 3-O-methylglucose transport were reduced by 32-40% in transgenic mice with proportional defects involving total hindlimb [14C]glucose uptake, lactate production, and muscle glycogen synthesis. To address the hypothesis that muscle insulin resistance could promote an increase in the accretion of body fat, carcass analysis was performed using two independent lines of transgenic mice. Although body weights were normal, transgenic mice had a 22-38% increase in body fat, with a reciprocal decrease (10-15%) in body protein. Mean gonadal fat pad weight was also increased in transgenic mice. Skeletal muscle histology and fiber type distribution were not affected. To determine whether muscle-specific insulin resistance was sufficient to cause impaired glucose tolerance, oral glucose tolerance tests were performed with 6-month-old transgenic and control mice. Fasting glucose levels were increased by 25%, and peak values were 22-40% higher in transgenic mice. Transgenic mice also had a 37% decrease in plasma lactate levels and modest increases in levels of plasma triglycerides and FFA (29% and 15%, respectively). We conclude that 1) severe defects in muscle insulin receptor function result in impaired insulin-stimulated glucose uptake and metabolism in this tissue; 2) muscle

  4. Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients

    PubMed Central

    Handisurya, Ammon; Kerscher, Corinna; Tura, Andrea; Herkner, Harald; Payer, Berit Anna; Mandorfer, Mattias; Werzowa, Johannes; Winnicki, Wolfgang; Reiberger, Thomas; Kautzky-Willer, Alexandra; Pacini, Giovanni; Säemann, Marcus; Schmidt, Alice

    2016-01-01

    Background Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. Methods In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). Results After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82–441.92) vs. 468.80 (414.27–488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032–0.106) vs. 0.083 (0.054–0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. Conclusions HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV

  5. Chinese herbal medicines for people with impaired glucose tolerance or impaired fasting blood glucose

    PubMed Central

    Grant, Suzanne J; Bensoussan, Alan; Chang, Dennis; Kiat, Hosen; Klupp, Nerida L; Liu, Jian Ping; Li, Xun

    2011-01-01

    Background Around 308 million people worldwide are estimated to have impaired glucose tolerance (IGT); 25% to 75% of these will develop diabetes within a decade of initial diagnosis. At diagnosis, half will have tissue-related damage and all have an increased risk for coronary heart disease. Objectives The objective of this review was to assess the effects and safety of Chinese herbal medicines for the treatment of people with impaired glucose tolerance or impaired fasting glucose (IFG). Search strategy We searched the following databases: The Cochrane Library, PubMed, EMBASE, AMED, a range of Chinese language databases, SIGLE and databases of ongoing trials. Selection criteria Randomised clinical trials comparing Chinese herbal medicines with placebo, no treatment, pharmacological or non-pharmacological interventions in people with IGT or IFG were considered. Data collection and analysis Two authors independently extracted data. Trials were assessed for risk of bias against key criteria: random sequence generation, allocation concealment, blinding of participants, outcome assessors and intervention providers, incomplete outcome data, selective outcome reporting and other sources of bias. Main results This review examined 16 trials lasting four weeks to two years involving 1391 participants receiving 15 different Chinese herbal medicines in eight different comparisons. No trial reported on mortality, morbidity or costs. No serious adverse events like severe hypoglycaemia were observed. Meta-analysis of eight trials showed that those receiving Chinese herbal medicines combined with lifestyle modification were more than twice as likely to have their fasting plasma glucose levels return to normal levels (i.e. fasting plasma glucose <7.8 mmol/L and 2hr blood glucose <11.1 mmol/L) compared to lifestyle modification alone (RR 2.07; 95% confidence intervall (CI) 1.52 to 2.82). Those receiving Chinese herbs were less likely to progress to diabetes over the duration of the

  6. Improvements in glucose tolerance with Bikram Yoga in older obese adults: a pilot study.

    PubMed

    Hunter, Stacy D; Dhindsa, Mandeep; Cunningham, Emily; Tarumi, Takashi; Alkatan, Mohammed; Tanaka, Hirofumi

    2013-10-01

    Bikram yoga is an exotic form of physical activity combining hatha yoga and thermal therapy that could positively impact metabolic health. Although this increasingly popular alternative exercise may be ideal for obese adults due to its low impact nature, few studies have elucidated the health benefits associated with it. As an initial step, we determined the effect of Bikram yoga on glucose tolerance. Fourteen young lean and 15 older obese subjects completed an 8-week Bikram yoga intervention in which classes were completed 3 times per week. Glucose tolerance was assessed using a 75 g oral glucose tolerance test. The area under the glucose curve following the oral glucose tolerance test was significantly reduced as a result of the Bikram Yoga intervention in older obese (P < 0.05) but not in young lean subjects. We concluded that a short-term Bikram yoga intervention improved glucose tolerance in older obese, but not in young lean adults. PMID:24138995

  7. Metabolic profile of normal glucose-tolerant subjects with elevated 1-h plasma glucose values

    PubMed Central

    Pramodkumar, Thyparambil Aravindakshan; Priya, Miranda; Jebarani, Saravanan; Anjana, Ranjit Mohan; Mohan, Viswanathan; Pradeepa, Rajendra

    2016-01-01

    Aim: The aim of this study was to compare the metabolic profiles of subjects with normal glucose tolerance (NGT) with and without elevated 1-h postglucose (1HrPG) values during an oral glucose tolerance test (OGTT). Methodology: The study group comprised 996 subjects without known diabetes seen at tertiary diabetes center between 2010 and 2014. NGT was defined as fasting plasma glucose <100 mg/dl (5.5 mmol/L) and 2-h plasma glucose <140 mg/dl (7.8 mmol/L) after an 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose) OGTT. Anthropometric measurements and biochemical investigations were done using standardized methods. The prevalence rate of generalized and central obesity, hypertension, dyslipidemia, and metabolic syndrome (MS) was determined among the NGT subjects stratified based on their 1HrPG values as <143 mg/dl, ≥143–<155 mg/dl, and ≥155 mg/dl, after adjusting for age, sex, body mass index (BMI), waist circumference, alcohol consumption, smoking, and family history of diabetes. Results: The mean age of the 996 NGT subjects was 48 ± 12 years and 53.5% were male. The mean glycated hemoglobin for subjects with 1HrPG <143 mg/dl was 5.5%, for those with 1HrPG ≥143–<155 mg/dl, 5.6% and for those with 1HrPG ≥155 mg/dl, 5.7%. NGT subjects with 1HrPG ≥143–<155 mg/dl and ≥155 mg/dl had significantly higher BMI, waist circumference, systolic and diastolic blood pressure, triglyceride, total cholesterol/high-density lipoprotein (HDL) ratio, triglyceride/HDL ratio, leukocyte count, and gamma glutamyl aminotransferase (P < 0.05) compared to subjects with 1HrPG <143 mg/dl. The odds ratio for MS for subjects with 1HrPG ≥143 mg/dl was 1.84 times higher compared to subjects with 1HrPG <143 mg/dl taken as the reference. Conclusion: NGT subjects with elevated 1HrPG values have a worse metabolic profile than those with normal 1HrPG during an OGTT. PMID:27730069

  8. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes.

  9. Hypothalamic POMC Deficiency Improves Glucose Tolerance Despite Insulin Resistance by Increasing Glycosuria.

    PubMed

    Chhabra, Kavaljit H; Adams, Jessica M; Fagel, Brian; Lam, Daniel D; Qi, Nathan; Rubinstein, Marcelo; Low, Malcolm J

    2016-03-01

    Hypothalamic proopiomelanocortin (POMC) is essential for the physiological regulation of energy balance; however, its role in glucose homeostasis remains less clear. We show that hypothalamic arcuate nucleus (Arc)POMC-deficient mice, which develop severe obesity and insulin resistance, unexpectedly exhibit improved glucose tolerance and remain protected from hyperglycemia. To explain these paradoxical phenotypes, we hypothesized that an insulin-independent pathway is responsible for the enhanced glucose tolerance. Indeed, the mutant mice demonstrated increased glucose effectiveness and exaggerated glycosuria relative to wild-type littermate controls at comparable blood glucose concentrations. Central administration of the melanocortin receptor agonist melanotan II in mutant mice reversed alterations in glucose tolerance and glycosuria, whereas, conversely, administration of the antagonist Agouti-related peptide (Agrp) to wild-type mice enhanced glucose tolerance. The glycosuria of ArcPOMC-deficient mice was due to decreased levels of renal GLUT 2 (rGLUT2) but not sodium-glucose cotransporter 2 and was associated with reduced renal catecholamine content. Epinephrine treatment abolished the genotype differences in glucose tolerance and rGLUT2 levels, suggesting that reduced renal sympathetic nervous system (SNS) activity is the underlying mechanism for the observed glycosuria and improved glucose tolerance in ArcPOMC-deficient mice. Therefore, the ArcPOMC-SNS-rGLUT2 axis is potentially an insulin-independent therapeutic target to control diabetes. PMID:26467632

  10. Enhanced glucose tolerance by intravascularly administered piceatannol in freely moving healthy rats.

    PubMed

    Oritani, Yukihiro; Okitsu, Teru; Nishimura, Eisaku; Sai, Masahiko; Ito, Tatsuhiko; Takeuchi, Shoji

    2016-02-12

    Piceatannol is a phytochemical in the seeds of passion fruit that has a hypoglycemic effect when orally administered. To elucidate the contribution of intact and metabolites of piceatannol after gastro-intestinal absorption to hypoglycemic effect, we examined the influence of piceatannol and isorhapontigenin on blood glucose concentrations during fasting and glucose tolerance tests by administering them intravascularly to freely moving healthy rats. We found that intravascularly administered piceatannol reduced the blood glucose concentrations during both fasting and glucose tolerance tests, but isorhapontigenin did not during either of them. Furthermore, we found that piceatannol increased the insulinogenic index during glucose tolerance tests and that piceatannol had no influence on insulin sensitivity by performing hyperinsulinemic euglycemic clamping tests. These results suggest that piceatannol orally intaken may enhance glucose tolerance by the effect of intact piceatannol through enhanced early-phase secretion of insulin. Therefore, oral intake of piceatannol might contribute to proper control of postprandial glycemic excursions in healthy subjects.

  11. Insulin Secretory Defect and Insulin Resistance in Isolated Impaired Fasting Glucose and Isolated Impaired Glucose Tolerance

    PubMed Central

    Aoyama-Sasabe, Sae; Fukushima, Mitsuo; Xin, Xin; Taniguchi, Ataru; Nakai, Yoshikatsu; Mitsui, Rie; Takahashi, Yoshitaka; Tsuji, Hideaki; Yabe, Daisuke; Yasuda, Koichiro; Kurose, Takeshi; Inagaki, Nobuya; Seino, Yutaka

    2016-01-01

    Objective. To investigate the characteristics of isolated impaired glucose tolerance (IGT) and isolated impaired fasting glucose (IFG), we analyzed the factors responsible for elevation of 2-hour postchallenge plasma glucose (2 h PG) and fasting plasma glucose (FPG) levels. Methods. We investigated the relationship between 2 h PG and FPG levels who underwent 75 g OGTT in 5620 Japanese subjects at initial examination for medical check-up. We compared clinical characteristics between isolated IGT and isolated IFG and analyzed the relationships of 2 h PG and FPG with clinical characteristics, the indices of insulin secretory capacity, and insulin sensitivity. Results. In a comparison between isolated IGT and isolated IFG, insulinogenic index was lower in isolated IGT than that of isolated IFG (0.43 ± 0.34 versus 0.50 ± 0.47, resp.; p < 0.01). ISI composite was lower in isolated IFG than that of isolated IGT (6.87 ± 3.38 versus 7.98 ± 4.03, resp.; p < 0.0001). In isolated IGT group, insulinogenic index showed a significant correlation with 2 h PG (r = −0.245, p < 0.0001) and had the strongest correlation with 2 h PG (β = −0.290). In isolated IFG group, ISI composite showed a significant correlation with FPG (r = −0.162, p < 0.0001) and had the strongest correlation with FPG (β = −0.214). Conclusions. We have elucidated that decreased early-phase insulin secretion is the most important factor responsible for elevation of 2 h PG levels in isolated IGT subjects, and decreased insulin sensitivity is the most important factor responsible for elevation of FPG levels in isolated IFG subjects. PMID:26788515

  12. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

    PubMed

    Grassi, Davide; Desideri, Giovambattista; Mai, Francesca; Martella, Letizia; De Feo, Martina; Soddu, Daniele; Fellini, Emanuela; Veneri, Mariangela; Stamerra, Cosimo A; Ferri, Claudio

    2015-11-18

    Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases. PMID:26126077

  13. Cocoa, glucose tolerance, and insulin signaling: cardiometabolic protection.

    PubMed

    Grassi, Davide; Desideri, Giovambattista; Mai, Francesca; Martella, Letizia; De Feo, Martina; Soddu, Daniele; Fellini, Emanuela; Veneri, Mariangela; Stamerra, Cosimo A; Ferri, Claudio

    2015-11-18

    Experimental and clinical evidence reported that some polyphenol-rich natural products may offer opportunities for the prevention and treatment of type 2 diabetes, due to their biological properties. Natural products have been suggested to modulate carbohydrate metabolism by various mechanisms, such as restoring β-cell integrity and physiology and enhancing insulin-releasing activity and glucose uptake. Endothelium is fundamental in regulating arterial function, whereas insulin resistance plays a pivotal role in pathophysiological mechanisms of prediabetic and diabetic states. Glucose and insulin actions in the skeletal muscle are improved by insulin-dependent production of nitric oxide, favoring capillary recruitment, vasodilatation, and increased blood flow. Endothelial dysfunction, with decreased nitric oxide bioavailability, is a critical step in the development of atherosclerosis. Furthermore, insulin resistance has been described, at least in part, to negatively affect endothelial function. Consistent with this, conditions of insulin resistance are usually linked to endothelial dysfunction, and the exposure of the endothelial cells to cardiovascular risk factors such as hypertension, dyslipidemia, and hyperglycemia is associated with reduced nitric oxide bioavailability, resulting in impaired endothelial-dependent vasodilatation. Moreover, endothelial dysfunction has been described as an independent predictor of cardiovascular risk and events. Cocoa and cocoa flavonoids may positively affect the pathophysiological mechanisms involved in insulin resistance and endothelial dysfunction with possible benefits in the prevention of cardiometabolic diseases.

  14. Impaired glucose tolerance: influence by environmental and hereditary factors.

    PubMed

    Cederholm, J; Wibell, L

    1991-01-01

    The influence on impaired glucose tolerance (IGT) by obesity, physical leisure time activity (PLTA), family histories of diabetes mellitus (DM) and other characteristics were evaluated in a health survey of 807 middle-aged females and males, with the rate of IGT 8.4% (WHO-criteria). Independent (adjusted for covariates) odds ratios concerning IGT were estimated. The ratios were 5.3 with the presence of obesity and 2.2. (ns) with low compared to high PLTA. In a subgroup of summarized environmental factors (obesity and low PLTA versus no obesity and high PLTA, n = 339), the independent odds ratio for IGT was 9.6 with obesity and low PLTA. With one 1st degree DM relative the odds ratio for IGT was 3.1. The ratio was increased both with the presence of relatives with non-insulin-dependent diabetes mellitus and with the presence of relatives with insulin-treated diabetes. Diabetic mothers yielded a higher ratio for IGT than diabetic fathers. In conclusion, the independent relative risk for IGT in this Swedish middle-aged urban sample was about two times higher with environmental factors (obesity only/obesity with low PLTA) than with one 1st degree DM relative.

  15. Effects of calcium channel blockers on glucose tolerance, inflammatory state, and circulating progenitor cells in non-diabetic patients with essential hypertension: a comparative study between Azelnidipine and amlodipine on glucose tolerance and endothelial function - a crossover trial (AGENT)

    PubMed Central

    2011-01-01

    Background Hypertension is associated with impaired glucose tolerance and insulin resistance. Medical treatment that interferes with various steps in the renin-angiotensin system improves glucose tolerance and insulin resistance. However, it remains unclear if long-acting calcium channel blockers (CCBs) such as azelnidipine and amlodipine affect glucose tolerance and insulin resistance in clinical practice. Methods Seventeen non-diabetic patients with essential hypertension who had controlled blood pressure levels using amlodipine (5 mg/day) were enrolled in this study. After randomization, either azelnidipine (16 mg/day) or amlodipine (5 mg/day) was administered in a crossover design for 12-weeks. At baseline and the end of each CCB therapy, samples of blood and urine were collected and 75 g oral glucose tolerance test (OGTT) was performed. In addition, hematopoietic progenitor cells (HPCs) were measured at each point by flow cytometry and endothelial functions were measured by fingertip pulse amplitude tonometry using EndoPAT. Results Although blood pressure levels were identical after each CCB treatment, the heart rate significantly decreased after azelnidipine administration than that after amlodipine administration (P < 0.005). Compared with amlodipine administration, azelnidipine significantly decreased levels of glucose and insulin 120 min after the 75 g OGTT (both P < 0.05). Serum levels of high-sensitivity C-reactive protein (P = 0.067) and interleukin-6 (P = 0.035) were decreased. Although endothelial functions were not different between the two medication groups, the number of circulating HPCs was significantly increased after azelnidipine administration (P = 0.016). Conclusions These results suggest that azelnidipine treatment may have beneficial effects on glucose tolerance, insulin sensitivity, the inflammatory state, and number of circulating progenitor cells in non-diabetic patients with essential hypertension. PMID:21906391

  16. Acidosis effects on insulin response during glucose tolerance tests in Jersey cows.

    PubMed

    Bigner, D R; Goff, J P; Faust, M A; Burton, J L; Tyler, H D; Horst, R L

    1996-12-01

    The effect of metabolic alkalosis and acidosis on insulin response to glucose tolerance tests was determined for cows fed a high cation diet to induce a state of metabolic acidosis. The anion diet to induce a state of metabolic acidosis. The glucose tolerance test (500 mg of glucose/kg of BW infused i.v. over 10 min) caused a rapid increase in plasma glucose and insulin concentrations. Plasma glucose concentrations were highest, and plasma insulin concentrations were lowest, during metabolic acidosis. These results suggest that insulin secretion is impaired during metabolic acidosis, which may reduce tissue uptake of glucose. Correction of metabolic acidosis by oral administration of sodium bicarbonate prior to glucose tolerance testing increased blood pH and bicarbonate concentrations and partially restored insulin response to the glucose tolerance test. Interestingly, sodium bicarbonate also caused an elevation in plasma cortisol concentrations. We concluded that glucose utilization is altered in cows with metabolic acidosis. The correction of acidosis associated with diseases such as diarrhea and ketosis may improve the therapeutic benefit of glucose infusions used to treat these diseases.

  17. Post-glucose-load urinary C-peptide and glucose concentration obtained during OGTT do not affect oral minimal model-based plasma indices.

    PubMed

    Jainandunsing, Sjaam; Wattimena, J L Darcos; Rietveld, Trinet; van Miert, Joram N I; Sijbrands, Eric J G; de Rooij, Felix W M

    2016-05-01

    The purpose of this study was to investigate how renal loss of both C-peptide and glucose during oral glucose tolerance test (OGTT) relate to and affect plasma-derived oral minimal model (OMM) indices. All individuals were recruited during family screening between August 2007 and January 2011 and underwent a 3.5-h OGTT, collecting nine plasma samples and urine during OGTT. We obtained the following three subgroups: normoglycemic, at risk, and T2D. We recruited South Asian and Caucasian families, and we report separate analyses if differences occurred. Plasma glucose, insulin, and C-peptide concentrations were analyzed as AUCs during OGTT, OMM estimate of renal C-peptide secretion, and OMM beta-cell and insulin sensitivity indices were calculated to obtain disposition indices. Post-glucose load glucose and C-peptide in urine were measured and related to plasma-based indices. Urinary glucose corresponded well with plasma glucose AUC (Cau r = 0.64, P < 0.01; SA r = 0.69, P < 0.01), S I (Cau r = -0.51, P < 0.01; SA r = -0.41, P < 0.01), Φ dynamic (Cau r = -0.41, P < 0.01; SA r = -0.57, P < 0.01), and Φ oral (Cau r = -0.61, P < 0.01; SA r = -0.73, P < 0.01). Urinary C-peptide corresponded well to plasma C-peptide AUC (Cau r = 0.45, P < 0.01; SA r = 0.33, P < 0.05) and OMM estimate of renal C-peptide secretion (r = 0.42, P < 0.01). In general, glucose excretion plasma threshold for the presence of glucose in urine was ~10-10.5 mmol L(-1) in non-T2D individuals, but not measurable in T2D individuals. Renal glucose secretion during OGTT did not influence OMM indices in general nor in T2D patients (renal clearance range 0-2.1 %, with median 0.2 % of plasma glucose AUC). C-indices of urinary glucose to detect various stages of glucose intolerance were excellent (Cau 0.83-0.98; SA 0.75-0.89). The limited role of renal glucose secretion validates the neglecting of urinary glucose secretion in kinetic models of glucose homeostasis using plasma glucose concentrations. Both C

  18. Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age.

    PubMed

    Coon, P J; Rogus, E M; Drinkwater, D; Muller, D C; Goldberg, A P

    1992-10-01

    The relationships of body composition and physical fitness [maximal aerobic capacity (VO2max)] to the decline in insulin sensitivity with age were examined in healthy older (47-73 yr; n = 36) and young (19-36 yr; n = 13) men. In 18 older men with normal glucose tolerance (OGTT), glucose disposal rates (M) during hyperinsulinemic euglycemic clamps correlated negatively with the waist to hip ratio (WHR; r = -0.77; P < .001) and percent body fat (r = -0.46; P < 0.05) and positively with VO2max (r = 0.54; P < 0.05), but not with age. Similar relationships existed in the 36 older men with a spectrum of OGTT responses; however, only WHR was independently related to M (r2 = 0.32; P < 0.01). In the older men with normal OGTT, M (mean +/- SEM, 7.88 +/- 0.43 mg/kg fat-free mass.min) was not different from that in the young men (8.56 +/- 0.47; P = NS). Furthermore, in older and young men with normal OGTT matched for WHR, percent fat, or VO2max, glucose disposal was comparable at sequential 15-min intervals during the clamp and in its relationship to insulin concentrations at the tissue level (multicompartmental analysis). In contrast, despite higher steady state plasma insulin levels during the clamp, M was significantly lower in the older men with a higher WHR, greater percent fat, lower VO2max, or impaired OGTT. Thus, in healthy older men up to the age of 73 yr, insulin sensitivity and glucose tolerance are affected primarily by the regional body fat distribution, not age, obesity, or VO2max.

  19. Glucose tolerance: hypothesis testing on Malaysian diabetic community.

    PubMed

    Gillani, Syed Wasif; Sari, Yelly Oktavia; Sulaiman, Syed Azhar Syed; Baig, Mirza R

    2014-01-01

    Our study objective was to evaluate glucose tolerance and effecting factors among diabetes patients' with home care program (PHCP) in Malaysian community. A 24-week longitudinal quasi-experimental -single blind - pre/post-test study design was used to assess the effectiveness of a diabetes education program to enhance self-care practices. An attrition rate of 25% implied longitudinal design of the study in the calculation of sample size. Hence the sample size of the study was 106 subjects (53 cases and 53 focus group). The level of significance was set at 0.05. Ethical clearance had been made prior to conducting this study. Of the 109 subjects who met the study-entry criteria, 3 subjects declined to participate due to lack of time and interest. No significant parameters were revealed in the demographic and clinical characteristics of participants who completed the study. Focus group showed significant reduction in HbA1c value with mean 1.1% as compared to cases with a mean 0.06%. Similarly, hypothesis on self-care management suggest significantly improved practices among focus group [M=2.94, SD=2.25] for case group M=0.47, SD=1.36; t[127.64]=-8.23, p≤0.001] with moderate effect size [eta squared=0.06]. Total physical activity was defined as the combination of non-leisure and leisure activities. There was a statistically significant difference for increase in total physical levels between the focus [M=14.01, SD=6.41] and case groups [13.21, SD=5.22; t[148.04]=-3.15, p=0.002] with no difference in the non-leisure activity [p=0.43]. As for the case group, there was no significant difference in SMBG practices from baseline [M=0.70, SD=1.35] to follow-up [M=0.47, SD=1.36, t[72]=0.97, P=0.34] and no relationship was found between the number of blood glucose tests done with demographic or clinical variables. This study offered improved self-care practices and physical activity after PHCP but with problematic dietary care. This might be due to social and cultural habits

  20. Valine Pyrrolidide Preserves Intact Glucose-Dependent Insulinotropic Peptide and Improves Abnormal Glucose Tolerance in Minipigs With Reduced β-Cell Mass

    PubMed Central

    Rolin, Bidda; Ribel, Ulla; Wilken, Michael; Deacon, Carolyn F.; Svendsen, Ove; Gotfredsen, Carsten F.; Carr, Richard David

    2003-01-01

    The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are important in blood glucose regulation.However, both incretin hormones are rapidly degraded by the enzyme dipeptidyl peptidase IV (DPPIV). The concept of DPPIV inhibition as a treatment for type 2 diabetes was evaluated in a new large animal model of insulin-deficient diabetes and reduced β-cell mass, the nicotinamide (NIA) (67 mg/kg) and streptozotocin (STZ) (125 mg/kg)–treated minipig, using the DPPIV inhibitor, valine pyrrolidide (VP) (50 mg/kg).VP did not significantly affect levels of intact GLP-1 but increased levels of intact GIP (from 4543 ± 1880 to 9208 ± 3267 pM × min; P<.01), thus improving glucose tolerance (area under the curve [AUC] for glucose reduced from 1904 ± 480 to 1582 ± 353 mM × min;P = .05).VP did not increase insulin levels during the oral glucose tolerance test (OGTT) but increased the insulinogenic index in normal animals (from 83 ± 42 to 192 ± 108; P < .05), but not after NIA + STZ, possibly because of less residual insulin secretory capacity in these animals. GIP seems to contribute to the antihyperglycemic effect of VP in this model; however, additional mechanisms for the effect of DPPIV inhibition cannot be excluded. The authors conclude that DPPIV inhibitors may be useful to treat type 2 diabetes, even when this is due to reduced β-cell mass. PMID:14630571

  1. Perfluorooctanoic acid exposure for 28 days affects glucose homeostasis and induces insulin hypersensitivity in mice

    NASA Astrophysics Data System (ADS)

    Yan, Shengmin; Zhang, Hongxia; Zheng, Fei; Sheng, Nan; Guo, Xuejiang; Dai, Jiayin

    2015-06-01

    Perfluoroalkyl acids (PFAAs) are widely used in many applications due to their unique physical and chemical characteristics. Because of the increasing prevalence of metabolic syndromes, including obesity, dyslipidemia and insulin resistance, concern has arisen about the roles of environmental pollutants in such diseases. Earlier epidemiologic studies showed a potential association between perfluorooctanoic acid (PFOA) and glucose metabolism, but how PFOA influences glucose homeostasis is still unknown. Here, we report on the modulation of the phosphatidylinositol 3-kinase-serine/threonine protein kinase (PI3K-AKT) signaling pathway in the livers of mice after 28 d of exposure to PFOA. Compared with normal mice, PFOA exposure significantly decreased the expression of the phosphatase and tensin homologue (PTEN) protein and affected the PI3K-AKT signaling pathway in the liver. Tolerance tests further indicated that PFOA exposure induced higher insulin sensitivity and glucose tolerance in mice. Biochemical analysis revealed that PFOA exposure reduced hepatic glycogen synthesis, which might be attributed to gluconeogenesis inhibition. The levels of several circulating proteins were altered after PFOA exposure, including proteins potentially related to diabetes and liver disease. Our results suggest that PFOA affected glucose metabolism and induced insulin hypersensitivity in mice.

  2. Factors Affecting Accuracy and Time Requirements of a Glucose Oxidase-Peroxidase Assay for Determination of Glucose

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Accurate and rapid assays for glucose are desirable for analysis of glucose and starch in food and feedstuffs. An established colorimetric glucose oxidase-peroxidase method for glucose was modified to reduce analysis time, and evaluated for factors that affected accuracy. Time required to perform t...

  3. Acute Effects of Decaffeinated Coffee and the Major Coffee Components Chlorogenic Acid and Trigonelline on Glucose Tolerance

    PubMed Central

    van Dijk, Aimée E.; Olthof, Margreet R.; Meeuse, Joke C.; Seebus, Elin; Heine, Rob J.; van Dam, Rob M.

    2009-01-01

    OBJECTIVE Coffee consumption has been associated with lower risk of type 2 diabetes. We evaluated the acute effects of decaffeinated coffee and the major coffee components chlorogenic acid and trigonelline on glucose tolerance. RESEARCH DESIGN AND METHODS We conducted a randomized crossover trial of the effects of 12 g decaffeinated coffee, 1 g chlorogenic acid, 500 mg trigonelline, and placebo (1 g mannitol) on glucose and insulin concentrations during a 2-h oral glucose tolerance test (OGTT) in 15 overweight men. RESULTS Chlorogenic acid and trigonelline ingestion significantly reduced glucose (−0.7 mmol/l, P = 0.007, and −0.5 mmol/l, P = 0.024, respectively) and insulin (−73 pmol/l, P = 0.038, and −117 pmol/l, P = 0.007) concentrations 15 min following an OGTT compared with placebo. None of the treatments affected insulin or glucose area under the curve values during the OGTT compared with placebo. CONCLUSIONS Chlorogenic acid and trigonelline reduced early glucose and insulin responses during an OGTT. PMID:19324944

  4. Acute hyperglycemia alters von Willebrand factor but not the fibrinolytic system in elderly subjects with normal or impaired glucose tolerance.

    PubMed

    Coppola, Ludovico; Coppola, Antonino; Grassia, Antonio; Mastrolorenzo, Luigia; Lettieri, Biagio; De Lucia, Domenico; De Nanzio, Annarita; Gombos, Giorgio

    2004-10-01

    To assess whether acute hyperglycemia affects fibrinolytic balance in elderly subjects with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT), 40 non-obese elderly subjects (20 NGT, age 68 +/- 8 years; and 20 IGT, age 69 +/- 11 years) were studied. On two experimental days, randomly allocated and spaced 1 week apart, plasma concentrations of glucose, insulin, fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor type 1 and von Willebrand factor (vWF) were measured in each subject at baseline (0) and 30, 60, 90, 120 min after the ingestion of 75 g glucose or a similarly sweet dose of aspartame (250 mg) (control test). In both NGT and IGT elderly subjects, tissue plasminogen activator, plasminogen activator inhibitor type 1 and fibrinogen plasma levels did not significantly change after both oral aspartame and glucose load. In IGT subjects, vWF plasmatic levels decreased after glucose (not aspartame) oral load, reaching the minimum level at 90 min after load (82.7 +/- 7.8 versus 93.7 +/- 10.2, P <0.01). These results demonstrate that acute hyperglycemia does not modify plasma fibrinolysis in elderly subjects. The decrease of plasma concentration of vWF in IGT elderly subjects requires cautious interpretation and further extensive investigations.

  5. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    SciTech Connect

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-03-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific /sup 125/I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific /sup 125/I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity.

  6. Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion.

    PubMed Central

    Zenobi, P D; Graf, S; Ursprung, H; Froesch, E R

    1992-01-01

    Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia. PMID:1601998

  7. Electroacupuncture improves glucose tolerance through cholinergic nerve and nitric oxide synthase effects in rats.

    PubMed

    Lin, Rong-Tsung; Chen, Ching-Yuan; Tzeng, Chung-Yuh; Lee, Yu-Chen; Cheng, Yu-Wen; Chen, Ying-I; Ho, Wai-Jane; Cheng, Juei-Tang; Lin, Jaung-Geng; Chang, Shih-Liang

    2011-04-25

    The purpose of this investigation was to evaluate the effect and mechanisms of electroacupuncture (EA) at the bilateral Zusanli acupoints (ST-36) on glucose tolerance in normal rats. Intravenous glucose tolerance test (IVGTT) was performed to examine the effects of electroacupuncture (EA) on glucose tolerance in rats. The EA group underwent EA at the ST-36, with settings of 15 Hz, 10 mA, and 60 min; the control group underwent the same treatments, but without EA. Atropine, hemicholinium-3 (HC-3) or NG-nitro-L-arginine methyl ester (L-NAME) were injected into the rats alone or simultaneously and EA was performed to investigate differences in plasma glucose levels compared to the control group. Plasma samples were obtained for assaying plasma glucose and free fatty acid (FFA) levels. Western blot was done to determine the insulin signal protein and nNOS to exam the correlation between EA and improvement in glucose tolerance. The EA group had significantly lower plasma glucose levels compared to the control group. Plasma glucose levels differed significantly between the EA and control groups after the administration of L-NAME, atropine, or HC-3 treatments alone, but there were no significant differences in plasma glucose with combined treatment of L-NAME and atropine or L-NAME and HC-3. EA decreased FFA levels and enhanced insulin signal protein (IRS1) and nNOS activities in skeletal muscle during IVGTT. In summary, EA stimulated cholinergic nerves and nitric oxide synthase for lowering plasma FFA levels to improve glucose tolerance. PMID:21376780

  8. Serum progranulin concentrations are not responsive during oral lipid tolerance test and oral glucose tolerance test.

    PubMed

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2015-07-01

    The postprandial regulation of progranulin by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of progranulin in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn at 0 hours (h) (fasting) and at 2, 4, and 6 h in OLTT or 1 and 2 h in OGTT. A novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of progranulin were measured by enzyme-linked immunosorbent assay (ELISA). Circulating progranulin levels remained unchanged during OLTT and OGTT. Fasting progranulin levels ranged between 31.3±8.7 and 40.6±7.7 ng/ml and were not different in subgroups addressing BMI, gender, family history, smoking habits, and hormonal contraception. There was a reciprocal correlation of progranulin with HDL (negative) and LDL cholesterol levels (positive). In healthy adults, fasting and postprandial circulating progranulin levels are not different in BMI subgroups. Oral uptake of carbohydrates and lipids does not influence circulating progranulin levels in a short-term manner. A postprandial and short-term regulation of this adipokine is absent, at least in healthy subjects. There is a negative correlation of progranulin with HDL cholesterol, but a positive correlation with LDL cholesterol. This reciprocal association might be of physiological importance for an individual's atherosclerotic risk. PMID:25565096

  9. Evolution of Glucose Tolerance After Treatment of Acromegaly: A Study in 57 Patients.

    PubMed

    Jonas, C; Maiter, D; Alexopoulou, O

    2016-05-01

    The aim of our study was to evaluate the evolution of glucose metabolism in 57 patients after treatment of their acromegaly and to determine risk factors for the persistence of abnormal glucose tolerance. Therefore, we performed IGF-I measurements, oral glucose tolerance tests (OGTTs), and HOMA to evaluate insulin sensitivity (HOMA-S) and β-cell function (HOMA-β) at diagnosis and at last visit (median follow-up 7 years). At diagnosis of acromegaly, 14 patients (25%) were diabetic and 15 (26%) had impaired glucose tolerance, whereas at the last visit, 32% were diabetic and 26% remained glucose intolerant. There was a decrease in fasting glucose (median - 7.0 mg/dl) in the 20 patients cured by surgery, whereas it increased in the 28 patients controlled under medical therapy (median + 2.0 mg/dl; p<0.05 vs. cured group) and in the 9 patients with active disease (median + 4.0 mg/dl). Loss of β-cell function was more pronounced in the patients under medical treatment (median - 87.9%) vs. the cured group (median - 30.4%; p<0.05). There was a decrease in HbA1c between diagnosis and last visit in patients under pegvisomant (mean - 19.2 mmol/mol) vs. a small increase in patient treated by somatostatin analogues (+ 3.4 mmol/mol; p<0.05). Independent risk factors for persistent abnormal glucose tolerance were the glucose tolerance status at diagnosis and ongoing treatment with somatostatin analogues. In conclusion, we found that more than 50% of patients still have IGT or diabetes after treatment of acromegaly. Improvement of glucose metabolism is mainly observed in cured patients and in patients treated with pegvisomant. PMID:26849822

  10. Glucose tolerance and peripheral glucose utilization in rainbow trout (Oncorhynchus mykiss), American eel (Anguilla rostrata), and black bullhead catfish (Ameiurus melas).

    PubMed

    Legate, N J; Bonen, A; Moon, T W

    2001-04-01

    This study tests the hypothesis that glucose tolerance in fish is related to nutrient preference and is correlated with white muscle glucose transporter and phosphorylation (hexokinase) activities. Glucose clearance was investigated in the carnivorous rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata) (feeding and fasting) and the omnivorous black bullhead catfish (Ameiurus melas). Glucose tolerance was assessed by an intravenous glucose tolerance test, injecting 250 mg glucose/kg body weight and tracking blood glucose concentrations over 24 h. Both feeding eel and feeding catfish returned plasma glucose levels to baseline within 60 min of glucose injection. Glucose values remained elevated for more than 360 min in both the food-deprived eel and the feeding rainbow trout. Glucose transport studies in white muscle membrane vesicles provided evidence for the presence of a stereospecific, saturable glucose transporter in all three species. Affinity constants (K(m)) ranged from 8 to 14 mM while V(max) values ranged from 75 to 150 pmol/s/mg protein. Neither kinetic parameter differed significantly between species. Cytochalasin B and phloretin did not significantly inhibit glucose transport, implying that these transporters are unlike the mammalian muscle glucose transporters (GLUT). In fact, Northern and Western blot analyses of mRNA and protein from white and red muscles and heart did not detect a mammalian-type GLUT-1 or -4 in any of the species examined. Glucose phosphorylation indicated the presence of a hexokinase activity (low K(m) enzyme) but again there were no differences in kinetic parameters between species. These studies demonstrate that glucose tolerance in fish is species-dependent but none of the parameters examined clearly differentiate between the species examined. Certainly a stereospecific glucose transporter exists in white skeletal muscle of the fish studied but no molecular or kinetic similarities to the mammalian GLUTs were

  11. Impaired glucose tolerance in rats fed low-carbohydrate, high-fat diets.

    PubMed

    Bielohuby, Maximilian; Sisley, Stephanie; Sandoval, Darleen; Herbach, Nadja; Zengin, Ayse; Fischereder, Michael; Menhofer, Dominik; Stoehr, Barbara J M; Stemmer, Kerstin; Wanke, Rüdiger; Tschöp, Matthias H; Seeley, Randy J; Bidlingmaier, Martin

    2013-11-01

    Moderate low-carbohydrate/high-fat (LC-HF) diets are widely used to induce weight loss in overweight subjects, whereas extreme ketogenic LC-HF diets are used to treat neurological disorders like pediatric epilepsy. Usage of LC-HF diets for improvement of glucose metabolism is highly controversial; some studies suggest that LC-HF diets ameliorate glucose tolerance, whereas other investigations could not identify positive effects of these diets or reported impaired insulin sensitivity. Here, we investigate the effects of LC-HF diets on glucose and insulin metabolism in a well-characterized animal model. Male rats were fed isoenergetic or hypocaloric amounts of standard control diet, a high-protein "Atkins-style" LC-HF diet, or a low-protein, ketogenic, LC-HF diet. Both LC-HF diets induced lower fasting glucose and insulin levels associated with lower pancreatic β-cell volumes. However, dynamic challenge tests (oral and intraperitoneal glucose tolerance tests, insulin-tolerance tests, and hyperinsulinemic euglycemic clamps) revealed that LC-HF pair-fed rats exhibited impaired glucose tolerance and impaired hepatic and peripheral tissue insulin sensitivity, the latter potentially being mediated by elevated intramyocellular lipids. Adjusting visceral fat mass in LC-HF groups to that of controls by reducing the intake of LC-HF diets to 80% of the pair-fed groups did not prevent glucose intolerance. Taken together, these data show that lack of dietary carbohydrates leads to glucose intolerance and insulin resistance in rats despite causing a reduction in fasting glucose and insulin concentrations. Our results argue against a beneficial effect of LC-HF diets on glucose and insulin metabolism, at least under physiological conditions. Therefore, use of LC-HF diets for weight loss or other therapeutic purposes should be balanced against potentially harmful metabolic side effects.

  12. The influence on cognition of the interaction between the macro-nutrient content of breakfast and glucose tolerance.

    PubMed

    Nabb, Samantha; Benton, David

    2006-01-30

    Previously it has been found that both missing breakfast and having poorer glucose tolerance were associated with better memory. The present study therefore examined the impact of eight breakfasts, in a factorial design, that contained either high or low levels of carbohydrate, fat or protein. The meals were designed to vary the rate of release of glucose into the blood stream. Memory, reaction times and vigilance were assessed 30, 75 and 120 min following breakfast. Using fasting blood glucose levels as a measure of glucose tolerance, better memory was found to be associated with better glucose tolerance and the consumption of meals that more slowly release glucose into the blood. The effects of the meals on reaction times and vigilance were opposite to those with memory in that higher levels of blood glucose tended to be associated with better performance. It was concluded that individual differences in glucose tolerance interact with the glycaemic load of a meal to influence cognitive functioning. PMID:16225896

  13. Detecting Prediabetes and Diabetes: Agreement between Fasting Plasma Glucose and Oral Glucose Tolerance Test in Thai Adults

    PubMed Central

    Aekplakorn, Wichai; Tantayotai, Valla; Numsangkul, Sakawduan; Sripho, Wilarwan; Tatsato, Nutchanat; Burapasiriwat, Tuanjai; Pipatsart, Rachada; Sansom, Premsuree; Luckanajantachote, Pranee; Chawarokorn, Pongpat; Thanonghan, Anek; Lakhamkaew, Watchira; Mungkung, Aungsumalin; Boonkean, Rungnapa; Chantapoon, Chanidsa; Kungsri, Mayuree; Luanseng, Kasetsak; Chaiyajit, Kornsinun

    2015-01-01

    Aim. To evaluate an agreement in identifying dysglycemia between fasting plasma glucose (FPG) and the 2 hr postprandial glucose tolerance test (OGTT) in a population with high risk of diabetes. Methods. A total of 6,884 individuals aged 35–65 years recruited for a community-based diabetes prevention program were tested for prediabetes including impaired fasting glucose (IFG) or impaired glucose tolerance (IGT), and diabetes. The agreement was assessed by Kappa statistics. Logistic regression was used to examine factors associated with missed prediabetes and diabetes by FPG. Results. A total of 2671 (38.8%) individuals with prediabetes were identified. The prevalence of prediabetes identified by FPG and OGTT was 32.2% and 22.3%, respectively. The proportions of diabetes classified by OGTT were two times higher than those identified by FPG (11.0% versus 5.4%, resp.). The Kappa statistics for agreement of both tests was 0.55. Overall, FPG missed 46.3% of all prediabetes and 54.7% of all diabetes cases. Prediabetes was more likely to be missed by FPG among female, people aged <45 yrs, and those without family history of diabetes. Conclusion. The detection of prediabetes and diabetes using FPG only may miss half of the cases. Benefit of adding OGTT to FPG in some specific groups should be confirmed. PMID:26347060

  14. Ampicillin-Improved Glucose Tolerance in Diet-Induced Obese C57BL/6NTac Mice Is Age Dependent

    PubMed Central

    Rune, I.; Hansen, C. H. F.; Ellekilde, M.; Nielsen, D. S.; Skovgaard, K.; Rolin, B. C.; Lykkesfeldt, J.; Josefsen, K.; Tranberg, B.; Kihl, P.; Hansen, A. K.

    2013-01-01

    Ampicillin has been shown to improve glucose tolerance in mice. We hypothesized that this effect is present only if treatment is initiated prior to weaning and that it disappears when treatment is terminated. High-fat fed C57BL/6NTac mice were divided into groups that received Ampicillin at different ages or not at all. We found that both diet and Ampicillin significantly changed the gut microbiota composition in the animals. Furthermore, there was a significant improvement in glucose tolerance in Ampicillin-treated, five-week-old mice compared to nontreated mice in the control group. At study termination, expressions of mRNA coding for tumor necrosis factor, serum amyloid A, and lactase were upregulated, while the expression of tumor necrosis factor (ligand) superfamily member 15 was downregulated in the ileum of Ampicillin-treated mice. Higher dendritic cell percentages were found systemically in high-fat diet mice, and a lower tolerogenic dendritic cell percentage was found both in relation to high-fat diet and late Ampicillin treatment. The results support our hypothesis that a “window” exists early in life in which an alteration of the gut microbiota affects glucose tolerance as well as development of gut immunity and that this window may disappear after weaning. PMID:24369539

  15. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  16. Hepatocyte retinoid X receptor-alpha-deficient mice have reduced food intake, increased body weight, and improved glucose tolerance.

    PubMed

    Wan, Yu-Jui Yvonne; Han, Guang; Cai, Yan; Dai, Tiane; Konishi, Tamiko; Leng, Ai-She

    2003-02-01

    Hepatocyte retinoid X receptor (RXR)alpha-deficient mice and wild-type mice were fed either a regular or a high-saturated-fat diet for 12 wk to study the functional role of hepatocyte RXRalpha in fatty acid and carbohydrate metabolism. Food intake was significantly reduced in hepatocyte RXRalpha-deficient mice when either diet was used. The amount of food intake was negatively associated with serum leptin level. Although mutant mice ate less, body weight and fat content were significantly higher in mutant than wild-type mice. Examination of the expression of peroxisome proliferator-activated receptor-alpha target genes indicated that the peroxisome proliferator-activated receptor-alpha-mediated pathway was compromised in the mutant mice, which, in turn, might affect fatty-acid metabolism and result in increased body weight and fat content. Although mutant mice were obese, they demonstrated the same degree of insulin sensitivity and the same level of serum insulin as the wild-type mice. However, these mutant mice have improved glucose tolerance. To explore a mechanism that may be responsible for the improved glucose tolerance, serum IGF-I level was examined. Serum IGF-1 level was significantly increased in mutant mice compared with wild-type mice. Taken together, hepatocyte RXRalpha deficiency increases leptin level and reduces food intake. Those mice also develop obesity, with an unexpected improvement of glucose tolerance. The result also suggests that an increase in serum IGF-I level might be one of the mechanisms leading to improved glucose tolerance in hepatocyte RXRalpha-deficient mice.

  17. Long-Term Feeding of Chitosan Ameliorates Glucose and Lipid Metabolism in a High-Fructose-Diet-Impaired Rat Model of Glucose Tolerance.

    PubMed

    Liu, Shing-Hwa; Cai, Fang-Ying; Chiang, Meng-Tsan

    2015-12-10

    This study was designed to investigate the effects of long-term feeding of chitosan on plasma glucose and lipids in rats fed a high-fructose (HF) diet (63.1%). Male Sprague-Dawley rats aged seven weeks were used as experimental animals. Rats were divided into three groups: (1) normal group (normal); (2) HF group; (3) chitosan + HF group (HF + C). The rats were fed the experimental diets and drinking water ad libitum for 21 weeks. The results showed that chitosan (average molecular weight was about 3.8 × 10⁵ Dalton and degree of deacetylation was about 89.8%) significantly decreased body weight, paraepididymal fat mass, and retroperitoneal fat mass weight, but elevated the lipolysis rate in retroperitoneal fats of HF diet-fed rats. Supplementation of chitosan causes a decrease in plasma insulin, tumor necrosis factor (TNF)-α, Interleukin (IL)-6, and leptin, and an increase in plasma adiponectin. The HF diet increased hepatic lipids. However, intake of chitosan reduced the accumulation of hepatic lipids, including total cholesterol (TC) and triglyceride (TG) contents. In addition, chitosan elevated the excretion of fecal lipids in HF diet-fed rats. Furthermore, chitosan significantly decreased plasma TC, low-density lipoprotein cholesterol (LDL-C), very-low-density lipoprotein cholesterol (VLDL-C), the TC/high-density lipoprotein cholesterol (HDL-C) ratio, and increased the HDL-C/(LDL-C + VLDL-C) ratio, but elevated the plasma TG and free fatty acids concentrations in HF diet-fed rats. Plasma angiopoietin-like 4 (ANGPTL4) protein expression was not affected by the HF diet, but it was significantly increased in chitosan-supplemented, HF-diet-fed rats. The high-fructose diet induced an increase in plasma glucose and impaired glucose tolerance, but chitosan supplementation decreased plasma glucose and improved impairment of glucose tolerance and insulin tolerance. Taken together, these results indicate that supplementation with chitosan can improve the impairment of

  18. The impact of years since menopause on the development of impaired glucose tolerance.

    PubMed

    Wu, S I; Chou, P; Tsai, S T

    2001-02-01

    This is a community-based population survey carried out by the Yang-Ming Crusade to investigate the impact of years since menopause on the development of glucose intolerance in post-menopausal women. A total of 5412 women were screened with fasting plasma glucose. Those with fasting plasma glucose levels between 5.5 and 7.8 mM were given an oral glucose tolerance test. Among the 5412 women screened, 2039 (37.7%) were post-menopausal with a median age at menopause of 49 years. Pre-menopausal women showed impaired glucose tolerance (IGT) and diabetes mellitus (DM) prevalences of 3.7% and 3.1% respectively, whereas the corresponding figures for post-menopausal women were 8.4% and 17.6%, respectively. Comparing DM versus normal glucose tolerance (NGT) and IGT versus NGT as dependent variables in logistic regression analysis, menopause status was significantly associated with DM and IGT. In post-menopausal women, after maintaining body mass index, waist-hip ratio, systolic blood pressure, diastolic blood pressure, family history of DM, age at menopause, cholesterol, high density lipoprotein cholesterol and triglycerides as controls, years since menopause was the only significant factor associated with IGT (OR = 1.05, 95%CI 1.01-1.08) and years since menopause was not associated with DM. Further analysis indicated years since menopause (OR = 1.06, 95%CI, 1.01-1.11) was the only factor significantly associated with IGT for women whose age at menopause was greater than 49 years. Our study indicates that in subjects who have not undergone hormone replacement therapy and whose age at menopause is greater than 49 years, an increase in years since menopause confers a negative influence on glucose tolerance and increases the risk of IGT by 6% for each year after menopause.

  19. Effect of a Prolonged Altitude Expedition on Glucose Tolerance and Abdominal Fatness

    ERIC Educational Resources Information Center

    Chen, Mu-Tsung; Lee, Wen-Chih; Chen, Shih-Chang; Chen, Chiu-Chou; Chen, Chung-Yu; Lee, Shin-Da; Jensen, Jorgen; Kuo, Chia-Hua

    2010-01-01

    In the present study, we investigated the effect of a long-term mountain expedition on glucose tolerance and insulin action. Twelve registered mountaineers ages 31 years (SD = 1.1) participated in a 25-day expedition at a 2,200-3,800-m altitude with an average duration of 8 hr per day. Arterial oxygen saturation (SaO[subscript 2]) was…

  20. GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

    PubMed Central

    Altinova, Alev Eroglu; Akturk, Mujde; Gulbahar, Ozlem; Arslan, Emre; Ors Sendogan, Damla; Yetkin, Ilhan; Toruner, Fusun Balos

    2016-01-01

    Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state.

  1. GDF-15 and Hepcidin Levels in Nonanemic Patients with Impaired Glucose Tolerance

    PubMed Central

    Altinova, Alev Eroglu; Akturk, Mujde; Gulbahar, Ozlem; Arslan, Emre; Ors Sendogan, Damla; Yetkin, Ilhan; Toruner, Fusun Balos

    2016-01-01

    Aims. Growth Differentiation Factor-15 (GDF-15) has been suggested as one of the regulators of hepcidin, an important regulatory peptide for iron deposition. Current data is conflicting about the relationship between hepcidin and disorders of glucose metabolism. We aimed to investigate serum hepcidin and GDF-15 concentrations and their associations with each other, in nonanemic subjects with impaired glucose tolerance (IGT) in comparison with the nonanemic subjects with normal glucose tolerance (NGT). Methods. Thirty-seven subjects with IGT and 32 control subjects with NGT, who were age-, gender-, and body mass index- (BMI-) matched, were included in the study. Results. Serum GDF-15 levels were significantly higher in IGT compared to NGT. There were no differences in hepcidin, interleukin-6, and high sensitive C-reactive protein levels between the groups. We found a positive correlation between GDF-15 and hepcidin levels. There were also positive correlations between GDF-15 and age, uric acid, creatinine, and area under the curve for glucose (AUC-G). Hepcidin was correlated positively with ferritin levels. In the multiple regression analysis, GDF-15 concentrations were independently associated with age, uric acid, and AUC-G. Conclusions. Impaired glucose tolerance is associated with increased GDF-15 levels even in the absence of anemia, but the levels of hepcidin are not significantly altered in prediabetic state. PMID:27642607

  2. Diabetes, impaired glucose tolerance, and metabolic biomarkers in individuals with normal glucose tolerance are inversely associated with lung function: the Jackson Heart Study.

    PubMed

    Hickson, DeMarc A; Burchfiel, Cecil M; Liu, Jiankang; Petrini, Marcy F; Harrison, Kimystian; White, Wendy B; Sarpong, Daniel F

    2011-08-01

    The objectives of this study were to test the hypothesis that diabetes and impaired glucose tolerance (IGT), diabetes control and diabetes duration, and metabolic biomarkers in adults with normal glucose tolerance (NGT) are inversely associated with spirometry-measured lung function. We conducted a cross-sectional observational cohort study that included nonsmoking African American adults (n = 2,945; mean age = 52.5 ± 12.6 years; 69.2% female), who were free of cardiovascular disease, from the Jackson Heart Study. The interventions were diabetes, metabolic biomarkers and lung function. We measured the associations of glycemia with forced expiratory volume (FEV) in 1 s, FEV in 6 s, and vital capacity. Multivariable adjusted mean lung function values were lower among adults with diabetes and IGT (in women only, but not after adjustment for waist circumference) than adults with NGT. Among adults with diabetes, no associations were observed between lung function and diabetes control or duration. In women with NGT, lower lung function was consistently associated with higher glucose levels and less consistently with higher insulin levels and insulin resistance. Lower lung function was consistently associated with higher insulin levels and insulin resistance and less consistently associated with insulin and hemoglobin A1c in men with NGT. Overall, our findings generally support the hypothesis that diabetes, IGT, and increased levels of metabolic biomarkers in individuals with NGT are inversely associated with lung function in African Americans, independent of adiposity.

  3. Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119.

    PubMed

    Park, Eun-Young; Kim, Eung-Hwi; Kim, Chul-Young; Kim, Mi-Hwi; Choung, Jin-Seung; Oh, Yoon-Sin; Moon, Hong-Sub; Jun, Hee-Sook

    2016-01-01

    G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. We screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo. Human GPR119 activation was measured in GeneBLAzer T-Rex GPR119-CRE-bla CHO-K1 cells; intracellular cAMP levels and insulin secretion were measured in INS-1 cells; and GLP-1 release was measured in GLUTag cells. Glucose tolerance tests and serum plasma insulin levels were measured in normal C57BL6 mice and diabetic db/db mice. AD extract-treated cells showed significant increases in GPR119 activation, intracellular cAMP levels, GLP-1 levels and glucose-stimulated insulin secretion as compared with controls. In normal mice, a single treatment with AD extract improved glucose tolerance and increased insulin secretion. Treatment with multiple doses of AD extract or n-hexane fraction improved glucose tolerance in diabetic db/db mice. Imperatorin, phellopterin and isoimperatorin were identified in the active fraction of AD extract. Among these, phellopterin activated GPR119 and increased active GLP-1 and insulin secretion in vitro and enhanced glucose tolerance in normal and db/db mice. We suggest that phellopterin might have a therapeutic potential for the treatment of type 2 diabetes. PMID:27391814

  4. Metabolic inflexibility is a common feature of impaired fasting glycaemia and impaired glucose tolerance.

    PubMed

    Færch, Kristine; Vaag, Allan

    2011-12-01

    Metabolic flexibility reflects the ability to switch from lipid to carbohydrate oxidation during insulin stimulation. Impaired metabolic flexibility is related to insulin resistance and type 2 diabetes, but whether metabolic flexibility is impaired in individuals with the pre-diabetic states isolated impaired fasting glycaemia (i-IFG) and isolated impaired glucose tolerance (i-IGT) is unknown. Using the gold standard euglycaemic hyperinsulinaemic clamp technique combined with indirect calorimetry, we measured peripheral insulin sensitivity, lipid and glucose oxidation, and thus metabolic flexibility in 66 individuals with normal glucose tolerance (NGT, n = 20), i-IFG (n = 18) and i-IGT (n = 28). During insulin stimulation, individuals with i-IGT displayed reduced insulin sensitivity including reduced glucose oxidation. Interestingly, those with i-IFG exhibited reduced glucose oxidation and a slightly elevated lipid oxidation rate during insulin infusion despite having normal total peripheral glucose disposal. Thus, metabolic flexibility was significantly reduced in individuals with both i-IFG and i-IGT even after adjustment for BMI and insulin sensitivity. The data indicate that metabolic inflexibility may precede the development of overt peripheral insulin resistance in pre-diabetic individuals. However, prospective studies are needed to confirm this notion. PMID:21207234

  5. Pre-germinated brown rice reduced both blood glucose concentration and body weight in Vietnamese women with impaired glucose tolerance.

    PubMed

    Bui, Thi Nhung; Le, Thi Hop; Nguyen, Do Huy; Tran, Quang Binh; Nguyen, Thi Lam; Le, Danh Tuyen; Nguyen, Do Van Anh; Vu, Anh Linh; Aoto, Hiromichi; Okuhara, Yasuhide; Ito, Yukihiko; Yamamoto, Shigeru; Kise, Mitsuo

    2014-01-01

    We have reported that newly diagnosed type 2 diabetes mellitus (DM) patients in Vietnam have a low body mass index (BMI) of around 23 and that the major factor for this is high white rice (WR) intake. Brown rice (BR) is known to be beneficial in the control of blood glucose levels; however, it has the property of unpleasant palatability. Pre-germinated brown rice (PGBR) is slightly germinated by soaking BR in water as this reduces the hardness of BR and makes it easier to eat. This study was designed to evaluate the effect of a 4-mo PGBR administration on various parameters in Vietnamese women aged 45-65 y with impaired glucose tolerance (IGT). Sixty subjects were divided into a WR or PGBR group. For the first 2 wk, WR was replaced by 50% PGBR, then for 2 wk by 75% PGBR and from the second month 100%. Before the beginning of the study and at the end of the study, 1) anthropometric measurements, 2) a nutrition survey for 3 nonconsecutive days by the 24 h recall method and 3) blood biochemical examinations were conducted. Fasting plasma concentrations of glucose and lipids and the obesity-related measurements and blood pressure were favorably improved only in the PGBR diet group. The present results suggest that replacing WR with PGBR for 4 mo may be useful in controlling body weight as well as blood glucose and lipid levels in Vietnamese women with IGT.

  6. A preliminary investigation of EZSCAN™ screening for impaired glucose tolerance and diabetes in a patient population

    PubMed Central

    CHEN, XIAOLU; CHEN, LIZHU; DING, RONGJING; SHI, QIUTING; ZHANG, YUANYUAN; HU, DAYI

    2015-01-01

    EZSCAN™ is a non-invasive technology that evaluates sweat gland dysfunction using electrochemical skin conductance measurements, providing an opportunity to determine the risk of impaired glucose tolerance (IGT) and diabetes mellitus (DM). This study was conducted with the aims of detecting IGT and DM and investigating the efficacy and cut-off points of the EZSCAN test in a patient population. The traditional serum and plasma glucose tests were used as comparators. In this cross-sectional study, 270 previously undiagnosed patients (180 women and 90 men) with a high risk of glucose metabolism disorders (≥45 years old) were enrolled. All patients underwent an oral glucose tolerance test (OGTT) and hemoglobin A1c (HbA1c), fasting plasma glucose (FPG) and EZSCAN tests. Forty (14.8%) patients had newly diagnosed DM (NDM), 79 (29.3%) had IGT and 151 (55.9%) had normal glucose tolerance. The EZSCAN values of these groups were 48±11, 47±11 and 34±13%, respectively. For all patients, the correlation coefficient of EZSCAN was 0.462 with the OGTT (P<0.001), 0.182 with the FPG test (P<0.001) and 0.379 with the HbA1c test (P<0.001). The EZSCAN cut-off point for the detection of IGT was 37% [sensitivity, 82%; specificity, 62%; area under the curve (AUC), 0.778], and the cut-off point for NDM was 50% (sensitivity, 53%; specificity, 59%; AUC, 0.528). This study demonstrated that the non-invasive EZSCAN system is an effective screening tool for the detection of glucose dysfunction in the population tested, and that its performance in detecting previously undiagnosed IGT is superior to its performance in detecting DM. PMID:26136878

  7. ADRB2 haplotype is associated with glucose tolerance and insulin sensitivity in obese postmenopausal women.

    PubMed

    Prior, Steven J; Goldberg, Andrew P; Ryan, Alice S

    2011-02-01

    The β(2)-adrenergic receptor (ADRB2) mediates obesity, cardiorespiratory fitness, and insulin resistance. We examined the hypothesis that ADRB2 Arg16Gly-Gln27Glu haplotype is associated with body composition, glucose tolerance, and insulin sensitivity in obese, postmenopausal women. Obese (>35% body fat), postmenopausal (age 45-75 years) women (n = 123) underwent genotyping, dual-energy X-ray absorptiometry, and computed tomography scans, exercise testing (VO(2(max))), 2-h oral glucose tolerance tests (OGTTs), and hyperinsulinemic-euglycemic clamps (80 mU/m(2)/min). Analysis of covariance (ANCOVA) tested for differences among haplotypes, with race, % body fat, and VO(2(max)) as covariates. We found that ADRB2 haplotype was independently associated with % body fat, abdominal fat distribution, VO(2(max)), insulin sensitivity (M/ΔInsulin), and glucose tolerance (ANOVA, P < 0.05 for all). Women homozygous for Gly16-Gln27 haplotype had the highest % body fat (52.7 ± 1.9%), high abdominal fat, low M/ΔInsulin (0.49 ± 0.08 mg/kg/min/pmol/l/10(2)), and impaired glucose tolerance (IGT) during an OGTT (G(120) = 10.2 ± 0.9 mmol/l). Women homozygous for Gly16-Glu27 haplotype also had low M/ΔInsulin (0.51 ± 0.05 mg/kg/min/pmol/l/10(2)) and IGT (G(120) = 8.2 ± 0.7 mmol/l). Subjects with Arg16-Gln27/Gly16-Gln27 haplotype combination had the highest VO(2(max)) (1.84 ± 0.07 l/min) and M/ΔInsulin (0.7 ± 0.04 mg/kg/min/pmol/l/10(2)), and normal glucose tolerance (G(120) = 6.4 ± 0.4 mmol/l), despite being obese. These data show associations of the ADRB2 Arg16Gly-Gln27Glu haplotype with VO(2(max)) and body composition, and an independent association with glucose metabolism, which persists after controlling for body composition and fitness. This suggests that ADRB2 haplotypes may mediate insulin action, glucose tolerance, and potentially risk for type 2 diabetes mellitus (T2DM) in obese, postmenopausal women.

  8. Effect of Chinese Herbal Medicine Jinlida Granule in Treatment of Patients with Impaired Glucose Tolerance

    PubMed Central

    Shi, Ya-Lin; Liu, Wen-Juan; Zhang, Xiao-Fang; Su, Wei-Juan; Chen, Ning-Ning; Lu, Shu-Hua; Wang, Li-Ying; Shi, Xiu-Lin; Li, Zhi-Bin; Yang, Shu-Yu

    2016-01-01

    Background: Diabetes mellitus (DM) remains a major health problem worldwide. Several clinical trials have shown the superiority of the Traditional Chinese Medicine in delaying or reversing the development and progression of DM. This study aimed to evaluate the efficacy of Jinlida (JLD) granule, a Chinese herbal recipe, in the treatment of impaired glucose tolerance (IGT) and its effect on the prevention of DM. Methods: Sixty-five IGT patients were randomized to receive one bag of JLD granules three times daily (JLD group, n = 34) or no drug intervention (control group, n = 31) for 12 weeks. Oral glucose tolerance test, glycated hemoglobin A1c (HbA1c), body mass index, blood lipids levels, fasting insulin, and insulin resistance calculated using homeostatic model assessment (HOMA-IR) of all the patients were observed and compared before and after the treatment. Results: Sixty-one participants completed the trial (32 in JLD group and 29 in the control group). There were statistically significant decreases in HbA1c (P < 0.001), 2-h plasma glucose (P < 0.001), and HOMA-IR (P = 0.029) in JLD group compared with the control group after 12 weeks of treatment. After 12 weeks of treatment, two (6.9%) patients returned to normal blood glucose, and five (17.2%) patients turned into DM in control group, while in the JLD group, 14 (43.8%) returned to normal blood glucose and 2 (6.2%) turned into DM. There was a significant difference in the number of subjects who had normal glucose at the end of the study between two groups (P = 0.001). Conclusions: JLD granule effectively improved glucose control, increased the conversion of IGT to normal glucose, and improved the insulin resistance in patients with IGT. This Chinese herbal medicine may have a clinical value for IGT. PMID:27647185

  9. Development of diagnotors based on time-average values of plasma glucose and immunoreactive insulin levels during intravenous glucose tolerance testing

    NASA Astrophysics Data System (ADS)

    Denisova, Tatyana P.; Malinov, Igor A.; Malinova, Lidia I.; Brook, Sergey B.

    2000-04-01

    The diagnostic algorithm of glucose-insulinic violations for the patients with a clinically obvious atherosclerosis of coronary arteries, non-insulin dependent diabetes mellitus and persons with the heritable predisposition to these forms of pathology was designed. The realization of intravenous glucose tolerance test in specially fitted groups of patients served as basis of the algorithm.

  10. Sourdough-leavened bread improves postprandial glucose and insulin plasma levels in subjects with impaired glucose tolerance.

    PubMed

    Maioli, Mario; Pes, Giovanni Mario; Sanna, Manuela; Cherchi, Sara; Dettori, Mariella; Manca, Elena; Farris, Giovanni Antonio

    2008-06-01

    Sourdough bread has been reported to improve glucose metabolism in healthy subjects. In this study postprandial glycaemic and insulinaemic responses were evaluated in subjects with impaired glucose tolerance (IGT) who had a meal containing sourdough bread leavened with lactobacilli, in comparison to a reference meal containing bread leavened with baker yeast. Sixteen IGT subjects (age range 52-75, average BMI 29.9 +/- 4.2 kg/ m2) were randomly given a meal containing sourdough bread (A) and a meal containing the reference bread (B) in two separate occasions at the beginning of the study and after 7 days. Sourdough bread was leavened for 8 h using a starter containing autochthonous Saccharomyces cerevisiae and several bacilli able to produce a significant amount of D-and L-lactic acid, whereas the reference bread was leavened for 2 h with commercial baker yeast containing Saccharomyces cerevisiae. Plasma glucose and insulin levels were measured at time 0, 30, 60, 120, and 180 min. In IGT subjects sourdough bread induced a significantly lower plasma glucose response at 30 minutes (p = 0.048) and a smaller incremental area under curve (AUC) delta 0-30 and delta 0-60 min (p = 0.020 and 0.018 respectively) in comparison to the bread leavened with baker yeast. Plasma insulin response to this type of bread showed lower values at 30 min (p = 0.045) and a smaller AUC delta 0-30 min (p = 0.018). This study shows that in subjects with IGT glycaemic and insulinaemic responses after the consumption of sourdough bread are lower than after the bread leavened with baker yeast. This effect is likely due to the lactic acid produced during dough leavening as well as the reduced availability of simple carbohydrates. Thus, sour-dough bread may potentially be of benefit in subjects with impaired glucose metabolism.

  11. Glucose-tolerant β-glucosidase retrieved from a Kusaya gravy metagenome.

    PubMed

    Uchiyama, Taku; Yaoi, Katusro; Miyazaki, Kentaro

    2015-01-01

    β-glucosidases (BGLs) hydrolyze cello-oligosaccharides to glucose and play a crucial role in the enzymatic saccharification of cellulosic biomass. Despite their significance for the production of glucose, most identified BGLs are commonly inhibited by low (∼mM) concentrations of glucose. Therefore, BGLs that are insensitive to glucose inhibition have great biotechnological merit. We applied a metagenomic approach to screen for such rare glucose-tolerant BGLs. A metagenomic library was created in Escherichia coli (∼10,000 colonies) and grown on LB agar plates containing 5-bromo-4-chloro-3-indolyl-β-D-glucoside, yielding 828 positive (blue) colonies. These were then arrayed in 96-well plates, grown in LB, and secondarily screened for activity in the presence of 10% (w/v) glucose. Seven glucose-tolerant clones were identified, each of which contained a single bgl gene. The genes were classified into two groups, differing by two nucleotides. The deduced amino acid sequences of these genes were identical (452 aa) and found to belong to the glycosyl hydrolase family 1. The recombinant protein (Ks5A7) was overproduced in E. coli as a C-terminal 6 × His-tagged protein and purified to apparent homogeneity. The molecular mass of the purified Ks5A7 was determined to be 54 kDa by SDS-PAGE, and 160 kDa by gel filtration analysis. The enzyme was optimally active at 45°C and pH 5.0-6.5 and retained full or 1.5-2-fold enhanced activity in the presence of 0.1-0.5 M glucose. It had a low KM (78 μM with p-nitrophenyl β-D-glucoside; 0.36 mM with cellobiose) and high V max (91 μmol min(-1) mg(-1) with p-nitrophenyl β-D-glucoside; 155 μmol min(-1) mg(-1) with cellobiose) among known glucose-tolerant BGLs and was free from substrate (0.1 M cellobiose) inhibition. The efficient use of Ks5A7 in conjunction with Trichoderma reesei cellulases in enzymatic saccharification of alkaline-treated rice straw was demonstrated by increased production of glucose. PMID:26136726

  12. Glucose-tolerant β-glucosidase retrieved from a Kusaya gravy metagenome

    PubMed Central

    Uchiyama, Taku; Yaoi, Katusro; Miyazaki, Kentaro

    2015-01-01

    β-glucosidases (BGLs) hydrolyze cello-oligosaccharides to glucose and play a crucial role in the enzymatic saccharification of cellulosic biomass. Despite their significance for the production of glucose, most identified BGLs are commonly inhibited by low (∼mM) concentrations of glucose. Therefore, BGLs that are insensitive to glucose inhibition have great biotechnological merit. We applied a metagenomic approach to screen for such rare glucose-tolerant BGLs. A metagenomic library was created in Escherichia coli (∼10,000 colonies) and grown on LB agar plates containing 5-bromo-4-chloro-3-indolyl-β-D-glucoside, yielding 828 positive (blue) colonies. These were then arrayed in 96-well plates, grown in LB, and secondarily screened for activity in the presence of 10% (w/v) glucose. Seven glucose-tolerant clones were identified, each of which contained a single bgl gene. The genes were classified into two groups, differing by two nucleotides. The deduced amino acid sequences of these genes were identical (452 aa) and found to belong to the glycosyl hydrolase family 1. The recombinant protein (Ks5A7) was overproduced in E. coli as a C-terminal 6 × His-tagged protein and purified to apparent homogeneity. The molecular mass of the purified Ks5A7 was determined to be 54 kDa by SDS-PAGE, and 160 kDa by gel filtration analysis. The enzyme was optimally active at 45°C and pH 5.0–6.5 and retained full or 1.5–2-fold enhanced activity in the presence of 0.1–0.5 M glucose. It had a low KM (78 μM with p-nitrophenyl β-D-glucoside; 0.36 mM with cellobiose) and high Vmax (91 μmol min-1 mg-1 with p-nitrophenyl β-D-glucoside; 155 μmol min-1 mg-1 with cellobiose) among known glucose-tolerant BGLs and was free from substrate (0.1 M cellobiose) inhibition. The efficient use of Ks5A7 in conjunction with Trichoderma reesei cellulases in enzymatic saccharification of alkaline-treated rice straw was demonstrated by increased production of glucose. PMID:26136726

  13. Beneficial effect of chromium-rich yeast on glucose tolerance and blood lipids in elderly subjects.

    PubMed

    Offenbacher, E G; Pi-Sunyer, F X

    1980-11-01

    Twenty-four volunteers, mean age 78, including eight mildly non-insulin-dependent diabetics, were randomly allocated to one of two groups and were fed (daily for 8 wk) 9 g of either chromium-rich brewers' yeast (experimental) or chromium-poor torula yeast (control). Before and after yeast supplementation, the serum glucose and insulin response to 100 g oral glucose was measured at 30 min intervals for 2 h. Fasting serum cholesterol, total lipids, and triglycerides were also determined. In the total experimental group (normals + diabetics) and in both the diabetic and nondiabetic experimental subgroups, glucose tolerance improved significantly and insulin output decreased after supplementation. Cholesterol and total lipids fell significantly after supplementation in the total experimental group. The cholesterol decrease was particularly marked in hypercholesterolemic subjects (cholesterol > 300 mg/dl). In the control group, no significant change in glucose tolerance, insulin, triglycerides, or total lipids was found. Cholesterol was significantly lowered in the nondiabetic but not in the diabetic group. Thus, chromium-rich brewers' yeast improved glucose tolerance and total lipids in elderly subjects, while chromium-poor torula yeast did not. An improvement in insulin sensitivity also occurred with brewers' yeast supplementation. This supports the thesis that elderly people may have a low level of chromium and that an effective source for chromium repletion, such as brewers' yeast, may improve their carbohydrate tolerance and total lipids. The improvement in serum cholesterol in some control subjects, as well as in the total experimental group, also suggests the presence of a hypocholesterolemic factor other than chromium in both brewers' and torula yeast.

  14. Lactose in milk replacer can partly be replaced by glucose, fructose, or glycerol without affecting insulin sensitivity in veal calves.

    PubMed

    Pantophlet, A J; Gilbert, M S; van den Borne, J J G C; Gerrits, W J J; Roelofsen, H; Priebe, M G; Vonk, R J

    2016-04-01

    Calf milk replacer (MR) contains 40 to 50% lactose. Lactose strongly fluctuates in price and alternatives are desired. Also, problems with glucose homeostasis and insulin sensitivity (i.e., high incidence of hyperglycemia and hyperinsulinemia) have been described for heavy veal calves (body weight >100 kg). Replacement of lactose by other dietary substrates can be economically attractive, and may also positively (or negatively) affect the risk of developing problems with glucose metabolism. An experiment was designed to study the effects of replacing one third of the dietary lactose by glucose, fructose, or glycerol on glucose homeostasis and insulin sensitivity in veal calves. Forty male Holstein-Friesian (body weight=114 ± 2.4 kg; age=97 ± 1.4 d) calves were fed an MR containing 462 g of lactose/kg (CON), or an MR in which 150 g of lactose/kg of MR was replaced by glucose (GLU), fructose (FRU), or glycerol (GLY). During the first 10d of the trial, all calves received CON. The CON group remained on this diet and the other groups received their experimental diets for a period of 8 wk. Measurements were conducted during the first (baseline) and last week of the trial. A frequently sampled intravenous glucose tolerance test was performed to assess insulin sensitivity and 24 h of urine was collected to measure glucose excretion. During the last week of the trial, a bolus of 1.5 g of [U-(13)C] substrates was added to their respective meals and plasma glucose, insulin, and (13)C-glucose responses were measured. Insulin sensitivity was low at the start of the trial and remained low [1.2 ± 0.1 and 1.0 ± 0.1 (mU/L)(-1) × min(-1)], and no treatment effect was noted. Glucose excretion was low at the start of the trial (3.4 ± 1.0 g/d), but increased in CON and GLU calves (26.9 ± 3.9 and 43.0 ± 10.6g/d) but not in FRU and GLY calves. Postprandial glucose was higher in GLU, lower in FRU, and similar in GLY compared with CON calves. Postprandial insulin was lower in FRU

  15. Personalized Metabolomics for Predicting Glucose Tolerance Changes in Sedentary Women After High-Intensity Interval Training

    PubMed Central

    Kuehnbaum, Naomi L.; Gillen, Jenna B.; Gibala, Martin J.; Britz-McKibbin, Philip

    2014-01-01

    High-intensity interval training (HIIT) offers a practical approach for enhancing cardiorespiratory fitness, however its role in improving glucose regulation among sedentary yet normoglycemic women remains unclear. Herein, multi-segment injection capillary electrophoresis-mass spectrometry is used as a high-throughput platform in metabolomics to assess dynamic responses of overweight/obese women (BMI > 25, n = 11) to standardized oral glucose tolerance tests (OGTTs) performed before and after a 6-week HIIT intervention. Various statistical methods were used to classify plasma metabolic signatures associated with post-prandial glucose and/or training status when using a repeated measures/cross-over study design. Branched-chain/aromatic amino acids and other intermediates of urea cycle and carnitine metabolism decreased over time in plasma after oral glucose loading. Adaptive exercise-induced changes to plasma thiol redox and orthinine status were measured for trained subjects while at rest in a fasting state. A multi-linear regression model was developed to predict changes in glucose tolerance based on a panel of plasma metabolites measured for naïve subjects in their untrained state. Since treatment outcomes to physical activity are variable between-subjects, prognostic markers offer a novel approach to screen for potential negative responders while designing lifestyle modifications that maximize the salutary benefits of exercise for diabetes prevention on an individual level. PMID:25164777

  16. Personalized metabolomics for predicting glucose tolerance changes in sedentary women after high-intensity interval training.

    PubMed

    Kuehnbaum, Naomi L; Gillen, Jenna B; Gibala, Martin J; Britz-McKibbin, Philip

    2014-01-01

    High-intensity interval training (HIIT) offers a practical approach for enhancing cardiorespiratory fitness, however its role in improving glucose regulation among sedentary yet normoglycemic women remains unclear. Herein, multi-segment injection capillary electrophoresis-mass spectrometry is used as a high-throughput platform in metabolomics to assess dynamic responses of overweight/obese women (BMI > 25, n = 11) to standardized oral glucose tolerance tests (OGTTs) performed before and after a 6-week HIIT intervention. Various statistical methods were used to classify plasma metabolic signatures associated with post-prandial glucose and/or training status when using a repeated measures/cross-over study design. Branched-chain/aromatic amino acids and other intermediates of urea cycle and carnitine metabolism decreased over time in plasma after oral glucose loading. Adaptive exercise-induced changes to plasma thiol redox and orthinine status were measured for trained subjects while at rest in a fasting state. A multi-linear regression model was developed to predict changes in glucose tolerance based on a panel of plasma metabolites measured for naïve subjects in their untrained state. Since treatment outcomes to physical activity are variable between-subjects, prognostic markers offer a novel approach to screen for potential negative responders while designing lifestyle modifications that maximize the salutary benefits of exercise for diabetes prevention on an individual level.

  17. Plasma volume expansion from the intravenous glucose tolerance test before and after hip replacement surgery

    PubMed Central

    2013-01-01

    Background Hyperosmotic glucose is injected intravenously when an intravenous glucose tolerance test (IVGTT) is initiated. The extent and time period of plasma volume expansion that occurs in response to the glucose load has not been studied in the perioperative setting. Methods Twenty-two non-diabetic patients aged between 57 and 76 years (mean 68) underwent an IVGTT, during which 0.3 g/kg of glucose 30% (1 ml/kg) was injected as a bolus over one minute, one day before and two days after hip replacement surgery. Twelve blood samples were collected over 75 minutes from each patient. The turnover of both the exogenous glucose and the injected fluid volume was calculated by means of mass balance and volume kinetic analysis. Results The IVGTT raised plasma glucose by 9 mmol/L and the plasma volume by 8%. The extracellular fluid volume increased by 320 (SD 60) ml of which 2/3 could be accounted for in the plasma. The half-life of the exogenous glucose averaged 30 minutes before surgery and 36 minutes postoperatively (P < 0.02). The glucose elimination governed 86% of the decay of the plasma volume expansion, which occurred with a half-life of 12 minutes before to 21 minutes after the surgery (median, P < 0.001). Conclusion Hyperosmotic glucose translocated intracellular water to the plasma volume rather than to the entire extracellular fluid volume. The preferential re-distribution acts to dilute the plasma concentrations used to quantify insulin sensitivity and ß-cell function from an IVGTT. The greater-than-expected plasma dilution lasted longer after than before surgery. PMID:23978219

  18. Diurnal Variation in Oral Glucose Tolerance: Blood Sugar and Plasma Insulin Levels Morning, Afternoon, and Evening

    PubMed Central

    Jarrett, R. J.; Baker, I. A.; Keen, H.; Oakley, N. W.

    1972-01-01

    Twenty-four subjects received three oral glucose tolerance tests, in the morning, afternoon, and evening of separate days. The mean blood sugar levels in the afternoon and evening tests were similar, and they were both significantly higher than those in the morning test. Plasma immunoreactive insulin levels, however, were highest in the morning test. The pattern of insulin levels during the afternoon and evening tests resembled that described as typical of maturity-onset diabetes. PMID:5058728

  19. Small-molecule ghrelin receptor antagonists improve glucose tolerance, suppress appetite, and promote weight loss.

    PubMed

    Esler, William P; Rudolph, Joachim; Claus, Thomas H; Tang, Weifeng; Barucci, Nicole; Brown, Su-Ellen; Bullock, William; Daly, Michelle; Decarr, Lynn; Li, Yaxin; Milardo, Lucinda; Molstad, David; Zhu, Jian; Gardell, Stephen J; Livingston, James N; Sweet, Laurel J

    2007-11-01

    Ghrelin, through action on its receptor, GH secretagogue receptor type 1a (GHS-R1a), exerts a variety of metabolic functions including stimulation of appetite and weight gain and suppression of insulin secretion. In the present study, we examined the effects of novel small-molecule GHS-R1a antagonists on insulin secretion, glucose tolerance, and weight loss. Ghrelin dose-dependently suppressed insulin secretion from dispersed rat islets. This effect was fully blocked by a GHS-R1a antagonist. Consistent with this observation, a single oral dose of a GHS-R1a antagonist improved glucose homeostasis in an ip glucose tolerance test in rat. Improvement in glucose tolerance was attributed to increased insulin secretion. Daily oral administration of a GHS-R1a antagonist to diet-induced obese mice led to reduced food intake and weight loss (up to 15%) due to selective loss of fat mass. Pair-feeding experiments indicated that weight loss was largely a consequence of reduced food intake. The impact of a GHS-R1a antagonist on gastric emptying was also examined. Although the GHS-R1a antagonist modestly delayed gastric emptying at the highest dose tested (10 mg/kg), delayed gastric emptying does not appear to be a requirement for weight loss because lower doses produced weight loss without an effect on gastric emptying. Consistent with the hypothesis that ghrelin regulates feeding centrally, the anorexigenic effects of potent GHS-R1a antagonists in mice appeared to correspond with their brain exposure. These observations demonstrate that GHS-R1a antagonists have the potential to improve the diabetic condition by promoting glucose-dependent insulin secretion and promoting weight loss.

  20. No difference in exogenous carbohydrate oxidation during exercise in children with and without impaired glucose tolerance.

    PubMed

    Chu, Lisa; Morrison, Katherine M; Riddell, Michael C; Raha, Sandeep; Timmons, Brian W

    2016-09-01

    The capacity to match carbohydrate (CHO) utilization with availability is impaired in insulin-resistant, obese adults at rest. Understanding exogenous carbohydrate (CHOexo) oxidation during exercise and its association to insulin resistance (IR) is important, especially in children at risk for type 2 diabetes. Our objective was to examine the oxidative efficiency of CHOexo during exercise in obese children with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Children attended two visits and were identified as NGT (n = 22) or IGT (n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of <7.8 mmol/l or ≥7.8 mmol/l, respectively. Anthropometry, body composition, and aerobic fitness (V̇o2max) were assessed. Insulin and glucose at baseline, 30, 60, 90, and 120 min during the OGTT were used to calculate measures of insulin sensitivity. On a separate day, a (13)C-enriched CHO drink was ingested before exercise (3 × 20 min bouts) at 45% V̇o2max Breath measurements were collected to calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during exercise was similar in IGT (17.0 ± 3.6%) compared with NGT (17.1 ± 4.4%) (P = 0.90) despite lower whole body insulin sensitivity in IGT at rest (P = 0.02). Area under the curve for insulin (AUCins) measured at rest during the OGTT was greater in IGT compared with NGT (P = 0.04). The ability of skeletal muscle to utilize CHOexo was not impaired during exercise in children with IGT. PMID:27493197

  1. No difference in exogenous carbohydrate oxidation during exercise in children with and without impaired glucose tolerance.

    PubMed

    Chu, Lisa; Morrison, Katherine M; Riddell, Michael C; Raha, Sandeep; Timmons, Brian W

    2016-09-01

    The capacity to match carbohydrate (CHO) utilization with availability is impaired in insulin-resistant, obese adults at rest. Understanding exogenous carbohydrate (CHOexo) oxidation during exercise and its association to insulin resistance (IR) is important, especially in children at risk for type 2 diabetes. Our objective was to examine the oxidative efficiency of CHOexo during exercise in obese children with normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). Children attended two visits and were identified as NGT (n = 22) or IGT (n = 12) based on 2-h oral glucose tolerance test (OGTT) glucose levels of <7.8 mmol/l or ≥7.8 mmol/l, respectively. Anthropometry, body composition, and aerobic fitness (V̇o2max) were assessed. Insulin and glucose at baseline, 30, 60, 90, and 120 min during the OGTT were used to calculate measures of insulin sensitivity. On a separate day, a (13)C-enriched CHO drink was ingested before exercise (3 × 20 min bouts) at 45% V̇o2max Breath measurements were collected to calculate CHOexo oxidative efficiency. CHOexo oxidative efficiency during exercise was similar in IGT (17.0 ± 3.6%) compared with NGT (17.1 ± 4.4%) (P = 0.90) despite lower whole body insulin sensitivity in IGT at rest (P = 0.02). Area under the curve for insulin (AUCins) measured at rest during the OGTT was greater in IGT compared with NGT (P = 0.04). The ability of skeletal muscle to utilize CHOexo was not impaired during exercise in children with IGT.

  2. Detection of Abnormal Glucose Tolerance in Africans Is Improved by Combining A1C With Fasting Glucose: The Africans in America Study

    PubMed Central

    Thoreson, Caroline K.; O'Connor, Michelle Y.; Ricks, Madia; Chung, Stephanie T.; Tulloch-Reid, Marshall K.; Lozier, Jay N.; Sacks, David B.

    2015-01-01

    OBJECTIVE Abnormal glucose tolerance is rising in sub-Saharan Africa. Hemoglobin A1c by itself and in combination with fasting plasma glucose (FPG) is used to diagnose abnormal glucose tolerance. The diagnostic ability of A1C in Africans with heterozygous variant hemoglobin, such as sickle cell trait or hemoglobin C trait, has not been rigorously evaluated. In U.S.-based Africans, we determined by hemoglobin status the sensitivities of 1) FPG ≥5.6 mmol/L, 2) A1C ≥ 5.7% (39 mmol/mol), and 3) FPG combined with A1C (FPG ≥5.6 mmol/L and/or A1C ≥5.7% [39 mmol/mol]) for the detection of abnormal glucose tolerance. RESEARCH DESIGN AND METHODS An oral glucose tolerance test (OGTT) was performed in 216 African immigrants (68% male, age 37 ± 10 years [mean ± SD], range 20–64 years). Abnormal glucose tolerance was defined as 2-h glucose ≥7.8 mmol/L. RESULTS Variant hemoglobin was identified in 21% (46 of 216). Abnormal glucose tolerance occurred in 33% (72 of 216). When determining abnormal glucose tolerance from the OGTT (2-h glucose ≥7.8 mmol/L), sensitivities of FPG for the total, normal, and variant hemoglobin groups were 32%, 32%, and 33%, respectively. Sensitivities for A1C were 53%, 54%, and 47%. For FPG and A1C combined, sensitivities were 64%, 63%, and 67%. Sensitivities for FPG and A1C and the combination did not vary by hemoglobin status (all P > 0.6). For the entire cohort, sensitivity was higher for A1C than FPG and for both tests combined than for either test alone (all P values ≤ 0.01). CONCLUSIONS No significant difference in sensitivity of A1C by variant hemoglobin status was detected. For the diagnosis of abnormal glucose tolerance in Africans, the sensitivity of A1C combined with FPG is significantly superior to either test alone. PMID:25338926

  3. Plasma Lactate Levels Increase during Hyperinsulinemic Euglycemic Clamp and Oral Glucose Tolerance Test.

    PubMed

    Berhane, Feven; Fite, Alemu; Daboul, Nour; Al-Janabi, Wissam; Msallaty, Zaher; Caruso, Michael; Lewis, Monique K; Yi, Zhengping; Diamond, Michael P; Abou-Samra, Abdul-Badi; Seyoum, Berhane

    2015-01-01

    Insulin resistance, which plays a central role in the pathogenesis of type 2 diabetes (T2D), is an early indicator that heralds the occurrence of T2D. It is imperative to understand the metabolic changes that occur at the cellular level in the early stages of insulin resistance. The objective of this study was to determine the pattern of circulating lactate levels during oral glucose tolerance test (OGTT) and hyperinsulinemic euglycemic clamp (HIEC) study in normal nondiabetic subjects. Lactate and glycerol were determined every 30 minutes during OGTT and HIEC on 22 participants. Lactate progressively increased throughout the HIEC study period (P < 0.001). Participants with BMI < 30 had significantly higher mean M-values compared to those with BMI ≥ 30 at baseline (P < 0.05). This trend also continued throughout the OGTT. In addition, those with impaired glucose tolerance test (IGT) had significantly higher mean lactate levels compared to those with normal glucose tolerance (P < 0.001). In conclusion, we found that lactate increased during HIEC study, which is a state of hyperinsulinemia similar to the metabolic milieu seen during the early stages in the development of T2D. PMID:25961050

  4. Use of anesthesia dramatically alters the oral glucose tolerance and insulin secretion in C57Bl/6 mice.

    PubMed

    Windeløv, Johanne A; Pedersen, Jens; Holst, Jens J

    2016-06-01

    Evaluation of the impact of anesthesia on oral glucose tolerance in mice. Anesthesia is often used when performing OGTT in mice to avoid the stress of gavage and blood sampling, although anesthesia may influence gastrointestinal motility, blood glucose, and plasma insulin dynamics. C57Bl/6 mice were anesthetized using the following commonly used regimens: (1) hypnorm/midazolam repetitive or single injection; (2) ketamine/xylazine; (3) isoflurane; (4) pentobarbital; and (5) A saline injected, nonanesthetized group. Oral glucose was administered at time 0 min and blood glucose measured in the time frame -15 to +150 min. Plasma insulin concentration was measured at time 0 and 20 min. All four anesthetic regimens resulted in impaired glucose tolerance compared to saline/no anesthesia. (1) hypnorm/midazolam increased insulin concentrations and caused an altered glucose tolerance; (2) ketamine/xylazine lowered insulin responses and resulted in severe hyperglycemia throughout the experiment; (3) isoflurane did not only alter the insulin secretion but also resulted in severe hyperglycemia; (4) pentobarbital resulted in both increased insulin secretion and impaired glucose tolerance. All four anesthetic regimens altered the oral glucose tolerance, and we conclude that anesthesia should not be used when performing metabolic studies in mice. PMID:27255361

  5. Family resemblance for glucose tolerance in a Melanesian population, the Tolai.

    PubMed

    King, H; Rao, D C; Bhatia, K; Koki, G; Collins, A; Zimmet, P

    1989-01-01

    Path analysis of family resemblance for plasma glucose concentration, 2 h after an oral glucose challenge, failed to detect significant genetic heritability. There were no intergenerational differences and marital resemblance was moderate. Over one-third of sibling environmental similarity was due to non-inherited factors. Cultural inheritance was very strong, tending to mimic genetic inheritance, and cultural heritability was considerable. Measures of obesity were included in the environmental index, an estimate of familial environment, in this analysis, for comparability with previous studies. Since obesity appears, in part, to be a heritable trait, in future studies a bivariate approach to family resemblance for both glucose tolerance and obesity could yield important additional insight.

  6. Glucose tolerance normalization following transplantation of pig pancreatic primordia into non-immunosuppressed diabetic ZDF rats.

    PubMed

    Rogers, Sharon A; Chen, Feng; Talcott, Mike; Liapis, Helen; Hammerman, Marc R

    2006-11-01

    Pancreas or pancreatic islet transplantation in humans is limited by organ availability, and success of the latter is negatively impacted upon by tissue loss post-transplantation and limited potential for expansion of beta cells. A way to overcome the supply and expansion problems is to xenotransplant embryonic tissue. Previously, we have shown that beta cells originating from embryonic day (E) 28 (E28) pig pancreatic primordia transplanted into the mesentery of streptozotocin-diabetic (type 1) Lewis rats engraft without the need for host immune-suppression and normalize glucose tolerance. Here we show long-term engraftment of pig beta cells within liver, pancreas and mesenteric lymph nodes post-transplantation of E28 pig pancreatic primordia into diabetic ZDF rats, a model for type 2 diabetes. Porcine insulin is present in circulation after an oral glucose load. Glucose tolerance is normalized in transplanted ZDF hosts and insulin sensitivity restored in formerly diabetic ZDF males. Release of porcine insulin in vitro from tissue originating in transplanted rats occurs within 1 min of glucose stimulation characteristic of first-phase secretion from beta cells. Of potential importance for application of this transplantation technology to treatment of type 2 diabetes in humans and confirmatory of our previous findings in Lewis rats, no host immunosuppression is required for engraftment of E28 pig pancreatic primordia. PMID:17138051

  7. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

    PubMed Central

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217. PMID:26798650

  8. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

    PubMed

    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p < 0.05), did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p < 0.05), while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  9. Effect of an Acute Bout of Kettlebell Exercise on Glucose Tolerance in Sedentary Men: A Preliminary Study

    PubMed Central

    GREENWALD, SAMANTHA; SEGER, EDWARD; NICHOLS, DAVID; RAY, ANDREW D.; RIDEOUT, TODD C.; GOSSELIN, LUC E.

    2016-01-01

    Impaired glucose tolerance can have significant health consequences. The purposes of this preliminary study were to examine whether a single session of kettlebell exercise improves acute post-exercise glucose tolerance in sedentary individuals, and whether it was as effective as high-intensity interval running. Six sedentary male subjects underwent a two-hour oral glucose tolerance test following three different conditions: 1) control (no exercise); 2) kettlebell exercise (2 sets of 7 exercises, 15 repetitions per exercise with 30 seconds rest between each exercise); or 3) high-intensity interval running (10 one-minute intervals at a workload corresponding to 90% VO2max interspersed with one-minute active recovery periods). Blood glucose and insulin levels were measured before (0 minutes), and 60 and 120 minutes after glucose ingestion. Both kettlebell and high-intensity interval running exercise significantly lowered blood glucose 60 minutes after glucose ingestion compared with control. However, there was no significant difference in blood glucose between the two exercise conditions at any time point. In addition, there were no significant differences in insulin concentration between high intensity interval running, kettlebell, and control conditions at all time points. Results indicate that an acute bout of kettlebell exercise is as effective as high intensity interval running at improving glucose tolerance in sedentary young men. PMID:27766136

  10. The opposing effects of the flavonoids isoquercitrin and sissotrin, isolated from Pterospartum tridentatum, on oral glucose tolerance in rats.

    PubMed

    Paulo, Alexandra; Martins, Sofia; Branco, Pedro; Dias, Teresa; Borges, Carlos; Rodrigues, Ana Isabel; Costa, Maria do Céu; Teixeira, Adriano; Mota-Filipe, Hélder

    2008-04-01

    The effect of an aqueous extract of Pterospartum tridentatum on the blood glucose levels of normal Wistar rats was investigated in a situation of oral glucose challenge. The extract at 300 mg/kg showed an antihyperglycaemic effect in the first 30 min after glucose challenge but then the blood glucose levels rose above those of the control group, indicating the presence of compounds with different effects on glucose tolerance. Nine compounds of isoflavone and flavonol skeletons were identified in the extract by HPLC-ESI-MS(n), four of them being identified for the first time in this species. The isoflavone sissotrin and the flavonol derivative, isoquercitrin, were selected for the oral glucose tolerance test. Isoquercitrin (100 mg/kg) showed time-dependent antihyperglycaemic activity by delaying the post-oral glucose load glycaemic peak at 30 min, as did the sodium-dependent glucose transporter inhibitor phloridzin (100 mg/kg). In contrast, sissotrin (100 mg/kg) showed an opposite effect, impairing glucose tolerance. In conclusion, these preliminary results indicate that the effect of the extract on blood glucose may be either antihyperglycaemic or hyperglycaemic. Additionally, as far as is known, these are the first in vivo results on the acute antihyperglycaemic potential of isoquercitrin.

  11. Altered Skeletal Muscle Fatty Acid Handling in Subjects with Impaired Glucose Tolerance as Compared to Impaired Fasting Glucose

    PubMed Central

    Goossens, Gijs H.; Moors, Chantalle C. M.; Jocken, Johan W. E.; van der Zijl, Nynke J.; Jans, Anneke; Konings, Ellen; Diamant, Michaela; Blaak, Ellen E.

    2016-01-01

    Altered skeletal muscle fatty acid (FA) metabolism contributes to insulin resistance. Here, we compared skeletal muscle FA handling between subjects with impaired fasting glucose (IFG; n = 12 (7 males)) and impaired glucose tolerance (IGT; n = 14 (7 males)) by measuring arterio-venous concentration differences across forearm muscle. [2H2]-palmitate was infused intravenously, labeling circulating endogenous triacylglycerol (TAG) and free fatty acids (FFA), whereas [U-13C]-palmitate was incorporated in a high-fat mixed-meal, labeling chylomicron-TAG. Skeletal muscle biopsies were taken to determine muscle TAG, diacylglycerol (DAG), FFA, and phospholipid content, their fractional synthetic rate (FSR) and degree of saturation, and gene expression. Insulin sensitivity was assessed using a hyperinsulinemic-euglycemic clamp. Net skeletal muscle glucose uptake was lower (p = 0.018) and peripheral insulin sensitivity tended to be reduced (p = 0.064) in IGT as compared to IFG subjects. Furthermore, IGT showed higher skeletal muscle extraction of VLDL-TAG (p = 0.043), higher muscle TAG content (p = 0.025), higher saturation of FFA (p = 0.004), lower saturation of TAG (p = 0.017) and a tendency towards a lower TAG FSR (p = 0.073) and a lower saturation of DAG (p = 0.059) versus IFG individuals. Muscle oxidative gene expression was lower in IGT subjects. In conclusion, increased liver-derived TAG extraction and reduced lipid turnover of saturated FA, rather than DAG content, in skeletal muscle accompany the more pronounced insulin resistance in IGT versus IFG subjects. PMID:26985905

  12. Poor sleep quality is associated with impaired glucose tolerance in women after gestational diabetes.

    PubMed

    Ferrari, U; Künzel, H; Tröndle, K; Rottenkolber, M; Kohn, D; Fugmann, M; Banning, F; Weise, M; Sacco, V; Hasbargen, U; Hutter, S; Parhofer, K G; Kloiber, S; Ising, M; Seissler, J; Lechner, A

    2015-06-01

    We analyzed the association of sleep quality and glucose metabolism in women after gestational diabetes (pGDM) and in women after normoglycemic pregnancy (controls). Data during pregnancy and a visit within the first 15 months after delivery were collected from 61 pGDM and 30 controls in a prospective cohort study. This included a medical history, physical examination, questionnaires (Pittsburgh Sleep Quality Index (PSQI), and Perceived Stress Scale (PSS)), and 5-point oral glucose tolerance test with insulin measurements to determine indices of insulin sensitivity and insulin secretion. We used Spearman correlation coefficients and multivariate regression models for analysis.9.3 ± 3.2 months after delivery, pGDM had significantly higher fasting and 2 h glucose levels and lower insulin sensitivity than controls. There was no significant difference in age, BMI and sleep quality as assessed with the PSQI between the two groups. The PSQI score correlated with the ogtt-2 h plasma glucose in pGDM (δ = 0.41; p = 0.0012), but not in controls. This association was confirmed with a multivariate linear regression model with adjustment for age, BMI and months post-delivery. Perceived stress was an independent risk factor (OR 1.12; 95% CI 1.02-1.23) for impaired sleep. Our findings suggest that post-delivery sleep quality significantly influences glucose tolerance in women after GDM and that impaired sleep is associated with increased stress perception. Measures to improve of sleep quality and reduce perceived stress should therefore be tested as additional strategies to prevent progression to type 2 diabetes after GDM. PMID:25930074

  13. Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

    PubMed Central

    Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

    2014-01-01

    The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

  14. Zinc status affects glucose homeostasis and insulin secretion in patients with thalassemia.

    PubMed

    Fung, Ellen B; Gildengorin, Ginny; Talwar, Siddhant; Hagar, Leah; Lal, Ashutosh

    2015-06-02

    Up to 20% of adult patients with Thalassemia major (Thal) live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years) with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05) and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048). Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (-19.0 ± 9.6 μg/dL), showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL) and insulin to glucose ratios at 120 min post glucose dose (p = 0.05). Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient.

  15. Zinc Status Affects Glucose Homeostasis and Insulin Secretion in Patients with Thalassemia

    PubMed Central

    Fung, Ellen B.; Gildengorin, Ginny; Talwar, Siddhant; Hagar, Leah; Lal, Ashutosh

    2015-01-01

    Up to 20% of adult patients with Thalassemia major (Thal) live with diabetes, while 30% may be zinc deficient. The objective of this study was to explore the relationship between zinc status, impaired glucose tolerance and insulin sensitivity in Thal patients. Charts from thirty subjects (16 male, 27.8 ± 9.1 years) with Thal were reviewed. Patients with low serum zinc had significantly lower fasting insulin, insulinogenic and oral disposition indexes (all p < 0.05) and elevated glucose response curve, following a standard 75 g oral load of glucose compared to those with normal serum zinc after controlling for baseline (group × time interaction p = 0.048). Longitudinal data in five patients with a decline in serum zinc over a two year follow up period (−19.0 ± 9.6 μg/dL), showed consistent increases in fasting glucose (3.6 ± 3.2 mg/dL) and insulin to glucose ratios at 120 min post glucose dose (p = 0.05). Taken together, these data suggest that the frequently present zinc deficiency in Thal patients is associated with decreased insulin secretion and reduced glucose disposal. Future zinc trials will require modeling of oral glucose tolerance test data and not simply measurement of static indices in order to understand the complexities of pancreatic function in the Thal patient. PMID:26043030

  16. Oral Administration of Collagen Hydrolysates Improves Glucose Tolerance in Normal Mice Through GLP-1-Dependent and GLP-1-Independent Mechanisms.

    PubMed

    Iba, Yoshinori; Yokoi, Koji; Eitoku, Itsuka; Goto, Masaki; Koizumi, Seiko; Sugihara, Fumihito; Oyama, Hiroshi; Yoshimoto, Tadashi

    2016-09-01

    The aim of this study was to evaluate the antidiabetic properties of collagen hydrolysates (CHs). CHs exhibited dipeptidyl peptidase-IV inhibitory activity and stimulated glucagon-like-peptide-1 (GLP-1) secretion in vitro. We also determined whether CHs improve glucose tolerance in normal mice. Oral administration of CHs suppressed the glycemic response during the oral and intraperitoneal glucose tolerance tests (OGTT and IPGTT), but the effects were weaker in IPGTT than in OGTT. CHs had no effect on the gastric emptying rate. A pretreatment with the GLP-1 receptor antagonist, exendin 9-39 (Ex9), partially reversed the glucose-lowering effects of CHs, but only when coadministered with glucose. CHs administered 45 min before the glucose load potentiated the glucose-stimulated insulin secretion. This potentiating effect on insulin secretion was not reversed by the pretreatment with Ex9, it appeared to be enhanced. These results suggest that CHs improve glucose tolerance by inhibiting intestinal glucose uptake and enhancing insulin secretion, and also demonstrated that GLP-1 was partially involved in the inhibition of glucose uptake, but not essential for the enhancement of insulin secretion. PMID:27540823

  17. Overexpression of a proton-coupled vacuolar glucose exporter impairs freezing tolerance and seed germination.

    PubMed

    Klemens, Patrick A W; Patzke, Kathrin; Trentmann, Oliver; Poschet, Gernot; Büttner, Michael; Schulz, Alexander; Marten, Irene; Hedrich, Rainer; Neuhaus, H Ekkehard

    2014-04-01

    Arabidopsis vacuoles harbor, besides sugar transporter of the TMT-type, an early response to dehydration like 6 (ERDL6) protein involved in glucose export into the cytosol. However, the mode of transport of ERDL6 and the plant's feedback to overexpression of its activity on essential properties such as, for example, seed germination or freezing tolerance, remain unexplored. Using patch-clamp studies on vacuoles expressing AtERDL6 we demonstrated directly that this carrier operates as a proton-driven glucose exporter. Overexpression of BvIMP, the closest sugar beet (Beta vulgaris) homolog to AtERDL6, in Arabidopsis leads surprisingly to impaired seed germination under both conditions, sugar application and low environmental temperatures, but not under standard conditions. Upon cold treatment, BvIMP overexpressor plants accumulated lower quantities of monosaccharides than the wild-type, a response in line with the reduced frost tolerance of the transgenic Arabidopsis plants, and the fact that cold temperatures inhibits BvIMP transcription in sugar beet leaves. With these findings we show that the tight control of vacuolar sugar import and export is a key requisite for cold tolerance and seed germination of plants.

  18. Overexpression of a proton-coupled vacuolar glucose exporter impairs freezing tolerance and seed germination.

    PubMed

    Klemens, Patrick A W; Patzke, Kathrin; Trentmann, Oliver; Poschet, Gernot; Büttner, Michael; Schulz, Alexander; Marten, Irene; Hedrich, Rainer; Neuhaus, H Ekkehard

    2014-04-01

    Arabidopsis vacuoles harbor, besides sugar transporter of the TMT-type, an early response to dehydration like 6 (ERDL6) protein involved in glucose export into the cytosol. However, the mode of transport of ERDL6 and the plant's feedback to overexpression of its activity on essential properties such as, for example, seed germination or freezing tolerance, remain unexplored. Using patch-clamp studies on vacuoles expressing AtERDL6 we demonstrated directly that this carrier operates as a proton-driven glucose exporter. Overexpression of BvIMP, the closest sugar beet (Beta vulgaris) homolog to AtERDL6, in Arabidopsis leads surprisingly to impaired seed germination under both conditions, sugar application and low environmental temperatures, but not under standard conditions. Upon cold treatment, BvIMP overexpressor plants accumulated lower quantities of monosaccharides than the wild-type, a response in line with the reduced frost tolerance of the transgenic Arabidopsis plants, and the fact that cold temperatures inhibits BvIMP transcription in sugar beet leaves. With these findings we show that the tight control of vacuolar sugar import and export is a key requisite for cold tolerance and seed germination of plants. PMID:24329902

  19. Spectral analysis of time functions of plasma glucose and immunoreactive insulin during intravenous glucose tolerance testing on atherosclerosis and noninsulin-dependent diabetes mellitus

    NASA Astrophysics Data System (ADS)

    Malinov, Igor A.; Denisova, Tatyana P.; Malinova, Lidia I.; Brook, Sergey B.

    2000-04-01

    The time functions of plasma glucose and insulin obtained during intravenous glucose tolerance test were approximated by sections of Fourier series. The convincing quantitative and quality distinctions of amplitudes both phases of the first and second harmonics of decomposition of the indicated time functions are obtained. These distinctions were used as a basis of diagnostic algorithm of metabolic violations appropriate for atherosclerosis and non-insulin dependent diabetes mellitus in clinically obvious and preclinical stages.

  20. Dosakaya Juice Assuages Development of Sucrose Induced Impaired Glucose Tolerance and Imbalance in Antioxidant Defense

    PubMed Central

    Kumar, Dommati Anand; Sweeya, Pisupati S. R.; Shukla, Srishti; Anusha, Sanga Venkata; Akshara, Dasari; Madhusudana, Kuncha; Tiwari, Ashok Kumar

    2015-01-01

    Objective: The objective was to explore the effect of Dosakaya (DK) (Cucumis melo var. chito) juice on sucrose induced dysglycemia and disturbances in antioxidant defense in rats. Materials and Methods: Rats were preconditioned with DK juice before administration of sucrose beverage continuously for 1-month. Blood glucose tolerance test and glutathione (GSH) homeostasis pathways in kidney were analyzed in different group of animals at the end of the study. Results: DK juice diffused (P < 0.001) hypertriglyceridemia inducing effect of sucrose and arrested sucrose induced weight gain. It improved glucose tolerance ability by significantly reducing (P < 0.05) first-hour glycemic excursion and decreasing 2 h glycemic load (P < 0.05) following oral glucose tolerance test in sucrose fed animals. Furthermore, disturbances in antioxidant defense mechanisms in terms of GSH homeostasis in kidney were restored due to juice feeding. DK juice administration checked reduction in GSH-S-transferase and glyoxalase-I activity, thus, significantly mitigated lipid peroxidation (P < 0.05), and formation of advanced glycation end-products (P < 0.001) in kidney and serum (P < 0.01). Quantitative analysis of juice found it a rich source of protein and polyphenols. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis revealed the presence of multiple protein bands in whole fruit juice. Therefore, SDS-PAGE protein fingerprint of DK juice may serve as a quality control tool for standardization of juice. Conclusion: The whole fruit juice of DK may become cost-effective, affordable health beverage in extenuating ill-health effects of sugar consumption. This is the first report identifying DK juice in preventing development dysglycemia, dyslipidemia, and oxidative stress induced due to chronic sucrose feeding in rats. SUMMARY Chronic sucrose consumption induced development of dysglycemia and also impaired antioxidant defense mechanism in rats. The oral administration of

  1. Beta-Cell ARNT Is Required for Normal Glucose Tolerance in Murine Pregnancy

    PubMed Central

    Lau, Sue Mei; Cha, Kuan Minn; Karunatillake, Ayesha; Stokes, Rebecca A.; Cheng, Kim; McLean, Mark; Cheung, N. W.; Gonzalez, Frank J.; Gunton, Jenny E.

    2013-01-01

    Aims Insulin secretion increases in normal pregnancy to meet increasing demands. Inability to increase beta-cell function results in gestational diabetes mellitus (GDM). We have previously shown that the expression of the transcription factor ARNT (Aryl-hydrocarbon Receptor Nuclear Translocator) is reduced in the islets of humans with type 2 diabetes. Mice with a beta-cell specific deletion of ARNT (β-ARNT mice) have impaired glucose tolerance secondary to defective insulin secretion. We hypothesised that ARNT is required to increase beta-cell function during pregnancy, and that β-ARNT mice would be unable to compensate for the beta-cell stress of pregnancy. The aims of this study were to investigate the mechanisms of ARNT regulation of beta-cell function and glucose tolerance in pregnancy. Methods β-ARNT females were mated with floxed control (FC) males and FC females with β-ARNT males. Results During pregnancy, β-ARNT mice had a marked deterioration in glucose tolerance secondary to defective insulin secretion. There was impaired beta-cell proliferation in late pregnancy, associated with decreased protein and mRNA levels of the islet cell-cycle regulator cyclinD2. There was also reduced expression of Irs2 and G6PI. In contrast, in control mice, pregnancy was associated with a 2.1-fold increase in ARNT protein and a 1.6-fold increase in cyclinD2 protein, and with increased beta-cell proliferation. Conclusions Islet ARNT increases in normal murine pregnancy and beta-cell ARNT is required for cyclinD2 induction and increased beta-cell proliferation in pregnancy. PMID:24204824

  2. Prenatal depressive symptoms and abnormalities of glucose tolerance during pregnancy among Hispanic women.

    PubMed

    Ertel, Karen A; Silveira, Marushka; Pekow, Penelope; Braun, Barry; Manson, JoAnn E; Solomon, Caren G; Markenson, Glenn; Chasan-Taber, Lisa

    2014-02-01

    The aim of this study is to prospectively examine the association between maternal depressive symptoms in early pregnancy and risk of abnormal glucose tolerance (AGT) and impaired glucose tolerance (IGT) in mid-pregnancy. We evaluated this association among 934 participants in Proyecto Buena Salud, a prospective cohort study of Hispanic (predominantly Puerto Rican) women in Western Massachusetts. Depressive symptoms were assessed in early pregnancy using the 10-item Edinburgh Postnatal Depression Scale. Scores ≥13 indicated at least probable minor depression and scores ≥15 indicated probable major depression. AGT and IGT were diagnosed using American Diabetes Association criteria. In early pregnancy, 247 (26.5 %) participants experienced at least minor depression and 163 (17.4 %) experienced major depression. A total of 123 (13.2 %) were classified with AGT and 56 (6.0 %) were classified with IGT. In fully-adjusted models, the odds ratio for AGT associated with minor depression was 1.20 (95 % CI 0.77-1.89) and for major depression was 1.34 (95 % CI 0.81-2.23). The odds ratio for IGT associated with minor depression was 1.22 (95 % CI 0.62-2.40) and for major depression was 1.53 (95 % CI 0.73-3.22). We did not observe an association with continuous screening glucose measures. Findings in this prospective cohort of Hispanic women did not indicate a statistically significant association between minor or major depression in early pregnancy and AGT or screening glucose values in mid-pregnancy. Due to the small number of cases of IGT, our ability to evaluate the association between depression and IGT risk was constrained.

  3. The effect of short-term metformin treatment on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance: a pilot study.

    PubMed

    Krysiak, Robert; Okrzesik, Joanna; Okopien, Boguslaw

    2015-05-01

    Metformin was found to affect plasma levels of some pituitary hormones. This study was aimed at investigating whether metformin treatment has an impact on plasma prolactin levels in bromocriptine-treated patients with hyperprolactinaemia and impaired glucose tolerance. The study included 27 patients with hyperprolactinaemia, who had been treated for at least 6 months with bromocriptine. Based on prolactin levels, bromocriptine-treated patients were divided into two groups: patients with elevated (group A, n = 12) and patients with normal (group B, n = 15) prolactin levels. The control group included 16 age-, sex- and weight-matched hyperprolactinaemia-free individuals with impaired glucose tolerance (group C).The lipid profile, fasting plasma glucose levels, the homeostatic model assessment of insulin resistance ratio (HOMA-IR), glycated haemoglobin, as well as plasma levels of prolactin, thyrotropin and insulin-like growth factor-1 (IGF-1) were assessed at baseline and after 4 months of metformin treatment (2.55-3 g daily). In all treatment groups, metformin reduced HOMA-IR, plasma triglycerides and 2-h postchallenge plasma glucose. In patients with hyperprolactinaemia, but not in the other groups of patients, metformin slightly reduced plasma levels of prolactin, and this effect correlated weakly with the metabolic effects of this drug. Our study shows that metformin decreases plasma prolactin levels only in patients with elevated levels of this hormone. The obtained results suggest that metformin treatment may bring some benefits to hyperprolactinaemic patients with coexisting glucose metabolism disturbances already receiving dopamine agonist therapy.

  4. Short-Term Estrogen Replacement Effects on Insulin Sensitivity and Glucose Tolerance in At-Risk Cats for Feline Diabetes Mellitus

    PubMed Central

    Wara, Allison; Hunsucker, Sara; Bove, Krystal; Backus, Robert

    2015-01-01

    Male domestic cats that are neutered and overweight are at an increased risk for developing a type-2-like diabetes mellitus. Beneficial effects of 17β-estradiol (E2) on glucose homeostasis may be lost with neutering and thereby account for increased diabetes risk. To evaluate this, adult male neutered overweight cats (n=6) were given daily E2 (1.0 μg/kg) or vehicle (Vh; ethanol, 1.0μL/kg) in a single crossover trial of 14-day periods with a 7-day washout. The E2 and Vh were voluntarily ingested on food. The E2 dosage was determined in a pre-trial to significantly and transiently reduce food intake with no measurable change in plasma E2 concentration. During treatments, physical activity was assessed with collar-mounted accelerometers on days 9-11, and tests of intravenous insulin tolerance and intravenous glucose tolerance were conducted on days 13 and 14, respectively. Over the 14 days, E2 compared to Vh treatment reduced (p=0.03) food intake (- 22%) but not enough to significantly reduce body weight; activity counts were not significantly changed. With E2 compared to Vh treatment, the late-phase plasma insulin response of the glucose tolerance test was less (p=0.03) by 31%, while glucose tolerance and insulin sensitivity indexes were not significantly changed. The results indicate that oral E2 at a dosage that moderately affects food intake may reduce insulin requirement for achieving glucose homeostasis in neutered male cats. Further investigation is needed to identify the mechanism underlying the E2 effect. PMID:26086714

  5. Short-Term Estrogen Replacement Effects on Insulin Sensitivity and Glucose Tolerance in At-Risk Cats for Feline Diabetes Mellitus.

    PubMed

    Wara, Allison; Hunsucker, Sara; Bove, Krystal; Backus, Robert

    2015-01-01

    Male domestic cats that are neutered and overweight are at an increased risk for developing a type-2-like diabetes mellitus. Beneficial effects of 17β-estradiol (E2) on glucose homeostasis may be lost with neutering and thereby account for increased diabetes risk. To evaluate this, adult male neutered overweight cats (n=6) were given daily E2 (1.0 μg/kg) or vehicle (Vh; ethanol, 1.0 μL/kg) in a single crossover trial of 14-day periods with a 7-day washout. The E2 and Vh were voluntarily ingested on food. The E2 dosage was determined in a pre-trial to significantly and transiently reduce food intake with no measurable change in plasma E2 concentration. During treatments, physical activity was assessed with collar-mounted accelerometers on days 9-11, and tests of intravenous insulin tolerance and intravenous glucose tolerance were conducted on days 13 and 14, respectively. Over the 14 days, E2 compared to Vh treatment reduced (p=0.03) food intake (- 22%) but not enough to significantly reduce body weight; activity counts were not significantly changed. With E2 compared to Vh treatment, the late-phase plasma insulin response of the glucose tolerance test was less (p=0.03) by 31%, while glucose tolerance and insulin sensitivity indexes were not significantly changed. The results indicate that oral E2 at a dosage that moderately affects food intake may reduce insulin requirement for achieving glucose homeostasis in neutered male cats. Further investigation is needed to identify the mechanism underlying the E2 effect.

  6. Hyperproinsulinemia in a three-generation Caucasian family due to mutant proinsulin (Arg{sup 65}{yields}His) not associated with impaired glucose tolerance: The contribution of mutant proinsulin to insulin bioactivity

    SciTech Connect

    Roder, M.E.; Vissing, H.; Nauck, M.A.

    1996-04-01

    Familial hyperproinsulinemia is a genetic abnormality characterized by an increased proportion of proinsulin immunoreactivity in the circulation due to mutations affecting the posttranslational processing of proinsulin. In affected Japanese families, this has been associated with noninsulin-dependent diabetes mellitus or impaired glucose tolerance. A three-generation Caucasian family with hyperproinsulinemia was identified through unexplained hyperinsulinemia in a normal volunteer participating in a metabolic study. High pressure liquid chromatography analysis of fasting plasma revealed a major peak eluting close to the position of proinsulin. Direct sequencing of the proinsulin gene exon 3 showed a heterozygous point mutation (CGT{yields}CAT) resulting in the substitution of Arg{yields}His in position 65 (corresponding to the AC cleavage site) in the index case, his mother, and his maternal grandmother. All affected subjects had normal oral glucose tolerance. In the basal state and after oral glucose administration, their proinsulin responses were slightly reduced. However, when calculating insulin bioactivity by assuming 9% activity for mutant Arg{sup 65}{yields}His proinsulin, responses in affected subjects were comparable to those in normal subjects. In conclusion, our data demonstrate hyperproinsulinemia in a three-generation Caucasian family due to heterozygous mutant Arg{sup 65}{yields}His proinsulin. This was not associated with impaired glucose tolerance. These results suggest that this mutation in the heterozygous state per se does not affect glucose tolerance and that the biological activity of mutant proinsulin contributes to glucose homeostasis in this family. The association of the same mutation with impaired glucose tolerance or diabetes in previous studies may be the result of selection bias or associated conditions (e.g. the genetic background of the kindreds examined). 29 refs., 5 figs., 3 tabs.

  7. [HbA1c is not enough in screening for impaired glucose metabolism. Glucose tolerance tests are also needed, as shown in Swedish prospective epidemiological study].

    PubMed

    Hellgren, Margareta; Daka, Bledar; Larsson, Charlotte

    2015-09-29

    An HbA1c threshold of ≥ 42 mmol/mol has been proposed to diagnose prediabetes. The sensitivity, specificity and positive predictive value of the proposed threshold for detection of individuals with prediabetes was examined in a study of 573 randomly selected individuals from Vara and Skövde. In addition, the utility of the FINDRISC questionnaire and of a fasting glucose test in combination with three short questions concerning BMI, heredity for type 2 diabetes and known hypertension was examined. Results from an oral glucose tolerance test were used as reference. The sensitivity of HbA1c and FINDRISC to detect individuals with IGT was 16 and 26 per cent respectively. Questions regarding BMI, heredity and hypertension together with a fasting glucose test yielded a sensitivity of 50%, but a lower specificity and positive predictive value. We conclude that HbA1c inefficiently detected individuals with impaired glucose tolerance and that oral glucose tolerance tests can still preferably be recommended.

  8. Limited OXPHOS capacity in white adipocytes is a hallmark of obesity in laboratory mice irrespective of the glucose tolerance status

    PubMed Central

    Schöttl, Theresa; Kappler, Lisa; Fromme, Tobias; Klingenspor, Martin

    2015-01-01

    Objective Several human and rodent obesity studies speculate on a causal link between altered white adipocyte mitochondria in the obese state and changes in glucose homeostasis. We here aimed to dissect whether alterations in white adipocyte mitochondrial respiratory function are a specific phenomenon of obesity or impaired glucose tolerance or both. Methods Mature white adipocytes were purified from posterior subcutaneous and intraabdominal epididymal fat of four murine obesity models characterized by either impaired or normal oral glucose tolerance. Bioenergetic profiles, including basal, leak, and maximal respiration, were generated using high-resolution respirometry. Cell respiratory control ratios were calculated to evaluate mitochondrial respiratory function. Results Maximal respiration capacity and cell respiratory control ratios were diminished in white adipocytes of each of the four murine obesity models, both in the absence and the presence of impaired glucose tolerance. Limitation was more pronounced in adipocytes of intraabdominal versus subcutaneous fat. Conclusion Reduced mitochondrial respiratory capacity in white adipocytes is a hallmark of murine obesity irrespective of the glucose tolerance status. Impaired respiratory capacity in white adipocytes solely is not sufficient for the development of systemic glucose intolerance. PMID:26413469

  9. Chlorogenic acid differentially affects postprandial glucose and glucose-dependent insulinotropic polypeptide response in rats.

    PubMed

    Tunnicliffe, Jasmine M; Eller, Lindsay K; Reimer, Raylene A; Hittel, Dustin S; Shearer, Jane

    2011-10-01

    Regular coffee consumption significantly lowers the risk of type 2 diabetes (T2D). Coffee contains thousands of compounds; however, the specific component(s) responsible for this reduced risk is unknown. Chlorogenic acids (CGA) found in brewed coffee inhibit intestinal glucose uptake in vitro. The objective of this study was to elucidate the mechanisms by which CGA acts to mediate blood glucose response in vivo. Conscious, unrestrained, male Sprague-Dawley rats were chronically catheterized and gavage-fed a standardized meal (59% carbohydrate, 25% fat, 12% protein), administered with or without CGA (120 mg·kg(-1)), in a randomized crossover design separated by a 3-day washout period. Acetaminophen was co-administered to assess the effects of CGA on gastric emptying. The incretins glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) were measured. GLP-1 response in the presence of glucose and CGA was further examined, using the human colon cell line NCI-H716. Total area under the curve (AUC) for blood glucose was significantly attenuated in rats fed CGA (p < 0.05). Despite this, no differences in plasma insulin or nonesterified fatty acids were observed, and gastric emptying was not altered. Plasma GIP response was blunted in rats fed CGA, with a lower peak concentration and AUC up to 180 min postprandially (p < 0.05). There were no changes in GLP-1 secretion in either the in vivo or in vitro study. In conclusion, CGA treatment resulted in beneficial effects on blood glucose response, with alterations seen in GIP concentrations. Given the widespread consumption and availability of coffee, CGA may be a viable prevention tool for T2D. PMID:21977912

  10. Cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and by stimulating insulin secretion in vitro.

    PubMed

    Hafizur, Rahman M; Hameed, Abdul; Shukrana, Mishkat; Raza, Sayed Ali; Chishti, Sidra; Kabir, Nurul; Siddiqui, Rehan A

    2015-02-15

    Although the anti-diabetic activity of cinnamic acid, a pure compound from cinnamon, has been reported but its mechanism(s) is not yet clear. The present study was designed to explore the possible mechanism(s) of anti-diabetic activity of cinnamic acid in in vitro and in vivo non-obese type 2 diabetic rats. Non-obese type 2 diabetes was developed by injecting 90 mg/kg streptozotocin in 2-day-old Wistar pups. Cinnamic acid and cinnamaldehyde were administered orally to diabetic rats for assessing acute blood glucose lowering effect and improvement of glucose tolerance. Additionally, insulin secretory activity of cinnamic acid and cinnamaldehyde was evaluated in isolated mice islets. Cinnamic acid, but not cinnamaldehyde, decreased blood glucose levels in diabetic rats in a time- and dose-dependent manner. Oral administration of cinnamic acid with 5 and 10 mg/kg doses to diabetic rats improved glucose tolerance in a dose-dependent manner. The improvement by 10 mg/kg cinnamic acid was comparable to that of standard drug glibenclamide (5 mg/kg). Further in vitro studies showed that cinnamaldehyde has little or no effect on glucose-stimulated insulin secretion; however, cinnamic acid significantly enhanced glucose-stimulated insulin secretion in isolated islets. In conclusion, it can be said that cinnamic acid exerts anti-diabetic activity by improving glucose tolerance in vivo and stimulating insulin secretion in vitro.

  11. Withdrawal of dietary phytoestrogens in adult male rats affects hypothalamic regulation of food intake, induces obesity and alters glucose metabolism.

    PubMed

    Andreoli, María Florencia; Stoker, Cora; Rossetti, María Florencia; Alzamendi, Ana; Castrogiovanni, Daniel; Luque, Enrique H; Ramos, Jorge Guillermo

    2015-02-01

    The absence of phytoestrogens in the diet during pregnancy has been reported to result in obesity later in adulthood. We investigated whether phytoestrogen withdrawal in adult life could alter the hypothalamic signals that regulate food intake and affect body weight and glucose homeostasis. Male Wistar rats fed from conception to adulthood with a high phytoestrogen diet were submitted to phytoestrogen withdrawal by feeding a low phytoestrogen diet, or a high phytoestrogen-high fat diet. Withdrawal of dietary phytoestrogens increased body weight, adiposity and energy intake through an orexigenic hypothalamic response characterized by upregulation of AGRP and downregulation of POMC. This was associated with elevated leptin and T4, reduced TSH, testosterone and estradiol, and diminished hypothalamic ERα expression, concomitant with alterations in glucose tolerance. Removing dietary phytoestrogens caused manifestations of obesity and diabetes that were more pronounced than those induced by the high phytoestrogen-high fat diet intake.

  12. Proinflammatory and Prothrombotic State in Subjects with Different Glucose Tolerance Status before Cardiovascular Disease

    PubMed Central

    Isordia-Salas, Irma; Galván-Plata, María Eugenia; Leaños-Miranda, Alfredo; Aguilar-Sosa, Eberth; Anaya-Gómez, Francisco; Majluf-Cruz, Abraham; Santiago-Germán, David

    2014-01-01

    Background. Inflammation has been associated with insulin resistance, type 2 diabetes mellitus (T2DM), and atherothrombosis. Aim. To determine differences in levels of proinflammatory and prothrombotic markers such as high sensitivity C-reactive protein (hs-CRP) and fibrinogen in subjects with normal glucose tolerance (NGT), prediabetes, and T2DM and to establish their relationship with other cardiovascular risk factors before clinical manifestations of cardiovascular disease. Methods. We conducted a nonrandomized, cross-sectional assay in a hospital at México City. The levels of hs-CRP and fibrinogen were measured and compared according to glucose tolerance status. Results. We enrolled 1047 individuals and they were distributed into NGT n = 473, pre-DM n = 250, and T2DM n = 216. There was a statistical difference between NGT and T2DM groups for fibrinogen (P = 0.01) and hs-CRP (P = 0.05). Fibrinogen and hs-CRP showed a significant positive correlation coefficient (r = 0.53, P<0.0001). In a multiple stepwise regression analysis, the variability in fibrinogen levels was explained by age, HbA1c, and hs-CRP (adjusted R2 = 0.31, P<0.0001), and for hs-CRP it was explained by BMI and fibrinogen (adjusted R2 = 0.33, P<0.0001). Conclusion. Inflammation and prothrombotic state are present in people with T2DM lacking cardiovascular disease. Fibrinogen and Hs-CRP are positively correlated. Fibrinogen and hs-CRP concentrations are predominantly determined by BMI rather than glucose levels. PMID:24772446

  13. Allele Summation of Diabetes Risk Genes Predicts Impaired Glucose Tolerance in Female and Obese Individuals

    PubMed Central

    Hatziagelaki, Erifili; Ketterer, Caroline; Heni, Martin; Machicao, Fausto; Stefan, Norbert; Staiger, Harald; Häring, Hans-Ulrich; Fritsche, Andreas

    2012-01-01

    Introduction Single nucleotide polymorphisms (SNPs) in approximately 40 genes have been associated with an increased risk for type 2 diabetes (T2D) in genome-wide association studies. It is not known whether a similar genetic impact on the risk of prediabetes (impaired glucose tolerance [IGT] or impaired fasting glycemia [IFG]) exists. Methods In our cohort of 1442 non-diabetic subjects of European origin (normal glucose tolerance [NGT] n = 1046, isolated IFG n = 142, isolated IGT n = 140, IFG+IGT n = 114), an impact on glucose homeostasis has been shown for 9 SNPs in previous studies in this specific cohort. We analyzed these SNPs (within or in the vicinity of the genes TCF7L2, KCNJ11, HHEX, SLC30A8, WFS1, KCNQ1, MTNR1B, FTO, PPARG) for association with prediabetes. Results The genetic risk load was significantly associated with the risk for IGT (p = 0.0006) in a model including gender, age, BMI and insulin sensitivity. To further evaluate potential confounding effects, we stratified the population on gender, BMI and insulin sensitivity. The association of the risk score with IGT was present in female participants (p = 0.008), but not in male participants. The risk score was significantly associated with IGT (p = 0.008) in subjects with a body mass index higher than 30 kg/m2 but not in non-obese individuals. Furthermore, only in insulin resistant subjects a significant association between the genetic load and the risk for IGT (p = 0.01) was found. Discussion We found that T2D genetic risk alleles cause an increased risk for IGT. This effect was not present in male, lean and insulin sensitive subjects, suggesting a protective role of beneficial environmental factors on the genetic risk. PMID:22768041

  14. Increased skeletal muscle mitochondrial efficiency in rats with fructose-induced alteration in glucose tolerance.

    PubMed

    Crescenzo, Raffaella; Bianco, Francesca; Coppola, Paola; Mazzoli, Arianna; Cigliano, Luisa; Liverini, Giovanna; Iossa, Susanna

    2013-12-14

    In the present study, the effect of long-term fructose feeding on skeletal muscle mitochondrial energetics was investigated. Measurements in isolated tissue were coupled with the determination of whole-body energy expenditure and insulin sensitivity. A significant increase in plasma NEFA, as well as in skeletal muscle TAG and ceramide, was found in fructose-fed rats compared with the controls, together with a significantly higher plasma insulin response to a glucose load, while no significant variation in plasma glucose levels was found. Significantly lower RMR values were found in fructose-fed rats starting from week 4 of the dietary treatment. Skeletal muscle mitochondrial mass and degree of coupling were found to be significantly higher in fructose-fed rats compared with the controls. Significantly higher lipid peroxidation was found in fructose-fed rats, together with a significant decrease in superoxide dismutase activity. Phosphorylated Akt levels normalised to plasma insulin levels were significantly lower in fructose-fed rats compared with the controls. In conclusion, a fructose-rich diet has a deep impact on a metabolically relevant tissue such as skeletal muscle. In this tissue, the consequences of high fructose feeding are altered glucose tolerance, elevated mitochondrial biogenesis and increased mitochondrial coupling. This latter modification could have a detrimental metabolic effect by causing oxidative stress and energy sparing that contribute to the high metabolic efficiency of fructose-fed rats.

  15. CMKLR1 deficiency influences glucose tolerance and thermogenesis in mice on high fat diet.

    PubMed

    Huang, Chen; Wang, Miaomiao; Ren, Lirong; Xiang, Liang; Chen, Jie; Li, Mengxia; Xiao, Tianxia; Ren, Peigen; Xiong, Likuan; Zhang, Jian V

    2016-04-29

    Obesity has become a global epidemic disease, contributing to increases in the prevalence of type 2 diabetes. CMKLR1, one of the receptors for chemerin, has a wide range of functions in physiological and pathological activity, including innate and adaptive immunity, inflammation, metabolism and reproduction. In our study, CMKLR1 deficiency did not influence the gain of body weight but did exacerbate glucose intolerance, increase serum insulin level, and promote insulin resistance in mice on high fat diets. The expression of thermogenesis related genes was examined and indicated to decrease in CMKLR1 knockout (KO) mice in both normal and cold environments, which indicated CMKLR1 influence the thermogenesis process. Cold exposure induced significant body mass decrease and improved glucose tolerance and insulin resistance in wild type HFD mice but had no obvious effect on CMKLR1 KO HFD mice. In vitro, loss of CMKLR1 did not significantly influence the differentiation of stromal vascular fibroblasts (SVFs) derived from adipose tissue, but did suppress the expression of thermogenesis related genes. Collectively, these data demonstrate that CMKLR1 deficiency induces inbalance of glucose metabolism and impairs the cold induced-thermogenesis process in high diet models. PMID:26972253

  16. Waist circumference and cardiorespiratory fitness are independently associated with glucose tolerance and insulin resistance in obese women.

    PubMed

    Shalev-Goldman, Einat; McGuire, K Ashlee; Ross, Robert

    2014-03-01

    The purpose of this study was to determine the independent associations between physical activity (PA), cardiorespiratory fitness (CRF), abdominal obesity and insulin action in obese women. We studied 141 abdominally obese women (waist circumference (WC): 106.4 ± 10.2 cm). PA duration (min/day) and intensity (counts/min) were obtained by accelerometry. CRF was measured using a treadmill. WC was measured at the iliac crest; abdominal adiposity was measured by magnetic resonance imaging. Glucose and insulin measures were obtained during a 75-g, 2-h glucose tolerance test. The homeostasis model of assessment iHOMA2-IS was used to estimate insulin sensitivity. PA duration and intensity were not associated with glucose or insulin metabolism (p > 0.05). However, moderate-to-vigorous PA (MVPA) duration was associated with fasting insulin and iHOMA2-IS (p < 0.01). CRF was associated with fasting insulin and iHOMA2-IS (r = 0.27, p ≤ 0.01), whereas WC was associated with fasting insulin (r = 0.50, p < 0.01) and iHOMA2-IS (r = -0.52, p ≤ 0.01). Following adjustment for CRF, MVPA, and age, WC remained associated with fasting glucose, insulin, 2-h glucose and iHOMA2-IS (r = -0.44, p ≤ 0.01). CRF was associated with fasting glucose as well as 1- and 2-h glucose (r = 0.24, p < 0.01) after adjusting for WC, MVPA, and age. MVPA was not associated with glucose or insulin measures after control for CRF and WC (p > 0.05). Mediation analysis revealed that CRF and WC combined mediated the relationship between MVPA and both glucose tolerance and insulin resistance (p < 0.05). In conclusion, among abdominally obese women, WC and CRF are independently associated with measures of glucose tolerance and insulin resistance and mediate the association between MVPA and insulin resistance.

  17. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice

    PubMed Central

    Rune, Ida; Rolin, Bidda; Larsen, Christian; Nielsen, Dennis Sandris; Kanter, Jenny E.; Bornfeldt, Karin E.; Lykkesfeldt, Jens; Buschard, Karsten; Kirk, Rikke Kaae; Christoffersen, Berit; Fels, Johannes Josef; Josefsen, Knud; Kihl, Pernille; Hansen, Axel Kornerup

    2016-01-01

    The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings

  18. Modulating the Gut Microbiota Improves Glucose Tolerance, Lipoprotein Profile and Atherosclerotic Plaque Development in ApoE-Deficient Mice.

    PubMed

    Rune, Ida; Rolin, Bidda; Larsen, Christian; Nielsen, Dennis Sandris; Kanter, Jenny E; Bornfeldt, Karin E; Lykkesfeldt, Jens; Buschard, Karsten; Kirk, Rikke Kaae; Christoffersen, Berit; Fels, Johannes Josef; Josefsen, Knud; Kihl, Pernille; Hansen, Axel Kornerup

    2016-01-01

    The importance of the gut microbiota (GM) in disease development has recently received increased attention, and numerous approaches have been made to better understand this important interplay. For example, metabolites derived from the GM have been shown to promote atherosclerosis, the underlying cause of cardiovascular disease (CVD), and to increase CVD risk factors. Popular interest in the role of the intestine in a variety of disease states has now resulted in a significant proportion of individuals without coeliac disease switching to gluten-free diets. The effect of gluten-free diets on atherosclerosis and cardiovascular risk factors is largely unknown. We therefore investigated the effect of a gluten-free high-fat cholesterol-rich diet, as compared to the same diet in which the gluten peptide gliadin had been added back, on atherosclerosis and several cardiovascular risk factors in apolipoprotein E-deficient (Apoe-/-) mice. The gluten-free diet transiently altered GM composition in these mice, as compared to the gliadin-supplemented diet, but did not alter body weights, glucose tolerance, insulin levels, plasma lipids, or atherosclerosis. In parallel, other Apoe-/- mice fed the same diets were treated with ampicillin, a broad-spectrum antibiotic known to affect GM composition. Ampicillin-treatment had a marked and sustained effect on GM composition, as expected. Furthermore, although ampicillin-treated mice were slightly heavier than controls, ampicillin-treatment transiently improved glucose tolerance both in the absence or presence of gliadin, reduced plasma LDL and VLDL cholesterol levels, and reduced aortic atherosclerotic lesion area. These results demonstrate that a gluten-free diet does not seem to have beneficial effects on atherosclerosis or several CVD risk factors in this mouse model, but that sustained alteration of GM composition with a broad-spectrum antibiotic has beneficial effects on CVD risk factors and atherosclerosis. These findings

  19. Resistant maltodextrin promotes fasting glucagon-like peptide-1 secretion and production together with glucose tolerance in rats.

    PubMed

    Hira, Tohru; Ikee, Asuka; Kishimoto, Yuka; Kanahori, Sumiko; Hara, Hiroshi

    2015-07-14

    Glucagon-like peptide-1 (GLP-1), which is produced and released from enteroendocrine L cells, plays pivotal roles in postprandial glycaemia. The ingestion of resistant maltodextrin (RMD), a water-soluble non-digestible saccharide, improves the glycaemic response. In the present study, we examined whether the continuous feeding of RMD to rats affected GLP-1 levels and glycaemic control. Male Sprague-Dawley rats (6 weeks of age) were fed an American Institute of Nutrition (AIN)-93G-based diet containing either cellulose (5 %) as a control, RMD (2.5 or 5 %), or fructo-oligosaccharides (FOS, 2.5 or 5 %) for 7 weeks. During the test period, an intraperitoneal glucose tolerance test (IPGTT) was performed after 6 weeks. Fasting GLP-1 levels were significantly higher in the 5 % RMD group than in the control group after 6 weeks. The IPGTT results showed that the glycaemic response was lower in the 5 % RMD group than in the control group. Lower caecal pH, higher caecal tissue and content weights were observed in the RMD and FOS groups. Proglucagon mRNA levels were increased in the caecum and colon of both RMD and FOS groups, whereas caecal GLP-1 content was increased in the 5 % RMD group. In addition, a 1 h RMD exposure induced GLP-1 secretion in an enteroendocrine L-cell model, and single oral administration of RMD increased plasma GLP-1 levels in conscious rats. The present study demonstrates that continuous ingestion of RMD increased GLP-1 secretion and production in normal rats, which could be stimulated by its direct and indirect (enhanced gut fermentation) effects on GLP-1-producing cells, and contribute to improving glucose tolerance.

  20. Glucose tolerance, blood lipid, insulin and glucagon concentration after single or continuous administration of aspartame in diabetics.

    PubMed

    Okuno, G; Kawakami, F; Tako, H; Kashihara, T; Shibamoto, S; Yamazaki, T; Yamamoto, K; Saeki, M

    1986-04-01

    A nutritive sweetener, aspartame (L-aspartyl-L-phenylalanine methylester) was administered orally to normal controls and diabetic patients in order to evaluate effects on blood glucose, lipids and pancreatic hormone secretion. An oral glucose tolerance test was also performed in the same subjects as a control study of aspartame administration. In 7 normal controls and 22 untreated diabetics, a single dose of 500 mg aspartame, equivalent to 100 g glucose in sweetness, induced no increase in blood glucose concentration. Rather, a small but significant decrease in blood glucose was noticed 2 or 3 h after administration. The decrease in blood glucose was found to be smallest in the control and became greater as the diabetes increased in severity. No significant change in blood insulin or glucagon concentration during a 3-h period was observed in either the controls or the diabetics. The second study was designed to determine the effects of 2 weeks' continuous administration of 125 mg aspartame, equal in sweetness to the mean daily consumption of sugar (20-30 g) in Japan, to 9 hospitalized diabetics with steady-state glycemic control. The glucose tolerance showed no significant change after 2 weeks' administration. Fasting, 1 h and 2 h postprandial blood glucose, blood cholesterol, triglyceride and HDL-cholesterol were also unaffected. From these and other published results, aspartame would seem to be a useful alternative nutrient sweetener for patients with diabetes mellitus.

  1. A Novel Insulin Resistance Index to Monitor Changes in Insulin Sensitivity and Glucose Tolerance: the ACT NOW Study

    PubMed Central

    Tripathy, Devjit; Cobb, Jeff E.; Gall, Walter; Adam, Klaus-Peter; George, Tabitha; Schwenke, Dawn C.; Banerji, MaryAnn; Bray, George A.; Buchanan, Thomas A.; Clement, Stephen C.; Henry, Robert R.; Kitabchi, Abbas E.; Mudaliar, Sunder; Ratner, Robert E.; Stentz, Frankie B.; Reaven, Peter D.; Musi, Nicolas; Ferrannini, Ele

    2015-01-01

    Objective: The objective was to test the clinical utility of Quantose MQ to monitor changes in insulin sensitivity after pioglitazone therapy in prediabetic subjects. Quantose MQ is derived from fasting measurements of insulin, α-hydroxybutyrate, linoleoyl-glycerophosphocholine, and oleate, three nonglucose metabolites shown to correlate with insulin-stimulated glucose disposal. Research Design and Methods: Participants were 428 of the total of 602 ACT NOW impaired glucose tolerance (IGT) subjects randomized to pioglitazone (45 mg/d) or placebo and followed for 2.4 years. At baseline and study end, fasting plasma metabolites required for determination of Quantose, glycated hemoglobin, and oral glucose tolerance test with frequent plasma insulin and glucose measurements to calculate the Matsuda index of insulin sensitivity were obtained. Results: Pioglitazone treatment lowered IGT conversion to diabetes (hazard ratio = 0.25; 95% confidence interval = 0.13–0.50; P < .0001). Although glycated hemoglobin did not track with insulin sensitivity, Quantose MQ increased in pioglitazone-treated subjects (by 1.45 [3.45] mg·min−1·kgwbm−1) (median [interquartile range]) (P < .001 vs placebo), as did the Matsuda index (by 3.05 [4.77] units; P < .0001). Quantose MQ correlated with the Matsuda index at baseline and change in the Matsuda index from baseline (rho, 0.85 and 0.79, respectively; P < .0001) and was progressively higher across closeout glucose tolerance status (diabetes, IGT, normal glucose tolerance). In logistic models including only anthropometric and fasting measurements, Quantose MQ outperformed both Matsuda and fasting insulin in predicting incident diabetes. Conclusions: In IGT subjects, Quantose MQ parallels changes in insulin sensitivity and glucose tolerance with pioglitazone therapy. Due to its strong correlation with improved insulin sensitivity and its ease of use, Quantose MQ may serve as a useful clinical test to identify and monitor therapy in

  2. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    PubMed

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  3. β-Cell Glucagon-Like Peptide-1 Receptor Contributes to Improved Glucose Tolerance After Vertical Sleeve Gastrectomy.

    PubMed

    Garibay, Darline; McGavigan, Anne K; Lee, Seon A; Ficorilli, James V; Cox, Amy L; Michael, M Dodson; Sloop, Kyle W; Cummings, Bethany P

    2016-09-01

    Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible for this remain incompletely defined. Glucagon-like peptide-1 (GLP-1) is a gut hormone that contributes to the maintenance of glucose homeostasis and is elevated after VSG. VSG-induced increases in postprandial GLP-1 secretion have been proposed to contribute to the glucoregulatory benefits of VSG; however, previous work has been equivocal. In order to test the contribution of enhanced β-cell GLP-1 receptor (GLP-1R) signaling we used a β-cell-specific tamoxifen-inducible GLP-1R knockout mouse model. Male β-cell-specific Glp-1r(β-cell+/+) wild type (WT) and Glp-1r(β-cell-/-) knockout (KO) littermates were placed on a high-fat diet for 6 weeks and then switched to high-fat diet supplemented with tamoxifen for the rest of the study. Mice underwent sham or VSG surgery after 2 weeks of tamoxifen diet and were fed ad libitum postoperatively. Mice underwent oral glucose tolerance testing at 3 weeks and were euthanized at 6 weeks after surgery. VSG reduced body weight and food intake independent of genotype. However, glucose tolerance was only improved in VSG WT compared with sham WT, whereas VSG KO had impaired glucose tolerance relative to VSG WT. Augmentation of glucose-stimulated insulin secretion during the oral glucose tolerance test was blunted in VSG KO compared with VSG WT. Therefore, our data suggest that enhanced β-cell GLP-1R signaling contributes to improved glucose regulation after VSG by promoting increased glucose-stimulated insulin secretion. PMID:27501183

  4. Maternal dietary protein supplement confers long-term sex-specific beneficial consequences of obesity resistance and glucose tolerance to the offspring in Brandt's voles.

    PubMed

    Lou, Mei-Fang; Shen, Wei; Fu, Rong-Shu; Zhang, Xue-Ying; Wang, De-Hua

    2015-04-01

    Maternal under- or over-nutrition not only alters neonatal body mass but also increases the risk of metabolic disorders in adulthood. Little is known about how maternal dietary protein affects offspring fitness in wild rodents. The present study was conducted to test the hypothesis that maternal dietary protein supplement has a long-term beneficial effect on offspring fitness in Brandt's vole (Lasiopodomys brandtii), a herbivorous rodent model. The vole dams were fed either a control (18% protein) or high-protein (36% protein) diet throughout pregnancy and lactation. After weaning, all offspring received a control diet till 14 weeks old. Energetic parameters, serum leptin concentration and glucose tolerance were measured. The adult offspring were fed high-fat diet for 8 weeks, and body weight and food intake were measured. No difference was observed in litter size, litter mass or pup mass before weaning. Maternal protein supplement increased body mass and the mass of reproductive organ but decreased digestibility and fat deposition and alleviated HFD-induced obesity especially in the males. Glucose tolerance was elevated in the offspring from maternal protein supplement, especially in the females. The accelerated growth may be associated with high serum leptin concentration at weaning, a state of leptin resistance, and the low digestibility may predispose obesity resistance especially in male offspring from maternal high-protein diet. These data demonstrate that maternal protein supplement confers the long-term sex-specific beneficial consequences of accelerated growth and improved obesity resistance and glucose tolerance of their offspring.

  5. Energized by love: thinking about romantic relationships increases positive affect and blood glucose levels.

    PubMed

    Stanton, Sarah C E; Campbell, Lorne; Loving, Timothy J

    2014-10-01

    We assessed the impact of thinking of a current romantic partner on acute blood glucose responses and positive affect over a short period of time. Participants in romantic relationships were randomly assigned to reflect on their partner, an opposite-sex friend, or their morning routine. Blood glucose levels were assessed prior to reflection, as well as at 10 and 25 min postreflection. Results revealed that individuals in the routine and friend conditions exhibited a decline in glucose over time, whereas individuals in the partner condition did not exhibit this decline (rather, a slight increase) in glucose over time. Reported positive affect following reflection was positively associated with increases in glucose, but only for individuals who reflected on their partner, suggesting this physiological response reflects eustress. These findings add to the literature on eustress in relationships and have implications for relationship processes.

  6. Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

    PubMed

    Ince, Hülya; Taşdemir, Haydar Ali; Aydin, Murat; Ozyürek, Hamit; Tilki, Hacer Erdem

    2015-07-01

    The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test. PMID:25342307

  7. Evaluation of Nerve Conduction Studies in Obese Children With Insulin Resistance or Impaired Glucose Tolerance.

    PubMed

    Ince, Hülya; Taşdemir, Haydar Ali; Aydin, Murat; Ozyürek, Hamit; Tilki, Hacer Erdem

    2015-07-01

    The aim of the study was to investigate nerve conduction studies in terms of neuropathic characteristics in obese patients who were in prediabetes stage and also to determine the abnormal findings. The study included 69 obese adolescent patients between April 2009 and December 2010. All patients and control group underwent motor (median, ulnar, tibial, and peroneal) and sensory (median, ulnar, sural, and medial plantar) nerve conduction studies and sympathetic skin response test. Sensory response amplitude of the medial plantar nerve was significantly lower in the patients with impaired glucose tolerance and insulin resistance. To our knowledge, the present study is the first study demonstrating the development of sensory and autonomic neuropathy due to metabolic complications of obesity in adolescent children even in the period without development of diabetes mellitus. We recommend that routine electrophysiological examinations be performed, using medial plantar nerve conduction studies and sympathetic skin response test.

  8. Clustering of hypertension, abnormal glucose tolerance, hypercholesterolaemia and obesity in Malaysian adult population.

    PubMed

    Lim, T O; Ding, L M; Zaki, M; Merican, I; Kew, S T; Maimunah, A H; Rozita, H H; Rugayah, B

    2000-06-01

    We determine the prevalence and determinants of clustering of hypertension, abnormal glucose tolerance, hypercholesterolaemia and overweight in Malaysia. A national probability sample of 17,392 individuals aged 30 years or older had usable data. 61% of adults had at least one risk factor, 27% had 2 or more risk factors. The observed frequency of 4 factors cluster was 6 times greater than that expected by chance. Indian and Malay women were at particular high risk of risk factors clustering. Individuals with a risk factor had 1.5 to 3 times higher prevalence of other risk factors. Ordinal regression analyses show that higher income, urban residence and physical inactivity were independently associated with risk factors clustering, lending support to the hypotheses that risk factors clustering is related to lifestyle changes brought about by modernisation and urbanisation. In conclusion, risk factor clustering is highly prevalent among Malaysian adults. Treatment and prevention programme must emphasise the multiple risk factor approach.

  9. Insulin resistance in the oral glucose tolerance test--a link with hypertension.

    PubMed

    Cederholm, J; Wibell, L

    1991-03-01

    Insulin resistance was evaluated in 807 middle-aged subjects at a health survey, with use of an index measured in 75 g oral glucose tolerance tests. The mean value of insulin resistance was higher in a hypertensive group than among the normotensives, independent of body mass index, physical activity, smoking sex, age, and thiazide treatment. One-third of the hypertensives had a high resistance value. Another third of the hypertensives, and also about one-third of the normotensives, had a slightly increased resistance. The remaining third of the hypertensives had a normal-low resistance. A high resistance was also independently related to obesity, low physical leisure time activity, and a family history of NIDDM, but not to a family history of hypertension. The statistical analysis implied a sequence of events: low physical activity might cause high resistance, which in turn might cause high blood pressure.

  10. Dyrk1A induces pancreatic β cell mass expansion and improves glucose tolerance.

    PubMed

    Rachdi, Latif; Kariyawasam, Dulanjalee; Aïello, Virginie; Herault, Yann; Janel, Nathalie; Delabar, Jean-Maurice; Polak, Michel; Scharfmann, Raphaël

    2014-01-01

    Type 2 diabetes is caused by a limited capacity of insulin-producing pancreatic β cells to increase their mass and function in response to insulin resistance. The signaling pathways that positively regulate functional β cell mass have not been fully elucidated. DYRK1A (also called minibrain/MNB) is a member of the dual-specificity tyrosine phosphorylation-regulated kinase (DYRK) family. A significant amount of data implicates DYRK1A in brain growth and Down syndrome, and recent data indicate that Dyrk1A haploinsufficient mice have a low functional β cell mass. Here we ask whether Dyrk1A upregulation could be a way to increase functional β cell mass. We used mice overexpressing Dyrk1A under the control of its own regulatory sequences (mBACTgDyrk1A). These mice exhibit decreased glucose levels and hyperinsulinemia in the fasting state. Improved glucose tolerance is observed in these mice as early as 4 weeks of age. Upregulation of Dyrk1A in β cells induces expansion of β cell mass through increased proliferation and cell size. Importantly, mBACTgDyrk1A mice are protected against high-fat-diet-induced β cell failure through increase in β cell mass and insulin sensitivity. These studies show the crucial role of the DYRK1A pathway in the regulation of β cell mass and carbohydrate metabolism in vivo. Activating the DYRK1A pathway could thus represent an innovative way to increase functional β cell mass. PMID:24870561

  11. Corneal Confocal Microscopy Detects Neuropathy in Subjects With Impaired Glucose Tolerance

    PubMed Central

    Asghar, Omar; Petropoulos, Ioannis N.; Alam, Uazman; Jones, Wendy; Jeziorska, Maria; Marshall, Andrew; Ponirakis, Georgios; Fadavi, Hassan; Boulton, Andrew J.M.; Tavakoli, Mitra

    2014-01-01

    OBJECTIVE Impaired glucose tolerance (IGT) represents one of the earliest stages of glucose dysregulation and is associated with macrovascular disease, retinopathy, and microalbuminuria, but whether IGT causes neuropathy is unclear. RESEARCH DESIGN AND METHODS Thirty-seven subjects with IGT and 20 age-matched control subjects underwent a comprehensive evaluation of neuropathy by assessing symptoms, neurological deficits, nerve conduction studies, quantitative sensory testing, heart rate variability deep breathing (HRVdb), skin biopsy, and corneal confocal microscopy (CCM). RESULTS Subjects with IGT had a significantly increased neuropathy symptom profile (P < 0.001), McGill pain index (P < 0.001), neuropathy disability score (P = 0.001), vibration perception threshold (P = 0.002), warm threshold (P = 0.006), and cool threshold (P = 0.03), with a reduction in intraepidermal nerve fiber density (P = 0.03), corneal nerve fiber density (P < 0.001), corneal nerve branch density (P = 0.002), and corneal nerve fiber length (P = 0.05). No significant difference was found in sensory and motor nerve amplitude and conduction velocity or HRVdb. CONCLUSIONS Subjects with IGT have evidence of neuropathy, particularly small-fiber damage, which can be detected using skin biopsy and CCM. PMID:24969581

  12. [Effect of aging and physical inactivity on glucose tolerance and insulin sensitivity].

    PubMed

    Sato, Y; Yamanouchi, K; Nakajima, H; Shinozaki, T; Fujii, S; Chikada, N; Suzuki, Y; Chikada, K; Kato, K; Oshida, Y

    1990-09-01

    It has been well documented that glucose intolerance is associated with aging, but it is not yet clear whether this phenomenon is due to the aging process itself or is secondary to the appearance of other age-related conditions among which physical inactivity is one of most important variables. To evaluate the effect of aging process and/or physical inactivity on insulin action, this study was undertaken using the euglycemic insulin clamp technique and the oral glucose tolerance test (OGTT). Subjects without diabetes mellitus and other serious diseases consisted of 14 non-obese aged individuals and 10 young controls (YC group), ranging in age from 63 to 85 yrs, and from 19 to 21 yrs, respectively. The aged individuals were further divided into two groups (one was termed as the AS group, in which 7 aged subjects had been confined to bed for at least 3 months and the other was termed as the AC group in which 7 aged controls kept their daily physical activity such as walking). The results of OGTT did not show any remarkable differences between AC and YC groups. In the AS group, however, glucose intolerance and low insulin response during OGTT were observed. In view of the tissue insulin action, MCR, which is thought as a reliable marker for tissue insulin action, evaluated by euglycemic insulin clamp was 5.31 +/- 0.68, 8.57 +/- 1.20, 9.60 +/- 0.35 ml/kg/min in the AS, AC and YC groups, respectively (AS less than AC, p less than 0.05, AS less than YC, p less than 0.01, AC less than YCM, N.S.).(ABSTRACT TRUNCATED AT 250 WORDS)

  13. Postpartum Glucose Testing Rates Following Gestational Diabetes Mellitus and Factors Affecting Testing Non-compliance from Four Tertiary Centers in Korea.

    PubMed

    Cho, Geum Joon; An, Jung-Joo; Choi, Suk-Joo; Oh, Soo-Young; Kwon, Han-Sung; Hong, Soon-Cheol; Kwon, Ja-Young

    2015-12-01

    The purpose of this study was to investigate postpartum glucose testing rates in patients with gestational diabetes mellitus (GDM) and to determine factors affecting testing non-compliance in the Korean population. This was a retrospective study of 1,686 patients with GDM from 4 tertiary centers in Korea and data were obtained from medical records. Postpartum glucose testing was conducted using a 2-hr 75-g oral glucose tolerance, fasting glucose, or hemoglobin A1C test. Test results were categorized as normal, prediabetic, and diabetic. The postpartum glucose testing rate was 44.9% (757/1,686 patients); and of 757 patients, 44.1% and 18.4% had pre-diabetes and diabetes, respectively. According to the multivariate analysis, patients with a high parity, larger weight gain during pregnancy, and referral from private clinics due to reasons other than GDM treatment were less likely to receive postpartum glucose testing. However, patients who had pharmacotherapy for GDM were more likely to be screened. In this study, 55.1% of patients with GDM failed to complete postpartum glucose testing. Considering the high prevalence of diabetes (18.4%) at postpartum, clinicians should emphasize the importance of postpartum diabetes screening to patients with factors affecting testing noncompliance.

  14. Identification of Differential Responses to an Oral Glucose Tolerance Test in Healthy Adults

    PubMed Central

    Morris, Ciara; O’Grada, Colm; Ryan, Miriam; Roche, Helen M.; Gibney, Michael J.; Gibney, Eileen R.; Brennan, Lorraine

    2013-01-01

    Background In recent years an individual’s ability to respond to an acute dietary challenge has emerged as a measure of their biological flexibility. Analysis of such responses has been proposed to be an indicator of health status. However, for this to be fully realised further work on differential responses to nutritional challenge is needed. This study examined whether metabolic phenotyping could identify differential responders to an oral glucose tolerance test (OGTT) and examined the phenotypic basis of the response. Methods and Results A total of 214 individuals were recruited and underwent challenge tests in the form of an OGTT and an oral lipid tolerance test (OLTT). Detailed biochemical parameters, body composition and fitness tests were recorded. Mixed model clustering was employed to define 4 metabotypes consisting of 4 different responses to an OGTT. Cluster 1 was of particular interest, with this metabotype having the highest BMI, triacylglycerol, hsCRP, c-peptide, insulin and HOMA- IR score and lowest VO2max. Cluster 1 had a reduced beta cell function and a differential response to insulin and c-peptide during an OGTT. Additionally, cluster 1 displayed a differential response to the OLTT. Conclusions This work demonstrated that there were four distinct metabolic responses to the OGTT. Classification of subjects based on their response curves revealed an “at risk” metabolic phenotype. PMID:23991163

  15. Beta-cell function, incretin effect, and incretin hormones in obese youth along the span of glucose tolerance from normal to prediabetes to Type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Using the hyperglycemic and euglycemic clamp, we demonstrated impaired Beta-cell function in obese youth with increasing dysglycemia. Herein we describe oral glucose tolerance test (OGTT)-modeled Beta-cell function and incretin effect in obese adolescents spanning the range of glucose tolerance. Bet...

  16. 25-hydroxyvitamin D in obese youth across the spectrum of glucose tolerance from normal to prediabetes to type 2 diabetes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this study was to 1) determine if plasma 25-hydroxyvitamin D (25[OH]D) concentrations differ among obese youth with normal glucose tolerance (NGT) versus prediabetes versus type 2 diabetes and 2) assess the relationships between 25(OH)D and in vivo insulin sensitivity and Beta-cell ...

  17. Inhibition of pancreatic β-cell Ca2+/calmodulin-dependent protein kinase II reduces glucose-stimulated calcium influx and insulin secretion, impairing glucose tolerance.

    PubMed

    Dadi, Prasanna K; Vierra, Nicholas C; Ustione, Alessandro; Piston, David W; Colbran, Roger J; Jacobson, David A

    2014-05-01

    Glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells is caused by Ca(2+) entry via voltage-dependent Ca(2+) channels. CaMKII is a key mediator and feedback regulator of Ca(2+) signaling in many tissues, but its role in β-cells is poorly understood, especially in vivo. Here, we report that mice with conditional inhibition of CaMKII in β-cells show significantly impaired glucose tolerance due to decreased GSIS. Moreover, β-cell CaMKII inhibition dramatically exacerbates glucose intolerance following exposure to a high fat diet. The impairment of islet GSIS by β-cell CaMKII inhibition is not accompanied by changes in either glucose metabolism or the activities of KATP and voltage-gated potassium channels. However, glucose-stimulated Ca(2+) entry via voltage-dependent Ca(2+) channels is reduced in islet β-cells with CaMKII inhibition, as well as in primary wild-type β-cells treated with a peptide inhibitor of CaMKII. The levels of basal β-cell cytoplasmic Ca(2+) and of endoplasmic reticulum Ca(2+) stores are also decreased by CaMKII inhibition. In addition, CaMKII inhibition suppresses glucose-stimulated action potential firing frequency. These results reveal that CaMKII is a Ca(2+) sensor with a key role as a feed-forward stimulator of β-cell Ca(2+) signals that enhance GSIS under physiological and pathological conditions.

  18. Anti-hyperglycaemic activity of swietenia macrophylla king (meliaceae) seed extracts in normoglycaemic rats undergoing glucose tolerance tests

    PubMed Central

    2013-01-01

    Background Swietenia macrophylla King (Meliaceae) is used to treat diabetes mellitus in Malaysia. This study aims to evaluate the anti-hyperglycaemic potential of petroleum ether (PE), chloroform (CE) and methanol (ME) extracts of S. macrophylla seeds, in normoglycaemic and streptozotocin (STZ)-induced diabetic rats. Methods Following treatment of normoglycaemic rats with S. macrophylla seed extracts, hypoglycaemic and intraperitoneal glucose tolerance tests (IPGTT) were performed, and blood glucose concentrations were measured. Similarly, glucose concentrations were measured after 1 and 14 days of extract treatment of STZ-induced diabetic rats. Glucose absorption by isolated everted intestine and glucose uptake by isolated abdominal muscle were tested after treatment with seed extracts. Gas chromatography mass spectrometry (GC-MS) analysis was performed on PE of S. macrophylla seeds to identify the compounds responsible for its activity. Results None of the extracts had a significant effect on the blood glucose levels of 60 randomly selected normoglycaemic (normal) and diabetic rats undergoing hypoglycaemic tests. PE, however, significantly reduced blood glucose levels in 30 randomly selected normoglycaemic rats undergoing IPGTT tests 30–120 minutes after glucose administration. Repeated doses of 1000 mg/kg and 500 mg/kg PE to STZ-induced diabetic rats for 14 days did not reduce blood glucose levels significantly. PE did not significantly reduced the intestinal absorption of glucose, but significantly increased glucose uptake by abdominal muscle in the absence or presence of insulin. GC-MS analysis indicated that diterpenes, triterpenoids, fatty acid methyl esters, aldehydes and phytosterols may be responsible for the glucose lowering effects of PE. Conclusion PE extracts of S. macrophylla seeds showed anti-hyperglycaemic activity on IPGTTs . GC-MS analysis on the PE revealed that several compounds, including fucosterol and β-sitosterol, may be responsible for

  19. Insulin and glucose regulation.

    PubMed

    Ralston, Sarah L

    2002-08-01

    Abnormally high or low blood glucose and insulin concentrations after standardized glucose tolerance tests can reflect disorders such as pituitary dysfunction, polysaccharide storage myopathies, and other clinical disorders. Glucose and insulin responses, however, are modified by the diet to which the animal has adapted, time since it was last fed, and what it was fed. Body fat (obesity), fitness level, physiologic status, and stress also alter glucose and insulin metabolism. Therefore, it is important to consider these factors when evaluating glucose and insulin tests, especially if only one sample it taken. This article describes the factors affecting glucose and insulin metabolism in horses and how they might influence the interpretation of standardized tests of glucose tolerance.

  20. Efficacy of Garcinia Cambogia on Body Weight, Inflammation and Glucose Tolerance in High Fat Fed Male Wistar Rats

    PubMed Central

    Sripradha, Ramalingam

    2015-01-01

    Introduction: Obesity leads to derangements in lipid and glucose homeostasis resulting in various metabolic complications. Plants containing vital phytochemicals are known to posses anti obesity properties and have proved to exert beneficial effects in obesity. Objectives: The present study was aimed to investigate the effects of Garcinia Cambogia on body weight, glucose tolerance and inflammation in high fat diet fed male Wistar rats. Materials and Methods: Five month old male wistar rats (n=40) were divided into four groups. Two groups were fed with standard rodent diet and the remaining two with 30% high fat diet. One group in each of the two sets received the crude ethanolic extract of Garcinia Cambogia at a dose of 400mg/kg body weight/day for ten weeks. Body weight, intraperitoneal glucose tolerance test, leptin, tumour necrosis factor-α (TNF-α) and renal function (urea, creatinine, uric acid) were studied. Results: High fat diet fed rats showed increased body weight gain, glucose intolerance, elevated levels of plasma leptin and TNF-α. Supplementation of Garcinia Cambogia extract (GE) along with high fat diet significantly decreased body weight gain, glucose intolerance, plasma leptin and TNF-α level. No significant changes were observed in the renal function parameters in any of the groups. Conclusion: Supplementation of the Garcinia Cambogia extract with high fat diet reduced body weight gain, inflammation and glucose intolerance. PMID:25859449

  1. Galápagos mockingbirds tolerate introduced parasites that affect Darwin's finches.

    PubMed

    Knutie, Sarah A; Owen, Jeb P; McNew, Sabrina M; Bartlow, Andrew W; Arriero, Elena; Herman, Jordan M; DiBlasi, Emily; Thompson, Michael; Koop, Jennifer A H; Clayton, Dale H

    2016-04-01

    Introduced parasites threaten native host species that lack effective defenses. Such parasites increase the risk of extinction, particularly in small host populations like those on islands. If some host species are tolerant to introduced parasites, this could amplify the risk of the parasite to vulnerable host species. Recently, the introduced parasitic nest fly Philornis downsi has been implicated in the decline of Darwin's finch populations in the Galápagos Islands. In some years, 100% of finch nests fail due to P. downsi; however, other common host species nesting near Darwin's finches, such as the endemic Galápagos mockingbird (Mimus parvulus), appear to be less affected by P. downsi. We compared effects of P. downsi on mockingbirds and medium ground finches (Geospiza fortis) on Santa Cruz Island in the Galápagos. We experimentally manipulated the abundance of P. downsi in nests of mockingbirds and finches to measure the direct effect of the parasite on the reproductive success of each species of host. We also compared immunological and behavioral responses by each species of host to the fly. Although nests of the two host species had similar parasite densities, flies decreased the fitness of finches but not mockingbirds. Neither host species had a significant antibody-mediated immune response to P. downsi. Moreover, finches showed no significant increase in begging, parental provisioning, or plasma glucose levels in response to the flies. In contrast, parasitized mockingbird nestlings begged more than nonparasitized mockingbird nestlings. Greater begging was correlated with increased parental provisioning behavior, which appeared to compensate for parasite damage. The results of our study suggest that finches are negatively affected by P. downsi because they do not have such behavioral mechanisms for energy compensation. In contrast, mockingbirds are capable of compensation, making them tolerant hosts, and a possible indirect threat to Darwin's finches.

  2. Galápagos mockingbirds tolerate introduced parasites that affect Darwin's finches.

    PubMed

    Knutie, Sarah A; Owen, Jeb P; McNew, Sabrina M; Bartlow, Andrew W; Arriero, Elena; Herman, Jordan M; DiBlasi, Emily; Thompson, Michael; Koop, Jennifer A H; Clayton, Dale H

    2016-04-01

    Introduced parasites threaten native host species that lack effective defenses. Such parasites increase the risk of extinction, particularly in small host populations like those on islands. If some host species are tolerant to introduced parasites, this could amplify the risk of the parasite to vulnerable host species. Recently, the introduced parasitic nest fly Philornis downsi has been implicated in the decline of Darwin's finch populations in the Galápagos Islands. In some years, 100% of finch nests fail due to P. downsi; however, other common host species nesting near Darwin's finches, such as the endemic Galápagos mockingbird (Mimus parvulus), appear to be less affected by P. downsi. We compared effects of P. downsi on mockingbirds and medium ground finches (Geospiza fortis) on Santa Cruz Island in the Galápagos. We experimentally manipulated the abundance of P. downsi in nests of mockingbirds and finches to measure the direct effect of the parasite on the reproductive success of each species of host. We also compared immunological and behavioral responses by each species of host to the fly. Although nests of the two host species had similar parasite densities, flies decreased the fitness of finches but not mockingbirds. Neither host species had a significant antibody-mediated immune response to P. downsi. Moreover, finches showed no significant increase in begging, parental provisioning, or plasma glucose levels in response to the flies. In contrast, parasitized mockingbird nestlings begged more than nonparasitized mockingbird nestlings. Greater begging was correlated with increased parental provisioning behavior, which appeared to compensate for parasite damage. The results of our study suggest that finches are negatively affected by P. downsi because they do not have such behavioral mechanisms for energy compensation. In contrast, mockingbirds are capable of compensation, making them tolerant hosts, and a possible indirect threat to Darwin's finches

  3. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis. PMID:24656388

  4. Green tea decoction improves glucose tolerance and reduces weight gain of rats fed normal and high-fat diet.

    PubMed

    Snoussi, Chahira; Ducroc, Robert; Hamdaoui, Mohamed Hédi; Dhaouadi, Karima; Abaidi, Houda; Cluzeaud, Francoise; Nazaret, Corinne; Le Gall, Maude; Bado, André

    2014-05-01

    Green tea containing polyphenols exerts antidiabetic and antiobesity effects, but the mechanisms involved are not fully understood. In this study, we first analyzed and compared polyphenol compounds [epigallocatechin gallate (EGCG), epigallocatechin (EGC)] in decoction of green tea leaves versus usual green tea extracts. Second, the effects of acute (30 min) or chronic (6 weeks) oral administration of green tea decoction (GTD) on intestinal glucose absorption were studied in vitro in Ussing chamber, ex vivo using isolated jejunal loops and in vivo through glucose tolerance tests. Finally, we explore in rat model fed normal or high-fat diet the effects of GTD on body weight, blood parameters and on the relative expression of glucose transporters SGLT-1, GLUT2 and GLUT4. GTD cooked for 15 min contained the highest amounts of phenolic compounds. In fasted rats, acute administration of GTD inhibited SGLT-1 activity, increased GLUT2 activity and improved glucose tolerance. Similarly to GTD, acute administration of synthetic phenolic compounds (2/3 EGCG+1/3 EGC) inhibited SGLT-1 activity. Chronic administration of GTD in rat fed high-fat diet reduced body weight gain, circulating triglycerides and cholesterol and improved glucose tolerance. GTD-treated rats for 6 weeks display significantly reduced SGLT-1 and increased GLUT2 mRNA levels in the jejunum mucosa. Moreover, adipose tissue GLUT4 mRNA levels were increased. These results indicate that GTD, a traditional beverage rich in EGCG and EGC reduces intestinal SGLT-1/GLUT2 ratio, a hallmark of regulation of glucose absorption in enterocyte, and enhances adipose GLUT4 providing new insights in its possible role in the control of glucose homeostasis.

  5. Changes in glucose tolerance and plasma insulin during lipid-lowering treatment with diet, clofibrate and niceritrol.

    PubMed

    Lithell, H; Vessby, B; Hellsing, K

    1982-06-01

    In an effort to reduce serum lipids in patients with atherosclerotic manifestations, a combined treatment with a conventional lipid-lowering diet, clofibrate and niceritrol was used. The effect on glucose metabolism of such treatment was studied. Among the 106 patients 66 took the full dose of both drugs and of these 51 were weight-stable and non-diabetic. The effects of the diet and the drugs were evaluated in this subsample. Diet had no effect on fasting blood glucose concentration, the K value of an intravenous glucose tolerance test (IVGTT) and concentrations of serum insulin. Niceritrol treatment was associated with increased blood glucose, decreased K value, elevated fasting serum insulin and serum insulin at 60 min during IVGTT. Clofibrate had the opposite effects to niceritrol and when both drugs were combined, carbohydrate metabolism was unchanged compared with the pre-treatment state. PMID:7052096

  6. Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity

    PubMed Central

    Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori

    2014-01-01

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut−/−) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut−/− mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut−/− mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut−/− mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis. PMID:25331291

  7. Impairment of vesicular ATP release affects glucose metabolism and increases insulin sensitivity.

    PubMed

    Sakamoto, Shohei; Miyaji, Takaaki; Hiasa, Miki; Ichikawa, Reiko; Uematsu, Akira; Iwatsuki, Ken; Shibata, Atsushi; Uneyama, Hisayuki; Takayanagi, Ryoichi; Yamamoto, Akitsugu; Omote, Hiroshi; Nomura, Masatoshi; Moriyama, Yoshinori

    2014-10-21

    Neuroendocrine cells store ATP in secretory granules and release it along with hormones that may trigger a variety of cellular responses in a process called purinergic chemical transmission. Although the vesicular nucleotide transporter (VNUT) has been shown to be involved in vesicular storage and release of ATP, its physiological relevance in vivo is far less well understood. In Vnut knockout (Vnut(-/-)) mice, we found that the loss of functional VNUT in adrenal chromaffin granules and insulin granules in the islets of Langerhans led to several significant effects. Vesicular ATP accumulation and depolarization-dependent ATP release were absent in the chromaffin granules of Vnut(-/-) mice. Glucose-responsive ATP release was also absent in pancreatic β-cells in Vnut(-/-) mice, while glucose-responsive insulin secretion was enhanced to a greater extent than that in wild-type tissue. Vnut(-/-) mice exhibited improved glucose tolerance and low blood glucose upon fasting due to increased insulin sensitivity. These results demonstrated an essential role of VNUT in vesicular storage and release of ATP in neuroendocrine cells in vivo and suggest that vesicular ATP and/or its degradation products act as feedback regulators in catecholamine and insulin secretion, thereby regulating blood glucose homeostasis.

  8. Are the WHO (1980) criteria for the 75 g oral glucose tolerance test appropriate for pregnant women?

    PubMed

    Cheng, L C; Salmon, Y M

    1993-07-01

    To assess the normal response to the 75 gm oral glucose tolerance test (OGTT) in normal pregnant women, healthy Chinese and Malay women who had been referred to the antenatal clinic of the Department of Reproductive Medicine, Kandang Kerbau Hospital, Singapore, were evaluated. The women were selected on the basis of having none of the generally accepted risk factors for diabetes mellitus: their age was 35 years, they weighed 80 kg, they did not have a personal history of diabetes or a family history of diabetes or a family history of diabetes in first degree relatives, nor did they have a history of babies weighing 4000 gm at birth, still-births, neonatal deaths, congenital malformations, or recurrent miscarriages. All OGTTs were performed after 28 weeks of gestation. The fasting blood sample was taken from the antecubital vein. Further samples were taken 1 and 2 hours after the glucose drink. A glucose analyzer using 5 mcl of plasma was employed. The analytical method was based on the glucose oxidase/peroxidase/aminophenazone process. There was no significant difference in mean glucose levels at corresponding points of the OGTT in Chinese and Malay women. correlation calculations confirmed the absence of any influence of gestational age after 28 weeks on glucose tolerance. Of the 64 women, 47 were Chinese and 17 Malays; 20 wee nulliparous, and 44 were parous. Their mean age was 27.2 years (range 18-35). The mean birthweight of the infants was 3140 gm (range 2094-4240 gm). There were 33 female and 31 male infants. The mean apgar scores at 1 and 5 min were 8.8 (range 7-9) and 9.0 (range 6-10). The mean values and the proposed upper limits of normality for the 75 gm OGTT were 3.9 and 4.9 mmol/1, respectively. 6 women had abnormal OGTT results according to the WHO criteria (fasting glucose 6 mmol/1; 2 hour glucose 8 mmol/1).

  9. Mild insulin resistance during oral glucose tolerance test (OGTT) in women with acne.

    PubMed

    Aizawa, H; Niimura, M

    1996-08-01

    The purpose of this study was to evaluate serum levels of basal insulin and glucose-stimulated insulin, and to evaluate their correlations with androgen levels in women with acne. Serum levels of total testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEA-S), sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IFG-1), and immunoreactive insulin (IRI) were measured and compared in thirty women with moderate or severe acne and thirteen healthy controls. Serum FT, DHT and DHEA-S levels in the acne group were significantly higher than those in the control group. In the acne group, there were no significant correlations between insulin or IGF-1 levels and T, FT, DHT and SHBG, despite the positive correlation between insulin and IGF-1. In order to determine the effects of insulin secretion as a dynamic response to an oral glucose tolerance test (OGTT) on serum androgen levels in acne patients, we examined the responses of serum insulin and androgen levels to a 75 g, 2 hour OGTT in the acne group and in the control group. Basal insulin levels were not significantly higher than those in the control group, but the summed insulin levels during the OGTT in the acne group were significantly higher than those in the control group. Serum T and FT levels in the acne group decreased during the OGTT, but these changes were not so significant when compared to normal controls. In conclusion, we tried to demonstrate mild insulin resistance during the OGTT in acne patients. However, postmeal transient hyperinsulinemia does not seem to play an important role in determining hyperandrogenemia in acne patients. PMID:8854583

  10. Antidiabetic efficacy of bradykinin antagonist R-954 on glucose tolerance test in diabetic type 1 mice.

    PubMed

    Catanzaro, Orlando L; Dziubecki, Damian; Obregon, Pablo; Rodriguez, Ricardo R; Sirois, Pierre

    2010-04-01

    Insulin-dependent diabetes mellitus (type 1 diabetes) is an inflammatory autoimmune disease associated with many complications including nephropathy, retinopathy, neuropathy and hyperalgesia. Experimental evidence has shown that the bradykinin B1 receptor (BKB1-R) is involved in the development of type 1 diabetes and found to be upregulated alongside the disease. In the present study the effects of the selective BKB1-R antagonist the R-954 (Ac-Orn-[Oic(2), alpha-MePhe(5), D-beta Nal(7), Ile(8) ]des-Arg(9)-BK and the BKB1-R agonist des Arg(9)-BK (DBK) were studied on diabetic hyperglycemia. Diabetic type 1 was induced in C57 BL/KsJ mdb male mice by five consecutives doses of STZ (45mg/kg i.p.). A glucose tolerance test (GTT) was performed by an intraperitoneal administration of glucose, 8, 12 and 18days after the diabetes induction. The induction of type 1 diabetes provoked a significant hyperglycemia levels in diabetic mice at 12 and 18days after STZ. The administration of R-954 (400microg/kg i.p.) at 12 and 18days after STZ returned the glycemia levels of this animals to normal values. In addition the administration of DKB (300microg/kg i.p.) significantly potentiated the diabetes-induced hyperglycemia; this effect that was totally reversed by R-954. These results provide further evidence for the implication of BKB1-R in the type 1 diabetes mellitus (insulitis). PMID:20092893

  11. Prevalence of and Factors Influencing Impaired Glucose Tolerance Among Hepatitis B Carriers

    PubMed Central

    Park, Boyoung; Jung, Kyu-Won; Oh, Chang-Mo; Choi, Kui Son; Suh, Mina; Jun, Jae Kwan

    2014-01-01

    Abstract Diabetes is associated with a poor prognosis for liver disease, particularly in chronic hepatitis carriers. We investigated the prevalence of factors associated with impaired glucose tolerance (IGT) including diabetes and impaired fasting glucose (IFG) among individuals with hepatitis B virus (HBV) infection. We used data from the Korean National Health and Nutrition Examination Survey, a nationwide cross-sectional survey conducted between 2007 and 2011. Sociodemographic information was collected using a structured questionnaire. The HBV surface antigen, liver enzymes, and lipid profile were measured from blood samples. IFG was found in 18.1% of HBV carriers and 19.3% of noncarriers (P = 0.25). Diabetes was observed in 10.0% of HBV carriers and 12.2% of noncarriers (P = 0.08). Lower level of educational attainment was associated with a higher prevalence of IGT: high school education (odds ratio [OR] = 1.94 [95% confidence interval (CI) 1.14–3.29] and less than a high school education (OR = 3.20 [95% CI, 1.66–6.15] vs more than or equal to a college education. Elevated alanine transaminase and triglyceride by 10 were associated with increased risk of IGT (OR = 1.10 [95% CI, 1.01–1.20] and OR = 1.04 [95% CI, 1.01–1.07], respectively). Being a man and older in age were associated with a higher prevalence of IGT, and individuals with a low body mass index were at lower risk for IGT. Given the synergistic effect of diabetes and HBV infection on liver disease prognosis, we recommend targeted IGT screening and follow-up for HBV carriers. These efforts should include health policies and intervention programs aimed at reducing educational disparities and encouraging early control of elevated liver enzymes or lipid profiles. PMID:25365406

  12. Impaired HDL cholesterol efflux in metabolic syndrome is unrelated to glucose tolerance status: the CODAM study

    PubMed Central

    Annema, Wijtske; Dikkers, Arne; de Boer, Jan Freark; van Greevenbroek, Marleen M. J.; van der Kallen, Carla J. H.; Schalkwijk, Casper G.; Stehouwer, Coen D. A.; Dullaart, Robin P. F.; Tietge, Uwe J. F.

    2016-01-01

    Type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) increase atherosclerotic cardiovascular disease risk. Cholesterol efflux capacity (CEC) is a key metric of the anti-atherosclerotic functionality of high-density lipoproteins (HDL). The present study aimed to delineate if T2DM and MetS cross-sectionally associate with altered CEC in a large high cardiometabolic risk population. CEC was determined from THP-1 macrophage foam cells towards apolipoprotein B-depleted plasma from 552 subjects of the CODAM cohort (288 controls, 126 impaired glucose metabolism [IGM], 138 T2DM). MetS was present in 297 participants. CEC was not different between different glucose tolerance categories but was lower in MetS (P < 0.001), at least partly attributable to lower HDL cholesterol (HDL-C) and apoA-I levels (P < 0.001 for each). Low grade inflammation was increased in IGM, T2DM and MetS as determined by a score comprising 8 different biomarkers (P < 0.05-< 0.001; n = 547). CEC inversely associated with low-grade inflammation taking account of HDL-C or apoA-I in MetS (P < 0.02), but not in subjects without MetS (interaction: P = 0.015). This study demonstrates that IGM and T2DM do not impact the HDL CEC function, while efflux is lower in MetS, partly dependent on plasma HDL-C levels. Enhanced low-grade inflammation in MetS may conceivably impair CEC even independent of HDL-C and apoA-I. PMID:27270665

  13. Importance of glucose-6-phosphate dehydrogenase (G6PDH) for vanillin tolerance in Saccharomyces cerevisiae.

    PubMed

    Nguyen, Trinh Thi My; Kitajima, Sakihito; Izawa, Shingo

    2014-09-01

    Vanillin is derived from lignocellulosic biomass and, as one of the major biomass conversion inhibitors, inhibits yeast growth and fermentation. Vanillin was recently shown to induce the mitochondrial fragmentation and formation of mRNP granules such as processing bodies and stress granules in Saccharomyces cerevisiae. Furfural, another major biomass conversion inhibitor, also induces oxidative stress and is reduced in an NAD(P)H-dependent manner to its less toxic alcohol derivative. Therefore, the pentose phosphate pathway (PPP), through which most NADPH is generated, plays a role in tolerance to furfural. Although vanillin also induces oxidative stress and is reduced to vanillyl alcohol in a NADPH-dependent manner, the relationship between vanillin and PPP has not yet been investigated. In the present study, we examined the importance of glucose-6-phosphate dehydrogenase (G6PDH), which catalyzes the rate-limiting NADPH-producing step in PPP, for yeast tolerance to vanillin. The growth of the null mutant of G6PDH gene (zwf1Δ) was delayed in the presence of vanillin, and vanillin was efficiently reduced in the culture of wild-type cells but not in the culture of zwf1Δ cells. Furthermore, zwf1Δ cells easily induced the activation of Yap1, an oxidative stress responsive transcription factor, mitochondrial fragmentation, and P-body formation with the vanillin treatment, which indicated that zwf1Δ cells were more susceptible to vanillin than wild type cells. These findings suggest the importance of G6PDH and PPP in the response of yeast to vanillin.

  14. Pre-Type 1 Diabetes Dysmetabolism: Maximal sensitivity achieved with Both Oral and Intravenous Glucose Tolerance Testing

    PubMed Central

    Barker, Jennifer M.; McFann, Kim; Harrison, Leonard C.; Fourlanos, Spiros; Krischer, Jeffrey; Cuthbertson, David; Chase, H. Peter; Eisenbarth, George S.; Group, the DPT-1 Study

    2007-01-01

    Objective To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and identify an optimal testing strategy for detecting pre-clinical diabetes. Study design Diabetes Prevention Trial Type 1 randomized subjects to oral (n=372) and parenteral (n=339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. Results Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of FPIR at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline BMI, FPIR and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal first phase insulin response (FPIR) and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs. 73%). Conclusions Most (97%) subjects had abnormal IVGTTs and/or OGTTs prior to the development of diabetes. The highest sensitivity is achieved using both tests. PMID:17188609

  15. Trefoil Factor 3 (TFF3) Is Regulated by Food Intake, Improves Glucose Tolerance and Induces Mucinous Metaplasia

    PubMed Central

    Ge, Hongfei; Gardner, Jonitha; Wu, Xiaosu; Rulifson, Ingrid; Wang, Jinghong; Xiong, Yumei; Ye, Jingjing; Belouski, Edward; Cao, Ping; Tang, Jie; Lee, Ki Jeong; Coberly, Suzanne; Wu, Xinle; Gupte, Jamila; Miao, Lynn; Yang, Li; Nguyen, Natalie; Shan, Bei; Yeh, Wen-Chen; Véniant, Murielle M.; Li, Yang; Baribault, Helene

    2015-01-01

    Trefoil factor 3 (TFF3), also called intestinal trefoil factor or Itf, is a 59 amino acid peptide found as a homodimer predominantly along the gastrointestinal tract and in serum. TFF3 expression is elevated during gastrointestinal adenoma progression and has been shown to promote mucosal wound healing. Here we show that in contrast to other trefoil factor family members, TFF1 and TFF2, TFF3 is highly expressed in mouse duodenum, jejunum and ileum and that its expression is regulated by food intake. Overexpression of TFF3 using a recombinant adeno-associated virus (AAV) vector, or daily administration of recombinant TFF3 protein in vivo improved glucose tolerance in a diet-induced obesity mouse model. Body weight, fasting insulin, triglyceride, cholesterol and leptin levels were not affected by TFF3 treatment. Induction of mucinous metaplasia was observed in mice with AAV-mediated TFF3 overexpression, however, no such adverse histological effect was seen after the administration of recombinant TFF3 protein. Altogether these results suggest that the therapeutic potential of targeting TFF3 to treat T2D may be limited. PMID:26083576

  16. How a tolerant past affects the present: historical tolerance and the acceptance of Muslim expressive rights.

    PubMed

    Smeekes, Anouk; Verkuyten, Maykel; Poppe, Edwin

    2012-11-01

    Three studies, conducted in The Netherlands, examined the relationship between a tolerant representation of national history and the acceptance of Muslim expressive rights. Following self-categorization theory, it was hypothesized that historical tolerance would be associated with greater acceptance of Muslim expressive rights, especially for natives who strongly identify with their national in-group. Furthermore, it was predicted that the positive effect of representations of historical tolerance on higher identifiers' acceptance could be explained by reduced perceptions of identity incompatibility. The results of Study 1 confirmed the first hypothesis, and the results of Study 2 and Study 3 supported the second hypothesis. These findings underline the importance of historical representations of the nation for understanding current reactions toward immigrants. Importantly, the results show that a tolerant representation of national history can elevate acceptance of immigrants, especially among natives who feel a relatively strong sense of belonging to their nation.

  17. Does hyperketonemia affect protein or glucose kinetics in postabsorptive or traumatized man

    SciTech Connect

    Crowe, P.J.; Royle, G.T.; Wagner, D.; Burke, J.F. )

    1989-10-01

    Leucine and glucose turnover were measured using simultaneous infusions of (13C)leucine and (2H)glucose before and during an infusion of Na DL-hydroxybutyrate (Na DL-HB) in overnight-fasted patients the day before and 3 days after total hip replacement. The ketone body infusion before surgery resulted in a significant increase in plasma leucine concentration and leucine turnover, while glucose concentration and turnover decreased. Surgery increased leucine turnover. Ketone body infusion after surgery caused a further increased leucine turnover while turnover fell as before surgery. We suggest that exogenous ketone bodies decrease hepatic glucose production and probably stimulate a rise in protein synthesis above breakdown leading to a decreased nitrogen excretion as observed by other investigators. Despite the metabolic adaptation to trauma, this response was not affected by surgery.

  18. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.

    PubMed

    Muoio, Deborah M; Noland, Robert C; Kovalik, Jean-Paul; Seiler, Sarah E; Davies, Michael N; DeBalsi, Karen L; Ilkayeva, Olga R; Stevens, Robert D; Kheterpal, Indu; Zhang, Jingying; Covington, Jeffrey D; Bajpeyi, Sudip; Ravussin, Eric; Kraus, William; Koves, Timothy R; Mynatt, Randall L

    2012-05-01

    The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance. By converting acetyl-CoA to its membrane permeant acetylcarnitine ester, CrAT regulates mitochondrial and intracellular carbon trafficking. Studies in muscle-specific Crat knockout mice, primary human skeletal myocytes, and human subjects undergoing L-carnitine supplementation support a model wherein CrAT combats nutrient stress, promotes metabolic flexibility, and enhances insulin action by permitting mitochondrial efflux of excess acetyl moieties that otherwise inhibit key regulatory enzymes such as pyruvate dehydrogenase. These findings offer therapeutically relevant insights into the molecular basis of metabolic inflexibility. PMID:22560225

  19. Return for Postpartum Oral Glucose Tolerance Test Following Gestational Diabetes Mellitus.

    PubMed

    Mohd Suan, Mohd Azri

    2015-09-01

    A cross-sectional study was conducted to assess the prevalence and characteristics of women who received a postpartum oral glucose tolerance test and to examine barriers as reported by women who failed to return for the test. Data were collected using a mobile phone-based short messaging service. Only 352 (81.9%) women returned for the test. Women who failed to return for the test were younger (30.1 vs 32.1, P = .003) and did not have a previous history of gestational diabetes (93.6% vs 84.9%, P = .043) compared to women who returned for the test. The commonest reasons given for not returning for the test was "Still waiting for the appointment date for the test" (37.2%), "had family/health problems" (11.5%), and "busy/no time" (10.3%). Flexible time for the test, active involvement from health care staff, and strengthening continuous care system were among the interventions needed to improve the return rate for this screening test.

  20. Return for Postpartum Oral Glucose Tolerance Test Following Gestational Diabetes Mellitus.

    PubMed

    Mohd Suan, Mohd Azri

    2015-09-01

    A cross-sectional study was conducted to assess the prevalence and characteristics of women who received a postpartum oral glucose tolerance test and to examine barriers as reported by women who failed to return for the test. Data were collected using a mobile phone-based short messaging service. Only 352 (81.9%) women returned for the test. Women who failed to return for the test were younger (30.1 vs 32.1, P = .003) and did not have a previous history of gestational diabetes (93.6% vs 84.9%, P = .043) compared to women who returned for the test. The commonest reasons given for not returning for the test was "Still waiting for the appointment date for the test" (37.2%), "had family/health problems" (11.5%), and "busy/no time" (10.3%). Flexible time for the test, active involvement from health care staff, and strengthening continuous care system were among the interventions needed to improve the return rate for this screening test. PMID:26041835

  1. Oocyte aging-induced Neuronatin (NNAT) hypermethylation affects oocyte quality by impairing glucose transport in porcine

    PubMed Central

    Gao, Ying-Ying; Chen, Li; Wang, Tao; Nie, Zheng-Wen; Zhang, Xia; Miao, Yi-Liang

    2016-01-01

    DNA methylation plays important roles in regulating many physiological behaviors; however, few studies were focused on the changes of DNA methylation during oocyte aging. Early studies showed that some imprinted genes’ DNA methylation had been changed in aged mouse oocytes. In this study, we used porcine oocytes to test the hypothesis that oocyte aging would alter DNA methylation pattern of genes and disturb their expression in age oocytes, which affected the developmental potential of oocytes. We compared several different types of genes and found that the expression and DNA methylation of Neuronatin (NNAT) were disturbed in aged oocytes significantly. Additional experiments demonstrated that glucose transport was impaired in aged oocytes and injection of NNAT antibody into fresh oocytes led to the same effects on glucose transport. These results suggest that the expression of NNAT was declined by elevating DNA methylation, which affected oocyte quality by decreasing the ability of glucose transport in aged oocytes. PMID:27782163

  2. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus.

    PubMed

    Zhang, Dali; Xiong, Wei; Jackson, Michael F; Parkinson, Fiona E

    2016-07-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5'-nucleotidase activity. Wild-type (CD73(+/+)) and ecto-5'-nucleotidase-deficient (CD73(-/-)) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73(+/+) mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73(+/+) mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg(2+) conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5'-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73(-/-) mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5'-nucleotidase activity. PMID:27189965

  3. Ethanol Tolerance Affects Endogenous Adenosine Signaling in Mouse Hippocampus

    PubMed Central

    Zhang, Dali; Xiong, Wei; Jackson, Michael F.

    2016-01-01

    Ethanol has many pharmacological effects, including increases in endogenous adenosine levels and adenosine receptor activity in brain. Ethanol consumption is associated with both positive and negative health outcomes, but tolerance to the behavioral effects of ethanol can lead to increased consumption, which increases the risk of negative health outcomes. The present study was performed to test whether a 7-day treatment with ethanol is linked to reduced adenosine signaling and whether this is a consequence of reduced ecto-5′-nucleotidase activity. Wild-type (CD73+/+) and ecto-5′-nucleotidase-deficient (CD73−/−) mice were treated with ethanol (2 g/kg) or saline for 7 days. In CD73+/+ mice, repeated ethanol treatment reduced the hypothermic and ataxic effects of acute ethanol, indicating the development of tolerance to the acute effects of ethanol. In CD73+/+ mice, this 7-day ethanol treatment led to increased hippocampal synaptic activity and reduced adenosine A1 receptor activity under both basal and low Mg2+ conditions. These effects of ethanol tolerance were associated with an 18% decrease in activity of ecto-5′-nucleotidase activity in hippocampal cell membranes. In contrast, ethanol treatment was not associated with changes in synaptic activity or adenosine signaling in hippocampus from CD73−/− mice. These data indicate that ethanol treatment is associated with a reduction in adenosine signaling through adenosine A1 receptors in hippocampus, mediated, at least in part, via reduced ecto-5′-nucleotidase activity. PMID:27189965

  4. Prevalence and risk factors of impaired glucose tolerance and diabetes mellitus at diagnosis of acromegaly: a study in 148 patients.

    PubMed

    Alexopoulou, Orsalia; Bex, Marie; Kamenicky, Peter; Mvoula, Augustine Bessomo; Chanson, Philippe; Maiter, Dominique

    2014-02-01

    Acromegaly is frequently associated with alterations of glucose metabolism but factors predisposing these patients to exhibit impaired glucose tolerance or overt diabetes at diagnosis are poorly understood. This study included 148 patients with newly diagnosed acromegaly (80 men; mean age: 45 ± 20 year). All patients underwent an oral glucose tolerance test (OGTT), unless already treated for diabetes. Insulin sensitivity (S) and β-cell function (B) were also evaluated by homeostasis model assessment (HOMA). Normal glucose tolerance (NGT) was observed in 67 patients (46 %), impaired fasting glycaemia (IFG) or glucose tolerance (IGT) were found in 39 (26 %), and diabetes mellitus (DM) in 42 (28 %). NGT patients were 10 years younger than patients with abnormal glucose metabolism (p < 0.001) and diabetic patients had a higher BMI (p < 0.05). While HOMA-S was similar, HOMA-B was reduced in the IFG/IGT group (p < 0.05) and further in the DM group (p < 0.001). IGF-I z-score was higher in IFG/IGT (5.2 ± 1.4) and DM patients (5.4 ± 1.3) than in NGT patients (4.4 ± 1.3; p < 0.05), but fasting and post-OGTT GH levels were not different between groups. In multivariate analyses, family history of diabetes and IGF-I were associated with hyperglycaemia, BMI and IGF-I predicted insulin resistance, and age was inversely correlated with β-cell function. Impaired glucose metabolism is present in more than 50 % of patients at diagnosis of acromegaly, and is associated with an older age, a higher BMI, a family history of diabetes and a higher IGF-I z-score, but not with fasting or post-OGTT GH levels.

  5. Corneal Confocal Microscopy Identifies Small-Fiber Neuropathy in Subjects With Impaired Glucose Tolerance Who Develop Type 2 Diabetes

    PubMed Central

    Azmi, Shazli; Ferdousi, Maryam; Petropoulos, Ioannis N.; Ponirakis, Georgios; Alam, Uazman; Fadavi, Hassan; Asghar, Omar; Marshall, Andrew; Atkinson, Andrew J.; Jones, Wendy; Boulton, Andrew J.M.; Tavakoli, Mitra; Jeziorska, Maria

    2015-01-01

    OBJECTIVE Impaired glucose tolerance (IGT) through to type 2 diabetes is thought to confer a continuum of risk for neuropathy. Identification of subjects at high risk of developing type 2 diabetes and, hence, worsening neuropathy would allow identification and risk stratification for more aggressive management. RESEARCH DESIGN AND METHODS Thirty subjects with IGT and 17 age-matched control subjects underwent an oral glucose tolerance test, assessment of neuropathic symptoms and deficits, quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy (CCM) to quantify corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) at baseline and annually for 3 years. RESULTS Ten subjects who developed type 2 diabetes had a significantly lower CNFD (P = 0.003), CNBD (P = 0.04), and CNFL (P = 0.04) compared with control subjects at baseline and a further reduction in CNFL (P = 0.006), intraepidermal nerve fiber density (IENFD) (P = 0.02), and mean dendritic length (MDL) (P = 0.02) over 3 years. Fifteen subjects who remained IGT and 5 subjects who returned to normal glucose tolerance had no significant baseline abnormality on CCM or IENFD but had a lower MDL (P < 0.0001) compared with control subjects. The IGT subjects showed a significant decrease in IENFD (P = 0.02) but no change in MDL or CCM over 3 years. Those who returned to NGT showed an increase in CNFD (P = 0.05), CNBD (P = 0.04), and CNFL (P = 0.05), but a decrease in IENFD (P = 0.02), over 3 years. CONCLUSIONS CCM and skin biopsy detect a small-fiber neuropathy in subjects with IGT who develop type 2 diabetes and also show a dynamic worsening or improvement in corneal and intraepidermal nerve morphology in relation to change in glucose tolerance status. PMID:25877814

  6. Development and assessment of the disposition index based on the oral glucose tolerance test in subjects with different glycaemic status.

    PubMed

    Santos, J L; Yévenes, I; Cataldo, L R; Morales, M; Galgani, J; Arancibia, C; Vega, J; Olmos, P; Flores, M; Valderas, J P; Pollak, F

    2016-06-01

    Insulin secretion and insulin sensitivity indexes are related by hyperbolic functions, allowing the calculation of the disposition index (DI) as the product of the acute insulin response (AIR) and the insulin sensitivity index (Si) from intravenous glucose tolerance test (IVGTT). Our objective was to develop an oral-DI based on the oral glucose tolerance test (OGTT) and to assess its association with glucose tolerance status. This research is structured in three studies. Study 1: OGTT were performed in 833 non-diabetic Chilean women (18-60 years) without family history of diabetes mellitus. Study 2: an independent group of n = 57 non-diabetic (18-46 years) without family history of diabetes mellitus carried out an OGTT and an abbreviated IVGTT. Study 3: a sample of 1674 Chilean adults (18-60 years) with different glycaemic status performed an OGTT. An adequate statistical fit for a rectangular hyperbola was found between the area under the curve of insulin-to-glucose ratio (AUCI/G-R) and the Matsuda ISI-COMP index (study 1). The oral-DI derived as AUCI/G-R × ISI-COMP was previously termed insulin-secretion-sensitivity index-2 (ISSI-2). ISSI-2 significantly correlated with DI from IVGTT (rho = 0.34; p = 0.009) (study 2). ISSI-2 shows important differences across groups of subjects with different glycaemic status (study 3). We have confirmed that ISSI-2 replicates the mathematical properties of DI, showing significant correlations with DI from the abbreviated MM-IVGTT. These results indicate that ISSI-2 constitutes a surrogate measure of insulin secretion relative to insulin sensitivity and emphasizes the pivotal role of impaired insulin secretion in the development of glucose homeostasis dysregulation.

  7. Effects of clozapine administration on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in male C57BL/6 mice: A parallel controlled study

    PubMed Central

    Yuan, Hai-Yan; Liang, Hai-Xia; Liang, Guang-Rong; Zhang, Gui-Xiang; Li, Huan-De

    2008-01-01

    Background: Clozapine has been associated with metabolic adverse events (AEs) (eg, elevated body weight, blood glucose concentrations, cholesterol, triglycerides [TG]), all of which have deleterious effects on health and medication compliance. However, little focus has been directed toward finding a suitable experimental model to study the metabolic AEs associated with clozapine. Objective: The aim of this study was to assess the effects of clozapine administration for 28 days on body weight, glucose tolerance, blood glucose concentrations, plasma lipids, and insulin in C57BL/6 mice. Methods: C57BL/6 mice were grouped and treated with clozapine 2 or 10 mg/kg or vehicle intraperitoneally QD for 28 days. Body weight was assessed on days 0 (baseline), 7, 14, 21, and 28, and glucose tolerance, blood glucose concentrations, insulin (calculated by insulin resistance index [IRI]), and plasma lipids (including total cholesterol, TG, high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol) were assessed on day 29. Results: Sixty 10-week-old, male C57BL/6 mice were included in the study and were divided into 3 groups (20 mice per group). The body weight significantly decreased in the clozapine 10-mg-treated group on days 14, 21, and 28 compared with the vehicle group (mean [SD] body weight: 21.61 [1.05] vs 22.79 [1.11], 22.53 [1.05] vs 24.17 [1.24], and 22.21 [1.07] vs 24.99 [1.39] g, respectively; all, P < 0.05). In the clozapine 10-mg/kg group, blood glucose concentrations significantly increased 0, 30, 60, and 120 minutes after glucose administration compared with the vehicle group (mean [SD]: 6.67 [1.25], 25.34 [5.85], 12.68 [3.39], and 7.52 [1.45] mmol/L, respectively, vs 4.61 [0.78], 21.54 [6.55], 11.46 [3.46], and 6.55 [1.42] mmol/L, respectively; all P < 0.05). The clozapine 10-mg/kg group also had significant increases in plasma insulin concentrations compared with the vehicle group (12.70 [5.27] vs 7.62 [4.54] μIU/mL; P < 0.05) and

  8. PPARα Agonist Fenofibrate Reduced the Secreting Load of β-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance.

    PubMed

    Liu, Jia; Lu, Rui; Wang, Ying; Hu, Yanjin; Jia, Yumei; Yang, Ning; Fu, Jing; Wang, Guang

    2016-01-01

    Hypertriglyceridemia is an important risk factor associated with insulin resistance and β-cell dysfunction. This study investigated the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and β-cell function in subjects with normal glucose tolerance. A total of 1974 subjects with normal glucose tolerance were divided into the normal TG group (NTG group, n = 1302) and hypertriglyceridemia group (HTG group, n = 672). Next, 92 patients selected randomly from 672 patients with hypertriglyceridemia were assigned to a 24-week fenofibrate treatment. The HTG group had increased waist circumference (WC), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) and decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG group (all P < 0.01). The 24-week fenofibrate treatment significantly decreased the WC, BMI, TG, HOMA-IR, and HOMA-β levels and increased the HDL-C levels in the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR: P < 0.05; TG, HDL-C, and HOMA-β: P < 0.01). The fenofibrate treatment significantly alleviated insulin resistance and reduced the secreting load of β-cells in the hypertriglyceridemia patients with normal glucose tolerance. PMID:27034649

  9. Age dependence of glucose tolerance in adult KK-Ay mice, a model of non-insulin dependent diabetes mellitus.

    PubMed

    Chakraborty, Goutam; Thumpayil, Sherin; Lafontant, David-Erick; Woubneh, Wolde; Toney, Jeffrey H

    2009-11-01

    Yellow KK mice carrying the 'yellow obese' gene Ay are a well established polygenic model for human non-insulin dependent diabetes mellitus. These animals develop marked adiposity and decreased glucose tolerance relative to their control littermates, KK mice. The authors monitored glucose tolerance in KK-Ay mice over time and observed a significant (Pglucose tolerance when maintained on a normal diet for 25 weeks or longer, due in part to increases in plasma levels of insulin and amylin.

  10. PPARα Agonist Fenofibrate Reduced the Secreting Load of β-Cells in Hypertriglyceridemia Patients with Normal Glucose Tolerance

    PubMed Central

    Liu, Jia; Lu, Rui; Wang, Ying; Hu, Yanjin; Jia, Yumei; Yang, Ning; Fu, Jing

    2016-01-01

    Hypertriglyceridemia is an important risk factor associated with insulin resistance and β-cell dysfunction. This study investigated the effects of hypertriglyceridemia and fenofibrate treatment on insulin sensitivity and β-cell function in subjects with normal glucose tolerance. A total of 1974 subjects with normal glucose tolerance were divided into the normal TG group (NTG group, n = 1302) and hypertriglyceridemia group (HTG group, n = 672). Next, 92 patients selected randomly from 672 patients with hypertriglyceridemia were assigned to a 24-week fenofibrate treatment. The HTG group had increased waist circumference (WC), body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), and homeostasis model assessment of β-cell function (HOMA-β) and decreased high-density lipoprotein cholesterol (HDL-C) compared with the NTG group (all P < 0.01). The 24-week fenofibrate treatment significantly decreased the WC, BMI, TG, HOMA-IR, and HOMA-β levels and increased the HDL-C levels in the patients with hypertriglyceridemia (WC, BMI, and HOMA-IR: P < 0.05; TG, HDL-C, and HOMA-β: P < 0.01). The fenofibrate treatment significantly alleviated insulin resistance and reduced the secreting load of β-cells in the hypertriglyceridemia patients with normal glucose tolerance. PMID:27034649

  11. Rosiglitazone fails to improve hypertriglyceridemia and glucose tolerance in CD36-deficient BN.SHR4 congenic rat strain.

    PubMed

    Seda, Ondrej; Kazdova, Ludmila; Krenova, Drahomira; Kren, Vladimir

    2003-01-15

    The favorable metabolic effects of thiazolidinediones are supposedly related to the peroxisome proliferator-activated receptor-gamma (PPARgamma)-driven changes in lipid metabolism, particularly in free fatty acid (FFA) trafficking. The fatty acid translocase CD36 is one of the proposed PPARgamma targets to mediate this action. We assessed the effect of rosiglitazone (RSG, Avandia) administration in two inbred rat strains, BN/Cub and BN.SHR4 congenic strain, differing in 10 cM proximal segment of chromosome 4. Rats were fed high-sucrose diet with or without RSG for 1 wk. In BN.SHR4, which carries defective Cd36 allele of SHR origin, RSG failed to improve glucose tolerance (assessed by the oral glucose tolerance test), did not lower triglyceridemia, nor induced increases in epididymal and retroperitoneal adipose tissue weights and adipose tissue glucose utilization, effects observed in BN/Cub. On the other hand, the RSG-treated BN.SHR4 showed lower concentrations of FFA and substantial increase in glycogen synthesis and glucose oxidation in skeletal muscle. Altogether, these results support involvement of CD36 in RSG action, suggesting this pharmacogenetic interaction may be of particular importance in CD36-deficient humans.

  12. Molecular Genetic Regulation of Slc30a8/ZnT8 Reveals a Positive Association With Glucose Tolerance

    PubMed Central

    Mitchell, Ryan K.; Hu, Ming; Chabosseau, Pauline L.; Cane, Matthew C.; Meur, Gargi; Bellomo, Elisa A.; Carzaniga, Raffaella; Collinson, Lucy M.; Li, Wen-Hong

    2016-01-01

    Zinc transporter 8 (ZnT8), encoded by SLC30A8, is chiefly expressed within pancreatic islet cells, where it mediates zinc (Zn2+) uptake into secretory granules. Although a common nonsynonymous polymorphism (R325W), which lowers activity, is associated with increased type 2 diabetes (T2D) risk, rare inactivating mutations in SLC30A8 have been reported to protect against T2D. Here, we generate and characterize new mouse models to explore the impact on glucose homeostasis of graded changes in ZnT8 activity in the β-cell. Firstly, Slc30a8 was deleted highly selectively in these cells using the novel deleter strain, Ins1Cre. The resultant Ins1CreZnT8KO mice displayed significant (P < .05) impairments in glucose tolerance at 10 weeks of age vs littermate controls, and glucose-induced increases in circulating insulin were inhibited in vivo. Although insulin release from Ins1CreZnT8KO islets was normal, Zn2+ release was severely impaired. Conversely, transgenic ZnT8Tg mice, overexpressing the transporter inducibly in the adult β-cell using an insulin promoter-dependent Tet-On system, showed significant (P < .01) improvements in glucose tolerance compared with control animals. Glucose-induced insulin secretion from ZnT8Tg islets was severely impaired, whereas Zn2+ release was significantly enhanced. Our findings demonstrate that glucose homeostasis in the mouse improves as β-cell ZnT8 activity increases, and remarkably, these changes track Zn2+ rather than insulin release in vitro. Activation of ZnT8 in β-cells might therefore provide the basis of a novel approach to treating T2D. PMID:26584158

  13. Cold tolerance in CCl4-treated rats and its modification by administration of garlic oil and glucose

    NASA Astrophysics Data System (ADS)

    Bhatia, B.; Ahujarai, P. L.

    1984-06-01

    Male Wistar rats weighing 150 200 g maintained under standard laboratory conditions and given Hindustan Lever Pellets and water ad libitum were exposed to -20°C for determination of the rate of fall of rectal temperature and survival time. The rate of fall of body temperature was significantly increased and the survival time was reduced, when animals were given an intraperitoneal injection of 1 ml/kg BW of CCl4 24 h but not 2 h earlier. Pre-treatment of the animals with 0.006 ml of garlic oil in a 2% solution of arachis oil for 3 days gave a significant protection to the animals against the CCl4-induced fall in cold tolerance. Administration of glucose orally 300 mg in 2 ml of saline eliminated the CCl4-induced fall in cold tolerance. The animals displayed a hypoglycemia 24 h, but not 2 h after injection of CCl4. CCl4-induced hypoglycemia was reduced by pre-treatment with garlic oil. The results indicate that the CCl4-induced reduction in cold tolerance is secondary to hypoglycemia and not due to the direct effect of CCl4 on the thermoregulatory mechanism in the CNS. The critical level of blood glucose below which the cold tolerance is reduced was found to be 76 mg/100 ml of blood.

  14. Six weeks' sebacic acid supplementation improves fasting plasma glucose, HbA1c and glucose tolerance in db/db mice

    PubMed Central

    Membrez, M; Chou, C J; Raymond, F; Mansourian, R; Moser, M; Monnard, I; Ammon-Zufferey, C; Mace, K; Mingrone, G; Binnert, C

    2010-01-01

    Aim: To investigate the impact of chronic ingestion of sebacic acid (SA), a 10-carbon medium-chain dicarboxylic acid, on glycaemic control in a mouse model of type 2 diabetes (T2D). Methods: Three groups of 15 db/db mice were fed for 6 weeks either a chow diet (Ctrl) or a chow diet supplemented with 1.5 or 15% (SA1.5% and SA15%, respectively) energy from SA. Fasting glycaemia was measured once a week and HbA1c before and after supplementation. An oral glucose tolerance test (OGTT) was performed at the end of the supplementation. Gene expression was determined by transcriptomic analysis on the liver of the Ctrl and SA15% groups. Results: After 42 days of supplementation, fasting glycaemia and HbA1c were ∼70 and 25% lower in the SA15% group compared with the other groups showing a beneficial effect of SA on hyperglycaemia. During OGTT, plasma glucose area under the curve was reduced after SA15% compared with the other groups. This effect was associated with a tendency for an improved insulin response. In the liver, Pck1 and FBP mRNA were statistically decreased in the SA15% compared with Ctrl suggesting a reduced hepatic glucose output induced by SA. Conclusion: Dietary supplementation of SA largely improves glycaemic control in a mouse model of T2D. This beneficial effect may be due to (i) an improved glucose-induced insulin secretion and (ii) a reduced hepatic glucose output. PMID:20977585

  15. Effect of Artocarpus heterophyllus and Asteracanthus longifolia on glucose tolerance in normal human subjects and in maturity-onset diabetic patients.

    PubMed

    Fernando, M R; Wickramasinghe, N; Thabrew, M I; Ariyananda, P L; Karunanayake, E H

    1991-03-01

    Investigations were carried out to evaluate the effects of hot-water extracts of Artocarpus heterophyllus leaves and Asteracanthus longifolia whole plant material on the glucose tolerance of normal human subjects and maturity-onset diabetic patients. The extracts of both Artocarpus heterophyllus and Asteracanthus longifolia significantly improved glucose tolerance in the normal subjects and the diabetic patients when investigated at oral doses equivalent to 20 g/kg of starting material.

  16. Quantity and quality of nocturnal sleep affect morning glucose measurement in acutely burned children.

    PubMed

    Mayes, Theresa; Gottschlich, Michele M; Khoury, Jane; Simakajornboon, Narong; Kagan, Richard J

    2013-01-01

    Hyperglycemia after severe burn injury has long been recognized, whereas sleep deprivation after burns is a more recent finding. The postburn metabolic effects of poor sleep are not clear despite reports in other populations demonstrating the association between sleep insufficiency and deleterious endocrine consequences. The aim of this study was to determine whether a relationship between sleep and glucose dynamics exists in acutely burned children. Two overnight polysomnography runs (2200 to 0600) per subject were conducted in 40 patients with a mean (± SEM) age of 9.4 ± 0.7 years, 50.1 ± 2.9% TBSA burn, and 43.2 ± 3.6% full-thickness injury. Serum glucose was drawn in the morning (0600) immediately after the sleep test. Insulin requirements during the 24-hour period preceding the 0600 glucose measurement were recorded. Generalized linear models were used by the authors to evaluate percent time in each stage of sleep, percent wake time, total sleep time, sleep efficiency, and morning serum glucose, accounting for insulin use. Increased time awake (P = .04, linear; P = .02, quadratic) and reduced time spent in stage 1 sleep (P = .03, linear) were associated with higher glucose levels. Sleep efficiency (P = .01, linear; P = .02, quadratic) and total sleep time (P = .01 linear; P = .02, quadratic) were inversely associated with glucose level. Morning glucose levels appear to be affected by the quality and quantity of overnight sleep in children who have sustained extensive burn injuries. Future research is needed to elucidate the metabolic and neuroendocrine consequences of sleep deprivation on metabolism after burns.

  17. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    PubMed Central

    2011-01-01

    Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H) or the alternation of chow (C) and an H diet (CH regimen) induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age. PMID:21943199

  18. Short-Term Thermal-Humidity Shock Affects Point-of-Care Glucose Testing

    PubMed Central

    Lam, Mandy; Curtis, Corbin M.; Ferguson, William J.; Vy, John H.; Truong, Anh-Thu; Sumner, Stephanie L.; Kost, Gerald J.

    2014-01-01

    The objective was to assess the effects of short-term (≤1 hour) static high temperature and humidity stresses on the performance of point-of-care (POC) glucose test strips and meters. Glucose meters are used by medical responders and patients in a variety of settings including hospitals, clinics, homes, and the field. Reagent test strips and instruments are potentially exposed to austere environmental conditions. Glucose test strips and meters were exposed to a mean relative humidity of 83.0% (SD = 8.0%) and temperature of 42°C (107.6°F, SD = 3.2) in a Tenney BTRC environmental chamber. Stressed and unstressed glucose reagent strips and meters were tested with spiked blood samples (n = 40 measurements per time point for each of 4 trials) after 15, 30, 45, and 60 minutes of exposure. Wilcoxon’s signed rank test was applied to compare measurements test strip and meter measurements to isolate and characterize the magnitude of meter versus test strip effects individually. Stressed POC meters and test strips produced elevated glucose results, with stressed meter bias as high as 20 mg/dL (17.7% error), and stressed test strip bias as high as 13 mg/dL (12.2% error). The aggregate stress effect on meter and test strips yielded a positive bias as high as 33 mg/dL (30.1% error) after 15 minutes of exposure. Short-term exposure (15 minutes) to high temperature and humidity can significantly affect the performance of POC glucose test strips and meters, with measurement biases that potentially affect clinical decision making and patient safety. PMID:24876542

  19. High prevalence of NIDDM and impaired glucose tolerance in Indian, Creole, and Chinese Mauritians. Mauritius Noncommunicable Disease Study Group.

    PubMed

    Dowse, G K; Gareeboo, H; Zimmet, P Z; Alberti, K G; Tuomilehto, J; Fareed, D; Brissonnette, L G; Finch, C F

    1990-03-01

    Mauritius, a multiethnic island nation in the southwestern Indian Ocean, has one of the world's highest diabetes mortality rates. The prevalence of both impaired glucose tolerance (IGT) and non-insulin-dependent diabetes mellitus (NIDDM) was investigated in 5080 Muslim and Hindu Indian, Creole (mixed African, European, and Indian origin), and Chinese Mauritian adults aged 25-74 yr who were selected by random cluster sampling. Based on a 75-g oral glucose tolerance test and World Health Organization criteria, the age-standardized prevalence of IGT was significantly greater in women (19.7%, 95% confidence interval [CI] 18.1-21.2) than in men (11.7%, CI 10.5-12.8). By contrast, the prevalence of NIDDM was similar in men (12.1%, CI 10.9-13.4) and women (11.7%, CI 10.5-12.8) for all ethnic groups combined. The sex difference in IGT prevalence was seen in all ethnic groups, but for NIDDM, the sex difference was not consistent across ethnic groups. However, age- and sex-standardized prevalence of IGT and NIDDM was remarkably similar across ethnic groups (16.2 and 12.4% in Hindu Indians, 15.3 and 13.3% in Muslim Indians, 17.5 and 10.4% in Creoles, and 16.6 and 11.9% in Chinese, respectively). Three new cases of diabetes were diagnosed for every two known cases. The high prevalence of abnormal glucose tolerance in Indian subjects is consistent with studies of other migrant Indian communities, but the findings in Creole and, in particular, Chinese subjects are unexpected. Potent environmental factors shared between ethnic groups in Mauritius may be responsible for the epidemic of glucose intolerance.

  20. Metabolic syndrome and the early detection of impaired glucose tolerance among professionals living in Beijing, China: a cross sectional study

    PubMed Central

    2013-01-01

    Background The purpose of this study is to investigate the association of metabolic syndrome (MS) and its components with the risk of impaired glucose tolerance (IGT) in high risk urban professionals. The goal is to improve the selection of candidates who would most benefit from an oral glucose tolerance test (OGTT). Methods This is a cross sectional study in which MS was identified by both the definitions proposed by the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF). Results There were 928 eligible subjects in the study, and 23.9% of them failed in OGTT. The odds ratio of IGT was increased 3.16-fold for MS defined by the NCEP criteria and 2.79-fold for the hyperglycemia factor alone. Both MS and hyperglycemia were shown to be acceptable measures to discriminate subjects with IGT from those with normal glucose tolerance (NGT). The clustering of any 1, 2, or ≥3 metabolic components resulted in increased odds ratios for IGT: i.e., 1.71, 2.38 and 5.92, respectively. Even without hyperglycemia in the cluster, an increased odds ratio was still observed. The risk of IGT increased dramatically when the fasting plasma glucose and waist circumference were both at their highest defined level. Conclusions MS and its components are associated with the increased risk of IGT. People with MS, one of its components, especially hyperglycemia and central obesity, or a cluster of its components are strong candidates for an OGTT in order to achieve early cost-effective detection of IGT. PMID:24499585

  1. Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans.

    PubMed

    Ciubotaru, Irina; Green, Stefan J; Kukreja, Subhash; Barengolts, Elena

    2015-11-01

    The importance of gut microbiota in pathogenesis of diabetes remains unknown. This study investigated the relationship between microbiota and metabolic markers in African American men (AAM) with prediabetes and hypovitaminosis D. The study was ancillary to a randomized trial of vitamin D supplementation with weekly ergocalciferol (50,000 IU) conducted in AAM veterans over 12 months (D Intervention in Veterans Affairs). Glycemic groups (Gr) were characterized based on changes in oral glucose tolerance between baseline and exit. Subjects with stable normal glucose tolerance were assigned to Gr-1 and those with stable prediabetes (impaired glucose tolerance and impaired fasting glucose) to Gr-2. Microbiota composition was analyzed in stool collected at the exit (n = 115) and compared between Gr-1 and Gr-2, as well as between the lowest and highest quartiles of dietary intake of energy and fat, hemoglobin A1c, and serum 25-hydroxyvitamin D (25[OH]D) level. Differences between Gr-1 and Gr-2 included the Bacteroidetes/Firmicutes and Bacteroidales/Clostridia ratios and differences in genera such as Ruminococcus and Dialister. Changes in specific taxa associated with the lowest and highest quartiles of 25(OH)D (eg, Ruminococcus, Roseburia, Blautia, Dorea) were clearly distinct from those of dietary intake (eg, Bacteroides, Bacteroides/Prevotella ratio) or A1c (eg, Faecalibacterium, Catenibacterium, Streptococcus). These findings suggest a novel interaction between microbiota and vitamin D and a role for microbiota in early stages of diabetes development. Although results suggest that specific taxa are associated with glycemic stability over time, a causative relationship between microbiota makeup and dysglycemia is still to be demonstrated. PMID:26209747

  2. T3 supplementation affects ventilatory timing & glucose levels in type 2 diabetes mellitus model.

    PubMed

    Bollinger, Stephen S; Weltman, Nathen Y; Gerdes, A Martin; Schlenker, Evelyn H

    2015-01-01

    Type II diabetes mellitus (T2DM) can affect ventilation, metabolism, and fasting blood glucose levels. Hypothyroidism may be a comorbidity of T2DM. In this study T2DM was induced in 20 female Sprague Dawley rats using Streptozotocin (STZ) and Nicotinamide (N). One of experimental STZ/N groups (N=10 per group) was treated with a low dose of triiodothyronine (T3). Blood glucose levels, metabolism and ventilation (in air and in response to hypoxia) were measured in the 3 groups. STZ/N-treated rats increased fasting blood glucose compared to control rats eight days and 2 months post-STZ/N injections indicating stable induction of T2DM state. Treatments had no effects on ventilation, metabolism or body weight. After one month of T3 supplementation, there were no physiological indications of hyperthyroidism, but T3 supplementation altered ventilatory timing and decreased blood glucose levels compared to STZ/N rats. These results suggest that low levels of T3 supplementation could offer modest effects on blood glucose and ventilatory timing in this T2M model.

  3. Self-reported tolerance influences prefrontal cortex hemodynamics and affective responses.

    PubMed

    Tempest, Gavin; Parfitt, Gaynor

    2016-02-01

    The relationship between cognitive and sensory processes in the brain contributes to the regulation of affective responses (pleasure-displeasure). Exercise can be used to manipulate sensory processes (by increasing physiological demand) in order to examine the role of dispositional traits that may influence an individual's ability to cognitively regulate these responses. With the use of near infrared spectroscopy, in this study we examined the influence of self-reported tolerance upon prefrontal cortex (PFC) hemodynamics and affective responses. The hemodynamic response was measured in individuals with high or low tolerance during an incremental exercise test. Sensory manipulation was standardized against metabolic processes (ventilatory threshold [VT] and respiratory compensation point [RCP]), and affective responses were recorded. The results showed that the high-tolerance group displayed a larger hemodynamic response within the right PFC above VT (which increased above RCP). The low-tolerance group showed a larger hemodynamic response within the left PFC above VT. The high-tolerance group reported a more positive/less negative affective response above VT. These findings provide direct neurophysiological evidence of differential hemodynamic responses within the PFC that are associated with tolerance in the presence of increased physiological demands. This study supports the role of dispositional traits and previous theorizing into the underlying mechanisms (cognitive vs. sensory processes) of affective responses. PMID:26337703

  4. Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice.

    PubMed

    Irimia, Jose M; Meyer, Catalina M; Peper, Caron L; Zhai, Lanmin; Bock, Cheryl B; Previs, Stephen F; McGuinness, Owen P; DePaoli-Roach, Anna; Roach, Peter J

    2010-04-23

    Conversion to glycogen is a major fate of ingested glucose in the body. A rate-limiting enzyme in the synthesis of glycogen is glycogen synthase encoded by two genes, GYS1, expressed in muscle and other tissues, and GYS2, primarily expressed in liver (liver glycogen synthase). Defects in GYS2 cause the inherited monogenic disease glycogen storage disease 0. We have generated mice with a liver-specific disruption of the Gys2 gene (liver glycogen synthase knock-out (LGSKO) mice), using Lox-P/Cre technology. Conditional mice carrying floxed Gys2 were crossed with mice expressing Cre recombinase under the albumin promoter. The resulting LGSKO mice are viable, develop liver glycogen synthase deficiency, and have a 95% reduction in fed liver glycogen content. They have mild hypoglycemia but dispose glucose less well in a glucose tolerance test. Fed, LGSKO mice also have a reduced capacity for exhaustive exercise compared with mice carrying floxed alleles, but the difference disappears after an overnight fast. Upon fasting, LGSKO mice reach within 4 h decreased blood glucose levels attained by control floxed mice only after 24 h of food deprivation. The LGSKO mice maintain this low blood glucose for at least 24 h. Basal gluconeogenesis is increased in LGSKO mice, and insulin suppression of endogenous glucose production is impaired as assessed by euglycemic-hyperinsulinemic clamp. This observation correlates with an increase in the liver gluconeogenic enzyme phosphoenolpyruvate carboxykinase expression and activity. This mouse model mimics the pathophysiology of glycogen storage disease 0 patients and highlights the importance of liver glycogen stores in whole body glucose homeostasis.

  5. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster

    PubMed Central

    Wagner, Anika E.; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-01-01

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies. PMID:26375250

  6. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster.

    PubMed

    Wagner, Anika E; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-10-13

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.

  7. Probiotic Lactobacillus gasseri SBT2055 improves glucose tolerance and reduces body weight gain in rats by stimulating energy expenditure.

    PubMed

    Shirouchi, Bungo; Nagao, Koji; Umegatani, Minami; Shiraishi, Aya; Morita, Yukiko; Kai, Shunichi; Yanagita, Teruyoshi; Ogawa, Akihiro; Kadooka, Yukio; Sato, Masao

    2016-08-01

    Probiotic Lactobacillus gasseri SBT2055 (LG2055) reduces postprandial TAG absorption and exerts anti-obesity effects in rats and humans; however, the underlying mechanisms are not fully understood. In the present study, we addressed the mechanistic insights of the anti-obesity activity of LG2055 by feeding Sprague-Dawley rats diets containing skimmed milk fermented or not by LG2055 for 4 weeks and by analysing energy expenditure, glucose tolerance, the levels of SCFA in the caecum and serum inflammatory markers. Rats fed the LG2055-containing diet demonstrated significantly higher carbohydrate oxidation in the dark cycle (active phase for rats) compared with the control group, which resulted in a significant increase in energy expenditure. LG2055 significantly reduced cumulative blood glucose levels (AUC) compared with the control diet after 3 weeks and increased the molar ratio of butyrate:total SCFA in the caecum after 4 weeks. Furthermore, the LG2055-supplemented diet significantly reduced the levels of serum amyloid P component - an indicator of the inflammatory process. In conclusion, our results demonstrate that, in addition to the inhibition of dietary TAG absorption reported previously, the intake of probiotic LG2055 enhanced energy expenditure via carbohydrate oxidation, improved glucose tolerance and attenuated inflammation, suggesting multiple additive and/or synergistic actions underlying the anti-obesity effects exerted by LG2055. PMID:27267802

  8. Th1/Th17 Plasticity Is a Marker of Advanced β Cell Autoimmunity and Impaired Glucose Tolerance in Humans

    PubMed Central

    Reinert-Hartwall, Linnea; Honkanen, Jarno; Salo, Harri M.; Nieminen, Janne K.; Luopajärvi, Kristiina; Härkönen, Taina; Veijola, Riitta; Simell, Olli; Ilonen, Jorma; Peet, Aleksandr; Tillmann, Vallo; Knip, Mikael; Knip, Mikael; Koski, Katriina; Koski, Matti; Härkönen, Taina; Ryhänen, Samppa; Hämäläinen, Anu-Maaria; Ormisson, Anne; Peet, Aleksandr; Tillmann, Vallo; Ulich, Valentina; Kuzmicheva, Elena; Mokurov, Sergei; Markova, Svetlana; Pylova, Svetlana; Isakova, Marina; Shakurova, Elena; Petrov, Vladimir; Dorshakova, Natalya V.; Karapetyan, Tatyana; Varlamova, Tatyana; Ilonen, Jorma; Kiviniemi, Minna; Alnek, Kristi; Janson, Helis; Uibo, Raivo; Salum, Tiit; von Mutius, Erika; Weber, Juliane; Ahlfors, Helena; Kallionpää, Henna; Laajala, Essi; Lahesmaa, Riitta; Lähdesmäki, Harri; Moulder, Robert; Nieminen, Janne; Ruohtula, Terhi; Vaarala, Outi; Honkanen, Hanna; Hyöty, Heikki; Kondrashova, Anita; Oikarinen, Sami; Harmsen, Hermie J. M.; De Goffau, Marcus C.; Welling, Gjalt; Alahuhta, Kirsi; Virtanen, Suvi M.

    2015-01-01

    Upregulation of IL-17 immunity and detrimental effects of IL-17 on human islets have been implicated in human type 1 diabetes. In animal models, the plasticity of Th1/Th17 cells contributes to the development of autoimmune diabetes. In this study, we demonstrate that the upregulation of the IL-17 pathway and Th1/Th17 plasticity in peripheral blood are markers of advanced β cell autoimmunity and impaired β cell function in human type 1 diabetes. Activated Th17 immunity was observed in the late stage of preclinical diabetes in children with β cell autoimmunity and impaired glucose tolerance, but not in children with early β cell autoimmunity. We found an increased ratio of IFN-γ/IL-17 expression in Th17 cells in children with advanced β cell autoimmunity, which correlated with HbA1c and plasma glucose concentrations in an oral glucose tolerance test, and thus impaired β cell function. Low expression of Helios was seen in Th17 cells, suggesting that Th1/Th17 cells are not converted thymus-derived regulatory T cells. Our results suggest that the development of Th1/Th17 plasticity may serve as a biomarker of disease progression from β cell autoantibody positivity to type 1 diabetes. These data in human type 1 diabetes emphasize the role of Th1/Th17 plasticity as a potential contributor to tissue destruction in autoimmune conditions. PMID:25480564

  9. A Randomized Clinical Trial of an Intensive Behavior Education Program in Gestational Diabetes Mellitus Women Designed to Improve Glucose Levels on the 2-Hour Oral Glucose Tolerance Test.

    PubMed

    Durnwald, Celeste P; Kallan, Michael J; Allison, Kelly C; Sammel, Mary D; Wisch, Susan; Elovitz, Michal; Parry, Samuel

    2016-10-01

    Objective To evaluate whether women with gestational diabetes mellitus (GDM) enrolled in an intensive behavior education program (IBEP) demonstrate lower mean fasting glucose levels on the 2-hour 75 g oral glucose tolerance test (2-hour OGTT) at 6 to 12 weeks postpartum compared with women who undergo routine GDM management. Study Design A prospective randomized controlled trial of women diagnosed with GDM was conducted. Exclusion criteria were GDM diagnosis ≥ 33 weeks or < 20 weeks. Women were randomly assigned to one of two treatment arms: (1) routine GDM management or (2) an IBEP. Women underwent a 2-hour OGTT at 6 to 12 weeks postpartum. Fisher exact test, t-test, and Wilcoxon rank sum test were used as appropriate. Results Of the 101 women randomized, 49 were assigned to IBEP and 52 received routine GDM management. There was no difference in mean fasting and 2-hour glucose levels on the postpartum 2-hour OGTT between the IBEP and routine management group (88.5 ± 22.9 mg/dL vs. 85.2 ± 13.3 mg/dL, p = 0.49 and 109.8 ± 38.5 mg/dL vs. 109.4 ± 40.8 mg/dL, p = 0.97, respectively). Conclusion GDM women enrolled in a healthy lifestyle intervention program did not demonstrate lower glucose values on the postpartum 2-hour OGTT.

  10. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    PubMed

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results.

  11. Comparison of glycosylated hemoglobin with the oral glucose tolerance test. A study in subjects with normoglycemia, glucose intolerance and non-insulin-dependent diabetes mellitus.

    PubMed

    Cederholm, J; Ronquist, G; Wibell, L

    1984-10-01

    At a health survey of 819 subjects, 47-54 years old, the rate of glucose intolerance (GI) was 6.2% (51 subjects) according to 75 g oral glucose tolerance tests (OGTT) and WHO criteria. In GI-subjects, the mean HbA1 was 7.3% (10th-90th percentile range 6.2-8.3%), and significantly higher than the mean HbA1 in 150 subjects with normal OGTT, which was 6.5% (10th-90th percentile range 5.7-7.4%). With an upper normal limit of 7.8% (mean + 2 SD) only 20% of all GI-subjects had a raised HbA1. The differences between 31 GI-subjects, with low HbA1 (mean 6.9%), and 20 GI-subjects, with relatively high HbA1 (mean 7.9%), were not significant with respect to fasting and 2-hour blood glucose, area under glucose curve, body mass index, index of physical activity, rate of hypertension or rate of first degree relatives with diabetes. In an unselected group of 157 subjects, sampled consecutively during the first part of the survey, the mean HbA1 was 6.6% (10th-90th percentile range 5.8-7.5 %) 150 subjects were those with normal OGTT, 6 subjects had GI and only one subject had previously unknown diabetes. No distinct correlations between HbA1 and OGTT fasting or 2 hour values were found in this sample. No correlation was found within the separate groups of 51 GI-subjects and 150 normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

  12. Predictive Value of Glucose Parameters Obtained From Oral Glucose Tolerance Tests in Identifying Individuals at High Risk for the Development of Diabetes in Korean Population.

    PubMed

    Yang, Hae Kyung; Ha, Hee-Sung; Rhee, Marie; Lee, Jin-Hee; Park, Yong-Moon; Kwon, Hyuk-Sang; Yim, Hyeon-Woo; Kang, Moo-Il; Lee, Won-Chul; Son, Ho-Young; Lee, Seung-Hwan; Yoon, Kun-Ho

    2016-03-01

    Previous studies suggest that the future risk for type 2 diabetes is not similar among subjects in the same glucose tolerance category. In this study, we aimed to evaluate simple intuitive indices to identify subjects at high risk for future diabetes development by using 0, 30, 120 minute glucose levels obtained during 75 g OGTTs from participants of a prospective community-based cohort in Korea.Among subjects enrolled at the Chungju Metabolic disease Cohort, those who performed an OGTT between 2007 and 2010 and repeated the test between 2011 and 2014 were recruited after excluding subjects with diabetes at baseline. Subjects were categorized according to their 30 minute glucose (G30) and the difference between 120 and 0 minute glucose (G(120-0)) levels with cutoffs of 9.75 and 2.50 mmol/L, respectively.Among 1126 subjects, 117 (10.39%) developed type 2 diabetes after 4 years. In diabetes nonconverters, increased insulin resistance was accompanied by compensatory insulin secretion, but this was not observed in converters during 4 years of follow-up. Subjects with G(120-0) ≥ 2.50 mmol/L or G30 ≥ 9.75 mmol/L demonstrated lower degrees of insulin secretion, higher degrees of insulin resistance, and ∼6-fold higher risk of developing future diabetes compared to their lower counterparts after adjustment for possible confounding factors. Moreover, subjects with high G(120-0) and high G30 demonstrated 22-fold higher risk for diabetes development compared to subjects with low G(120-0) and low G30.By using the G(120-0) and G30 values obtained during the OGTT, which are less complicated measurements than previously reported methods, we were able to select individuals at risk for future diabetes development. Further studies in different ethnicities are required to validate our results. PMID:26962830

  13. Do glucose and lipid metabolism affect cancer development in Nagasaki atomic bomb survivors?

    PubMed

    Hida, Ayumi; Akahoshi, Masazumi; Toyama, Kyoko; Imaizumi, Misa; Soda, Midori; Maeda, Renju; Ichimaru, Shinichiro; Nakashima, Eiji; Eguchi, Katsumi

    2005-01-01

    The relationship between lipid or glucose metabolism and cancer has not yet been elucidated. We conducted 75-g oral glucose tolerance tests (75-g OGTTs) and lipid measurements between 1983 and 1985 in 516 Nagasaki atomic bomb survivors. Excluding those who already had cancer at the baseline examinations and those who developed cancers or died of any cause within 5 yr after the baseline examinations, we determined incident cancer cases until 2000 in the remaining 451 subjects (214 males and 237 females) and evaluated, by means of the Cox proportional hazard model, whether glucose or lipid metabolism predicts cancer development. The age- and sex-adjusted relative risk (RR) for incident cancer was 0.903 (95% confidence interval, CI = 0.842-0.968), 1.740 (95% CI = 1.238-2.446), 1.653 (95% CI = 0.922-2.965), and 1.024 (95% CI = 0.996-1.053) for total cholesterol (10 mg/dl), radiation dose (1 Sv), smoking, and 1-h blood glucose (1-h BG; 10 mg/dl) in 75-g OGTTs, respectively. Multiple regression analysis of age, sex, smoking, body mass index, 1-h BG, triglycerides, total cholesterol, high-density lipoprotein cholesterol, and radiation dose also showed that total cholesterol was negatively (RR = 0.872; 95% CI = 0.793-0.958) and radiation dose positively (RR = 1.809; 95% CI = 1.252-2.613) related to incident cancer. Cholesterol could be negatively and radiation dose positively associated with cancer development independently.

  14. PICK1 Deficiency Impairs Secretory Vesicle Biogenesis and Leads to Growth Retardation and Decreased Glucose Tolerance

    PubMed Central

    Jansen, Anna M.; Jin, Chunyu; Rickhag, Mattias; Lund, Viktor K.; Jensen, Morten; Bhatia, Vikram; Sørensen, Gunnar; Madsen, Andreas N.; Xue, Zhichao; Møller, Siri K.; Woldbye, David; Qvortrup, Klaus; Huganir, Richard; Stamou, Dimitrios; Kjærulff, Ole; Gether, Ulrik

    2013-01-01

    Secretory vesicles in endocrine cells store hormones such as growth hormone (GH) and insulin before their release into the bloodstream. The molecular mechanisms governing budding of immature secretory vesicles from the trans-Golgi network (TGN) and their subsequent maturation remain unclear. Here, we identify the lipid binding BAR (Bin/amphiphysin/Rvs) domain protein PICK1 (protein interacting with C kinase 1) as a key component early in the biogenesis of secretory vesicles in GH-producing cells. Both PICK1-deficient Drosophila and mice displayed somatic growth retardation. Growth retardation was rescued in flies by reintroducing PICK1 in neurosecretory cells producing somatotropic peptides. PICK1-deficient mice were characterized by decreased body weight and length, increased fat accumulation, impaired GH secretion, and decreased storage of GH in the pituitary. Decreased GH storage was supported by electron microscopy showing prominent reduction in secretory vesicle number. Evidence was also obtained for impaired insulin secretion associated with decreased glucose tolerance. PICK1 localized in cells to immature secretory vesicles, and the PICK1 BAR domain was shown by live imaging to associate with vesicles budding from the TGN and to possess membrane-sculpting properties in vitro. In mouse pituitary, PICK1 co-localized with the BAR domain protein ICA69, and PICK1 deficiency abolished ICA69 protein expression. In the Drosophila brain, PICK1 and ICA69 co-immunoprecipitated and showed mutually dependent expression. Finally, both in a Drosophila model of type 2 diabetes and in high-fat-diet-induced obese mice, we observed up-regulation of PICK1 mRNA expression. Our findings suggest that PICK1, together with ICA69, is critical during budding of immature secretory vesicles from the TGN and thus for vesicular storage of GH and possibly other hormones. The data link two BAR domain proteins to membrane remodeling processes in the secretory pathway of peptidergic endocrine

  15. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    PubMed

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  16. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    PubMed

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia. PMID:27319094

  17. Coconut-derived D-xylose affects postprandial glucose and insulin responses in healthy individuals

    PubMed Central

    Bae, Yun Jung; Bak, Youn-Kyung; Kim, Bumsik; Kim, Min-Sun; Lee, Jin-Hee

    2011-01-01

    Metabolic alterations including postprandial hyperglycemia have been implicated in the development of obesity-related diseases. Xylose is a sucrase inhibitor suggested to suppress the postprandial glucose surge. The objectives of this study were to assess the inhibitory effects of two different concentrations of xylose on postprandial glucose and insulin responses and to evaluate its efficacy in the presence of other macronutrients. Randomized double-blind cross-over studies were conducted to examine the effect of D-xylose on postprandial glucose and insulin response following the oral glucose tolerance test (OGTT). In study 1, the overnight-fasted study subjects (n = 49) consumed a test sucrose solution (50 g sucrose in 130 ml water) containing 0, 5, or 7.5 g D-xylose powder. In study 2, the overnight-fasted study subjects (n = 50) consumed a test meal (50 g sucrose in a 60 g muffin and 200 ml sucrose-containing solution). The control meal provided 64.5 g of carbohydrates, 4.5 g of fat, and 10 g of protein. The xylose meal was identical to the control meal except 5 g of xylose was added to the muffin mix. In study 1, the 5 g xylose-containing solutions exhibited significantly lower area under the glucose curve (AUCg) and area under the insulin curve (AUCi) values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P < 0.0001), 0-60 min (P < 0.0001, P < 0.0001), 0-90 min (P < 0.0001, P < 0.0001) and 0-120 min (P = 0.0071, P = 0.0016). In study 2, the test meal exhibited significantly lower AUCg and AUCi values for 0-15 min (P < 0.0001, P < 0.0001), 0-30 min (P < 0.0001, P < 0.0001), 0-45 min (P < 0.0001, P = 0.0005), 0-60 min (P = 0.0002, P = 0.0025), and 0-90 min (P = 0.0396, P = 0.0246). In conclusion, xylose showed an acute suppressive effect on the postprandial glucose and insulin surges. PMID:22259678

  18. Limitations in the use of indices using glucose and insulin levels to predict insulin sensitivity: impact of race and gender and superiority of the indices derived from oral glucose tolerance test in African Americans.

    PubMed

    Pisprasert, Veeradej; Ingram, Katherine H; Lopez-Davila, Maria F; Munoz, A Julian; Garvey, W Timothy

    2013-04-01

    OBJECTIVE To examine the utility of commonly used insulin sensitivity indices in nondiabetic European Americans (EAs) and African Americans (AAs). RESEARCH DESIGN AND METHODS Two-hundred forty nondiabetic participants were studied. Euglycemic-hyperinsulinemic clamp was the gold standard approach to assess glucose disposal rates (GDR) normalized by lean body mass. The homeostatic model assessment for insulin resistance (HOMA-IR) and the quantitative insulin sensitivity check index (QUICKI) were calculated from fasting plasma glucose and insulin (FIL). Oral glucose tolerance test (OGTT) was performed to determine Matsuda index, the simple index assessing insulin sensitivity (SI(is)OGTT), Avignon index, and Stomvoll index. Relationships among these indices with GDR were analyzed by multiple regression. RESULTS GDR values were similar in EA and AA subgroups; even so, AA exhibited higher FIL and were insulin-resistant compared with EA, as assessed by HOMA-IR, QUICKI, Matsuda index, SI(is)OGTT, Avignon index, and Stumvoll index. In the overall study population, GDR was significantly correlated with all studied insulin sensitivity indices (/r/ = 0.381-0.513); however, these indices were not superior to FIL in predicting GDR. Race and gender affected the strength of this relationship. In AA males, FIL and HOMA-IR were not correlated with GDR. In contrast, Matsuda index and SI(is)OGTT were significantly correlated with GDR in AA males, and Matsuda index was superior to HOMA-IR and QUICKI in AAs overall. CONCLUSIONS Insulin sensitivity indices based on glucose and insulin levels should be used cautiously as measures of peripheral insulin sensitivity when comparing mixed gender and mixed race populations. Matsuda index and SI(is)OGTT are reliable in studies that include AA males.

  19. Role of Haptoglobin in Polycystic Ovary Syndrome (PCOS), Obesity and Disorders of Glucose Tolerance in Premenopausal Women

    PubMed Central

    Álvarez-Blasco, Francisco; Martínez-García, Ma Ángeles; Luque-Ramírez, Manuel; Parraza, Naiara; San Millán, José L.; Escobar-Morreale, Héctor F.

    2009-01-01

    Background Hp2 alleles of the haptoglobin α–chain polymorphism reduce the anti-oxidant properties and increase the pro-inflammatory actions of this acute-phase protein in a gene-dosage fashion. We hypothesized that the haptoglobin polymorphism might contribute to the increased oxidative stress and low-grade chronic inflammation frequently associated with polycystic ovary syndrome, obesity, and abnormalities of glucose tolerance. Methodology/Principal Findings Serum haptoglobin and the haptoglobin α–chain polymorphism were determined in 141 patients with polycystic ovary syndrome and 102 non-hyperandrogenic women. Of the whole group of 243 premenopausal women, 117 were obese and 51 showed abnormal glucose tolerance. Although serum haptoglobin concentrations were similar in PCOS patients and controls, the former presented with an increased frequency of Hp2 alleles (62% vs. 52%, P = 0.023). Circulating haptoglobin levels increased with obesity (P<0.001), yet no association was found between obesity and haptoglobin genotypes. No differences were observed in haptoglobin levels or genotype frequencies depending on glucose tolerance. Fifty percent of the variation in serum haptoglobin concentrations was explained by the variability in serum C-reactive protein concentrations, BMI, insulin sensitivity and haptoglobin genotypes. Conclusions/Significance Serum haptoglobin concentrations in premenopausal women are largely dependent on the haptoglobin polymorphism and on the presence of obesity, with insulin resistance and chronic inflammation possibly modulating this relationship. The association of polycystic ovary syndrome with Hp2 alleles suggests that the anti-oxidant and anti-inflammatory properties of haptoglobin may be reduced in these patients. PMID:19440331

  20. Pancreatic islet transplantation in cynomolgus monkeys. Initial studies and evidence that cyclosporine impairs glucose tolerance in normal monkeys.

    PubMed

    Stegall, M D; Chabot, J; Weber, C; Reemtsma, K; Hardy, M A

    1989-12-01

    Using a model of streptozotocin-induced, ketosis-prone, insulin-dependent diabetes mellitus (IDDM) in the cynomolgus monkey, we performed 11 intraportal transplants of collagenase-digested, Ficoll-purified pancreatic islets (9 ABO-compatible allografts and 2 concordant baboon xenografts). Islets were pretreated with ultraviolet-B irradiation and recipients received cyclosporine A immunosuppression. Two grafts never functioned, five grafts showed evidence of partial function, and four grafts (three allografts and one xenograft) showed evidence of good function, with the animals independent of exogenous insulin with morning fasting blood glucose levels less than 200 mg/dl. Because two grafts functioned only after CsA was either tapered or discontinued, we performed a related study that showed that therapeutic doses of CsA (morning trough serum level 150-250 ng/ml) impaired intravenous glucose tolerance tests (IVGTT) of normal monkeys and may contributed to graft dysfunction in our islet transplantation model. The results show that there is a decrease in release of serum insulin during an IVGTT leading to impairment of glucose utilization, while serum glucagon remains unaffected. After cessation of CsA, the IVGTT did not return to normal for 28 days. Oral glucose tolerance tests were unaffected in CsA-treated monkeys. These initial studies show that the streptozotocin-diabetic monkey is a valuable model to study IDDM and islet transplantation in nonhuman primates. We also confirm studies in rodents, dogs, and sheep by showing that CsA partially inhibits beta cell function in normal monkeys.

  1. Insulin effects on glucose tolerance, hypermetabolic response, and circadian-metabolic protein expression in a rat burn and disuse model

    PubMed Central

    Pidcoke, Heather F.; Baer, Lisa A.; Wu, Xiaowu; Wolf, Steven E.; Aden, James K.

    2014-01-01

    Insulin controls hyperglycemia after severe burns, and its use opposes the hypermetabolic response. The underlying molecular mechanisms are poorly understood, and previous research in this area has been limited because of the inadequacy of animal models to mimic the physiological effects seen in humans with burns. Using a recently published rat model that combines both burn and disuse components, we compare the effects of insulin treatment vs. vehicle on glucose tolerance, hypermetabolic response, muscle loss, and circadian-metabolic protein expression after burns. Male Sprague-Dawley rats were assigned to three groups: cage controls (n = 6); vehicle-treated burn and hindlimb unloading (VBH; n = 11), and insulin-treated burn and hindlimb unloading (IBH; n = 9). With the exception of cage controls, rats underwent a 40% total body surface area burn with hindlimb unloading, then IBH rats received 12 days of subcutaneous insulin injections (5 units·kg−1·day−1), and VBH rats received an equivalent dose of vehicle. Glucose tolerance testing was performed on day 14, after which blood and tissues were collected for analysis. Body mass loss was attenuated by insulin treatment (VBH = 265 ± 17 g vs. IBH = 283 ± 14 g, P = 0.016), and glucose clearance capacity was increased. Soleus and gastrocnemius muscle loss was decreased in the IBH group. Insulin receptor substrate-1, AKT, FOXO-1, caspase-3, and PER1 phosphorylation was altered by injury and disuse, with levels restored by insulin treatment in almost all cases. Insulin treatment after burn and during disuse attenuated the hypermetabolic response, increased glucose clearance, and normalized circadian-metabolic protein expression patterns. Therapies aimed at targeting downstream effectors may provide the beneficial effects of insulin without hypoglycemic risk. PMID:24760998

  2. Glycemic variability in relation to oral disposition index in the subjects with different stages of glucose tolerance

    PubMed Central

    2013-01-01

    Background Glucose variability could be an independent risk factor for diabetes complications in addition to average glucose. The deficiency in islet β cell secretion and insulin sensitivity, the two important pathophysiological mechanisms of diabetes, are responsible for glycemic disorders. The oral disposition index evaluated by product of insulin secretion and sensitivity is a useful marker of islet β cell function. The aim of the study is to investigate glycemic variability in relation to oral disposition index in the subjects across a range of glucose tolerance from the normal to overt type 2 diabetes. Methods 75-g oral glucose tolerance test (OGTT) was performed in total 220 subjects: 47 with normal glucose regulation (NGR), 52 with impaired glucose metabolism (IGM, 8 with isolated impaired fasting glucose [IFG], 18 with isolated impaired glucose tolerance [IGT] and 26 with combined IFG and IGT), 61 screen-diagnosed diabetes by isolated 2-h glucose (DM2h) and 60 newly diagnosed diabetes by both fasting and 2-h glucose (DM). Insulin sensitivity index (Matsuda index, ISI), insulin secretion index (ΔI30/ΔG30), and integrated β cell function measured by the oral disposition index (ΔI30/ΔG30 multiplied by the ISI) were derived from OGTT. All subjects were monitored using the continuous glucose monitoring system for consecutive 72 hours. The multiple parameters of glycemic variability included the standard deviation of blood glucose (SD), mean of blood glucose (MBG), high blood glucose index (HBGI), continuous overlapping net glycemic action calculated every 1 h (CONGA1), mean of daily differences (MODD) and mean amplitude of glycemic excursions (MAGE). Results From the NGR to IGM to DM2h to DM group, the respective values of SD (mean ± SD) (0.9 ± 0.3, 1.5 ± 0.5, 1.9 ± 0.6 and 2.2 ± 0.6 mmol/), MBG (5.9 ± 0.5, 6.7 ± 0.7, 7.7 ± 1.0 and 8.7 ± 1.5 mmol/L), HGBI [median(Q1–Q3)][0.8(0.2–1.2), 2.0(1.2–3.7), 3

  3. Respiratory inhibitors affect incorporation of glucose into Saccharomyces cerevisiae cells, but not the activity of glucose transport.

    PubMed

    Walsh, M C; Smits, H P; van Dam, K

    1994-12-01

    Incubation of starved galactose-grown S. cerevisiae cells with cyanide reduced glucose uptake as measured over a 5-s period. The Vmax for glucose uptake was decreased by over a factor of two but the apparent affinity for glucose doubled. When measured in the sub-second time scale, however, there was no significant inhibition of glucose uptake, by cyanide, up to 200-ms, clearly demonstrating that, in cyanide treated cells, glucose uptake was not linear for the first 5-s. After a 200-ms exposure of untreated cells to radio-labelled glucose, less than 10% of the intracellular label resided in soluble uncharged compounds. In cyanide-treated cells up to 43% of the labelled compounds were uncharged, with a concurrent reduction of intracellular label residing in anionic compounds. The results suggest that, in the presence of 10 mM cyanide when respiration is inhibited, a reduction in the cellular ATP concentration causes a reduction in hexose-kinase activity which results in an accumulation of internal free glucose, which in turn causes a reduction in net glucose transport.

  4. Kinetics of metabolism of glucose, propionate and CO2 in steers as affected by injecting phlorizin and feeding propionate

    SciTech Connect

    Veenhuizen, J.J.; Russell, R.W.; Young, J.W.

    1988-11-01

    Effects of injecting phlorizin subcutaneously and/or feeding propionate on metabolism of glucose, propionate and CO2 were determined for four steers used in a 4 x 4 Latin square design. Isotope dilution techniques were used to determine a four-pool kinetic solution for the flux of carbon among plasma glucose, rumen propionate, blood CO2 and rumen CO2. Injecting 1 g of phlorizin twice daily for 19 d resulted in 7.1 mol glucose C/d being excreted in urine. The basal glucose production of 13.4 mol C/d was increased to 17.9 mol C/d with phlorizin. There was no change in glucose oxidation or propionate production. The percentage of plasma glucose derived from propionate was unaffected by phlorizin, but 54 +/- 0.4% of total propionate was converted to plasma glucose during phlorizin treatment versus 40 +/- 0.6% during the basal treatment. When propionate was fed (18.3 mol C/d) glucose production increased to 21.2 mol C/d from the basal value of 13.4 mol C/d, and propionate oxidation to CO2 increased to 14.9 mol C/d from the basal value of 4.1 mol C/d. Glucose derived from propionate was 43 +/- 5% for the basal treatment and 67 +/- 3% during propionate feeding. The percentage of propionate converted to plasma glucose and blood and rumen CO2 was not affected by feeding propionate. An increased need for glucose, because of glucose excretion during phlorizin treatment, caused an increased utilization of propionate for gluconeogenesis, but an increased availability of propionate caused an increase in glucose production without affecting the relative distribution of carbon from propionate.

  5. Noninvasive fat quantification of the liver and pancreas may provide potential biomarkers of impaired glucose tolerance and type 2 diabetes

    PubMed Central

    Dong, Zhi; Luo, Yanji; Cai, Huasong; Zhang, Zhongwei; Peng, Zhenpeng; Jiang, Mengjie; Li, Yanbing; Li, Chang; Li, Zi-Ping; Feng, Shi-Ting

    2016-01-01

    Abstract The aim of the study is to investigate if the fat content of the liver and pancreas may indicate impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM). A total of 83 subjects (34 men; aged 46.5 ± 13.5 years) were characterized as T2DM, IGT, or normal glucose tolerant (NGT). NGT individuals were stratified as <40 or ≥40 years. Standard laboratory tests were conducted for insulin resistance and β-cell dysfunction. The magnetic resonance imaging Dixon technique was used to determine fat distribution in the liver and pancreas. Correlations among liver and pancreatic fat volume fractions (LFVFs and PFVFs, respectively) and laboratory parameters were analyzed. Among the groups, fat distribution was consistent throughout sections of the liver and pancreas, and LFVFs closely correlated with PFVFs. LFVFs correlated more closely than PFVFs with insulin resistance and β-cell function. Both the LFVFs and PFVFs were the highest in the T2DM patients, less in the IGT, and least in the NGT; all differences were significant. The PFVFs of the NGT subjects ≥40 years were significantly higher than that of those <40 years. The fat content of the liver and pancreas, particularly the liver, may be a biomarker for IGT and T2DM. PMID:27281097

  6. Metformin use in children with obesity and normal glucose tolerance – effects on cardiovascular markers and intrahepatic fat

    PubMed Central

    Mauras, Nelly; DelGiorno, Charles; Hossain, Jobayer; Bird, Keisha; Killen, Kelleigh; Merinbaum, Debbie; Weltman, Arthur; Damaso, Ligeia; Balagopal, Prabhakaran

    2014-01-01

    Objective To determine if metformin improves markers of inflammation, thrombosis, and intrahepatic fat contents in children with uncomplicated obesity. Methods Obese children with normal glucose tolerance but elevated highly sensitive C-reactive protein (hsCRP) and/or fibrinogen concentrations (>2 standard deviations) were randomized to structured diet/exercise or diet/exercise and metformin for 6 months. Blood samples, dual energy X-ray absorptiometry data, and liver magnetic resonance images were obtained. Results Forty-two of 66 recruited children (7–18 years) completed 6 months. Weight loss was modest but more pronounced in the metformin group (−4.9±1.0 kg) than in the diet/exercise group (−1.7±1.1 kg, p<0.03), whereas hsCRP and fibrinogen decreased more in the diet/exercise pubertal group. Baseline intrahepatic fat was high but decreased only in the diet/exercise (not metformin) pubertal group. Conclusions Six months of metformin therapy improved weight loss and reduced abdominal adiposity, but did not enhance the beneficial effect of diet and exercise on markers related to inflammation, thrombosis, or hepatic fat in obese children with normal glucose tolerance. PMID:22570948

  7. Influence of physical activity and gender on arterial function in type 2 diabetes, normal and impaired glucose tolerance

    PubMed Central

    Eriksson, Maria J.; Fritz, Tomas; Nyberg, Gunnar; Östenson, Claes Göran; Krook, Anna; Zierath, Juleen R.; Caidahl, Kenneth

    2015-01-01

    To determine whether Nordic walking improves cardiovascular function in middle-aged women and men, we included 121 with normal glucose tolerance, 33 with impaired glucose tolerance and 47 with Type 2 diabetes mellitus in a randomized controlled study. The intervention group added Nordic walking 5 h/week for 4 months to their ordinary activities. Aortic pulse wave velocity, aortic augmentation index, stiffness index, reflection index, intima–media thickness in the radial and carotid arteries, echogenicity of the carotid intima–media and systemic vascular resistance were measured. While baseline blood pressure did not differ by gender or diagnosis, aortic augmentation index was found to be higher in women in all groups. Vascular function was unchanged with intervention, without differences by gender or diagnosis. In conclusion, 4 months of Nordic walking is an insufficient stimulus to improve vascular function. Future studies should consider hard endpoints in addition to measures of vascular health, as well as larger population groups, long-term follow-up and documented compliance to exercise training. PMID:26092821

  8. Effect of glucose on Listeria monocytogenes biofilm formation, and assessment of the biofilm's sanitation tolerance.

    PubMed

    Kyoui, Daisuke; Hirokawa, Eri; Takahashi, Hajime; Kuda, Takashi; Kimura, Bon

    2016-08-01

    Listeria monocytogenes is an important cause of human foodborne infections and its ability to form biofilms is a serious concern to the food industry. To reveal the effect of glucose conditions on biofilm formation of L. monocytogenes, 20 strains were investigated under three glucose conditions (0.1, 1.0, and 2.0% w v(-1)) by quantifying the number of cells in the biofilm and observing the biofilm structure after incubation for 24, 72, and 168 h. In addition, the biofilms were examined for their sensitivity to sodium hypochlorite. It was found that high concentrations of glucose reduced the number of viable cells in the biofilms and increased extracellular polymeric substance production. Moreover, biofilms formed at a glucose concentration of 1.0 or 2.0% were more resistant to sodium hypochlorite than those formed at a glucose concentration of 0.1%. This knowledge can be used to help design the most appropriate sanitation strategy. PMID:27353113

  9. Short-Term Regulation of Lipocalin-2 but not RBP-4 During Oral Lipid Tolerance Test and Oral Glucose Tolerance Test.

    PubMed

    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2016-02-01

    The postprandial regulation of lipocalin-2 and retinol binding protein-4 (RBP-4) by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of lipocalin-2 and RBP-4 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn after 0, 2, 4, and 6 h in OLTT and after 0, 1, and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of lipocalin-2 and RBP-4 were measured by enzyme-linked immunosorbent assay (ELISA). Whereas RBP-4 levels remained unchanged during OGTT, lipocalin-2 concentrations significantly decreased during OGTT. During OLTT, RBP-4 levels were not influenced, whereas lipocalin-2 levels decreased significantly and stepwise. Fasting concentrations of RBP-4 were negatively correlated with BMI and waist-hip ratio, whereas lipocalin-2 levels were positively associated with BMI and waist-hip ratio. Female users of hormonal contraception had higher RBP-4 levels than females not on contraceptives. There is no significant short-term regulation of RBP-4 by orally ingested lipids or carbohydrates. Lipocalin-2 is downregulated after lipid and carbohydrate ingestion and this kind of regulation was not predicted by age, sex, triglycerides, glucose, or insulin levels. PMID:26069091

  10. Triglycerides to High-Density Lipoprotein Cholesterol Ratio Can Predict Impaired Glucose Tolerance in Young Women with Polycystic Ovary Syndrome

    PubMed Central

    Song, Do Kyeong; Lee, Hyejin; Sung, Yeon-Ah

    2016-01-01

    Purpose The triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio could be related to insulin resistance (IR). We previously reported that Korean women with polycystic ovary syndrome (PCOS) had a high prevalence of impaired glucose tolerance (IGT). We aimed to determine the cutoff value of the TG/HDL-C ratio for predicting IR and to examine whether the TG/HDL-C ratio is useful for identifying individuals at risk of IGT in young Korean women with PCOS. Materials and Methods We recruited 450 women with PCOS (24±5 yrs) and performed a 75-g oral glucose tolerance test (OGTT). IR was assessed by a homeostasis model assessment index over that of the 95th percentile of regular-cycling women who served as the controls (n=450, 24±4 yrs). Results The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in women with PCOS. Among the women with PCOS who had normal fasting glucose (NFG), the prevalence of IGT was significantly higher in the women with PCOS who had a high TG/HDL-C ratio compared with those with a low TG/HDL-C ratio (15.6% vs. 5.6%, p<0.05). Conclusion The cutoff value of the TG/HDL-C ratio for predicting IR was 2.5 in young Korean women with PCOS, and women with NFG and a high TG/HDL-C ratio had a higher prevalence of IGT. Therefore, Korean women with PCOS with a TG/HDL-C ratio >2.5 are recommended to be administered an OGTT to detect IGT even if they have NFG. PMID:27593868

  11. Purification, Characterization, and Substrate Specificity of a Novel Highly Glucose-Tolerant β-Glucosidase from Aspergillus oryzae

    PubMed Central

    Riou, Christine; Salmon, Jean-Michel; Vallier, Marie-Jose; Günata, Ziya; Barre, Pierre

    1998-01-01

    Aspergillus oryzae was found to secrete two distinct β-glucosidases when it was grown in liquid culture on various substrates. The major form had a molecular mass of 130 kDa and was highly inhibited by glucose. The minor form, which was induced most effectively on quercetin (3,3′,4′,5,7-pentahydroxyflavone)-rich medium, represented no more than 18% of total β-glucosidase activity but exhibited a high tolerance to glucose inhibition. This highly glucose-tolerant β-glucosidase (designated HGT-BG) was purified to homogeneity by ammonium sulfate precipitation, gel filtration, and anion-exchange chromatography. HGT-BG is a monomeric protein with an apparent molecular mass of 43 kDa and a pI of 4.2 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing polyacrylamide gel electrophoresis, respectively. Using p-nitrophenyl-β-d-glucoside as the substrate, we found that the enzyme was optimally active at 50°C and pH 5.0 and had a specific activity of 1,066 μmol min−1 mg of protein−1 and a Km of 0.55 mM under these conditions. The enzyme is particularly resistant to inhibition by glucose (Ki, 1.36 M) or glucono-δ-lactone (Ki, 12.5 mM), another powerful β-glucosidase inhibitor present in wine. A comparison of the enzyme activities on various glycosidic substrates indicated that HGT-BG is a broad-specificity type of fungal β-glucosidase. It exhibits exoglucanase activity and hydrolyzes (1→3)- and (1→6)-β-glucosidic linkages most effectively. This enzyme was able to release flavor compounds, such as geraniol, nerol, and linalol, from the corresponding monoterpenyl-β-d-glucosides in a grape must (pH 2.9, 90 g of glucose liter−1). Other flavor precursors (benzyl- and 2-phenylethyl-β-d-glucosides) and prunin (4′,5,7-trihydroxyflavanone-7-glucoside), which contribute to the bitterness of citrus juices, are also substrates of the enzyme. Thus, this novel β-glucosidase is of great potential interest in wine and

  12. Purification, characterization, and substrate specificity of a novel highly glucose-tolerant beta-glucosidase from Aspergillus oryzae.

    PubMed

    Riou, C; Salmon, J M; Vallier, M J; Günata, Z; Barre, P

    1998-10-01

    Aspergillus oryzae was found to secrete two distinct beta-glucosidases when it was grown in liquid culture on various substrates. The major form had a molecular mass of 130 kDa and was highly inhibited by glucose. The minor form, which was induced most effectively on quercetin (3,3',4',5,7-pentahydroxyflavone)-rich medium, represented no more than 18% of total beta-glucosidase activity but exhibited a high tolerance to glucose inhibition. This highly glucose-tolerant beta-glucosidase (designated HGT-BG) was purified to homogeneity by ammonium sulfate precipitation, gel filtration, and anion-exchange chromatography. HGT-BG is a monomeric protein with an apparent molecular mass of 43 kDa and a pI of 4.2 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing polyacrylamide gel electrophoresis, respectively. Using p-nitrophenyl-beta-D-glucoside as the substrate, we found that the enzyme was optimally active at 50 degreesC and pH 5.0 and had a specific activity of 1,066 micromol min-1 mg of protein-1 and a Km of 0.55 mM under these conditions. The enzyme is particularly resistant to inhibition by glucose (Ki, 1. 36 M) or glucono-delta-lactone (Ki, 12.5 mM), another powerful beta-glucosidase inhibitor present in wine. A comparison of the enzyme activities on various glycosidic substrates indicated that HGT-BG is a broad-specificity type of fungal beta-glucosidase. It exhibits exoglucanase activity and hydrolyzes (1-->3)- and (1-->6)-beta-glucosidic linkages most effectively. This enzyme was able to release flavor compounds, such as geraniol, nerol, and linalol, from the corresponding monoterpenyl-beta-D-glucosides in a grape must (pH 2.9, 90 g of glucose liter-1). Other flavor precursors (benzyl- and 2-phenylethyl-beta-D-glucosides) and prunin (4',5,7-trihydroxyflavanone-7-glucoside), which contribute to the bitterness of citrus juices, are also substrates of the enzyme. Thus, this novel beta-glucosidase is of great potential

  13. Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease.

    PubMed

    Vandal, Milene; White, Phillip J; Chevrier, Geneviève; Tremblay, Cyntia; St-Amour, Isabelle; Planel, Emmanuel; Marette, Andre; Calon, Frederic

    2015-10-01

    Alzheimer's disease (AD) has been associated with type II diabetes (T2D) and obesity in several epidemiologic studies. To determine whether AD neuropathology can cause peripheral metabolic impairments, we investigated metabolic parameters in the triple-transgenic (3xTg)-AD mouse model of AD, compared with those in nontransgenic (non-Tg) controls, at 6, 8, and 14 mo of age. We found a more pronounced cortical Aβ accumulation (2- and 3.5-fold increase in Aβ42 in the soluble and insoluble protein fractions, respectively) in female 3xTg-AD mice than in the males. Furthermore, female 3xTg-AD mice displayed a significant deterioration in glucose tolerance (AUC, +118% vs. non-Tg mice at 14 mo). Fasting plasma insulin levels rose 2.5-fold from 6 to 14 mo of age in female 3xTg-AD mice. Glucose intolerance and cortical amyloid pathology worsened with age, and both were more pronounced in the females. Pancreatic amyloidopathy was revealed and could underlie the observed deficit in glycemic response in 3xTg-AD mice. The present results suggest that AD-like neuropathology extends to the pancreas in the 3xTg-AD mouse, leading to glucose intolerance and contributing to a pathologic self-amplifying loop between AD and T2D. PMID:26108977

  14. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance.

    PubMed

    Lowndes, Joshua; Sinnett, Stephanie S; Rippe, James M

    2015-10-23

    Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20-60 years old) were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US), one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ±13.0 vs. 74.5 ± 13.3 kg, p < 0.001), but the change in weight was comparable among groups (p > 0.05). There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L), insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L), or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05). These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others.

  15. Adaptations to exercise training within skeletal muscle in adults with type 2 diabetes or impaired glucose tolerance: a systematic review.

    PubMed

    Wang, Yi; Simar, David; Fiatarone Singh, Maria A

    2009-01-01

    The aim of this investigation was to review morphological and metabolic adaptations within skeletal muscle to exercise training in adults with type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). A comprehensive, systematic database search for manuscripts was performed from 1966 to March 2008 using computerized databases, including Medline, Premedline, CINAHL, AMED, EMBASE and SportDiscus. Three reviewers independently assessed studies for potential inclusion (exposure to exercise training, T2DM or IGT, muscle biopsy performed). A total of 18 exercise training studies were reviewed. All morphological and metabolic outcomes from muscle biopsies were collected. The metabolic outcomes were divided into six domains: glycogen, glucose facilitated transporter 4 (GLUT4) and insulin signalling, enzymes, markers of inflammation, lipids metabolism and so on. Beneficial adaptations to exercise were seen primarily in muscle fiber area and capillary density, glycogen, glycogen synthase and GLUT4 protein expressions. Few randomized controlled trials including muscle biopsy data existed, with a small number of subjects involved. More trials, especially robustly designed exercise training studies, are needed in this field. Future research should focus on the insulin signalling pathway to better understand the mechanism of the improvements in insulin sensitivity and glucose homeostasis in response to various modalities and doses of exercise in this cohort.

  16. Evaluation of bimetallic catalyst PtAg/C as a glucose-tolerant oxygen reduction cathode

    NASA Astrophysics Data System (ADS)

    Guerra-Balcázar, M.; Cuevas-Muñiz, F. M.; Álvarez-Contreras, L.; Arriaga, L. G.; Ledesma-García, J.

    2012-01-01

    PtAg/C nanoparticles were synthesized by chemical reduction and evaluated for the oxygen reduction reaction (ORR) in the absence and presence of glucose. PtAg/C catalyst formed onion-like layered structures, which are uniformly distributed on the support. PtAg/C showed activity comparable to that of Pt/C ETEK for ORR. Further, the catalyst exhibited high selectivity for ORR in the presence of glucose. PtAg/C was evaluated as cathode in a microfluidic fuel cell operated with high concentration of glucose (100 mM) as fuel. The results demonstrated that the use of PtAg/C as cathode electrode achieved higher selectivity and better performance compared with Pt/C catalyst.

  17. Esculentin-2CHa-Related Peptides Modulate Islet Cell Function and Improve Glucose Tolerance in Mice with Diet-Induced Obesity and Insulin Resistance

    PubMed Central

    Ojo, Opeolu O.; Srinivasan, Dinesh K.; Owolabi, Bosede O.; Vasu, Srividya; Conlon, J. Michael; Flatt, Peter R.; Abdel-Wahab, Yasser H. A.

    2015-01-01

    The frog skin host-defense peptide esculentin-2CHa (GFSSIFRGVA10KFASKGLGK D20LAKLGVDLVA30CKISKQC) displays antimicrobial, antitumor, and immunomodulatory properties. This study investigated the antidiabetic actions of the peptide and selected analogues. Esculentin-2CHa stimulated insulin secretion from rat BRIN-BD11 clonal pancreatic β-cells at concentrations greater than 0.3 nM without cytotoxicity by a mechanism involving membrane depolarization and increase of intracellular Ca2+. Insulinotropic activity was attenuated by activation of KATP channels, inhibition of voltage-dependent Ca2+ channels and chelation of extracellular Ca2+. The [L21K], [L24K], [D20K, D27K] and [C31S,C37S] analogues were more potent but less effective than esculentin-2CHa whereas the [L28K] and [C31K] analogues were both more potent and produced a significantly (P < 0.001) greater maximum response. Acute administration of [L28K]esculentin-2CHa (75 nmol/kg body weight) to high fat fed mice with obesity and insulin resistance enhanced glucose tolerance and insulin secretion. Twice-daily administration of this dose of [L28K]esculentin-2CHa for 28 days had no significant effect on body weight, food intake, indirect calorimetry or body composition. However, mice exhibited decreased non-fasting plasma glucose (P < 0.05), increased non-fasting plasma insulin (P < 0.05) as well as improved glucose tolerance and insulin secretion (P < 0.01) following both oral and intraperitoneal glucose loads. Impaired responses of isolated islets from high fat fed mice to established insulin secretagogues were restored by [L28K]esculentin-2CHa treatment. Peptide treatment was accompanied by significantly lower plasma and pancreatic glucagon levels and normalization of α-cell mass. Circulating triglyceride concentrations were decreased but plasma cholesterol and LDL concentrations were not significantly affected. The data encourage further investigation of the potential of esculentin-2CHa related peptides for

  18. High Physiological Omega-3 Fatty Acid Supplementation Affects Muscle Fatty Acid Composition and Glucose and Insulin Homeostasis in Obese Adolescents

    PubMed Central

    Dangardt, Frida; Chen, Yun; Gronowitz, Eva; Dahlgren, Jovanna; Friberg, Peter; Strandvik, Birgitta

    2012-01-01

    Obese adolescents have high concentrations of saturated fatty acids and low omega-3 long-chain polyunsaturated fatty acids (LCUFAs) in plasma phospholipids. We aimed to investigate effects of omega-3 LCPUFA supplementation to obese adolescents on skeletal muscle lipids and glucose and insulin homeostasis. Twenty-five obese adolescents (14–17 years old, 14 females) completed a randomized double-blind crossover study supplying capsules containing either 1.2 g omega-3 LCPUFAs or placebo, for 3 months each with a six-week washout period. Fasting blood glucose, insulin, leptin, adiponectin, and lipids were measured. Intravenous glucose tolerance test (IVGTT) and euglycemic-hyperinsulinemic clamp were performed, and skeletal muscle biopsies were obtained at the end of each period. The concentrations of EPA, DHA, and total omega-3 PUFA in muscle phospholipids increased in both sexes. In the females, omega-3 LCPUFA supplementation improved glucose tolerance by 39% (P = 0.04) and restored insulin concentration by 34% (P = 0.02) during IVGTT. Insulin sensitivity improved 17% (P = 0.07). In males, none of these parameters was influenced by omega-3 supplementation. Thus, three months of supplementation of omega-3 LCPUFA improved glucose and insulin homeostasis in obese girls without influencing body weight. PMID:22523671

  19. Evodiamine Inhibits Insulin-Stimulated mTOR-S6K Activation and IRS1 Serine Phosphorylation in Adipocytes and Improves Glucose Tolerance in Obese/Diabetic Mice

    PubMed Central

    Wang, Ting; Kusudo, Tatsuya; Takeuchi, Tamaki; Yamashita, Yukari; Kontani, Yasuhide; Okamatsu, Yuko; Saito, Masayuki; Mori, Nozomu; Yamashita, Hitoshi

    2013-01-01

    Evodiamine, an alkaloid extracted from the dried unripe fruit of the tree Evodia rutaecarpa Bentham (Rutaceae), reduces obesity and insulin resistance in obese/diabetic mice; however, the mechanism underlying the effect of evodiamine on insulin resistance is unknown. This study investigated the effect of evodiamine on signal transduction relating to insulin resistance using obese/diabetic KK-Ay mice and an in vitro adipocyte culture. There is a significant decrease in the mammalian target of rapamycin (mTOR) and ribosomal S6 protein kinase (S6K) signaling in white adipose tissue (WAT) in KK-Ay mice treated with evodiamine, in which glucose tolerance is improved. In addition, reduction of insulin receptor substrate 1 (IRS1) serine phosphorylation, an indicator of insulin resistance, was detected in their WAT, suggesting suppression of the negative feedback loop from S6K to IRS1. As well as the stimulation of IRS1 and Akt serine phosphorylation, insulin-stimulated phosphorylation of mTOR and S6K is time-dependent in 3T3-L1 adipocytes, whereas evodiamine does not affect their phosphorylation except for an inhibitory effect on mTOR phosphorylation. Moreover, evodiamine inhibits the insulin-stimulated phosphorylation of mTOR and S6K, leading to down-regulation of IRS1 serine phosphorylation in the adipocytes. Evodiamine also stimulates phosphorylation of AMP-activated protein kinase (AMPK), an important regulator of energy metabolism, which may cause down-regulation of mTOR signaling in adipocytes. A similar effect on AMPK, mTOR and IRS1 phosphorylation was found in adipocytes treated with rosiglitazone. These results suggest evodiamine improves glucose tolerance and prevents the progress of insulin resistance associated with obese/diabetic states, at least in part, through inhibition of mTOR-S6K signaling and IRS1 serine phosphorylation in adipocytes. PMID:24391749

  20. CNS Vitamin D improves glucose tolerance, hepatic insulin sensitivity, and reverses diet-induced obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low vitamin D levels have been correlated to both obesity and the development of type 2 diabetes (T2DM) although no causative mechanisms have been established. Vitamin D receptors are present in the hypothalamus, a region important in both weight and glucose regulation. The role of these receptors, ...

  1. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence

    PubMed Central

    Pasieka, Aoibhe M.; Rafacho, Alex

    2016-01-01

    Glucocorticoids (GCs) are steroid hormones that exert important physiological actions on metabolism. Given that GCs also exert potent immunosuppressive and anti-inflammatory actions, synthetic GCs such as prednisolone and dexamethasone were developed for the treatment of autoimmune- and inflammatory-related diseases. The synthetic GCs are undoubtedly efficient in terms of their therapeutic effects, but are accompanied by significant adverse effects on metabolism, specifically glucose metabolism. Glucose intolerance and reductions in insulin sensitivity are among the major concerns related to GC metabolic side effects, which may ultimately progress to type 2 diabetes mellitus. A number of pre-clinical and clinical studies have aimed to understand the repercussions of GCs on glucose metabolism and the possible mechanisms of GC action. This review intends to summarize the main alterations that occur in liver, skeletal muscle, adipose tissue, and pancreatic islets in the context of GC-induced glucose intolerance. For this, both experimental (animals) and clinical studies were selected and, whenever possible, the main cellular mechanisms involved in such GC-side effects were discussed. PMID:27527232

  2. Impact of Glucocorticoid Excess on Glucose Tolerance: Clinical and Preclinical Evidence.

    PubMed

    Pasieka, Aoibhe M; Rafacho, Alex

    2016-01-01

    Glucocorticoids (GCs) are steroid hormones that exert important physiological actions on metabolism. Given that GCs also exert potent immunosuppressive and anti-inflammatory actions, synthetic GCs such as prednisolone and dexamethasone were developed for the treatment of autoimmune- and inflammatory-related diseases. The synthetic GCs are undoubtedly efficient in terms of their therapeutic effects, but are accompanied by significant adverse effects on metabolism, specifically glucose metabolism. Glucose intolerance and reductions in insulin sensitivity are among the major concerns related to GC metabolic side effects, which may ultimately progress to type 2 diabetes mellitus. A number of pre-clinical and clinical studies have aimed to understand the repercussions of GCs on glucose metabolism and the possible mechanisms of GC action. This review intends to summarize the main alterations that occur in liver, skeletal muscle, adipose tissue, and pancreatic islets in the context of GC-induced glucose intolerance. For this, both experimental (animals) and clinical studies were selected and, whenever possible, the main cellular mechanisms involved in such GC-side effects were discussed. PMID:27527232

  3. Neonatal Exendin-4 Reduces Growth, Fat Deposition and Glucose Tolerance during Treatment in the Intrauterine Growth-Restricted Lamb

    PubMed Central

    Mohammad, Saidatul N. B.; De Blasio, Miles J.; Harland, M. Lyn; Simmons, Rebecca A.; Owens, Julie A.

    2013-01-01

    Background IUGR increases the risk of type 2 diabetes mellitus (T2DM) in later life, due to reduced insulin sensitivity and impaired adaptation of insulin secretion. In IUGR rats, development of T2DM can be prevented by neonatal administration of the GLP-1 analogue exendin-4. We therefore investigated effects of neonatal exendin-4 administration on insulin action and β-cell mass and function in the IUGR neonate in the sheep, a species with a more developed pancreas at birth. Methods Twin IUGR lambs were injected s.c. daily with vehicle (IUGR+Veh, n = 8) or exendin-4 (1 nmol.kg-1, IUGR+Ex-4, n = 8), and singleton control lambs were injected with vehicle (CON, n = 7), from d 1 to 16 of age. Glucose-stimulated insulin secretion and insulin sensitivity were measured in vivo during treatment (d 12–14). Body composition, β-cell mass and in vitro insulin secretion of isolated pancreatic islets were measured at d 16. Principal Findings IUGR+Veh did not alter in vivo insulin secretion or insulin sensitivity or β-cell mass, but increased glucose-stimulated insulin secretion in vitro. Exendin-4 treatment of the IUGR lamb impaired glucose tolerance in vivo, reflecting reduced insulin sensitivity, and normalised glucose-stimulated insulin secretion in vitro. Exendin-4 also reduced neonatal growth and visceral fat accumulation in IUGR lambs, known risk factors for later T2DM. Conclusions Neonatal exendin-4 induces changes in IUGR lambs that might improve later insulin action. Whether these effects of exendin-4 lead to improved insulin action in adult life after IUGR in the sheep, as in the PR rat, requires further investigation. PMID:23424667

  4. Overexpression and characterization of a glucose-tolerant β-glucosidase from T. aotearoense with high specific activity for cellobiose.

    PubMed

    Yang, Fang; Yang, Xiaofeng; Li, Zhe; Du, Chenyu; Wang, Jufang; Li, Shuang

    2015-11-01

    Thermoanaerobacterium aotearoense P8G3#4 produced β-glucosidase (BGL) intracellularly when grown in liquid culture on cellobiose. The gene bgl, encoding β-glucosidase, was cloned and sequenced. Analysis revealed that the bgl contained an open reading frame of 1314 bp encoding a protein of 446 amino acid residues, and the product belonged to the glycoside hydrolase family 1 with the canonical glycoside hydrolase family 1 (GH1) (β/α)8 TIM barrel fold. Expression of pET-bgl together with a chaperone gene cloned in vector pGro7 in Escherichia coli dramatically enhanced the crude enzyme activity to a specific activity of 256.3 U/mg wet cells, which resulted in a 9.2-fold increase of that obtained from the expression without any chaperones. The purified BGL exhibited relatively high thermostability and pH stability with its highest activity at 60 °C and pH 6.0. In addition, the activities of BGL were remarkably stimulated by the addition of 5 mM Na(+) or K(+). The enzyme showed strong ability to hydrolyze cellobiose with a K m and V max of 25.45 mM and 740.5 U/mg, respectively. The BGL was activated by glucose at concentration varying from 50 to 250 mM and tolerant to glucose inhibition with a K i of 800 mM glucose. The supplement of the purified BGL to the sugarcane bagasse hydrolysis mixture containing a commercial cellulase resulted in about 20 % enhancement of the released reducing sugars. These properties of the purified BGL should have important practical implication in its potential applications for better industrial production of glucose or bioethanol started from lignocellulosic biomass.

  5. A single subunit MCM6 from pea promotes salinity stress tolerance without affecting yield.

    PubMed

    Dang, Hung Quang; Tran, Ngoc Quang; Gill, Sarvajeet Singh; Tuteja, Renu; Tuteja, Narendra

    2011-05-01

    The eukaryotic pre-replicative complex (Pre-RC), including heterohexameric minichromosome maintenance (MCM2-7) proteins, ensures that the DNA in genome is replicated only once per cell division cycle. The MCMs provide DNA unwinding function during the DNA replication. Since MCM proteins play essential role in cell division and most likely are affected during stress conditions therefore their overexpression in plants may help in stress tolerance. But the role of MCMs in abiotic stress tolerance in plants has not been reported so far. In this study we report that: a) the MCM6 transcript is upregulated in pea plant in response to high salinity and cold stress and not with ABA, drought and heat stress; b) MCM6 overexpression driven by a constitutive cauliflower mosaic virus-35S promoter in tobacco plants confers salinity tolerance. The T(1) transgenics plants were able to grow to maturity and set normal viable seeds under continuous salinity stress, without yield penalty. It was observed that in salt-grown T(1) transgenic plants the Na(+) ions is mostly accumulated in mature leaves and not in seeds of T(1) transgenic lines as compared with the wild-type (WT) plants. T(1) transgenic plants exhibited better growth status under salinity stress conditions in comparison to WT plants. Furthermore, the T(1) transgenic plants maintained significantly higher levels of leaf chlorophyll content, net photosynthetic rate and therefore higher dry matter accumulation and yield with 200 mM NaCl as compared to the WT plants. Tolerance index data showed better salt tolerance potential of T(1) transgenic plants in comparison to WT. These findings provide first direct evidence that overexpression of single subunit MCM6 confers salinity stress tolerance without yield loss. The possible mechanism of salinity tolerance is discussed. These findings suggest that DNA replication machinery can be exploited for promoting stress tolerance in crop plants.

  6. Assessment of incretins in oral glucose and lipid tolerance tests may be indicative in the diagnosis of metabolic syndrome aggravation.

    PubMed

    Kiec-Klimczak, M; Malczewska-Malec, M; Razny, U; Zdzienicka, A; Gruca, A; Goralska, J; Pach, D; Gilis-Januszewska, A; Dembinska-Kiec, A; Hubalewska-Dydejczyk, A

    2016-04-01

    Incretins stimulated by oral meals are claimed to be protective for the pancreatic beta cells, to increase insulin secretion, to inhibit glucagon release, slow gastric emptying (glucagon-like peptide-1) and suppress appetite. Recently it has however been suggested that glucagon-like peptide-1 (GLP-1) is putative early biomarker of metabolic consequences of the obesity associated proinflammatory state. The study was aimed to compare the release of incretins and some of early markers of inflammation at the fasting and postprandial period induced by functional oral glucose as well as lipid load in healthy controls and patients with metabolic syndrome (MS) to see if functional tests may be helpful in searching for the inflammatory status of patients. Fifty patients with MS and 20 healthy volunteers (C) participated in this study. The 3-hour oral glucose (OGTT) and the 8-hour oral lipid (OLTT) tolerance tests were performed. At fasting leptin and adiponectin, as well as every 30 minutes of OGTT and every 2 hours of OLTT blood concentration of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucose, insulin, triglycerides, free fatty acids, glutathione peroxidase, interleukin-6, sE-selectin, monocyte chemoattractant protein-1 (MCP1) and visfatin were measured. At fasting and during both OGTT and OLTT the level of incretins did not differ between the MS and the C group. Both glucose and lipids reach food activated incretins secretion. Glucose was the main GLP-1 release activator, while the lipid load activated evidently GIP secretion. A significantly larger AUC-GIP after the lipid-rich meal over the carbohydrate meal was observed, while statistically bigger value of AUC-GLP-1 was noticed in OGTT than in OLTT (P < 0.001) within each of the investigated groups. In patients with the highest fasting plasma GIP concentration (3(rd) tertile), IL-6, MCP-1, sE-selectin and visfatin blood levels were increased and correlated with glutathione peroxydase, leptin

  7. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    PubMed

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance. PMID:20660065

  8. Saturated- and n-6 polyunsaturated-fat diets each induce ceramide accumulation in mouse skeletal muscle: reversal and improvement of glucose tolerance by lipid metabolism inhibitors.

    PubMed

    Frangioudakis, G; Garrard, J; Raddatz, K; Nadler, J L; Mitchell, T W; Schmitz-Peiffer, C

    2010-09-01

    Lipid-induced insulin resistance is associated with intracellular accumulation of inhibitory intermediates depending on the prevalent fatty acid (FA) species. In cultured myotubes, ceramide and phosphatidic acid (PA) mediate the effects of the saturated FA palmitate and the unsaturated FA linoleate, respectively. We hypothesized that myriocin (MYR), an inhibitor of de novo ceramide synthesis, would protect against glucose intolerance in saturated fat-fed mice, while lisofylline (LSF), a functional inhibitor of PA synthesis, would protect unsaturated fat-fed mice. Mice were fed diets enriched in saturated fat, n-6 polyunsaturated fat, or chow for 6 wk. Saline, LSF (25 mg/kg x d), or MYR (0.3 mg/kg x d) were administered by mini-pumps in the final 4 wk. Glucose homeostasis was examined by glucose tolerance test. Muscle ceramide and PA were analyzed by mass spectrometry. Expression of LASS isoforms (ceramide synthases) was evaluated by immunoblotting. Both saturated and polyunsaturated fat diets increased muscle ceramide and induced glucose intolerance. MYR and LSF reduced ceramide levels in saturated and unsaturated fat-fed mice. Both inhibitors also improved glucose tolerance in unsaturated fat-fed mice, but only LSF was effective in saturated fat-fed mice. The discrepancy between ceramide and glucose tolerance suggests these improvements may not be related directly to changes in muscle ceramide and may involve other insulin-responsive tissues. Changes in the expression of LASS1 were, however, inversely correlated with alterations in glucose tolerance. The demonstration that LSF can ameliorate glucose intolerance in vivo independent of the dietary FA type indicates it may be a novel intervention for the treatment of insulin resistance.

  9. Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance

    PubMed Central

    Sayers, Sophie R.; Reimann, Frank; Gribble, Fiona M.; Parker, Helen; Zac-Varghese, Sagen; Bloom, Stephen R.; Foretz, Marc; Viollet, Benoit; Rutter, Guy A.

    2016-01-01

    Background Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1) in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK) in these cells. Method Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre) to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay. Results Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01) in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01) and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01) GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01). Conclusion AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes. PMID:27010458

  10. Effects of colupulone, a component of hops and brewers yeast, and chromium on glucose tolerance and hepatic cytochrome P450 in nondiabetic and spontaneously diabetic mice.

    PubMed

    Mannering, G J; Shoeman, J A; Shoeman, D W

    1994-05-16

    Brewers yeast contains factors that increase and decrease glucose tolerance. Hop components (lupulones) that adhere to yeast during the brewing process elicit a variety of biological effects including the induction of hepatic cytochrome P4503A. Colupulone was tested for its effects on glucose tolerance and cytochrome P450. Serum glucose levels 30 min after the injection of glucose were lowered by colupulone in nondiabetic Swiss-Webster mice, elevated in diabetic C57B1/KSJ-db/db mice, and unaffected in nondiabetic C57B1/KSJ+m/+m mice. Colupulone lowered hemoglobin glycation slightly in +m/+m mice but not in db/db mice. The cytochrome P450 system was highly induced by colupulone in both db/db and +m/+m mice. Chromium, which acts in concert with the factor in yeast that enhances glucose tolerance, had little or no effect on the plasma glucose level or the cytochrome P450 system in either +m/+m or db/db mice.

  11. Glucose tolerance status is a better predictor of diabetes and cardiovascular outcomes than metabolic syndrome: a prospective cohort study

    PubMed Central

    2012-01-01

    Backround To evaluate the importance of oral glucose tolerance test (OGTT) in predicting diabetes and cardiovascular disease in patients with and without Metabolic Syndrome from a population treated in a primary care unit. Research design and methods A prospective cohort study was conducted with subjects regularly attending the primary care unit of Hospital de Clínicas de Porto Alegre. Participants underwent a 75 g OGTT. Metabolic syndrome definition was based on the criteria of IDF/AHA/NHLBI-2010. Results Participants mean age was 61 ± 12 years (males: 38%; whites: 67%). Of the 148 subjects included, 127 (86%) were followed for 36 ± 14 months, 21 (14%) were lost. Subjects were classified into four groups based on baseline OGTT: 29% normal (n = 43), 28% impaired fasting glucose (IFG; n = 42), 26% impaired glucose tolerance (IGT; n = 38), and 17% diabetes (n = 25). Metabolic syndrome prevalence was lower in normal group (28%), intermediate in IFG (62%) and IGT (65%) groups, and higher among subjects with diabetes (92%; P <0.001). Incidence of diabetes increased along with the stages of glucose metabolism disturbance (normal: 0%, IFG: 16%, IGT: 28%; P = 0.004). No patient with normal OGTT developed diabetes, regardless metabolic syndrome presence. Diabetes at baseline was the major determinant of cardiovascular disease occurrence (normal: 0%, IFG: 4%, IGT: 0%, diabetes: 24%; P = 0.001). In Cox-regression analysis, only the 2 h OGTT results were associated with diabetes (OR = 1.03; 95%CI 1.01–1.06; P <0.001) and cardiovascular disease development (OR = 1.013; 95%CI 1.002–1.025; P = 0.024). Conclusions In this sample of subjects undergoing diabetes screening, the OGTT predicted diabetes and cardiovascular disease more effectively than the metabolic syndrome status. PMID:22682107

  12. Prevalence of non-insulin-dependent diabetes mellitus and impaired glucose tolerance in two Algonquin communities in Quebec.

    PubMed Central

    Delisle, H F; Ekoé, J M

    1993-01-01

    OBJECTIVE: To assess and compare the prevalence of non-insulin-dependent diabetes mellitus (NIDDM) and impaired glucose tolerance (IGT) in two native Indian communities. DESIGN: Population-based study. SETTING: Two Algonquin communities in Quebec: River Desert and Lac Simon. PARTICIPANTS: All native Indian residents aged at least 15 years were eligible; 621 (59%) of them volunteered to enroll in the study. The participation rate was 49% in River Desert and 76% in Lac Simon. MAIN OUTCOME MEASURES: Fasting blood glucose level and serum glucose level 2 hours after 75-g oral glucose tolerance test, as described by the World Health Organization, in all subjects except those with confirmed diabetes. Other measures included body mass index (BMI), fat distribution and blood pressure. MAIN RESULTS: The age-sex standardized prevalence rate of NIDDM was 19% in Lac Simon (95% confidence interval [CI] 16% to 21%); this was more than twice the rate of 9% in River Desert (95% CI 7% to 11%). The IGT rates were comparable in the two communities (River Desert 5%, Lac Simon 6%). NIDDM and IGT were uncommon under the age of 35 years. Only in Lac Simon was the NIDDM prevalence rate significantly higher among the women than among the men (23% v. 14%); almost half of the women aged 35 years or more had diabetes. In Lac Simon the rate of marked obesity (BMI greater than 30) was significantly higher among the women than among the men (37% v. 19%; p < 0.001); this sex-related difference was not found in River Desert (rates 31% and 23% respectively). Previously undiagnosed NIDDM accounted for 25% of all the cases. NIDDM and IGT were significantly associated with high BMI, sum of skinfold thicknesses and waist:hip circumference ratio (p < 0.001). The subscapular:triceps skinfold ratio, however, did not display such an association, nor did the age-adjusted systolic blood pressure. CONCLUSIONS: The prevalence of NIDDM is high in Algonquin communities and may vary markedly between communities

  13. Exposure to Corticosterone Affects Host Resistance, but Not Tolerance, to an Emerging Fungal Pathogen

    PubMed Central

    Murone, Julie; DeMarchi, Joseph A.; Venesky, Matthew D.

    2016-01-01

    Host responses to pathogens include defenses that reduce infection burden (i.e., resistance) and traits that reduce the fitness consequences of an infection (i.e., tolerance). Resistance and tolerance are affected by an organism's physiological status. Corticosterone (“CORT”) is a hormone that is associated with the regulation of many physiological processes, including metabolism and reproduction. Because of its role in the stress response, CORT is also considered the primary vertebrate stress hormone. When secreted at high levels, CORT is generally thought to be immunosuppressive. Despite the known association between stress and disease resistance in domesticated organisms, it is unclear whether these associations are ecologically and evolutionary relevant in wildlife species. We conducted a 3x3 fully crossed experiment in which we exposed American toads (Anaxyrus [Bufo] americanus) to one of three levels of exogenous CORT (no CORT, low CORT, or high CORT) and then to either low or high doses of the pathogenic chytrid fungus Batrachochytrium dendrobatidis (“Bd”) or a sham exposure treatment. We assessed Bd infection levels and tested how CORT and Bd affected toad resistance, tolerance, and mortality. Exposure to the high CORT treatment significantly elevated CORT release in toads; however, there was no difference between toads given no CORT or low CORT. Exposure to CORT and Bd each increased toad mortality, but they did not interact to affect mortality. Toads that were exposed to CORT had higher Bd resistance than toads exposed to ethanol controls/low CORT, a pattern opposite that of most studies on domesticated animals. Exposure to CORT did not affect toad tolerance to Bd. Collectively, these results show that physiological stressors can alter a host’s response to a pathogen, but that the outcome might not be straightforward. Future studies that inhibit CORT secretion are needed to better our understanding of the relationship between stress physiology

  14. β-Glucosidase from the hyperthermophilic archaeon Thermococcus sp. is a salt-tolerant enzyme that is stabilized by its reaction product glucose.

    PubMed

    Sinha, Sushant K; Datta, Supratim

    2016-10-01

    β-Glucosidase (BG) is widely applied in the biofuel's industry, as part of a cellulase cocktail to catalyze the hydrolysis of the β-1,4 linkages that join two glucose molecules in a cellulose polymer. The hydrolysis step is generally recognized as the major limiting step in the development of efficient enzyme-based technologies for the conversion of lignocellulosic biomass to sugars and the production of biofuels due to the accumulation of the reaction product, glucose. Relieving this glucose inhibition of BG is therefore a major challenge. In this study, O08324, a putative BG gene encoded in the hyperthermophilic archaeon Thermococcus sp., was cloned and overexpressed in Escherichia coli. O08324 showed maximum activity between pH 5-6.8 and at 78 °C and was thermostable with a half-life of 860 min at 78 °C in the presence of 1.5 M glucose. O08324 was not inhibited by glucose up to the highest assayable concentration of 4 M and also shows no decrease in activity in the presence of up to 4 M of sodium chloride or potassium chloride. O08324 supplementation of Trichoderma viride cellulase enhanced glucose production by more than 50 % compared to a commercially available BG, when Avicel (10 %, w/v) was used as a substrate at 37 °C. Multiple sequence alignments across previously reported glucose-tolerant BGs shows that many conserved residues previously implicated in glucose tolerance are not conserved in this BG suggesting a need for a relook at understanding the molecular basis of glucose tolerance. PMID:27198723

  15. β-Glucosidase from the hyperthermophilic archaeon Thermococcus sp. is a salt-tolerant enzyme that is stabilized by its reaction product glucose.

    PubMed

    Sinha, Sushant K; Datta, Supratim

    2016-10-01

    β-Glucosidase (BG) is widely applied in the biofuel's industry, as part of a cellulase cocktail to catalyze the hydrolysis of the β-1,4 linkages that join two glucose molecules in a cellulose polymer. The hydrolysis step is generally recognized as the major limiting step in the development of efficient enzyme-based technologies for the conversion of lignocellulosic biomass to sugars and the production of biofuels due to the accumulation of the reaction product, glucose. Relieving this glucose inhibition of BG is therefore a major challenge. In this study, O08324, a putative BG gene encoded in the hyperthermophilic archaeon Thermococcus sp., was cloned and overexpressed in Escherichia coli. O08324 showed maximum activity between pH 5-6.8 and at 78 °C and was thermostable with a half-life of 860 min at 78 °C in the presence of 1.5 M glucose. O08324 was not inhibited by glucose up to the highest assayable concentration of 4 M and also shows no decrease in activity in the presence of up to 4 M of sodium chloride or potassium chloride. O08324 supplementation of Trichoderma viride cellulase enhanced glucose production by more than 50 % compared to a commercially available BG, when Avicel (10 %, w/v) was used as a substrate at 37 °C. Multiple sequence alignments across previously reported glucose-tolerant BGs shows that many conserved residues previously implicated in glucose tolerance are not conserved in this BG suggesting a need for a relook at understanding the molecular basis of glucose tolerance.

  16. SRA Gene Knockout Protects against Diet-induced Obesity and Improves Glucose Tolerance*

    PubMed Central

    Liu, Shannon; Sheng, Liang; Miao, Hongzhi; Saunders, Thomas L.; MacDougald, Ormond A.; Koenig, Ronald J.; Xu, Bin

    2014-01-01

    We have recently shown that the non-coding RNA, steroid receptor RNA activator (SRA), functions as a transcriptional coactivator of PPARγ and promotes adipocyte differentiation in vitro. To assess SRA function in vivo, we have generated a whole mouse Sra1 gene knock-out (SRA−/−). Here, we show that the Sra1 gene is an important regulator of adipose tissue mass and function. SRA is expressed at a higher level in adipose tissue than other organs in wild type mice. SRA−/− mice are resistant to high fat diet-induced obesity, with decreased fat mass and increased lean content. This lean phenotype of SRA−/− mice is associated with decreased expression of a subset of adipocyte marker genes and reduced plasma TNFα levels. The SRA−/− mice are more insulin sensitive, as evidenced by reduced fasting insulin, and lower blood glucoses in response to IP glucose and insulin. In addition, the livers of SRA−/− mice have fewer lipid droplets after high fat diet feeding, and the expression of lipogenesis-associated genes is decreased. To our knowledge, these data are the first to indicate a functional role for SRA in adipose tissue biology and glucose homeostasis in vivo. PMID:24675075

  17. Chronic Superantigen Exposure Induces Systemic Inflammation, Elevated Bloodstream Endotoxin, and Abnormal Glucose Tolerance in Rabbits: Possible Role in Diabetes

    PubMed Central

    Vu, Bao G.; Stach, Christopher S.; Kulhankova, Katarina; Salgado-Pabón, Wilmara; Klingelhutz, Aloysius J.

    2015-01-01

    ABSTRACT Excessive weight and obesity are associated with the development of diabetes mellitus type 2 (DMII) in humans. They also pose high risks of Staphylococcus aureus colonization and overt infections. S. aureus causes a wide range of severe illnesses in both healthy and immunocompromised individuals. Among S. aureus virulence factors, superantigens are essential for pathogenicity. In this study, we show that rabbits that are chronically exposed to S. aureus superantigen toxic shock syndrome toxin-1 (TSST-1) experience impaired glucose tolerance, systemic inflammation, and elevated endotoxin levels in the bloodstream, all of which are common findings in DMII. Additionally, such DMII-associated findings are also seen through effects of TSST-1 on isolated adipocytes. Collectively, our findings suggest that chronic exposure to S. aureus superantigens facilitates the development of DMII, which may lead to therapeutic targeting of S. aureus and its superantigens. PMID:25714716

  18. A signaling protease required for melanization in Drosophila affects resistance and tolerance of infections.

    PubMed

    Ayres, Janelle S; Schneider, David S

    2008-12-01

    Organisms evolve two routes to surviving infections-they can resist pathogen growth (resistance) and they can endure the pathogenesis of infection (tolerance). The sum of these two properties together defines the defensive capabilities of the host. Typically, studies of animal defenses focus on either understanding resistance or, to a lesser extent, tolerance mechanisms, thus providing little understanding of the relationship between these two mechanisms. We suggest there are nine possible pairwise permutations of these traits, assuming they can increase, decrease, or remain unchanged in an independent manner. Here we show that by making a single mutation in the gene encoding a protease, CG3066, active in the melanization cascade in Drosophila melanogaster, we observe the full spectrum of changes; these mutant flies show increases and decreases in their resistance and tolerance properties when challenged with a variety of pathogens. This result implicates melanization in fighting microbial infections and shows that an immune response can affect both resistance and tolerance to infections in microbe-dependent ways. The fly is often described as having an unsophisticated and stereotypical immune response where single mutations cause simple binary changes in immunity. We report a level of complexity in the fly's immune response that has strong ecological implications. We suggest that immune responses are highly tuned by evolution, since selection for defenses that alter resistance against one pathogen may change both resistance and tolerance to other pathogens.

  19. Continuous glucose monitoring in newborn infants: how do errors in calibration measurements affect detected hypoglycemia?

    PubMed

    Thomas, Felicity; Signal, Mathew; Harris, Deborah L; Weston, Philip J; Harding, Jane E; Shaw, Geoffrey M; Chase, J Geoffrey

    2014-05-01

    Neonatal hypoglycemia is common and can cause serious brain injury. Continuous glucose monitoring (CGM) could improve hypoglycemia detection, while reducing blood glucose (BG) measurements. Calibration algorithms use BG measurements to convert sensor signals into CGM data. Thus, inaccuracies in calibration BG measurements directly affect CGM values and any metrics calculated from them. The aim was to quantify the effect of timing delays and calibration BG measurement errors on hypoglycemia metrics in newborn infants. Data from 155 babies were used. Two timing and 3 BG meter error models (Abbott Optium Xceed, Roche Accu-Chek Inform II, Nova Statstrip) were created using empirical data. Monte-Carlo methods were employed, and each simulation was run 1000 times. Each set of patient data in each simulation had randomly selected timing and/or measurement error added to BG measurements before CGM data were calibrated. The number of hypoglycemic events, duration of hypoglycemia, and hypoglycemic index were then calculated using the CGM data and compared to baseline values. Timing error alone had little effect on hypoglycemia metrics, but measurement error caused substantial variation. Abbott results underreported the number of hypoglycemic events by up to 8 and Roche overreported by up to 4 where the original number reported was 2. Nova results were closest to baseline. Similar trends were observed in the other hypoglycemia metrics. Errors in blood glucose concentration measurements used for calibration of CGM devices can have a clinically important impact on detection of hypoglycemia. If CGM devices are going to be used for assessing hypoglycemia it is important to understand of the impact of these errors on CGM data.

  20. Role of diuretics, β blockers, and statins in increasing the risk of diabetes in patients with impaired glucose tolerance: reanalysis of data from the NAVIGATOR study

    PubMed Central

    Shen, Lan; Shah, Bimal R; Reyes, Eric M; Thomas, Laine; Wojdyla, Daniel; Diem, Peter; Leiter, Lawrence A; Charbonnel, Bernard; Mareev, Viacheslav; Horton, Edward S; Haffner, Steven M; Soska, Vladimir; Holman, Rury; Bethel, M Angelyn; Schaper, Frank; Sun, Jie-Lena; McMurray, John JV; Califf, Robert M

    2013-01-01

    Objective To examine the degree to which use of β blockers, statins, and diuretics in patients with impaired glucose tolerance and other cardiovascular risk factors is associated with new onset diabetes. Design Reanalysis of data from the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial. Setting NAVIGATOR trial. Participants Patients who at baseline (enrolment) were treatment naïve to β blockers (n=5640), diuretics (n=6346), statins (n=6146), and calcium channel blockers (n=6294). Use of calcium channel blocker was used as a metabolically neutral control. Main outcome measures Development of new onset diabetes diagnosed by standard plasma glucose level in all participants and confirmed with glucose tolerance testing within 12 weeks after the increased glucose value was recorded. The relation between each treatment and new onset diabetes was evaluated using marginal structural models for causal inference, to account for time dependent confounding in treatment assignment. Results During the median five years of follow-up, β blockers were started in 915 (16.2%) patients, diuretics in 1316 (20.7%), statins in 1353 (22.0%), and calcium channel blockers in 1171 (18.6%). After adjusting for baseline characteristics and time varying confounders, diuretics and statins were both associated with an increased risk of new onset diabetes (hazard ratio 1.23, 95% confidence interval 1.06 to 1.44, and 1.32, 1.14 to 1.48, respectively), whereas β blockers and calcium channel blockers were not associated with new onset diabetes (1.10, 0.92 to 1.31, and 0.95, 0.79 to 1.13, respectively). Conclusions Among people with impaired glucose tolerance and other cardiovascular risk factors and with serial glucose measurements, diuretics and statins were associated with an increased risk of new onset diabetes, whereas the effect of β blockers was non-significant. Trial registration ClinicalTrials.gov NCT00097786. PMID:24322398

  1. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance.

    PubMed

    Lowndes, Joshua; Sinnett, Stephanie S; Rippe, James M

    2015-10-01

    Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20-60 years old) were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US), one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ±13.0 vs. 74.5 ± 13.3 kg, p < 0.001), but the change in weight was comparable among groups (p > 0.05). There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L), insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L), or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05). These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others. PMID:26512691

  2. No Effect of Added Sugar Consumed at Median American Intake Level on Glucose Tolerance or Insulin Resistance

    PubMed Central

    Lowndes, Joshua; Sinnett, Stephanie S.; Rippe, James M.

    2015-01-01

    Excess sugar consumption may promote adverse changes in hepatic and total body insulin resistance. Debate continues over the effects of sugars at more typically consumed levels and whether the identity of the sugar consumed is important. In the present study participants (20–60 years old) were randomly assigned to one of five groups, three that consumed low fat milk with added fructose containing sugars in amounts equivalent to the 50th percentile of fructose consumption (US), one which consumed low-fat milk sweetened with glucose, and one unsweetened low-fat milk control group. The intervention lasted ten weeks. In the entire study population there was less than 1 kg increase in weight (73.6 ± 13.0 vs. 74.5 ± 13.3 kg, p < 0.001), but the change in weight was comparable among groups (p > 0.05). There were no changes in fasting glucose (49 ± 0.4 vs. 5.0 ± 0.5 mmol/L), insulin (56.9 ± 38.9 vs. 61.8 ± 50.0 pmol/L), or insulin resistance, as measured by the Homeostasis Model Assessment method (1.8 ± 1.3 vs. 2.0 ± 1.5, all p > 0.05). These data suggest that added sugar consumed at the median American intake level does not produce changes in measures of insulin sensitivity or glucose tolerance and that no sugar has more deleterious effects than others. PMID:26512691

  3. Endothelin-1 as a predictor of impaired glucose tolerance and type 2 diabetes--A longitudinal study in the Vara-Skövde Cohort.

    PubMed

    Olausson, Josefin; Daka, Bledar; Hellgren, Margareta I; Larsson, Charlotte A; Petzold, Max; Lindblad, Ulf; Jansson, Per-Anders

    2016-03-01

    We addressed whether endothelin-1, a marker of endothelial dysfunction, predicts impaired glucose tolerance (IGT) and type 2 diabetes mellitus (T2DM) in a population study in south-western Sweden. Follow-up after 9.7 years showed an association between circulating endothelin-1 levels at baseline and development of IGT/T2DM in women but not in men.

  4. Ectopic expression of ABSCISIC ACID 2/GLUCOSE INSENSITIVE 1 in Arabidopsis promotes seed dormancy and stress tolerance.

    PubMed

    Lin, Pei-Chi; Hwang, San-Gwang; Endo, Akira; Okamoto, Masanori; Koshiba, Tomokazu; Cheng, Wan-Hsing

    2007-02-01

    Abscisic acid (ABA) is an important phytohormone that plays a critical role in seed development, dormancy, and stress tolerance. 9-cis-Epoxycarotenoid dioxygenase is the key enzyme controlling ABA biosynthesis and stress tolerance. In this study, we investigated the effect of ectopic expression of another ABA biosynthesis gene, ABA2 (or GLUCOSE INSENSITIVE 1 [GIN1]) encoding a short-chain dehydrogenase/reductase in Arabidopsis (Arabidopsis thaliana). We show that ABA2-overexpressing transgenic plants with elevated ABA levels exhibited seed germination delay and more tolerance to salinity than wild type when grown on agar plates and/or in soil. However, the germination delay was abolished in transgenic plants showing ABA levels over 2-fold higher than that of wild type grown on 250 mm NaCl. The data suggest that there are distinct mechanisms underlying ABA-mediated inhibition of seed germination under diverse stress. The ABA-deficient mutant aba2, with a shorter primary root, can be restored to normal root growth by exogenous application of ABA, whereas transgenic plants overexpressing ABA2 showed normal root growth. The data reflect that the basal levels of ABA are essential for maintaining normal primary root elongation. Furthermore, analysis of ABA2 promoter activity with ABA2::beta-glucuronidase transgenic plants revealed that the promoter activity was enhanced by multiple prolonged stresses, such as drought, salinity, cold, and flooding, but not by short-term stress treatments. Coincidently, prolonged drought stress treatment led to the up-regulation of ABA biosynthetic and sugar-related genes. Thus, the data support ABA2 as a late expression gene that might have a fine-tuning function in mediating ABA biosynthesis through primary metabolic changes in response to stress. PMID:17189333

  5. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    PubMed

    Litwak, Sara A; Loh, Kim; Stanley, William J; Pappas, Evan G; Wali, Jibran A; Selck, Claudia; Strasser, Andreas; Thomas, Helen E; Gurzov, Esteban N

    2016-04-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14-17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity.

  6. p53-upregulated-modulator-of-apoptosis (PUMA) deficiency affects food intake but does not impact on body weight or glucose homeostasis in diet-induced obesity.

    PubMed Central

    Litwak, Sara A.; Loh, Kim; Stanley, William J.; Pappas, Evan G.; Wali, Jibran A.; Selck, Claudia; Strasser, Andreas; Thomas, Helen E.; Gurzov, Esteban N.

    2016-01-01

    BCL-2 proteins have been implicated in the control of glucose homeostasis and metabolism in different cell types. Thus, the aim of this study was to determine the role of the pro-apoptotic BH3-only protein, p53-upregulated-modulator-of-apoptosis (PUMA), in metabolic changes mediated by diet-induced obesity, using PUMA deficient mice. At 10 weeks of age, knockout and wild type mice either continued consuming a low fat chow diet (6% fat), or were fed with a high fat diet (23% fat) for 14–17 weeks. We measured body composition, glucose and insulin tolerance, insulin response in peripheral tissues, energy expenditure, oxygen consumption, and respiratory exchange ratio in vivo. All these parameters were indistinguishable between wild type and knockout mice on chow diet and were modified equally by diet-induced obesity. Interestingly, we observed decreased food intake and ambulatory capacity of PUMA knockout mice on high fat diet. This was associated with increased adipocyte size and fasted leptin concentration in the blood. Our findings suggest that although PUMA is dispensable for glucose homeostasis in lean and obese mice, it can affect leptin levels and food intake during obesity. PMID:27033313

  7. Low and high dietary protein:carbohydrate ratios during pregnancy affect materno-fetal glucose metabolism in pigs.

    PubMed

    Metges, Cornelia C; Görs, Solvig; Lang, Iris S; Hammon, Harald M; Brüssow, Klaus-Peter; Weitzel, Joachim M; Nürnberg, Gerd; Rehfeldt, Charlotte; Otten, Winfried

    2014-02-01

    Inadequate dietary protein during pregnancy causes intrauterine growth retardation. Whether this is related to altered maternal and fetal glucose metabolism was examined in pregnant sows comparing a high-protein:low-carbohydrate diet (HP-LC; 30% protein, 39% carbohydrates) with a moderately low-protein:high-carbohydrate diet (LP-HC; 6.5% protein, 68% carbohydrates) and the isoenergetic standard diet (ST; 12.1% protein, 60% carbohydrates). During late pregnancy, maternal and umbilical glucose metabolism and fetal hepatic mRNA expression of gluconeogenic enzymes were examined. During an i.v. glucose tolerance test (IVGTT), the LP-HC-fed sows had lower insulin concentrations and area under the curve (AUC), and higher glucose:insulin ratios than the ST- and the HP-LC-fed sows (P < 0.05). Insulin sensitivity and glucose clearance were higher in the LP-HC sows compared with ST sows (P < 0.05). Glucagon concentrations during postabsorptive conditions and IVGTT, and glucose AUC during IVGTT, were higher in the HP-LC group compared with the other groups (P < 0.001). (13)C glucose oxidation was lower in the HP-LC sows than in the ST and LP-HC sows (P < 0.05). The HP-LC fetuses were lighter and had a higher brain:liver ratio than the ST group (P < 0.05). The umbilical arterial inositol concentration was greater in the HP-LC group (P < 0.05) and overall small fetuses (230-572 g) had higher values than medium and heavy fetuses (≥573 g) (P < 0.05). Placental lactate release was lower in the LP-HC group than in the ST group (P < 0.05). Fetal glucose extraction tended to be lower in the LP-HC group than in the ST group (P = 0.07). In the HP-LC and LP-HC fetuses, hepatic mRNA expression of cytosolic phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC) was higher than in the ST fetuses (P < 0.05). In conclusion, the HP-LC and LP-HC sows adapted by reducing glucose turnover and oxidation and having higher glucose utilization, respectively. The HP-LC and LP

  8. Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice.

    PubMed

    Leandro, João G B; Espindola-Netto, Jair M; Vianna, Maria Carolina F; Gomez, Lilian S; DeMaria, Thaina M; Marinho-Carvalho, Monica M; Zancan, Patricia; Paula Neto, Heitor A; Sola-Penna, Mauro

    2016-03-28

    Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity. PMID:26863933

  9. Black Adzuki Bean (Vigna angularis) Extract Protects Pancreatic β Cells and Improves Glucose Tolerance in C57BL/6J Mice Fed a High-Fat Diet.

    PubMed

    Kim, Mina; Kim, Dae Keun; Cha, Youn-Soo

    2016-05-01

    Adzuki beans have long been cultivated as a food and folk medicine in East Asia. In this study, we investigated the effect of black adzuki bean (BAB) extract on pancreatic cells and determined their mechanism of action in impaired glucose tolerance in an animal model of type 2 diabetes. In addition, we performed functional gene annotation analysis to identify genes related to the regulation of glucose metabolism and insulin response. Treatment of pancreatic β cells with BAB extract (0.2 mg/mL) led to tolerance of the high glucose-induced glucotoxicity, resulting in a similar viability as cells maintained in normal glucose media. In addition, dietary supplementation with BAB extract significantly (P < .05) improved hyperglycemia and homeostasis model assessment of insulin resistance index (HOMA-IR) in high-fat diet-induced glucose-intolerant obese C57BL/6J mice. Our results suggest that BAB extract ameliorates hyperglycemia and glucose intolerance, and lowers HOMA-IR by regulating insulin secretion and response, and by maintaining the integrity of pancreatic β cells exposed to hyperglycemic conditions. PMID:27070495

  10. Factors affecting initial training success of blood glucose testing in captive chimpanzees (Pan troglodytes).

    PubMed

    Reamer, Lisa A; Haller, Rachel L; Thiele, Erica J; Freeman, Hani D; Lambeth, Susan P; Schapiro, Steven J

    2014-01-01

    Type 2 diabetes can be a problem for captive chimpanzees. Accurate blood glucose (BG) readings are necessary to monitor and treat this disease. Thus, obtaining voluntary samples from primates through positive reinforcement training (PRT) is critical. The current study assessed the voluntary participation of 123 chimpanzees in BG sampling and investigated factors that may contribute to individual success. All subjects participate in regular PRT sessions as part of a comprehensive behavioral management program. Basic steps involved in obtaining BG values include: voluntarily presenting a finger/toe; allowing digit disinfection; holding for the lancet device; and allowing blood collection onto a glucometer test strip for analysis. We recorded the level of participation (none, partial, or complete) when each chimpanzee was first asked to perform the testing procedure. Nearly 30% of subjects allowed the entire procedure in one session, without any prior specific training for the target behavior. Factors that affected this initial successful BG testing included sex, personality (chimpanzees rated higher on the factor "openness" were more likely to participate with BG testing), and past training performance for "present-for-injection" (chimpanzees that presented for their most recent anesthetic injection were more likely to participate). Neither age, rearing history, time since most recent anesthetic event nor social group size significantly affected initial training success. These results have important implications for captive management and training program success, underlining individual differences in training aptitude and the need for developing individual management plans in order to provide optimal care and treatment for diabetic chimpanzees in captivity.

  11. Factors affecting initial training success of blood glucose testing in captive chimpanzees (Pan troglodytes).

    PubMed

    Reamer, Lisa A; Haller, Rachel L; Thiele, Erica J; Freeman, Hani D; Lambeth, Susan P; Schapiro, Steven J

    2014-01-01

    Type 2 diabetes can be a problem for captive chimpanzees. Accurate blood glucose (BG) readings are necessary to monitor and treat this disease. Thus, obtaining voluntary samples from primates through positive reinforcement training (PRT) is critical. The current study assessed the voluntary participation of 123 chimpanzees in BG sampling and investigated factors that may contribute to individual success. All subjects participate in regular PRT sessions as part of a comprehensive behavioral management program. Basic steps involved in obtaining BG values include: voluntarily presenting a finger/toe; allowing digit disinfection; holding for the lancet device; and allowing blood collection onto a glucometer test strip for analysis. We recorded the level of participation (none, partial, or complete) when each chimpanzee was first asked to perform the testing procedure. Nearly 30% of subjects allowed the entire procedure in one session, without any prior specific training for the target behavior. Factors that affected this initial successful BG testing included sex, personality (chimpanzees rated higher on the factor "openness" were more likely to participate with BG testing), and past training performance for "present-for-injection" (chimpanzees that presented for their most recent anesthetic injection were more likely to participate). Neither age, rearing history, time since most recent anesthetic event nor social group size significantly affected initial training success. These results have important implications for captive management and training program success, underlining individual differences in training aptitude and the need for developing individual management plans in order to provide optimal care and treatment for diabetic chimpanzees in captivity. PMID:24706518

  12. Synthesized Peptides from Yam Dioscorin Hydrolysis in Silico Exhibit Dipeptidyl Peptidase-IV Inhibitory Activities and Oral Glucose Tolerance Improvements in Normal Mice.

    PubMed

    Lin, Yin-Shiou; Han, Chuan-Hsiao; Lin, Shyr-Yi; Hou, Wen-Chi

    2016-08-24

    RRDY, RL, and DPF were the top 3 of 21 peptides for inhibitions against dipeptidyl peptidase-IV (DPP-IV) from the pepsin hydrolysis of yam dioscorin in silico and were further investigated in a proof-of-concept study in normal ICR mice for regulating glucose metabolism by the oral glucose tolerance test (OGTT). The sample or sitagliptin (positive control) was orally administered by a feeding gauge; 30 min later, the glucose loads (2.5 g/kg) were performed. RRDY, yam dioscorin, or sitagliptin preload, but not DPF, lowered the area under the curve (AUC0-120) of blood glucose and DPP-IV activity and elevated the AUC0-120 of blood insulin, which showed significant differences compared to control (P < 0.05 or 0.001). These results suggested that RRDY and yam dioscorin might be beneficial in glycemic control in normal mice and need further investigations in diabetic animal models. PMID:27499387

  13. A novel role for Arabidopsis CBL1 in affecting plant responses to glucose and gibberellin during germination and seedling development.

    PubMed

    Li, Zhi-Yong; Xu, Zhao-Shi; Chen, Yang; He, Guang-Yuan; Yang, Guang-Xiao; Chen, Ming; Li, Lian-Cheng; Ma, You-Zhi

    2013-01-01

    Glucose and phytohormones such as abscisic acid (ABA), ethylene, and gibberellin (GA) coordinately regulate germination and seedling development. However, there is still inadequate evidence to link their molecular roles in affecting plant responses. Calcium acts as a second messenger in a diverse range of signal transduction pathways. As calcium sensors unique to plants, calcineurin B-like (CBL) proteins are well known to modulate abiotic stress responses. In this study, it was found that CBL1 was induced by glucose in Arabidopsis. Loss-of-function mutant cbl1 exhibited hypersensitivity to glucose and paclobutrazol, a GA biosynthetic inhibitor. Several sugar-responsive and GA biosynthetic gene expressions were altered in the cbl1 mutant. CBL1 protein physically interacted with AKINβ1, the regulatory β subunit of the SnRK1 complex which has a central role in sugar signaling. Our results indicate a novel role for CBL1 in modulating responses to glucose and GA signals.

  14. Hydrogen peroxide produced by glucose oxidase affects the performance of laccase cathodes in glucose/oxygen fuel cells: FAD-dependent glucose dehydrogenase as a replacement.

    PubMed

    Milton, Ross D; Giroud, Fabien; Thumser, Alfred E; Minteer, Shelley D; Slade, Robert C T

    2013-11-28

    Hydrogen peroxide production by glucose oxidase (GOx) and its negative effect on laccase performance have been studied. Simultaneously, FAD-dependent glucose dehydrogenase (FAD-GDH), an O2-insensitive enzyme, has been evaluated as a substitute. Experiments focused on determining the effect of the side reaction of GOx between its natural electron acceptor O2 (consumed) and hydrogen peroxide (produced) in the electrolyte. Firstly, oxygen consumption was investigated by both GOx and FAD-GDH in the presence of substrate. Relatively high electrocatalytic currents were obtained with both enzymes. O2 consumption was observed with immobilized GOx only, whilst O2 concentration remained stable for the FAD-GDH. Dissolved oxygen depletion effects on laccase electrode performances were investigated with both an oxidizing and a reducing electrode immersed in a single compartment. In the presence of glucose, dramatic decreases in cathodic currents were recorded when laccase electrodes were combined with a GOx-based electrode only. Furthermore, it appeared that the major loss of performance of the cathode was due to the increase of H2O2 concentration in the bulk solution induced laccase inhibition. 24 h stability experiments suggest that the use of O2-insensitive FAD-GDH as to obviate in situ peroxide production by GOx is effective. Open-circuit potentials of 0.66 ± 0.03 V and power densities of 122.2 ± 5.8 μW cm(-2) were observed for FAD-GDH/laccase biofuel cells.

  15. Glucose screening tests during pregnancy

    MedlinePlus

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... first step, you will have a glucose screening test: You DO NOT need to prepare or change ...

  16. Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation.

    PubMed

    Meakin, Paul J; Morrison, Vicky L; Sneddon, Claire C; Savinko, Terhi; Uotila, Liisa; Jalicy, Susan M; Gabriel, Jennie L; Kang, Li; Ashford, Michael L J; Fagerholm, Susanna C

    2015-01-01

    Beta2-integrins are important in leukocyte trafficking and function, and are regulated through the binding of cytoplasmic proteins, such as kindlin-3, to their intracellular domain. Here, we investigate the involvement of beta2-integrins in the regulation of metabolic disease using mice where the kindlin-3 binding site in the beta2-integrin cytoplasmic tail has been mutated (TTT/AAA-beta2-integrin knock-in (KI) mice), leading to expressed but dysfunctional beta2-integrins and significant neutrophilia in vivo. Beta2-integrin KI mice fed on a high fat diet showed normal weight gain, and normal accumulation of macrophages and lymphocytes in white adipose tissue (WAT) and liver, but increased neutrophil numbers especially in WAT. In addition, beta2-integrin KI mice fed on a high fat diet showed significantly increased peripheral insulin resistance in response to high-fat feeding. However, this was associated with improved glucose disposal following glucose load. Interestingly, beta2-integrin KI neutrophils produced more elastase in vitro, in response to stimulation. Beta2-integrin KI mice displayed variability of tissue inflammatory status, with liver and WAT exhibiting little or no difference in inflammation compared to high fat fed controls, whereas skeletal muscle demonstrated a raised inflammatory profile in association with higher elastase levels and diminished signalling through the IRS1-PKB pathway. In conclusion, although expression of dysfunctional beta2-integrins increased neutrophil production and infiltration into tissue, skeletal muscle was the most affected tissue exhibiting evidence of higher neutrophil activity and insulin resistance. Thus, beta2-integrins modulate glucose homeostasis during high fat feeding predominantly through actions on skeletal muscle to affect metabolic phenotype in vivo. PMID:26405763

  17. Cooking enhances beneficial effects of pea seed coat consumption on glucose tolerance, incretin, and pancreatic hormones in high-fat-diet-fed rats.

    PubMed

    Hashemi, Zohre; Yang, Kaiyuan; Yang, Han; Jin, Alena; Ozga, Jocelyn; Chan, Catherine B

    2015-04-01

    Pulses, including dried peas, are nutrient- and fibre-rich foods that improve glucose control in diabetic subjects compared with other fibre sources. We hypothesized feeding cooked pea seed coats to insulin-resistant rats would improve glucose tolerance by modifying gut responses to glucose and reducing stress on pancreatic islets. Glucose intolerance induced in male Sprague-Dawley rats with high-fat diet (HFD; 10% cellulose as fibre) was followed by 3 weeks of HFD with fibre (10%) provided by cellulose, raw-pea seed coat (RP), or cooked-pea seed coat (CP). A fourth group consumed low-fat diet with 10% cellulose. Oral and intraperitoneal glucose tolerance tests (oGTT, ipGTT) were done. CP rats had 30% and 50% lower glucose and insulin responses in oGTT, respectively, compared with the HFD group (P < 0.05) but ipGTT was not different. Plasma islet and incretin hormone concentrations were measured. α- and β-cell areas in the pancreas and density of K- and L-cells in jejunum and ileum were quantified. Jejunal expression of hexose transporters was measured. CP feeding increased fasting glucagon-like peptide 1 and glucose-stimulated gastric inhibitory polypeptide responses (P < 0.05), but K- and L-cells densities were comparable to HFD, as was abundance of SGLT1 and GLUT2 mRNA. No significant difference in β-cell area between diet groups was observed. α-cell area was significantly smaller in CP compared with RP rats (P < 0.05). Overall, our results demonstrate that CP feeding can reverse adverse effects of HFD on glucose homeostasis and is associated with enhanced incretin secretion and reduced α-cell abundance.

  18. DEXA MEASURED VISCERAL ADIPOSE TISSUE PREDICTS IMPAIRED GLUCOSE TOLERANCE AND METABOLIC SYNDROME IN OBESE CAUCASIAN AND AFRICAN AMERICAN WOMEN

    PubMed Central

    Bi, X; Seabolt, L; Shibao, C; Buchowski, M; Kang, H; Keil, CD; Tyree, R; Silver, HJ

    2016-01-01

    Background and Aims New methods to measure visceral adipose tissue (VAT) by DEXA may help discern sex, race and phenotype differences in the role of VAT in cardiometabolic risk. This study was designed to: a) compare relationships between cardiometabolic risk factors and DEXA-VAT, anthropometric and body composition measures; b) determine thresholds for DEXA-VAT by race; and c) determine the most robust predictors of impaired glucose tolerance (IGT) and metabolic syndrome (MetSx) in obese women. Methods VAT area (cm2) was measured using Lunar iDXA scanner in 229 obese (BMI 30-49.9) women age 21–69 years of European American (EA = 123) and African American (AA = 106) descent. Linear regression modeling and areas under the curve (AUC) compared relationships with cardiometabolic risk. Bootstrapping with LASSO regression modeling determined thresholds and predictors of IGT and MetSx. Results DEXA-VAT explained more of the variance in triglycerides, blood pressure, glucose and HOMA-IR compared to anthropometric and body composition variables. DEXA-VAT had the highest AUC for IGT (0.767) and MetSx (0.749). Including race and interactionXrace terms in modeling did not significantly change results. Thresholds at which probability was ≥ 50% for IGT or MetSx were lower in AA women (IGT: 2120cm2 AA vs 2550cm2 EA; MetSx: 1320cm2 AA vs 1713cm2 EA). The odds for IGT or MetSx was 3-fold greater with each standard deviation increase in DEXA-VAT. Conclusion DEXA-VAT provides robust clinical information regarding cardiometabolic risk in AA and EA women and has great potential in risk reduction efforts. PMID:25335442

  19. Oral Glucose Tolerance Testing identifies HIV+ infected women with Diabetes Mellitus (DM) not captured by standard DM definition

    PubMed Central

    Tian, Fang; Anastos, Kathryn; Cohen, Mardge H; Tien, Phyllis C

    2016-01-01

    Objective HIV-infected (HIV+) individuals may have differential risk of diabetes mellitus (DM) compared to the general population, and the optimal diagnostic algorithm for DM in HIV+ persons remains unclear. We aimed to assess the utility of oral glucose tolerance testing (OGTT) for DM diagnosis in a cohort of women with or at risk for HIV infection. Methods Using American Diabetic Association DM definitions, DM prevalence and incidence were assessed among women enrolled in the Women’s Interagency HIV Study. DM was defined by 2-hour OGTT ≥ 200 mg/dL (DM_OGTT) or a clinical definition (DM_C) that included any of the following: (i) anti-diabetic medication use or self-reported DM confirmed by either fasting glucose (FG) ≥126 mg/dL or HbA1c ≥ 6.5%, (ii) FG ≥ 126 mg/dL confirmed by a second FG ≥ 126 mg/dL or HbA1c 6.5%, or (iii) HbA1c 6.5% confirmed by FG ≥ 126 mg/dL cohort. Results Overall, 390 women (285 HIV+, median age 43 years; 105 HIV−, median age 37 years) were enrolled between 2003-2006. Over half of all women were African American. Using DM_C, DM prevalence rates were 5.6% and 2.8% among HIV+ and HIV− women, respectively. Among HIV+ women, adding DM_OGTT to DM_C increased DM prevalence from 5.6% to 7.4%, a 31% increase in the number of diabetes cases diagnosed (p=0.02). In HIV− women, no additional cases were diagnosed by DM-OGTT. Conclusion In HIV+ women, OGTT identified DM cases that were not identified by a standardized clinical definition. Further investigation is needed to determine whether OGTT should be considered as an adjunctive tool for DM diagnosis in the setting of HIV infection. PMID:27066296

  20. Knockdown of neuropeptide Y in the dorsomedial hypothalamus reverses high-fat diet-induced obesity and impaired glucose tolerance in rats.

    PubMed

    Kim, Yonwook J; Bi, Sheng

    2016-01-15

    Neuropeptide Y (NPY) in the dorsomedial hypothalamus (DMH) plays an important role in the regulation of energy balance. While DMH NPY overexpression causes hyperphagia and obesity in rats, knockdown of NPY in the DMH via adeno-associated virus (AAV)-mediated RNAi (AAVshNPY) ameliorates these alterations. Whether this knockdown has a therapeutic effect on obesity and glycemic disorder has yet to be determined. The present study sought to test this potential using a rat model of high-fat diet (HFD)-induced obesity and insulin resistance, mimicking human obesity with impaired glucose homeostasis. Rats had ad libitum access to rodent regular chow (RC) or HFD. Six weeks later, an oral glucose tolerance test (OGTT) was performed for verifying HFD-induced glucose intolerance. After verification, obese rats received bilateral DMH injections of AAVshNPY or the control vector AAVshCTL, and OGTT and insulin tolerance test (ITT) were performed at 16 and 18 wk after viral injection (23 and 25 wk on HFD), respectively. Rats were killed at 26 wk on HFD. We found that AAVshCTL rats on HFD remained hyperphagic, obese, glucose intolerant, and insulin resistant relative to lean control RC-fed rats receiving DMH injection of AAVshCTL, whereas these alterations were reversed in NPY knockdown rats fed a HFD. NPY knockdown rats exhibited normal food intake, body weight, glucose tolerance, and insulin sensitivity, as seen in lean control rats. Together, these results demonstrate a therapeutic action of DMH NPY knockdown against obesity and impaired glucose homeostasis in rats, providing a potential target for the treatment of obesity and diabetes.

  1. Systemic effects of epidural methylprednisolone injection on glucose tolerance in diabetic patients

    PubMed Central

    2011-01-01

    Background Several studies have shown that in diabetic patients, the glycemic profile was disturbed after intra-articular injection of corticosteroids. Little is known about the impact of epidural injection in such patients. The goal of this study was double, at first comparing the glycaemic profile in diabetic patients after a unique injection of 80 mg of acetate methylprednisolone either intra-articular or epidural and secondly to compare the amount of systemic diffusion of the drug after both procedures. Methods Seventeen patients were included. Glycemic changes were compared in 9 diabetic patients following intra-articular (4 patients) and epidural injections (5 patients). Epidural injections were performed using the sacral route under fluoroscopic control in patients with lumbar spinal stenosis. Diabetes control had to stable for more than 10 days and the renal function to be preserved. Blood glucose was monitored using a validated continuous measuring device (GMS, Medtronic) the day before and for two days following the injection. Results were expressed in the form of daily glycemic profiles and as by mean, peak and minimal values +/- SD. The urinary excretion of methylprednisolone after the 2 routes of injection was analyzed in 8 patients (4 in each group). Urine samples were cropped one hour before the injections, then 4 times during the first day and 3 times a week for 2 weeks. The measurements included the free and conjugated fraction Results The glycaemic profile remains unchanged with no significant changes in the group of the 5 diabetic patients receiving epidural injections. On the other end, the average peak and and mean values were enhanced up to 3 mmol/l above baseline two days after the infiltration in the groups of the 4 diabetic patients infiltrated intra-articular. The mean urinary excretion of the steroid was about ten times higher in the intra-articular versus epidural group: 7000 ng/ml versus 700 ng/ml. Looking at each individual there were

  2. The effects of an anxiety sensitivity intervention on anxiety, depression, and worry: Mediation through affect tolerances

    PubMed Central

    Norr, Aaron M.; Allan, Nicholas P.; Macatee, Richard J.; Keough, Meghan E.; Schmidt, Norman B.

    2014-01-01

    Recently there has been increased interest in emotional and physical tolerance risk factors for mood and anxiety disorders. Three tolerance risk factors that have been shown to be related are anxiety sensitivity (AS), distress tolerance (DT), and discomfort intolerance (DI). Although previous research has demonstrated these constructs are malleable, no research has investigated the effects of an AS intervention on DT or DI. Further, no studies have investigated whether changes in DT or DI play a role in mood and anxiety symptom amelioration due to an AS intervention. Participants (N=104), who were selected for elevated levels of AS, completed a single-session computer-assisted AS intervention or a control intervention and follow-up assessments at 1-week and 1-month post intervention. Results revealed that the intervention reduced AS and increased DT, but did not affect DI at the 1-week follow-up. Mediation analyses revealed that changes in AS and DT both mediated changes in symptoms (depression, anxiety, worry) due to the intervention at 1-month follow-up, however, when AS and DT were considered in the same model only the effect via AS remained significant. These results have important implications for the nature of the relationships between AS, DT, and DI as well as the specific mechanistic pathways through which an AS intervention ameliorates symptoms. PMID:24949907

  3. Serum Galanin Levels in Young Healthy Lean and Obese Non-Diabetic Men during an Oral Glucose Tolerance Test

    PubMed Central

    Sandoval-Alzate, Héctor Fabio; Agudelo-Zapata, Yessica; González-Clavijo, Angélica María; Poveda, Natalia E.; Espinel-Pachón, Cristian Felipe; Escamilla-Castro, Jorge Augusto; Márquez-Julio, Heidy Lorena; Alvarado-Quintero, Hernando; Rojas-Rodríguez, Fabián Guillermo; Arteaga-Díaz, Juan Manuel; Eslava-Schmalbach, Javier Hernando; Garcés-Gutiérrez, Maria Fernanda; Vrontakis, Maria; Castaño, Justo P.; Luque, Raul M.; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E.

    2016-01-01

    Galanin (GAL) is a neuropeptide involved in the homeostasis of energy metabolism. The objective of this study was to investigate the serum levels of GAL during an oral glucose tolerance test (OGTT) in lean and obese young men. This cross-sectional study included 30 obese non-diabetic young men (median 22 years; mean BMI 37 kg/m2) and 30 healthy lean men (median 23 years; mean BMI 22 kg/m2). Serum GAL was determined during OGTT. The results of this study include that serum GAL levels showed a reduction during OGTT compared with basal levels in the lean subjects group. Conversely, serum GAL levels increased significantly during OGTT in obese subjects. Serum GAL levels were also higher in obese non-diabetic men compared with lean subjects during fasting and in every period of the OGTT (p < 0.001). Serum GAL levels were positively correlated with BMI, total fat, visceral fat, HOMA–IR, total cholesterol, triglycerides and Leptin. A multiple regression analysis revealed that serum insulin levels at 30, 60 and 120 minutes during the OGTT is the most predictive variable for serum GAL levels (p < 0.001). In conclusion, serum GAL levels are significantly higher in the obese group compared with lean subjects during an OGTT. PMID:27550417

  4. Serum Galanin Levels in Young Healthy Lean and Obese Non-Diabetic Men during an Oral Glucose Tolerance Test.

    PubMed

    Sandoval-Alzate, Héctor Fabio; Agudelo-Zapata, Yessica; González-Clavijo, Angélica María; Poveda, Natalia E; Espinel-Pachón, Cristian Felipe; Escamilla-Castro, Jorge Augusto; Márquez-Julio, Heidy Lorena; Alvarado-Quintero, Hernando; Rojas-Rodríguez, Fabián Guillermo; Arteaga-Díaz, Juan Manuel; Eslava-Schmalbach, Javier Hernando; Garcés-Gutiérrez, Maria Fernanda; Vrontakis, Maria; Castaño, Justo P; Luque, Raul M; Diéguez, Carlos; Nogueiras, Rubén; Caminos, Jorge E

    2016-01-01

    Galanin (GAL) is a neuropeptide involved in the homeostasis of energy metabolism. The objective of this study was to investigate the serum levels of GAL during an oral glucose tolerance test (OGTT) in lean and obese young men. This cross-sectional study included 30 obese non-diabetic young men (median 22 years; mean BMI 37 kg/m(2)) and 30 healthy lean men (median 23 years; mean BMI 22 kg/m(2)). Serum GAL was determined during OGTT. The results of this study include that serum GAL levels showed a reduction during OGTT compared with basal levels in the lean subjects group. Conversely, serum GAL levels increased significantly during OGTT in obese subjects. Serum GAL levels were also higher in obese non-diabetic men compared with lean subjects during fasting and in every period of the OGTT (p < 0.001). Serum GAL levels were positively correlated with BMI, total fat, visceral fat, HOMA-IR, total cholesterol, triglycerides and Leptin. A multiple regression analysis revealed that serum insulin levels at 30, 60 and 120 minutes during the OGTT is the most predictive variable for serum GAL levels (p < 0.001). In conclusion, serum GAL levels are significantly higher in the obese group compared with lean subjects during an OGTT. PMID:27550417

  5. Lactobacillus rhamnosus GG improves glucose tolerance through alleviating ER stress and suppressing macrophage activation in db/db mice

    PubMed Central

    Park, Kun-Young; Kim, Bobae; Hyun, Chang-Kee

    2015-01-01

    Although recent studies have reported that Lactobacillus rhamnosus GG (LGG), the most extensively studied probiotic strain, exerts an anti-hyperglycemic effect on several rodent models, the underlying mechanism remains unclear. In this study, twenty male C57BL/KsJ-db/db (db/db) mice were divided into 2 groups, LGG-treated and control group, which received a daily dose of LGG (1 × 108 CFU per mouse) and PBS orally for 4 weeks, respectively. We observed that glucose tolerance was significantly improved in LGG-treated db/db mice. Insulin-stimulated Akt phosphorylation and GLUT4 translocation were higher in skeletal muscle of LGG-treated mice relative to their controls. It was also observed that LGG treatment caused significant reductions in endoplasmic reticulum (ER) stress in skeletal muscle and M1-like macrophage activation in white adipose tissues. Our results indicate that the anti-diabetic effect of LGG in db/db mice is associated with alleviated ER stress and suppressed macrophage activation, resulting in enhanced insulin sensitivity. These findings suggest a therapeutic potential of probiotics for prevention and treatment of type 2 diabetes. PMID:26060355

  6. Relation between Delayed Superfluous Insulin Secretion during An Oral Glucose Tolerance Test and Metabolic Disorders in Obese Japanese Children.

    PubMed

    Sato, Hidetoshi; Kikuchi, Toru; Harada, Waka; Yoshida, Hiroshi; Ito, Sueshi; Uchiyama, Makoto

    2011-04-01

    The aim of this study was to clarify the relation between postprandial hyperinsulinemia and metabolic disorders in obese children. Twenty-eight obese Japanese children (8.8-16.2 yr) were divided into four groups: without impaired liver function and dyslipidemia (Group A), with impaired liver function (Group B), with dyslipidemia (Group C), and with impaired liver function and dyslipidemia (Group D). The levels of PG, serum immunoreactive insulin (IRI) and serum C-peptide (CPR) were measured during an oral glucose tolerance test (OGTT). The subjects had delayed superfluous insulin and CPR secretion during the OGTT compared with healthy references. In regard to the insulin secretion pattern, Group A's response peaked at 60 min and then decreased gradually until 120 min, Group B's response peaked at 60 min, remained at the peak until 120 min and then decreased gradually until 180 min, Group C's response peaked at 120 min and then decreased gradually until 180 min, and Group D's response peaked at 120 min and remained at the peak until 180 min. These results suggest that delayed superfluous insulin secretion during an OGTT is related to metabolic disorders in obese Japanese children and that these patients will experience a vicious cycle of postprandial hyperinsulinemia and metabolic disorders. It is important to prevent healthy children from becoming obese and to improve management of childhood obesity.

  7. Cost-Effectiveness of a Short Message Service Intervention to Prevent Type 2 Diabetes from Impaired Glucose Tolerance

    PubMed Central

    Wong, Carlos K. H.; Jiao, Fang-Fang; Siu, Shing-Chung; Fung, Colman S. C.; Fong, Daniel Y. T.; Wong, Ka-Wai; Yu, Esther Y. T.; Lo, Yvonne Y. C.; Lam, Cindy L. K.

    2016-01-01

    Aims. To investigate the costs and cost-effectiveness of a short message service (SMS) intervention to prevent the onset of type 2 diabetes mellitus (T2DM) in subjects with impaired glucose tolerance (IGT). Methods. A Markov model was developed to simulate the cost and effectiveness outcomes of the SMS intervention and usual clinical practice from the health provider's perspective. The direct programme costs and the two-year SMS intervention costs were evaluated in subjects with IGT. All costs were expressed in 2011 US dollars. The incremental cost-effectiveness ratio was calculated as cost per T2DM onset prevented, cost per life year gained, and cost per quality adjusted life year (QALY) gained. Results. Within the two-year trial period, the net intervention cost of the SMS group was $42.03 per subject. The SMS intervention managed to reduce 5.05% onset of diabetes, resulting in saving $118.39 per subject over two years. In the lifetime model, the SMS intervention dominated the control by gaining an additional 0.071 QALY and saving $1020.35 per person. The SMS intervention remained dominant in all sensitivity analyses. Conclusions. The SMS intervention for IGT subjects had the superiority of lower monetary cost and a considerable improvement in preventing or delaying the T2DM onset. This trial is registered with ClinicalTrials.gov NCT01556880. PMID:26798647

  8. A novel cold-adapted and glucose-tolerant GH1 β-glucosidase from Exiguobacterium antarcticum B7.

    PubMed

    Crespim, Elaine; Zanphorlin, Letícia M; de Souza, Flavio H M; Diogo, José A; Gazolla, Alex C; Machado, Carla B; Figueiredo, Fernanda; Sousa, Amanda S; Nóbrega, Felipe; Pellizari, Vivian H; Murakami, Mário T; Ruller, Roberto

    2016-01-01

    A novel GH1 β-glucosidase (EaBgl1A) from a bacterium isolated from Antarctica soil samples was recombinantly overexpressed in Escherichia coli cells and characterized. The enzyme showed unusual pH dependence with maximum activity at neutral pH and retention of high catalytic activity in the pH range 6 to 9, indicating a catalytic machinery compatible with alkaline conditions. EaBgl1A is also a cold-adapted enzyme, exhibiting activity in the temperature range from 10 to 40°C with optimal activity at 30°C, which allows its application in industrial processes using low temperatures. Kinetic characterization revealed an enzymatic turnover (Kcat) of 6.92s(-1) (cellobiose) and 32.98s(-1) (pNPG) and a high tolerance for product inhibition, which is an extremely desirable feature for biotechnological purposes. Interestingly, the enzyme was stimulated by up to 200 mM glucose, whereas the commercial cocktails tested were found fully inhibited at this concentration. These properties indicate EaBgl1A as a promising biocatalyst for biotechnological applications where low temperatures are required.

  9. Eukaryotic release factor 1-2 affects Arabidopsis responses to glucose and phytohormones during germination and early seedling development.

    PubMed

    Zhou, Xiangjun; Cooke, Peter; Li, Li

    2010-01-01

    Germination and early seedling development are coordinately regulated by glucose and phytohormones such as ABA, GA, and ethylene. However, the molecules that affect plant responses to glucose and phytohormones remain to be fully elucidated. Eukaryotic release factor 1 (eRF1) is responsible for the recognition of the stop codons in mRNAs during protein synthesis. Accumulating evidence indicates that eRF1 functions in other processes in addition to translation termination. The physiological role of eRF1-2, a member of the eRF1 family, in Arabidopsis was examined here. The eRF1-2 gene was found to be specifically induced by glucose. Arabidopsis plants overexpressing eRF1-2 were hypersensitive to glucose during germination and early seedling development. Such hypersensitivity to glucose was accompanied by a dramatic reduction of the expression of glucose-regulated genes, chlorophyll a/b binding protein and plastocyanin. The hypersensitive response was not due to the enhanced accumulation of ABA. In addition, the eRF1-2 overexpressing plants showed increased sensitivity to paclobutrazol, an inhibitor of GA biosynthesis, and exogenous GA restored their normal growth. By contrast, the loss-of-function erf1-2 mutant exhibited resistance to paclobutrazol, suggesting that eRF1-2 may exert a negative effect on the GA signalling pathway. Collectively, these data provide evidence in support of a novel role of eRF1-2 in affecting glucose and phytohormone responses in modulating plant growth and development.

  10. Ambivalent role of gallated catechins in glucose tolerance in humans: a novel insight into non-absorbable gallated catechin-derived inhibitors of glucose absorption.

    PubMed

    Park, J H; Jin, J Y; Baek, W K; Park, S H; Sung, H Y; Kim, Y K; Lee, J; Song, D K

    2009-12-01

    Prolonged postprandial hyperglycemia is a detrimental factor for type 2 diabetes and obesity. The benefit of green tea extract (GTE) consumption still requires confirmation. We report the effects of circulating green tea catechins on blood glucose and insulin levels. Oral glucose loading 1 h after GTE ingestion in humans led to higher blood glucose and insulin levels than in control subjects. Gallated catechins were required for these effects, although within the intestinal lumen they have been known to decrease glucose and cholesterol absorption. Treatment with epigallocatechin-3-gallate hindered 2-deoxyglucose uptake into liver, fat, pancreatic beta-cell, and skeletal muscle cell lines. The glucose intolerance was ameliorated by gallated catechin-deficient GTE or GTE mixed with polyethylene glycol, which was used as an inhibitor of intestinal absorption of gallated catechins. These findings may suggest that the gallated catechin when it is in the circulation elevates blood glucose level by blocking normal glucose uptake into the tissues, resulting in secondary hyperinsulinemia, whereas it decreases glucose entry into the circulation when they are inside the intestinal lumen. These findings encourage the development of non-absorbable derivatives of gallated catechins for preventative treatment of type 2 diabetes and obesity, which would specifically induce only the positive luminal effect.

  11. Factors Affecting Initial Training Success of Blood Glucose Testing in Captive Chimpanzees (Pan troglodytes)

    PubMed Central

    Reamer, Lisa A.; Haller, Rachel L.; Thiele, Erica J.; Freeman, Hani D.; Lambeth, Susan P.; Schapiro, Steven J.

    2016-01-01

    Type 2 diabetes can be a problem for captive chimpanzees. Accurate blood glucose (BG) readings are necessary to monitor and treat this disease. Thus, obtaining voluntary samples from primates through positive reinforcement training (PRT) is critical. The current study assessed the voluntary participation of 123 chimpanzees in BG sampling and investigated factors that may contribute to individual success. All subjects participate in regular PRT sessions as part of a comprehensive behavioral management program. Basic steps involved in obtaining BG values include: voluntarily presenting a finger/toe; allowing digit disinfection; holding for the lancet device; and allowing blood collection onto a glucometer test strip for analysis. We recorded the level of participation (none, partial, or complete) when each chimpanzee was first asked to perform the testing procedure. Nearly 30% of subjects allowed the entire procedure in one session, without any prior specific training for the target behavior. Factors that affected this initial successful BG testing included sex, personality (chimpanzees rated higher on the factor “openness” were more likely to participate with BG testing), and past training performance for “present-for-injection” (chimpanzees that presented for their most recent anesthetic injection were more likely to participate). Neither age, rearing history, time since most recent anesthetic event nor social group size significantly affected initial training success. These results have important implications for captive management and training program success, underlining individual differences in training aptitude and the need for developing individual management plans in order to provide optimal care and treatment for diabetic chimpanzees in captivity. PMID:24706518

  12. Reactivity to negative affect in smokers: the role of implicit associations and distress tolerance in smoking cessation.

    PubMed

    Cameron, Amy; Reed, Kathleen Palm; Ninnemann, Andrew

    2013-12-01

    Avoidance of negative affect is one motivational factor that explains smoking cessation relapse during cessation attempts. This negative reinforcement model of smoking cessation and relapse has demonstrated the importance of one's ability to tolerate nicotine withdrawal symptoms, particularly negative affect states, in remaining abstinent from smoking. Distress tolerance and implicit associations are two individual constructs that may influence the strength of this relationship. In this pilot study the authors examined implicit associations related to avoidance and negative affect using a modified Implicit Association Test (IAT), a measure designed to examine implicit associations related to negative affect and avoidance, and the relationship of these associations to distress tolerance and smoking relapse. In total, 40 participants were recruited through community flyers as part of a larger smoking cessation study. Participants completed a brief smoking history, behavioral distress tolerance assessments, and the modified IAT. Smoking status was assessed via phone 3days and 6days post-quit date. Results from a Cox proportional hazard model revealed that implicit associations between avoidance and negative affect were significantly negatively correlated with time to relapse after a smoking cessation attempt, whereas the behavioral distress tolerance assessments did not predict time to relapse. This study provides novel information about the cognitive associations that may underlie avoidant behavior in smokers, and may be important for understanding smoking relapse when negative affect states are particularly difficult to tolerate. Authors discuss the importance of implicit associations in understanding smoking relapse and how they can be targeted in treatment.

  13. Rare sugar D-psicose improves insulin sensitivity and glucose tolerance in type 2 diabetes Otsuka Long-Evans Tokushima Fatty (OLETF) rats.

    PubMed

    Hossain, Mohammad A; Kitagaki, Shigeru; Nakano, Daisuke; Nishiyama, Akira; Funamoto, Yasunobu; Matsunaga, Toru; Tsukamoto, Ikuko; Yamaguchi, Fuminori; Kamitori, Kazuyo; Dong, Youyi; Hirata, Yuko; Murao, Koji; Toyoda, Yukiyasu; Tokuda, Masaaki

    2011-02-01

    A rare sugar, D-psicose has progressively been evaluated as a unique metabolic regulator of glucose and lipid metabolism, and thus represents a promising compound for the treatment of type 2 diabetes mellitus (T2DM). The present study was undertaken to examine the underlying effector organs of D-psicose in lowering blood glucose and abdominal fat by exploiting a T2DM rat model, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Rats were fed 5% D-psicose or 5% D-glucose supplemented in drinking water, and only water in the control for 13 weeks and the protective effects were compared. A non-diabetic Long-Evans Tokushima Otsuka (LETO), fed with water served as a counter control of OLETF. After 13 weeks feeding, D-psicose treatment significantly reduced the increase in body weight and abdominal fat mass. Oral glucose tolerance test (OGTT) showed the reduced blood glucose and insulin levels suggesting the improvement of insulin resistance in OLETF rats. Oil-red-O staining elucidated that D-psicose significantly reduced lipid accumulation in the liver. Immunohistochemical analysis showed D-psicose induced glucokinase translocation from nucleus to cytoplasm of the liver which enhances glucokinase activity and subsequent synthesis of glycogen in the liver. D-psicose also protected the pathological change of the β-cells of pancreatic islets. These data demonstrate that D-psicose controls blood glucose levels by reducing lipotoxicity in liver and by preserving pancreatic β-cell function.

  14. Fructose and glucose differentially affect aging and carbonyl/oxidative stress parameters in Saccharomyces cerevisiae cells.

    PubMed

    Semchyshyn, Halyna M; Lozinska, Liudmyla M; Miedzobrodzki, Jacek; Lushchak, Volodymyr I

    2011-05-15

    Fructose is commonly used as an industrial sweetener and has been excessively consumed in human diets in the last decades. High fructose intake is causative in the development of metabolic disorders, but the mechanisms underlying fructose-induced disturbances are under debate. Fructose compared to glucose has been found to be a more potent initiator of the glycation reaction. Therefore, we supposed that glucose and fructose might have different vital effects. Here we compare the effects of glucose and fructose on yeast cell viability and markers of carbonyl/oxidative stress. Analysis of the parameters in cells growing on glucose and fructose clearly reveals that yeast growing on fructose has higher levels of carbonyl groups in proteins, α-dicarbonyl compounds and reactive oxygen species. This may explain the observation that fructose-supplemented growth as compared with growth on glucose resulted in more pronounced age-related decline in yeast reproductive ability and higher cell mortality. The results are discussed from the point of view that fructose rather than glucose is more extensively involved in glycation and ROS generation in vivo, yeast aging and development of carbonyl/oxidative stress. It should be noted that carbohydrate restriction used in this study does not reveal a significant difference between markers of aging and carbonyl/oxidative stress in yeasts cultivated on glucose and fructose.

  15. Effect of the consumption of β-lactoglobulin and epigallocatechin-3-gallate with or without calcium on glucose tolerance in C57BL/6 mice.

    PubMed

    Carnovale, Valérie; Pilon, Geneviève; Britten, Michel; Bazinet, Laurent; Couillard, Charles

    2016-01-01

    Interactions between β-lactoglobulin (β-lg) and epigallocatechin-3-gallate (EGCG) may modulate their health benefits. The objective of this study was therefore to investigate the synergistic effect of consuming β-lg and EGCG complexes on glucose tolerance of C57BL/6 male mice given an oral glucose tolerance test (OGTT) and randomized to one of the following treatments administered prior to the OGTT: 1) simulated milk ultrafiltrate (SMUF(-)), 2) SMUF(-) + EGCG, 3) SMUF(-) + β-lg, 4) SMUF(-) + EGCG + β-lg, 5) SMUF + calcium (SMUF(+)) and 6) SMUF(+) + EGCG + β-lg. We found no significant between-group difference in postprandial glucose response. However, when mice were separated in those who received β-lg from those who did not, we found that the latter displayed significantly higher postprandial glucose concentrations. Our results support the beneficial impact of β-lg on glycemic control and suggest that concomitant EGCG or calcium consumption does not improve this effect. PMID:26960683

  16. Short-Term Thermal-Humidity Shock Affects Point-of-Care Glucose Testing: Implications for Health Professionals and Patients.

    PubMed

    Lam, Mandy; Louie, Richard F; Curtis, Corbin M; Ferguson, William J; Vy, John H; Truong, Anh-Thu; Sumner, Stephanie L; Kost, Gerald J

    2014-01-01

    The objective was to assess the effects of short-term (≤1 hour) static high temperature and humidity stresses on the performance of point-of-care (POC) glucose test strips and meters. Glucose meters are used by medical responders and patients in a variety of settings including hospitals, clinics, homes, and the field. Reagent test strips and instruments are potentially exposed to austere environmental conditions. Glucose test strips and meters were exposed to a mean relative humidity of 83.0% (SD = 8.0%) and temperature of 42°C (107.6°F, SD = 3.2) in a Tenney BTRC environmental chamber. Stressed and unstressed glucose reagent strips and meters were tested with spiked blood samples (n = 40 measurements per time point for each of 4 trials) after 15, 30, 45, and 60 minutes of exposure. Wilcoxon's signed rank test was applied to compare measurements test strip and meter measurements to isolate and characterize the magnitude of meter versus test strip effects individually. Stressed POC meters and test strips produced elevated glucose results, with stressed meter bias as high as 20 mg/dL (17.7% error), and stressed test strip bias as high as 13 mg/dL (12.2% error). The aggregate stress effect on meter and test strips yielded a positive bias as high as 33 mg/dL (30.1% error) after 15 minutes of exposure. Short-term exposure (15 minutes) to high temperature and humidity can significantly affect the performance of POC glucose test strips and meters, with measurement biases that potentially affect clinical decision making and patient safety. PMID:24876542

  17. Glucose tolerance factor extracted from yeast: oral insulin-mimetic and insulin-potentiating agent: in vivo and in vitro studies.

    PubMed

    Weksler-Zangen, Sarah; Mizrahi, Tal; Raz, Itamar; Mirsky, Nitsa

    2012-09-01

    In search for an effective oral treatment for diabetes, we examined the capacity of glucose tolerance factor (GTF) extracted from yeast and administered orally to reduce hyperglycaemia in rat models exhibiting insulin deficiency. The cellular effect of GTF on the insulin signalling pathway was investigated in vitro. GTF (oral bolus), insulin (intraperitoneal) or their combination was administered to streptozotocin-diabetic (STZ) or hyperglycaemic Cohen diabetic-sensitive (hyp-CDs) rats. Blood glucose (BG) and insulin levels were measured in the postprandial (PP) state and during an oral glucose tolerance test. Deoxy-glucose transport and insulin signal transduction were assessed in 3T3-L1 adipocytes and myoblasts incubated with the GTF. Low dose of insulin produced a 34 and 12·5 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. GTF induced a 33 and 17 % reduction in the PP-BG levels of hyp-CDs and STZ rats, respectively. When combined with insulin, a respective decrease (58 and 42 %) in BG levels was observed, suggesting a partially additive (hyp-CDs) or synergistic (STZ rats) effect of the GTF and insulin. GTF did not induce insulin secretion in hyp-CDs rats, yet it lowered their BG levels, proposing an effect on glucose clearance by peripheral tissues. GTF induced a dose-dependent increase in deoxy-glucose transport into myoblasts and fat cells similar to insulin, while the combined treatment resulted in augmented transport rate. GTF induced a dose- and time-dependent phosphorylation of insulin receptor substrate 1, Akt and mitogen-activated protein kinase independent of insulin receptor phosphorylation. GTF exerts remarkable insulin-mimetic and insulin-potentiating effects, both in vivo and in vitro. It produces an insulin-like effect by acting on cellular signals downstream of the insulin receptor. These results demonstrate a potential source for a novel oral medication for diabetes.

  18. Body size perceptions among Pakistani women in Norway participating in a controlled trial to prevent deterioration of glucose tolerance.

    PubMed

    Hussain, Aysha; Bjørge, Benedikte; Hjellset, Victoria T; Holmboe-Ottesen, Gerd; Wandel, Margareta

    2010-06-01

    South Asians are prone to diabetes type 2 and cardiovascular diseases, which can be prevented by a diet leading to weight reduction. Body size perceptions may influence compliance to dietary advice. The objective was to study body size perceptions among Pakistani immigrant women in Norway, enrolled in a controlled trial to prevent deterioration of glucose tolerance by focussing on diet and physical activity. Participants (n=198) were 25-62 years of age, 79.8% had BMI > 25 and mean BMI was 29.6. Data were collected by questionnaire interviews with Punjabi/Urdu speaking interviewers, and body weight and height were measured. This article is based on baseline data. Stunkard's Figure Rating Scale was used. The scale consists of nine figures, representing women with different body shapes, from very thin (1-2) to very obese (6-9). The women were asked which body size they thought would connote health and wealth. A significantly smaller body size was related to health (mean 2.9) than to wealth (mean 3.3), p<0.01, and both were smaller than their self-rated own body size (mean 5.7), p<0.01. The women perceived that Pakistanis in Norway prefer women to have a smaller body size (mean 3.4) than people in Pakistan (mean 4.5), but larger than Norwegians (mean 2.5). A discrepancy score was calculated between self-rated own body size and perceived body size preference among Pakistanis in Norway. BMI was positively associated, and level of education negatively associated, with the discrepancy score. The women related body size numbers to BMI similarly to what has been described for US women. In conclusion, body size preferences among Pakistani women in this study were within the range of normal weight. However, there was a large discrepancy between own self-rated body size and the perceived ideal for Pakistanis in Norway. PMID:20379892

  19. CD36-deficient congenic strains show improved glucose tolerance and distinct shifts in metabolic and transcriptomic profiles.

    PubMed

    Šedová, L; Liška, F; Křenová, D; Kazdová, L; Tremblay, J; Krupková, M; Corbeil, G; Hamet, P; Křen, V; Šeda, O

    2012-07-01

    Deficiency of fatty acid translocase Cd36 has been shown to have a major role in the pathogenesis of metabolic syndrome in the spontaneously hypertensive rat (SHR). We have tested the hypothesis that the effects of Cd36 mutation on the features of metabolic syndrome are contextually dependent on genomic background. We have derived two new congenic strains by introgression of limited chromosome 4 regions of SHR origin, both including the defective Cd36 gene, into the genetic background of a highly inbred model of insulin resistance and dyslipidemia, polydactylous (PD) rat strain. We subjected standard diet-fed adult males of PD and the congenic PD.SHR4 strains to metabolic, morphometric and transcriptomic profiling. We observed significantly improved glucose tolerance and lower fasting insulin levels in PD.SHR4 congenics than in PD. One of the PD.SHR4 strains showed lower triglyceride concentrations across major lipoprotein fractions combined with higher levels of low-density lipoprotein cholesterol compared with the PD progenitor. The hepatic transcriptome assessment revealed a network of genes differentially expressed between PD and PD.SHR4 with significant enrichment by members of the circadian rhythmicity pathway (Arntl (Bmal1), Clock, Nfil3, Per2 and Per3). In summary, the introduction of the chromosome 4 region of SHR origin including defective Cd36 into the PD genetic background resulted in disconnected shifts of metabolic profile along with distinct changes in hepatic transcriptome. The synthesis of the current results with those obtained in other Cd36-deficient strains indicates that the eventual metabolic effect of a deleterious mutation such as that of SHR-derived Cd36 is not absolute, but rather a function of complex interactions between environmental and genomic background, upon which it operates.

  20. The Relationships between Metabolic Disorders (Hypertension, Dyslipidemia, and Impaired Glucose Tolerance) and Computed Tomography-Based Indices of Hepatic Steatosis or Visceral Fat Accumulation in Middle-Aged Japanese Men

    PubMed Central

    Yokokawa, Hirohide; Naito, Toshio; Sasabe, Noriko; Okumura, Mitsue; Iijima, Kimiko; Shibuya, Katsuhiko; Hisaoka, Teruhiko; Fukuda, Hiroshi

    2016-01-01

    Background Most studies on the relationships between metabolic disorders (hypertension, dyslipidemia, and impaired glucose tolerance) and hepatic steatosis (HS) or visceral fat accumulation (VFA) have been cross-sectional, and thus, these relationships remain unclear. We conducted a retrospective cohort study to clarify the relationships between components of metabolic disorders and HS/VFA. Methods The participants were 615 middle-aged men who were free from serious liver disorders, diabetes, and HS/VFA and underwent multiple general health check-ups at our institution between 2009 and 2013. The data from the initial and final check-ups were used. HS and VFA were assessed by computed tomography. HS was defined as a liver to spleen attenuation ratio of ≤1.0. VFA was defined as a visceral fat cross-sectional area of ≥100 cm2 at the level of the navel. Metabolic disorders were defined using Japan’s metabolic syndrome diagnostic criteria. The participants were divided into four groups based on the presence (+) or absence (-) of HS/VFA. The onset rates of each metabolic disorder were compared among the four groups. Results Among the participants, 521, 55, 24, and 15 were classified as HS(-)/VFA(-), HS(-)/VFA(+), HS(+)/VFA(-), and HS(+)/VFA(+), respectively, at the end of the study. Impaired glucose tolerance was more common among the participants that exhibited HS or VFA (p = 0.05). On the other hand, dyslipidemia was more common among the participants that displayed VFA (p = 0.01). Conclusions It is likely that VFA is associated with impaired glucose tolerance and dyslipidemia, while HS might be associated with impaired glucose tolerance. Unfortunately, our study failed to detect associations between HS/VFA and metabolic disorders due to the low number of subjects that exhibited fat accumulation. Although our observational study had major limitations, we consider that it obtained some interesting results. HS and VFA might affect different metabolic disorders

  1. Salt tolerant plants increase nitrogen removal from biofiltration systems affected by saline stormwater.

    PubMed

    Szota, Christopher; Farrell, Claire; Livesley, Stephen J; Fletcher, Tim D

    2015-10-15

    Biofiltration systems are used in urban areas to reduce the concentration and load of nutrient pollutants and heavy metals entering waterways through stormwater runoff. Biofilters can, however be exposed to salt water, through intrusion of seawater in coastal areas which could decrease their ability to intercept and retain pollutants. We measured the effect of adding saline stormwater on pollutant removal by six monocotyledonous species with different levels of salt-tolerance. Carex appressa, Carex bichenoviana, Ficinia nodosa, Gahnia filum, Juncus kraussii and Juncus usitatus were exposed to six concentrations of saline stormwater, equivalent to electrical conductivity readings of: 0.09, 2.3, 5.5, 10.4, 20.0 and 37.6 mS cm(-1). Salt-sensitive species: C. appressa, C. bichenoviana and J. usitatus did not survive ≥10.4 mS cm(-1), removing their ability to take up nitrogen (N). Salt-tolerant species, such as F. nodosa and J. kraussii, maintained N-removal even at the highest salt concentration. However, their levels of water stress and stomatal conductance suggest that N-removal would not be sustained at concentrations ≥10.4 mS cm(-1). Increasing salt concentration indirectly increased phosphorus (P) removal, by converting dissolved forms of P to particulate forms which were retained by filter media. Salt concentrations ≥10 mS cm(-1) also reduced removal efficiency of zinc, manganese and cadmium, but increased removal of iron and lead, regardless of plant species. Our results suggest that biofiltration systems exposed to saline stormwater ≤10 mS cm(-1) can only maintain N-removal when planted with salt-tolerant species, while P removal and immobilisation of heavy metals is less affected by species selection.

  2. Salt tolerant plants increase nitrogen removal from biofiltration systems affected by saline stormwater.

    PubMed

    Szota, Christopher; Farrell, Claire; Livesley, Stephen J; Fletcher, Tim D

    2015-10-15

    Biofiltration systems are used in urban areas to reduce the concentration and load of nutrient pollutants and heavy metals entering waterways through stormwater runoff. Biofilters can, however be exposed to salt water, through intrusion of seawater in coastal areas which could decrease their ability to intercept and retain pollutants. We measured the effect of adding saline stormwater on pollutant removal by six monocotyledonous species with different levels of salt-tolerance. Carex appressa, Carex bichenoviana, Ficinia nodosa, Gahnia filum, Juncus kraussii and Juncus usitatus were exposed to six concentrations of saline stormwater, equivalent to electrical conductivity readings of: 0.09, 2.3, 5.5, 10.4, 20.0 and 37.6 mS cm(-1). Salt-sensitive species: C. appressa, C. bichenoviana and J. usitatus did not survive ≥10.4 mS cm(-1), removing their ability to take up nitrogen (N). Salt-tolerant species, such as F. nodosa and J. kraussii, maintained N-removal even at the highest salt concentration. However, their levels of water stress and stomatal conductance suggest that N-removal would not be sustained at concentrations ≥10.4 mS cm(-1). Increasing salt concentration indirectly increased phosphorus (P) removal, by converting dissolved forms of P to particulate forms which were retained by filter media. Salt concentrations ≥10 mS cm(-1) also reduced removal efficiency of zinc, manganese and cadmium, but increased removal of iron and lead, regardless of plant species. Our results suggest that biofiltration systems exposed to saline stormwater ≤10 mS cm(-1) can only maintain N-removal when planted with salt-tolerant species, while P removal and immobilisation of heavy metals is less affected by species selection. PMID:26150068

  3. Leucine supplementation does not affect protein turnover and impairs the beneficial effects of endurance training on glucose homeostasis in healthy mice.

    PubMed

    Costa Júnior, José M; Rosa, Morgana R; Protzek, André O; de Paula, Flávia M; Ferreira, Sandra M; Rezende, Luiz F; Vanzela, Emerielle C; Zoppi, Cláudio C; Silveira, Leonardo R; Kettelhut, Isis C; Boschero, Antonio C; de Oliveira, Camila A M; Carneiro, Everardo M

    2015-04-01

    Endurance exercise training as well as leucine supplementation modulates glucose homeostasis and protein turnover in mammals. Here, we analyze whether leucine supplementation alters the effects of endurance exercise on these parameters in healthy mice. Mice were distributed into sedentary (C) and exercise (T) groups. The exercise group performed a 12-week swimming protocol. Half of the C and T mice, designated as the CL and TL groups, were supplemented with leucine (1.5 % dissolved in the drinking water) throughout the experiment. As well known, endurance exercise training reduced body weight and the retroperitoneal fat pad, increased soleus mass, increased VO2max, decreased muscle proteolysis, and ameliorated peripheral insulin sensitivity. Leucine supplementation had no effect on any of these parameters and worsened glucose tolerance in both CL and TL mice. In the soleus muscle of the T group, AS-160(Thr-642) (AKT substrate of 160 kDa) and AMPK(Thr-172) (AMP-Activated Protein Kinase) phosphorylation was increased by exercise in both basal and insulin-stimulated conditions, but it was reduced in TL mice with insulin stimulation compared with the T group. Akt phosphorylation was not affected by exercise but was lower in the CL group compared with the other groups. Leucine supplementation increased mTOR phosphorylation at basal conditions, whereas exercise reduced it in the presence of insulin, despite no alterations in protein synthesis. In trained groups, the total FoxO3a protein content and the mRNA for the specific isoforms E2 and E3 ligases were reduced. In conclusion, leucine supplementation did not potentiate the effects of endurance training on protein turnover, and it also reduced its positive effects on glucose homeostasis.

  4. Kindling and sensitization as models for affective episode recurrence, cyclicity, and tolerance phenomena.

    PubMed

    Post, Robert M

    2007-01-01

    We use the non-homologous model of sensitization and kindling to help conceptualize processes occurring in the longitudinal course of bipolar disorder. The models help focus on the phenomena of episode recurrence, regression, and cycle acceleration occurring without medication and during treatment, when these progressive processes can re-emerge during tolerance development. The preclinical data suggest that it is the ratio of pathological versus adaptive factors mediated by changes in gene expression that mediate episode recurrence or suppression. During tolerance development, there may be selective loss of some episode-induced adaptive factors that may be re-engendered during a period off that medication. The models reveal long-term molecular changes induced by recurrent stresses, episodes of illness, and substances of abuse that can accumulate and lead to progressive increases in vulnerability to episode recurrence. The clinical and preclinical data converge in emphasizing the importance of prevention and early and sustained prophylaxis. New data also implicate brain-derived neurotrophic factor (BDNF) in genetic and environmental illness vulnerability and progression, as well as in the mechanisms of action of the mood stabilizers and antidepressants. Therapeutic agents may thus not only prevent recurrent affective episodes and their adverse consequences on the brain, behavior, and quality of life, but they may also be able to ameliorate the effects of stressors, and reverse or prevent some of the basic pathological brain mechanisms underlying illness progression.

  5. Identification of Risk Factors Affecting Impaired Fasting Glucose and Diabetes in Adult Patients from Northeast China

    PubMed Central

    Yin, Yutian; Han, Weiqing; Wang, Yuhan; Zhang, Yue; Wu, Shili; Zhang, Huiping; Jiang, Lingling; Wang, Rui; Zhang, Peng; Yu, Yaqin; Li, Bo

    2015-01-01

    Background: Besides genetic factors, the occurrence of diabetes is influenced by lifestyles and environmental factors as well as trace elements in diet materials. Subjects with impaired fasting glucose (IFG) have an increased risk of developing diabetes mellitus (DM). This study aimed to explore risk factors affecting IFG and diabetes in patients from Northeast China. Methods: A population-based, cross-sectional survey of chronic diseases and related risk factors was conducted in Jilin Province of Northeast China. All adult residents, aged 18–79, were invited to participate in this survey using the method of multistage stratified random cluster sampling. One hundred thirty-four patients with IFG or DM and 391 healthy control subjects were recruited. We compared demographic factors, body size measurements, healthy-related behaviors, and hair metallic element contents between IFG/diabetes patients and healthy individuals. Results: IFG/diabetes patients had a greater weight, waist, hip, and body mass index (BMI) than control subjects. Significant differences in the content of zinc (Zn), potassium (K), copper (Ca), and sodium (Na) as well as Cu/Zn ratios between IFG or DM patients and control subjects (p < 0.05) were also observed. Hair Cu, selenium (Se), and Na contents were positively correlated with blood glucose levels (Cu: rs = 0.135, p = 0.002; Se: rs = 0.110, p = 0.012; Na: rs = 0.091, p = 0.038). Polytomous logistic regression adjusting for age, sex, family history of diabetes and BMI, showed that subjects with high BMI were more likely to develop IFG and DM (IFG: OR = 1.15, OR 95% CI = 1.02–1.29; DM: OR = 1.15, OR 95% CI = 1.01–1.33). Moreover, rarely or never eating fruits was a risk factor for DM (OR = 5.46, OR 95% CI = 1.87–15.98) but not for IFG (OR = 1.70, OR 95% CI = 0.72–4.02). Subjects with abdominal obesity or DM history were more susceptible to DM (abdominal obesity: OR = 2.99, OR 95% CI = 1.07–8.37; DM history: OR = 2.69, OR 95% CI = 1

  6. Effect of dietary supplementation of different oils during the first or second half of pregnancy on the glucose tolerance of the sow.

    PubMed

    Corson, A M; Laws, J; Litten, J C; Dodds, P F; Lean, I J; Clarke, L

    2008-07-01

    Poor glucose tolerance may be an under-researched contributory factor in the high (10% to 20%) pre-weaning mortality rate observed in pigs. Insulin resistance commences at around week 12 of gestation in the sow, although there are conflicting reports in the literature about the extent to which insulin resistance is modulated by maternal diet. The aim of the study was to determine the effects of supplementing the maternal diet with different dietary oils during either the first half or the second half of gestation on the glucose tolerance of the sow. Sows were offered the control (C: n = 5) diet as pellets or the C diet plus 10% extra energy (n = 16 per group) derived from either: (i) extra pellets; (ii) palm oil; (iii) olive oil; (iv) sunflower oil; or (v) fish oil. Experimental diets were fed during either the first (G1) or second (G2) half of gestation. A glucose tolerance test (GTT) was conducted on day 108 of gestation by administering 0.5 g/kg glucose i.v. Blood samples were taken every 5 to 10 min for 90 min post administration. The change in body weight and backfat thickness during gestation was similar but both type and timing of dietary supplementation influenced litter size and weight. With the exception of the sunflower oil group, supplementing the maternal diet in G1 resulted in larger and heavier litters, particularly in mothers offered palm oil. Basal blood glucose concentrations tended to be more elevated in G1 than G2 groups, whilst plasma insulin concentrations were similar. Following a GTT, the adjusted area under the curve was greater in G1 compared to G2 sows, despite no differences in glucose clearance. Maternal diet appeared to influence the relationship between glucose curve characteristics following a GTT and litter outcome. In conclusion, the degree of insulin sensitivity can be altered by both the period during which maternal nutritional supplementation is offered and the fatty acid profile of the diet.

  7. The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats

    PubMed Central

    Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I.; Cruzblanca, Humberto; Mancilla, Evelyn

    2016-01-01

    Objective Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Materials and Methods Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Results Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable

  8. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    SciTech Connect

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya; Hirose, Takahisa; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

    2009-12-18

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  9. Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent

    USGS Publications Warehouse

    Williams, Wyatt I.; Friedman, Jonathan M.; Gaskin, John F.; Norton, Andrew P.

    2014-01-01

    Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others.

  10. Hybridization of an invasive shrub affects tolerance and resistance to defoliation by a biological control agent

    PubMed Central

    Williams, Wyatt I; Friedman, Jonathan M; Gaskin, John F; Norton, Andrew P

    2014-01-01

    Evolution has contributed to the successful invasion of exotic plant species in their introduced ranges, but how evolution affects particular control strategies is still under evaluation. For instance, classical biological control, a common strategy involving the utilization of highly specific natural enemies to control exotic pests, may be negatively affected by host hybridization because of shifts in plant traits, such as root allocation or chemical constituents. We investigated introgression between two parent species of the invasive shrub tamarisk (Tamarix spp.) in the western United States, and how differences in plant traits affect interactions with a biological control agent. Introgression varied strongly with latitude of origin and was highly correlated with plant performance. Increased levels of T. ramosissima introgression resulted in both higher investment in roots and tolerance to defoliation and less resistance to insect attack. Because tamarisk hybridization occurs predictably on the western U.S. landscape, managers may be able to exploit this information to maximize control efforts. Genetic differentiation in plant traits in this system underpins the importance of plant hybridization and may explain why some biological control releases are more successful than others. PMID:24665340

  11. Viral affects on metabolism: changes in glucose and glutamine utilization during human cytomegalovirus infection

    PubMed Central

    Yu, Yongjun; Clippinger, Amy J.; Alwine, James C.

    2011-01-01

    Human cytomegalovirus (HCMV) infection causes dramatic alterations of intermediary metabolism, similar to those found in tumor cells. In infected cells, glucose carbon is not completely broken down by the tricarboxylic acid (TCA) cycle for energy; instead it is used biosynthetically. This process requires increased glucose uptake, increased glycolysis and the diversion of glucose carbon, in the form of citrate, from the TCA cycle for use in HCMV-induced fatty acid biosynthesis. The diversion of citrate from the TCA cycle (cataplerosis) requires induction of enzymes to promote glutaminolysis, the conversion of glutamine to -ketoglutarate in order to maintain the TCA cycle (anaplerosis) and ATP production. Such changes could result in heretofore uncharacterized pathogenesis, potentially implicating HCMV as a subtle co-factor in many maladies, including oncogenesis. Recognition of the effects of HCMV, and other viruses, on host cell metabolism will provide new understanding of viral pathogenesis and novel avenues for antiviral therapy. PMID:21570293

  12. Insulin tolerance in laminitic ponies.

    PubMed Central

    Coffman, J R; Colles, C M

    1983-01-01

    Sensitivity to insulin was assessed in ponies episodically affected with chronic laminitis by measurement of blood glucose and arterial blood pressure during insulin tolerance tests. In terms of blood glucose values, laminitic ponies were significantly less sensitive to insulin than controls. Conversely, a post-insulin decline in diastolic, systolic and mean blood pressure values was significantly greater in laminitic ponies than in controls. PMID:6357412

  13. Effects of body composition and exercise capacity on glucose tolerance, insulin, and lipoprotein lipids in healthy older men: a cross-sectional and longitudinal intervention study.

    PubMed

    Coon, P J; Bleecker, E R; Drinkwater, D T; Meyers, D A; Goldberg, A P

    1989-12-01

    The relationships of age, body composition, and physical conditioning status to glucose tolerance, insulin, and lipoprotein levels were examined in 77 healthy, nonsmoking white male volunteers, aged 46 to 73 years with no evidence of coronary artery or endocrine-metabolic disease. The men had a wide range of body fat (13% to 39%), indexed as waist-to-hip ratio (WHR, 0.84 to 1.08), and maximal aerobic capacity (VO2max, 17 to 48 mL/kg.min). Multiple regression analysis with age, VO2max, WHR, and percent body fat as independent variables demonstrated that fasting plasma insulin, triglyceride (TG), and high density lipoprotein cholesterol (HDL-C) levels were independently related to both percent body fat and WHR. In contrast, fasting plasma glucose levels and insulin responses during oral glucose tolerance tests (OGTT) correlated independently with percent body fat, and glucose responses to OGTT correlated only with WHR. Although fasting plasma TG and HDL-C correlated with glucose and insulin levels, in multiple regression analyses only percent body fat and WHR were the significant independent variables. Fasting total and low density lipoprotein cholesterol values were not related to these variables. To test the effects of weight loss and exercise training on these relationships, 20 obese men of comparable age, percent body fat, WHR, and VO2max were randomly assigned to weight loss or aerobic exercise training programs. A 12% +/- 3% loss in body weight (P less than .01, mean +/- SD) resulted in a 19% +/- 9% decline in body fat (P less than .01) with no change in fat free mass, WHR, or VO2max.(ABSTRACT TRUNCATED AT 250 WORDS)

  14. Imeglimin normalizes glucose tolerance and insulin sensitivity and improves mitochondrial function in liver of a high-fat, high-sucrose diet mice model.

    PubMed

    Vial, Guillaume; Chauvin, Marie-Agnès; Bendridi, Nadia; Durand, Annie; Meugnier, Emmanuelle; Madec, Anne-Marie; Bernoud-Hubac, Nathalie; Pais de Barros, Jean-Paul; Fontaine, Éric; Acquaviva, Cécile; Hallakou-Bozec, Sophie; Bolze, Sébastien; Vidal, Hubert; Rieusset, Jennifer

    2015-06-01

    Imeglimin is the first in a new class of oral glucose-lowering agents currently in phase 2b development. Although imeglimin improves insulin sensitivity in humans, the molecular mechanisms are unknown. This study used a model of 16-week high-fat, high-sucrose diet (HFHSD) mice to characterize its antidiabetic effects. Six-week imeglimin treatment significantly decreased glycemia, restored normal glucose tolerance, and improved insulin sensitivity without modifying organs, body weights, and food intake. This was associated with an increase in insulin-stimulated protein kinase B phosphorylation in the liver and muscle. In liver mitochondria, imeglimin redirects substrate flows in favor of complex II, as illustrated by increased respiration with succinate and by the restoration of respiration with glutamate/malate back to control levels. In addition, imeglimin inhibits complex I and restores complex III activities, suggesting an increase in fatty acid oxidation, which is supported by an increase in hepatic 3-hydroxyacetyl-CoA dehydrogenase activity and acylcarnitine profile and the reduction of liver steatosis. Imeglimin also reduces reactive oxygen species production and increases mitochondrial DNA. Finally, imeglimin effects on mitochondrial phospholipid composition could participate in the benefit of imeglimin on mitochondrial function. In conclusion, imeglimin normalizes glucose tolerance and insulin sensitivity by preserving mitochondrial function from oxidative stress and favoring lipid oxidation in liver of HFHSD mice. PMID:25552598

  15. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    PubMed

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety. PMID:26987021

  16. Glucose-6-phosphate dehydrogenase regulation in the hepatopancreas of the anoxia-tolerant marine mollusc, Littorina littorea.

    PubMed

    Lama, Judeh L; Bell, Ryan A V; Storey, Kenneth B

    2013-01-01

    Glucose-6-phosphate dehydrogenase (G6PDH) gates flux through the pentose phosphate pathway and is key to cellular antioxidant defense due to its role in producing NADPH. Good antioxidant defenses are crucial for anoxia-tolerant organisms that experience wide variations in oxygen availability. The marine mollusc, Littorina littorea, is an intertidal snail that experiences daily bouts of anoxia/hypoxia with the tide cycle and shows multiple metabolic and enzymatic adaptations that support anaerobiosis. This study investigated the kinetic, physical and regulatory properties of G6PDH from hepatopancreas of L. littorea to determine if the enzyme is differentially regulated in response to anoxia, thereby providing altered pentose phosphate pathway functionality under oxygen stress conditions. Several kinetic properties of G6PDH differed significantly between aerobic and 24 h anoxic conditions; compared with the aerobic state, anoxic G6PDH (assayed at pH 8) showed a 38% decrease in K m G6P and enhanced inhibition by urea, whereas in pH 6 assays K m NADP and maximal activity changed significantly between the two states. The mechanism underlying anoxia-responsive changes in enzyme properties proved to be a change in the phosphorylation state of G6PDH. This was documented with immunoblotting using an anti-phosphoserine antibody, in vitro incubations that stimulated endogenous protein kinases versus protein phosphatases and significantly changed K m G6P, and phosphorylation of the enzyme with (32)P-ATP. All these data indicated that the aerobic and anoxic forms of G6PDH were the high and low phosphate forms, respectively, and that phosphorylation state was modulated in response to selected endogenous protein kinases (PKA or PKG) and protein phosphatases (PP1 or PP2C). Anoxia-induced changes in the phosphorylation state of G6PDH may facilitate sustained or increased production of NADPH to enhance antioxidant defense during long term anaerobiosis and/or during the transition

  17. Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy.

    PubMed

    Koethe, John R; Jenkins, Cathy A; Petucci, Christopher; Culver, Jeffrey; Shepherd, Bryan E; Sterling, Timothy R

    2016-05-01

    significantly differ according to HIV-status.HIV-infected women on non-nucleoside reverse transcriptase inhibitor-based ART had superior glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex-differences may not be specific to HIV infection. PMID:27175676

  18. Superior Glucose Tolerance and Metabolomic Profiles, Independent of Adiposity, in HIV-Infected Women Compared With Men on Antiretroviral Therapy

    PubMed Central

    Koethe, John R.; Jenkins, Cathy A.; Petucci, Christopher; Culver, Jeffrey; Shepherd, Bryan E.; Sterling, Timothy R.

    2016-01-01

    levels did not significantly differ according to HIV-status. HIV-infected women on non-nucleoside reverse transcriptase inhibitor-based ART had superior glucose tolerance and lower plasma metabolites associated with the development of diabetes compared with men with similar metabolic disease risk profiles. The relationship between sex and plasma metabolite levels did not significantly differ according to HIV-status among obese subjects, suggesting the observed sex-differences may not be specific to HIV infection. PMID:27175676

  19. Slow recovery of blood glucose in the insulin tolerance test during the prepartum transition period negatively impacts the nutritional status and reproductive performance postpartum of dairy cows.

    PubMed

    Lee, Hsu-Hsun; Kida, Katsuya; Miura, Ryotaro; Inokuma, Hisashi; Miyamoto, Akio; Kawashima, Chiho; Haneda, Shingo; Miyake, Yoh-Ichi; Matsui, Motozumi

    2012-04-01

    In peripartum dairy cows, insulin resistance (IR) increases to adjust the direction of energy to lactation after calving. To investigate the effect of prepartum IR on postpartum reproductive performance, the insulin tolerance test (ITT) was applied to 15 cows at 3 weeks (Pre21) and 10 days (Pre10) before the predicted calving date. Blood glucose area under the curve (AUC(glu)) within 120 min after administration of 0.05 IU/kg-BW insulin was calculated. The occurrence of first ovulation, days to first artificial insemination (AI) and first AI conception rate were recorded. Nutritional status postpartum was evaluated by blood chemical analysis. Based on AUC(glu) changes from Pre21 to Pre10, cows were classified into either the AUC-up group (AUC(glu) increase, n=5) or the AUC-down group (AUC(glu) decrease, n=10). There was no difference in the decrease in blood glucose at 30 min after insulin injection between groups, although glucose recovery from 30 to 60 min during the ITT was slow at Pre10 in the AUC-up group. The AUC-up group had a higher number of days to first AI and high glucose, total protein, globulin, γ-glutamyltransferase, triacylglycerol levels and a low albumin-globulin ratio at the 14th day postpartum. The present study infers that prepartum slow glucose recovery rather than insulin sensitivity might increase the potential for subclinical health problems postpartum and thus suppress reproductive performance. During the prepartum transition period, glucose dynamics in the ITT can be considered as a new indicator for the postpartum metabolic status and reproductive performance of dairy cows.

  20. [Activity of Vegetative Nervous System and Levels of Inflammatory Cytokines During Glucose Tolerance Test in Subjects With Optimal and High Normal Blood Pressure].

    PubMed

    Mangileva, T A

    2015-01-01

    Fourteen patients with high normal (main group) and 15 subjects with optimal (control group) blood pressure (BP) were examined. Fasting and postprandial (60 and 120 min after oral intake of glucose) levels of glucose, insulin, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and C-reactive protein were measured. At the same time spectral analysis of heart rate variability (HRV) was done. Body mass index (BMI) and insulin resistance index (as HOMA-IR) were calculated. In patients with high normal BP total power of HRV was decreased (p < 0.05) and dynamic changes of HRV after glucose loading were blunted. In persons with optimal BP transient elevation of low frequency component and low/high ratio in 60 min after onset of glucose tolerance test (GTT) were registered; values of both parameters were higher than in the main group (p < 0.05). Changes in vegetative nervous system activity in control group were accompanied by transient elevations of levels of inflammatory cytokines: IL-10 and TNF-α in 60 min, IL-6 in 120 min after GTT onset (p < 0.05), which at that moment were higher than in patients with high normal BP (p < 0.05). Fasting and postprandial insulin concentrations and glucose level 60 min after glucose intake were higher in patients from the main group (p < 0.05). In both groups positive correlations between BMI and HOMA-IR were observed (r1 = 0.70 & r2 = 0.78). Subjects with optimal and high normal BP have different variants of vegetative nervous system reactions to pulsatile hyperglycemia which is accompanied by changes of levels of inflammatory cytokines and worsening of carbohydrate metabolism in patients with high normal BP. PMID:26320287

  1. Structure-function relationships affecting the sensing mechanism of monolayer-protected cluster doped xerogel amperometric glucose biosensors.

    PubMed

    DiPasquale, Luke T; Poulos, Nicholas G; Hall, Jackson R; Minocha, Aastha; Bui, Tram Anh; Leopold, Michael C

    2015-07-15

    A systematic study of the structure-function relationships critical to understanding the sensing mechanism of 1st generation amperometric glucose biosensors with an embedded nanoparticle (NP) network is presented. Xerogel-based films featuring embedded glucose oxidase enzyme and doped with alkanethiolate-protected gold NPs, known as monolayer protected clusters (MPCs), exhibit significantly enhanced performance compared to analogous systems without NPs including higher sensitivity, faster response time, and extended linear/dynamic ranges. The proposed mechanism involves diffusion of the glucose to glucose oxidase within the xerogel, enzymatic reaction production of H2O2 with subsequent diffusion to the embedded network of MPCs where it is oxidized, an event immediately reported via fast electron transfer (ET) through the MPC system to the working electrode. Various aspects of the film construct and strategy are systematically probed using amperometry, voltammetry, and solid-state electronic conductivity measurements, including the effects of MPC peripheral chain length, MPC functionalization via place-exchange reaction, MPC core size, and the MPC density or concentration within the xerogel composite films. The collective results of these experiments support the proposed mechanism and identify interparticle spacing and the electronic communication through the MPC network is the most significant factor in the sensing scheme with the diffusional aspects of the mechanism that may be affected by film/MPC hydrophobicity and functionality (i.e., glucose and H2O2 diffusion) shown to be less substantial contributors to the overall enhanced performance. Understanding the structure-function relationships of effective sensing schemes allows for the employment of the strategy for future biosensor design toward clinically relevant targets.

  2. Structure-function relationships affecting the sensing mechanism of monolayer-protected cluster doped xerogel amperometric glucose biosensors.

    PubMed

    DiPasquale, Luke T; Poulos, Nicholas G; Hall, Jackson R; Minocha, Aastha; Bui, Tram Anh; Leopold, Michael C

    2015-07-15

    A systematic study of the structure-function relationships critical to understanding the sensing mechanism of 1st generation amperometric glucose biosensors with an embedded nanoparticle (NP) network is presented. Xerogel-based films featuring embedded glucose oxidase enzyme and doped with alkanethiolate-protected gold NPs, known as monolayer protected clusters (MPCs), exhibit significantly enhanced performance compared to analogous systems without NPs including higher sensitivity, faster response time, and extended linear/dynamic ranges. The proposed mechanism involves diffusion of the glucose to glucose oxidase within the xerogel, enzymatic reaction production of H2O2 with subsequent diffusion to the embedded network of MPCs where it is oxidized, an event immediately reported via fast electron transfer (ET) through the MPC system to the working electrode. Various aspects of the film construct and strategy are systematically probed using amperometry, voltammetry, and solid-state electronic conductivity measurements, including the effects of MPC peripheral chain length, MPC functionalization via place-exchange reaction, MPC core size, and the MPC density or concentration within the xerogel composite films. The collective results of these experiments support the proposed mechanism and identify interparticle spacing and the electronic communication through the MPC network is the most significant factor in the sensing scheme with the diffusional aspects of the mechanism that may be affected by film/MPC hydrophobicity and functionality (i.e., glucose and H2O2 diffusion) shown to be less substantial contributors to the overall enhanced performance. Understanding the structure-function relationships of effective sensing schemes allows for the employment of the strategy for future biosensor design toward clinically relevant targets. PMID:25819004

  3. Kinin B1 and B2 receptor deficiency protects against obesity induced by a high-fat diet and improves glucose tolerance in mice

    PubMed Central

    Morais, Rafael L; Silva, Elton D; Sales, Vicência M; Filippelli-Silva, Rafael; Mori, Marcelo A; Bader, Michael; Pesquero, João B

    2015-01-01

    The kallikrein-kinin system is well known for its role in pain and inflammation, and has been shown recently by our group to have a role also in the regulation of energy expenditure. We have demonstrated that B1 receptor knockout (B1KO) mice are resistant to obesity induced by a high-fat diet (HFD) and that B1 receptor expression in adipocytes regulates glucose tolerance and predisposition to obesity. However, it is also known that in the absence of B1 receptor, the B2 receptor is overexpressed and can take over the function of its B1 counterpart, rendering uncertain the role of each kinin receptor in these metabolic effects. Therefore, we investigated the impact of ablation of each kinin receptor on energy metabolism using double kinin receptor knockout (B1B2KO) mice. Our data show that B1B2KO mice were resistant to HFD-induced obesity, with lower food intake and feed efficiency when compared with wild-type mice. They also had lower blood insulin and leptin levels and higher glucose tolerance after treatment with an HFD. Gene expression for tumor necrosis factor-alpha and C-reactive protein, which are important genes for insulin resistance, was reduced in white adipose tissue, skeletal muscle, and the liver in B1B2KO mice after the HFD. In summary, our data show that disruption of kinin B1 and B2 receptors has a profound impact on metabolic homeostasis in mice, by improving glucose tolerance and preventing HFD-induced obesity. These novel findings could pave the way for development of new pharmacological strategies to treat metabolic disorders such as insulin resistance and obesity. PMID:26346752

  4. Molecular cloning and expression of thermostable glucose-tolerant β-glucosidase of Penicillium funiculosum NCL1 in Pichia pastoris and its characterization.

    PubMed

    Ramani, Gurusamy; Meera, Balasubramanian; Vanitha, Chinnathambi; Rajendhran, Jeyaprakash; Gunasekaran, Paramasamy

    2015-04-01

    A partial peptide sequence of β-glucosidase isoform (Bgl4) of Penicillium funiculosum NCL1 was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The cDNA (bgl4) encoding Bgl4 protein was cloned from P. funiculosum NCL1 RNA by consensus RT-PCR. The bgl4 gene encoded 857 amino acids that contained catalytic domains specific for glycoside hydrolase family 3. The cDNA was over-expressed in Pichia pastoris KM71H and the recombinant protein (rBgl4) was purified with the specific activity of 1,354.3 U/mg. The rBgl4 was a glycoprotein with the molecular weight of ~130 kDa and showed optimal activity at pH 5.0 and 60 °C. The enzyme was thermo-tolerant up to 60 °C for 60 min. The rBgl4 was highly active on aryl substrates with β-glucosidic, β-xylosidic linkages and moderately active on cellobiose and salicin. It showed remarkably high substrate conversion rate of 3,332 and 2,083 μmol/min/mg with the substrates p-nitrophenyl β-glucoside and cellobiose respectively. In addition, the rBgl4 showed tolerance to glucose concentration up to 400 mM. It exhibited twofold increase in glucose yield when supplemented with crude cellulase of Trichoderma reesei Rut-C30 in cellulose hydrolysis. These results suggested that rBgl4 is a thermo- and glucose-tolerant β-glucosidase and is a potential supplement for commercial cellulase in cellulose hydrolysis and thereby assures profitability in bioethanol production.

  5. Angiopoietin-like protein 4 improves glucose tolerance and insulin resistance but induces liver steatosis in high-fat-diet mice.

    PubMed

    Wang, Yi; Liu, Li-Ming; Wei, Li; Ye, Wei-Wei; Meng, Xiang-Ying; Chen, Feng; Xiao, Qian; Chen, Jian-Yang; Zhou, Yong

    2016-10-01

    Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator‑activated receptors, which are widely used as lipid‑lowering and anti‑diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high‑fat‑diet (HFD) C57 mice. In the present study, mice were divided into three groups, with standard chow mice as a normal control, adenovirus (adv)‑injected HFD mice as a model control and adv‑Angptl4‑injected HFD mice as the Angptl4+ group. Firstly, compared with the normal control group, mice in the model control group gained more body weight with severe liver steatosis and increased serum levels of triglyceride, total cholesterol, free fatty acids, alanine aminotransferase and aspartate aminotransferase. In the Angptl4+ group, Angptl4 reduced the weight growth rate, aggravated hepatic steatosis and further increased all the aforementioned serum indexes. Secondly, compared with the normal control, the model control group had a reduced glucose tolerance and developed insulin resistance. Angptl4 expression and the phosphorylation levels of several insulin signaling pathway‑associated genes, insulin receptor substrate 1, protein kinase B, janus kinase 2, signal transducer and activator of transcription 3 were downregulated in the liver samples. Adv‑Angptl4 injection was observed to improve glucose tolerance and insulin resistance. The genes measured were identified to be upregulated close to normal levels. All the results suggested that Angptl4 served an important role in lipid and glucose metabolism in HFD‑induced obese mice, and this may have a great significance for treatment of hyperlipidemia, diabetes, metabolic syndrome and other diseases.

  6. Angiopoietin-like protein 4 improves glucose tolerance and insulin resistance but induces liver steatosis in high-fat-diet mice.

    PubMed

    Wang, Yi; Liu, Li-Ming; Wei, Li; Ye, Wei-Wei; Meng, Xiang-Ying; Chen, Feng; Xiao, Qian; Chen, Jian-Yang; Zhou, Yong

    2016-10-01

    Angiopoietin-like protein 4 (Angptl4) is a secreted protein predominantly expressed in liver and adipose tissues, and has been identified as an adipokine. Angptl4 is the target gene of peroxisome proliferator‑activated receptors, which are widely used as lipid‑lowering and anti‑diabetic drugs, and previous studies have demonstrated that Angptl4 is able to directly stimulate adipocyte lipolysis. The current study focused on how Angptl4 was involved in regulating lipid and glucose metabolism in high‑fat‑diet (HFD) C57 mice. In the present study, mice were divided into three groups, with standard chow mice as a normal control, adenovirus (adv)‑injected HFD mice as a model control and adv‑Angptl4‑injected HFD mice as the Angptl4+ group. Firstly, compared with the normal control group, mice in the model control group gained more body weight with severe liver steatosis and increased serum levels of triglyceride, total cholesterol, free fatty acids, alanine aminotransferase and aspartate aminotransferase. In the Angptl4+ group, Angptl4 reduced the weight growth rate, aggravated hepatic steatosis and further increased all the aforementioned serum indexes. Secondly, compared with the normal control, the model control group had a reduced glucose tolerance and developed insulin resistance. Angptl4 expression and the phosphorylation levels of several insulin signaling pathway‑associated genes, insulin receptor substrate 1, protein kinase B, janus kinase 2, signal transducer and activator of transcription 3 were downregulated in the liver samples. Adv‑Angptl4 injection was observed to improve glucose tolerance and insulin resistance. The genes measured were identified to be upregulated close to normal levels. All the results suggested that Angptl4 served an important role in lipid and glucose metabolism in HFD‑induced obese mice, and this may have a great significance for treatment of hyperlipidemia, diabetes, metabolic syndrome and other diseases

  7. Effects of three day bed-rest on circulatory, metabolic and hormonal responses to oral glucose load in endurance trained athletes and untrained subjects

    NASA Technical Reports Server (NTRS)

    Smorawinski, J.; Kubala, P.; Kaciuba-Uociako, H.; Nazar, K.; Titow-Stupnicka, E.; Greenleaf, J. E.

    1996-01-01

    Endurance trained long distance runners and untrained individuals underwent three days of bed rest and oral glucose loading. Before and after bed rest, individuals were given glucose tolerance tests, and their heart rates, blood pressure, blood glucose levels, insulin levels, and catecholamine interactions were measured. Results indicated that glucose tolerance is more affected by bed rest-induced deconditioning in untrained individuals than in trained individuals.

  8. Tumor necrosis factor receptor-1 is essential for LPS-induced sensitization and tolerance to oxygen-glucose deprivation in murine neonatal organotypic hippocampal slices.

    PubMed

    Markus, Tina; Cronberg, Tobias; Cilio, Corrado; Pronk, Cornelis; Wieloch, Tadeusz; Ley, David

    2009-01-01

    Inflammation and ischemia have a synergistic damaging effect in the immature brain. The role of tumor necrosis factor (TNF) receptors 1 and 2 in lipopolysaccharide (LPS)-induced sensitization and tolerance to oxygen-glucose deprivation (OGD) was evaluated in neonatal murine hippocampal organotypic slices. Hippocampal slices from balb/c, C57BL/6 TNFR1(-/-), TNFR2(-/-), and wild-type (WT) mice obtained at P6 were grown in vitro for 9 days. Preexposure to LPS immediately before OGD increased propidium iodide-determined cell death in regions CA1, CA3, and dentate gyrus from 4 up to 48 h after OGD (P<0.001). Extending the time interval between LPS exposure and OGD to 72 h resulted in tolerance, that is reduced neuronal cell death after OGD (P<0.05). Slices from TNFR1(-/-) mice showed neither LPS-induced sensitization nor LPS-induced tolerance to OGD, whereas both effects were present in slices from TNFR2(-/-) and WT mice. Cytokine secretion (TNFalpha and interleukin-6) during LPS exposure was decreased in TNFR1(-/-) slices and increased in TNFR2(-/-) as compared with WT slices. We conclude that LPS induces sensitization or tolerance to OGD depending on the time interval between exposure to LPS and OGD in murine hippocampal slice cultures. Both paradigms are dependent on signaling through TNFR1.

  9. Children's and Adolescents' Tolerance for Divergent Beliefs: Exploring the Cognitive and Affective Dimensions of Moral Conviction in Our Youth

    ERIC Educational Resources Information Center

    Wright, Jennifer C.

    2012-01-01

    Moral conviction predicts interpersonal tolerance in adults, but its role in children and adolescents is not as well understood. This study measured moral conviction for a variety of issues along two separate dimensions--cognitive and affective--in children and adolescents (4th-12th grade). Results showed that, like adults, when children and…

  10. Defective copper transport in the copt5 mutant affects cadmium tolerance.

    PubMed

    Carrió-Seguí, Angela; Garcia-Molina, Antoni; Sanz, Amparo; Peñarrubia, Lola

    2015-03-01

    Cadmium toxicity interferes with essential metal homeostasis, which is a problem for both plant nutrition and the consumption of healthy food by humans. Copper uptake is performed by the members of the Arabidopsis high affinity copper transporter (COPT) family. One of the members, COPT5, is involved in copper recycling from the vacuole toward the cytosolic compartment. We show herein that copt5 mutants are more sensitive to cadmium stress than wild-type plants, as indicated by reduced growth. Exacerbated cadmium toxicity in copt5 mutants is due specifically to altered copper traffic through the COPT5 transporter. Three different processes which have been shown to affect cadmium tolerance are altered in copt5 mutants. First, ethylene biosynthesis diminishes under copper deficiency and, in the presence of cadmium, ethylene production diminishes further. Copper deficiency responses are also attenuated under cadmium treatment. Remarkably, while copt5 roots present higher oxidative stress toxicity symptoms than controls, aerial copt5 parts display lower oxidative stress, as seen by reduced cadmium delivery to shoots. Taken together, these results demonstrate that copper transport plays a key role in cadmium resistance, and suggest that oxidative stress triggers an NADPH oxidase-mediated signaling pathway, which contributes to cadmium translocation and basal plant resistance. The slightly lower cadmium levels that reach aerial parts in the copt5 mutants, irrespective of the copper content in the media, suggest a new biotechnological approach to minimize toxic cadmium entry into food chains.

  11. Comparison of single and combination diuretics on glucose tolerance (PATHWAY-3): protocol for a randomised double-blind trial in patients with essential hypertension

    PubMed Central

    Brown, Morris J; Williams, Bryan; MacDonald, Thomas M; Caulfield, Mark; Cruickshank, J Kennedy; McInnes, Gordon; Sever, Peter; Webb, David J; Salsbury, Jackie; Morant, Steve; Ford, Ian

    2015-01-01

    Introduction Thiazide diuretics are associated with increased risk of diabetes mellitus. This risk may arise from K+-depletion. We hypothesised that a K+-sparing diuretic will improve glucose tolerance, and that combination of low-dose thiazide with K+-sparing diuretic will improve both blood pressure reduction and glucose tolerance, compared to a high-dose thiazide. Methods and analysis This is a parallel-group, randomised, double-blind, multicentre trial, comparing hydrochlorothiazide 25–50 mg, amiloride 10–20 mg and combination of both diuretics at half these doses. A single-blind placebo run-in of 1 month is followed by 24 weeks of blinded active treatment. There is forced dose-doubling after 3 months. The Primary end point is the blood glucose 2 h after oral ingestion of a 75 g glucose drink (OGTT), following overnight fasting. The primary outcome is the difference between 2 h glucose at weeks 0, 12 and 24. Secondary outcomes include the changes in home systolic blood pressure (BP) and glycated haemoglobin and prediction of response by baseline plasma renin. Eligibility criteria are: age 18–79, systolic BP on permitted background treatment ≥140 mm Hg and home BP ≥130 mm Hg and one component of the metabolic syndrome additional to hypertension. Principal exclusions are diabetes, estimated-glomerular filtration rate <45 mL/min, abnormal plasma K+, clinic SBP >200 mm Hg or DBP >120 mm Hg (box 2). The sample size calculation indicates that 486 patients will give 80% power at α=0.01 to detect a difference in means of 1 mmol/L (SD=2.2) between 2 h glucose on hydrochlorothiazide and comparators. Ethics and dissemination PATHWAY-3 was approved by Cambridge South Ethics Committee, number 09/H035/19. The trial results will be published in a peer-reviewed scientific journal. Trial registration numbers Eudract number 2009-010068-41 and clinical trials registration number: NCT02351973. PMID:26253567

  12. A System Gone Berserk: How Are Zero-Tolerance Policies Really Affecting Schools?

    ERIC Educational Resources Information Center

    Martinez, Stephanie

    2009-01-01

    School administrators continue to use zero-tolerance policies as a one-size-fits-all, quick-fix solution to curbing discipline problems with students. Originally intended to address serious offenses such as possession of firearms, zero-tolerance policies are also now meant to address fighting and disrespect. Despite the seeming popularity of…

  13. MAPK14/p38α-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation

    PubMed Central

    Desideri, Enrico; Vegliante, Rolando; Cardaci, Simone; Nepravishta, Ridvan; Paci, Maurizio; Ciriolo, Maria Rosa

    2014-01-01

    Increased glycolytic flux is a common feature of many cancer cells, which have adapted their metabolism to maximize glucose incorporation and catabolism to generate ATP and substrates for biosynthetic reactions. Indeed, glycolysis allows a rapid production of ATP and provides metabolic intermediates required for cancer cells growth. Moreover, it makes cancer cells less sensitive to fluctuations of oxygen tension, a condition usually occurring in a newly established tumor environment. Here, we provide evidence for a dual role of MAPK14 in driving a rearrangement of glucose metabolism that contributes to limiting reactive oxygen species (ROS) production and autophagy activation in condition of nutrient deprivation. We demonstrate that MAPK14 is phosphoactivated during nutrient deprivation and affects glucose metabolism at 2 different levels: on the one hand, it increases SLC2A3 mRNA and protein levels, resulting in a higher incorporation of glucose within the cell. This event involves the MAPK14-mediated enhancement of HIF1A protein stability. On the other hand, MAPK14 mediates a metabolic shift from glycolysis to the pentose phosphate pathway (PPP) through the modulation of PFKFB3 (6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase 3) degradation by the proteasome. This event requires the presence of 2 distinct degradation sequences, KEN box and DSG motif Ser273, which are recognized by 2 different E3 ligase complexes. The mutation of either motif increases PFKFB3 resistance to starvation-induced degradation. The MAPK14-driven metabolic reprogramming sustains the production of NADPH, an important cofactor for many reduction reactions and for the maintenance of the proper intracellular redox environment, resulting in reduced levels of ROS. The final effect is a reduced activation of autophagy and an increased resistance to nutrient deprivation. PMID:25046111

  14. Association between maternal diet factors and hemoglobin levels, glucose tolerance, blood pressure and gestational age in a Hispanic population.

    PubMed

    Soto, Roxana; Guilloty, Natacha; Anzalota, Liza; Rosario, Zaira; Cordero, José F; Palacios, Cristina

    2015-06-01

    The aim of this study was to describe the dietary patterns of pregnant women in northern Puerto Rico and explore associations between diet factors with pregnancy related measurements. This analysis is based on the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT), a prospective cohort that is studying environmental risk factors for preterm births in PR. Participants completed a food frequency questionnaire (FFQ) around 20-28 weeks of gestation. The following pregnancy related measures were collected from the medical records: hemoglobin, blood glucose, blood pressure and gestational age. Potential associations between diet factors and pregnancy measures were assessed using chi square analysis with SPSS. A total of 180 participants completed the FFQ; low hemoglobin levels was found in 19.2%, high blood glucose levels was found in 21.1% by fasting blood glucose test and 24.6%by 1-hour 50 g oral glucose screening test, high blood pressure was found in 2.9% (systolic) and 6.5% (diastolic), and pre-term birth was found in 10.4% of the participants. High consumption of rice, desserts and sweets was associated with higher levels of fasting blood glucose levels (p < 0.05), while high consumption of vegetables was associated with higher 1-hour glucose challenge test (p < 0.05).No other significant associations were found. In conclusion, consumption of high dense energy food diets in pregnancy, such as rice, sweets and desserts, can lead to high levels of blood glucose and can be a potential predictor of other pregnancy complications during pregnancy in these study participants, such as gestational diabetes. PMID:26817380

  15. Fasting, post-OGTT challenge, and nocturnal free fatty acids in prediabetic versus normal glucose tolerant overweight and obese Latino adolescents.

    PubMed

    Toledo-Corral, Claudia M; Alderete, Tanya L; Richey, Joyce; Sequeira, Paola; Goran, Michael I; Weigensberg, Marc J

    2015-04-01

    Type 2 diabetes risk and its relationship to free fatty acid (FFA) exposure and visceral fat by prediabetes status in minority adolescents have yet to be explored. Therefore, the objective of this study was to examine the association of circulating FFA under varying conditions with prediabetes in Latino adolescents and to determine the relative relationships of FFA and visceral adiposity to insulin sensitivity, secretion, and β-cell function. Overweight or obese, but otherwise healthy Latino adolescent males and females (n = 164, 14.2 ± 2.5 years), were recruited for assessment of prediabetes, abdominal fat, and FFA levels taken at a fasting state (FFAF), during an OGTT (FFAOGTT), and overnight (FFANOCTURNAL). Prediabetic adolescents had a higher FFAF than those with normal glucose tolerance when controlling for age, sex, pubertal status, total percent body fat, and visceral fat. FFAOGTT and FFANOCTURNAL did not differ between participants with prediabetes and those with normal glucose tolerance after adjusting for covariates. Visceral fat was independently related to insulin sensitivity and secretion in pubertal adolescents; however, in post-pubertal adolescents, FFAF and visceral fat were both independent and negatively related to β-cell function. These results support a plausible progression of the lipotoxicity theory of diabetes development during the pubertal transition. PMID:25109287

  16. Gene cloning and characterization of a novel salt-tolerant and glucose-enhanced β-glucosidase from a marine streptomycete.

    PubMed

    Mai, Zhimao; Yang, Jian; Tian, Xinpeng; Li, Jie; Zhang, Si

    2013-03-01

    The gene BglNH encoding a β-glucosidase was cloned from a marine streptomycete. Sequence analysis revealed that BglNH encoded a 456-aa peptide with a calculated mass of 51 kDa. The deduced amino acid sequence of BglNH showed the highest identities of 61 % with known β-glucosidases and contained a catalytic domain which belonged to the glycoside hydrolase family 1. The gene BglNH was expressed in Escherichia coli and the recombinant enzyme (r-BglNH) was purified. The optimum pH and temperature of r-BglNH were pH6.0 and 45 °C, respectively. The r-BglNH displayed the typical salt-tolerant and glucose-enhanced characteristics. Its activity was remarkably enhanced in the presence of 0.5 M NaCl (rose more than 1.6-fold) and 0.1 M glucose (rose more than 1.4-fold). Moreover, r-BglNH displayed good pH stability and metal tolerance. It remained stable after incubating with buffers from pH4.0 to 10.0, and most metal ions had no significant inhibition on its activity. These properties indicate that r-BglNH is an ideal candidate for further research and industrial applications.

  17. Low glycaemic index diets improve glucose tolerance and body weight in women with previous history of gestational diabetes: a six months randomized trial

    PubMed Central

    2013-01-01

    Background Gestational Diabetes Mellitus (GDM) increases risks for type 2 diabetes and weight management is recommended to reduce the risk. Conventional dietary recommendations (energy-restricted, low fat) have limited success in women with previous GDM. The effect of lowering Glycaemic Index (GI) in managing glycaemic variables and body weight in women post-GDM is unknown. Objective To evaluate the effects of conventional dietary recommendations administered with and without additional low-GI education, in the management of glucose tolerance and body weight in Asian women with previous GDM. Method Seventy seven Asian, non-diabetic women with previous GDM, between 20- 40y were randomised into Conventional healthy dietary recommendation (CHDR) and low GI (LGI) groups. CHDR received conventional dietary recommendations only (energy restricted, low in fat and refined sugars, high-fibre). LGI group received advice on lowering GI in addition. Fasting and 2-h post-load blood glucose after 75 g oral glucose tolerance test (2HPP) were measured at baseline and 6 months after intervention. Anthropometry and dietary intake were assessed at baseline, three and six months after intervention. The study is registered at the Malaysian National Medical Research Register (NMRR) with Research ID: 5183. Results After 6 months, significant reductions in body weight, BMI and waist-to-hip ratio were observed only in LGI group (P<0.05). Mean BMI changes were significantly different between groups (LGI vs. CHDR: -0.6 vs. 0 kg/m2, P= 0.03). More subjects achieved weight loss ≥5% in LGI compared to CHDR group (33% vs. 8%, P=0.01). Changes in 2HPP were significantly different between groups (LGI vs. CHDR: median (IQR): -0.2(2.8) vs. +0.8 (2.0) mmol/L, P=0.025). Subjects with baseline fasting insulin≥2 μIU/ml had greater 2HPP reductions in LGI group compared to those in the CHDR group (−1.9±0.42 vs. +1.31±1.4 mmol/L, P<0.001). After 6 months, LGI group diets showed significantly lower

  18. Metagenomic approach for the isolation of a thermostable β-galactosidase with high tolerance of galactose and glucose from soil samples of Turpan Basin

    PubMed Central

    2013-01-01

    Background β-Galactosidases can be used to produce low-lactose milk and dairy products for lactose intolerant people. Although commercial β-galactosidases have outstanding lactose hydrolysis ability, their thermostability is low, and reaction products have strong inhibition to these enzymes. In addition, the β-galactosidases possessing simultaneously high thermostability and tolerance of galactose and glucose are still seldom reported until now. Therefore, identification of novel β-galactosidases with high thermostability and tolerance to reaction products from unculturable microorganisms accounting for over 99% of microorganisms in the environment via metagenomic strategy is still urgently in demand. Results In the present study, a novel β-galactosidase (Gal308) consisting of 658 amino acids was identified from a metagenomic library from soil samples of Turpan Basin in China by functional screening. After being overexpressed in Escherichia coli and purified to homogeneity, the enzymatic properties of Gal308 with N-terminal fusion tag were investigated. The recombinant enzyme displayed a pH optimum of 6.8 and a temperature optimum of 78°C, and was considerably stable in the temperature range of 40°C - 70°C with almost unchangeable activity after incubation for 60 min. Furthermore, Gal308 displayed a very high tolerance of galactose and glucose, with the highest inhibition constant Ki,gal (238 mM) and Ki,glu (1725 mM) among β-galactosidases. In addition, Gal308 also exhibited high enzymatic activity for its synthetic substrate o-nitrophenyl-β-D-galactopyranoside (ONPG, 185 U/mg) and natural substrate lactose (47.6 U/mg). Conclusion This study will enrich the source of β-galactosidases, and attract some attentions to β-galactosidases from extreme habitats and metagenomic library. Furthermore, the recombinant Gal308 fused with 156 amino acids exhibits many novel properties including high activity and thermostability at high temperatures, the pH optimum

  19. Expression of a dominant-negative Ras mutant does not affect stimulation of glucose uptake and glycogen synthesis by insulin.

    PubMed

    Dorrestijn, J; Ouwens, D M; Van den Berghe, N; Bos, J L; Maassen, J A

    1996-05-01

    It has previously been shown that insulin-induced stimulation of glucose uptake and glycogen synthesis requires activation of phosphatidylinositol-3-kinase (PI3kinase). Insulin also induces formation of RasGTP in cells and various studies have yielded inconsistent data with respect to the contribution of signalling pathways activated by RasGTP, to insulin-stimulated glucose uptake and glycogen synthesis. We have examined the requirement of RasGTP-mediated signalling for these insulin responses by expression of a dominant negative mutant of Ras (RasN17) in cells by vaccinia virus mediated gene transfer. This Ras-mutant abrogates the signalling pathways mediated by endogenous RasGTP. Subsequently, the ability of insulin to stimulate 2-deoxyglucose uptake and glycogen was examined. We observed that expression of RasN17 in 3T3L1 adipocytes did not affect the stimulation of hexose uptake by insulin. Similarly, expression of RasN17 in A14 cells, an NIH 3T3-derived cell line with high expression of insulin receptors, did not affect insulin-induced stimulation of glycogen synthesis. In both cell lines, insulin-induced phosphorylation of Mapkinase (Erk1,2) was abrogated after expression of RasN17, demonstrating the functional interference by RasN17 with signalling mediated by endogenous RasGTP. Wortmannin, an inhibitor of PI3kinase, abolished dose-dependently the insulin-induced stimulation of hexose uptake and glycogen synthesis without an effect on RasGTP levels in both cell types. We conclude that stimulation of glucose transport and glycogen synthesis by insulin occurs independently of RasGTP-mediated signalling.

  20. Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

    PubMed

    Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

    2016-06-01

    The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP. PMID:27160199

  1. Modest Salt Reduction Lowers Blood Pressure and Albumin Excretion in Impaired Glucose Tolerance and Type 2 Diabetes Mellitus: A Randomized Double-Blind Trial.

    PubMed

    Suckling, Rebecca J; He, Feng J; Markandu, Nirmala D; MacGregor, Graham A

    2016-06-01

    The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial, with a lack of well controlled, longer term, modest salt reduction trials in this group of patients, in spite of the marked increase in cardiovascular risk. We carried out a 12-week randomized double-blind, crossover trial of salt restriction with salt or placebo tablets, each for 6 weeks, in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure (BP). From salt to placebo, 24-hour urinary sodium was reduced by 49±9 mmol (2.9 g salt). This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg, (systolic BP; P<0.01). Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg (systolic BP, P<0.01 and diastolic BP, P<0.05), and albumin/creatinine ratio was reduced from 0.73 mg/mmol (0.5-1.5) to 0.64 mg/mmol (0.3-1.1; P<0.05). There was no significant change in fasting glucose, hemoglobin A1c, or insulin sensitivity. These results demonstrate that a modest reduction in salt intake, to approximately the amount recommended in public health guidelines, leads to significant and clinically relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP. The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP.

  2. Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model.

    PubMed

    Saito, Mikako; Kaneda, Asako; Sugiyama, Tae; Iida, Ryousuke; Otokuni, Keiko; Kaburagi, Misako; Matsuoka, Hideaki

    2015-01-01

    Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk(+/-)) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk(+/-) mice ranged from 0.41-0.68 versus that in wild (Gk(+/+)) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95-1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk(+/-) strain fed the CD, and Gk(+/-) strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk(+/-) strain developed in this study. PMID:25765873

  3. The Effect of Metformin and Metformin-Testosterone Combination on Cardiometabolic Risk Factors in Men with Late-onset Hypogonadism and Impaired Glucose Tolerance.

    PubMed

    Krysiak, R; Gilowski, W; Okopien, B

    2015-11-01

    No previous study has investigated the effect of metformin, administered alone or together with testosterone, on cardiometabolic risk factors in men with hypogonadism. The study included 30 men with late-onset hypogonadism (LOH) and impaired glucose tolerance (IGT) who had been complying with lifestyle intervention. After 12 weeks of metformin treatment (1.7 g daily), the participants were allocated to one of 2 groups treated for the following 12 weeks with oral testosterone undecanoate (120 mg daily, n=15) or not receiving androgen therapy (n=15). Plasma lipids, glucose homeostasis markers, as well as plasma levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), homocysteine and fibrinogen were determined before and after 12 and 24 weeks of therapy with the final dose of metformin. Patients with LOH and IGT had higher levels of hsCRP, homocysteine and fibrinogen than subjects with only LOH (n=12) or only IGT (n=15). Metformin administered alone improved insulin sensitivity, as well as reduced 2-h postchallenge plasma glucose and triglycerides. Testosterone-metformin combination therapy decreased also total and LDL cholesterol, uric acid, hsCRP, homocysteine and fibrinogen, as well as increased plasma testosterone. The effect of this combination therapy on testosterone, insulin sensitivity, hsCRP, homocysteine and fibrinogen was stronger than that of metformin alone. The obtained results indicate that IGT men with LOH receiving metformin may gain extra benefits if they are concomitantly treated with oral testosterone. PMID:26600057

  4. Production of a mouse strain with impaired glucose tolerance by systemic heterozygous knockout of the glucokinase gene and its feasibility as a prediabetes model

    PubMed Central

    SAITO, Mikako; KANEDA, Asako; SUGIYAMA, Tae; IIDA, Ryousuke; OTOKUNI, Keiko; KABURAGI, Misako; MATSUOKA, Hideaki

    2015-01-01

    Exon II of glucokinase (Gk) was deleted to produce a systemic heterozygous Gk knockout (Gk+/−) mouse. The relative expression levels of Gk in the heart, lung, liver, stomach, and pancreas in Gk+/− mice ranged from 0.41–0.68 versus that in wild (Gk+/+) mice. On the other hand, its expression levels in the brain, adipose tissue, and muscle ranged from 0.95–1.03, and its expression levels in the spleen and kidney were nearly zero. Gk knockout caused no remarkable off-target effect on the expression of 7 diabetes causing genes (Shp, Hnf1a, Hnf1b, Irs1, Irs2, Kir6.2, and Pdx1) in 10 organs. The glucose tolerance test was conducted to determine the blood glucose concentrations just after fasting for 24 h (FBG) and at 2 h after high-glucose application (GTT2h). The FBG-GTT2h plots obtained with the wild strain fed the control diet (CD), Gk+/− strain fed the CD, and Gk+/− strain fed the HFD were distributed in separate areas in the FBG-GTT2h diagram. The respective areas could be defined as the normal state, prediabetes state, and diabetes state, respectively. Based on the results, the criteria for prediabetes could be defined for the Gk+/− strain developed in this study. PMID:25765873

  5. Weaning marginally affects glucose transporter (GLUT4) expression in calf muscles and adipose tissues.

    PubMed

    Hocquette, J F; Castiglia-Delavaud, C; Graulet, B; Ferré, P; Picard, B; Vermorel, M

    1997-08-01

    The nutritional regulation of glucose transporter GLUT4 was studied in eight muscles and four adipose tissues from two groups of preruminant (PR) or ruminant (R) calves of similar age (170 d), empty body weight (194 kg) at slaughter, and level of net energy intake from birth onwards. Isocitrate dehydrogenase (EC 1.1.1.41) activity in muscles was not different between PR and R except in masseter muscle from the cheek (+71% in R; P < 0.003), which becomes almost constantly active at weaning for food chewing. Basal and maximally-insulin-stimulated glucose transport rate (GTR) per g tissue wet weight in rectus abdominis muscle were significantly higher in R calves (+31 and 41% respectively; P < 0.05). GLUT4 protein contents did not differ in muscles from PR and R except in masseter (+74% in R; P < 0.05) indicating that the increased GTR in rectus abdominis cannot be accounted for by an enhanced GLUT4 expression. GLUT4 mRNA levels did not differ between the two groups of animals in all muscles suggesting a regulation of GLUT4 at the protein level in masseter. GLUT4 number expressed on a per cell basis was lower in adipose tissue from R calves (-39%; P < 0.05) and higher in internal than in peripheral adipose tissues. In summary, the regulation of GLUT4 in calves at weaning differs markedly from that previously described in rodents (for review, see Girard et al. 1992). Furthermore, significant inter-individual variations were shown for metabolic activities in muscle and for biochemical variables in adipose tissue.

  6. Simulated and experimental evaluation of factors affecting the rate and extent of reductive dehalogenation of chloroethenes with glucose

    NASA Astrophysics Data System (ADS)

    Lee, Il-Su; Bae, Jae-Ho; Yang, Yanru; McCarty, Perry L.

    2004-10-01

    Carbohydrates such as molasses are being added to aquifers to serve as electron donors for reductive dehalogenation of chloroethenes. Glucose, as a model carbohydrate, was studied to better understand the processes involved and to evaluate the effectiveness for dehalogenation of different approaches for carbohydrate addition. A simulation model was developed and calibrated with experimental data for the reductive dehalogenation of tetrachloroethene to ethene via cis-1,2-dichloroethene. The model included fermentors that convert the primary donor (glucose) into butyrate, acetate and hydrogen, methanogens, and two separate dehalogenator groups. The dehalogenation groups use the hydrogen intermediate as an electron donor and the different haloethenes as electron acceptors through competitive inhibition. Model simulations suggest first that the initial relative population size of dehalogenators and H2-utilizing methanogens greatly affects the degree of dehalogenation achieved. Second, the growth and decay of biomass from soluble carbohydrate plays a significant role in reductive dehalogenation. Finally, the carbohydrate delivery strategies used (periodic versus batch addition and the time interval between periodic addition) greatly affect the degree of dehalogenation that can be obtained with a given amount of added carbohydrate.

  7. A locus in Drosophila sechellia affecting tolerance of a host plant toxin.

    PubMed

    Hungate, Eric A; Earley, Eric J; Boussy, Ian A; Turissini, David A; Ting, Chau-Ti; Moran, Jennifer R; Wu, Mao-Lien; Wu, Chung-I; Jones, Corbin D

    2013-11-01

    Many insects feed on only one or a few types of host. These host specialists often evolve a preference for chemical cues emanating from their host and develop mechanisms for circumventing their host's defenses. Adaptations like these are central to evolutionary biology, yet our understanding of their genetics remains incomplete. Drosophila sechellia, an emerging model for the genetics of host specialization, is an island endemic that has adapted to chemical toxins present in the fruit of its host plant, Morinda citrifolia. Its sibling species, D. simulans, and many other Drosophila species do not tolerate these toxins and avoid the fruit. Earlier work found a region with a strong effect on tolerance to the major toxin, octanoic acid, on chromosome arm 3R. Using a novel assay, we narrowed this region to a small span near the centromere containing 18 genes, including three odorant binding proteins. It has been hypothesized that the evolution of host specialization is facilitated by genetic linkage between alleles contributing to host preference and alleles contributing to host usage, such as tolerance to secondary compounds. We tested this hypothesis by measuring the effect of this tolerance locus on host preference behavior. Our data were inconsistent with the linkage hypothesis, as flies bearing this tolerance region showed no increase in preference for media containing M. citrifolia toxins, which D. sechellia prefers. Thus, in contrast to some models for host preference, preference and tolerance are not tightly linked at this locus nor is increased tolerance per se sufficient to change preference. Our data are consistent with the previously proposed model that the evolution of D. sechellia as a M. citrifolia specialist occurred through a stepwise loss of aversion and gain of tolerance to M. citrifolia's toxins.

  8. Rosuvastatin Treatment Affects Both Basal and Glucose-Induced Insulin Secretion in INS-1 832/13 Cells

    PubMed Central

    Salunkhe, Vishal A.; Elvstam, Olof; Eliasson, Lena; Wendt, Anna

    2016-01-01

    Rosuvastatin is a member of the statin family. Like the other statins it is prescribed to lower cholesterol levels and thereby reduce the risk of cardiovascular events. Rosuvastatin lowers the cholesterol levels by inhibiting the key enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the cholesterol producing mevalonate pathway. It has been recognized that apart from their beneficial lipid lowering effects, statins also exhibit diabetogenic properties. The molecular mechanisms behind these remain unresolved. To investigate the effects of rosuvastatin on insulin secretion, we treated INS-1 832/13 cells with varying doses (20 nM to 20 μM) of rosuvastatin for 48 h. At concentrations of 2 μM and above basal insulin secretion was significantly increased. Using diazoxide we could determine that rosuvastatin did not increase basal insulin secretion by corrupting the KATP channels. Glucose-induced insulin secretion on the other hand seemed to be affected differently at different rosuvastatin concentrations. Rosuvastatin treatment (20 μM) for 24–48 h inhibited voltage-gated Ca2+ channels, which lead to reduced depolarization-induced exocytosis of insulin-containing granules. At lower concentrations of rosuvastatin (≤ 2 μM) the stimulus-secretion coupling pathway was intact downstream of the KATP channels as assessed by the patch clamp technique. However, a reduction in glucose-induced insulin secretion could be observed with rosuvastatin concentrations as low as 200 nM. The inhibitory effects of rosuvastatin on glucose-induced insulin secretion could be reversed with mevalonate, but not squalene, indicating that rosuvastatin affects insulin secretion through its effects on the mevalonate pathway, but not through the reduction of cholesterol biosynthesis. Taken together, these data suggest that rosuvastatin has the potential to increase basal insulin secretion and reduce glucose-induced insulin secretion. The latter is possibly an unavoidable

  9. Rosuvastatin Treatment Affects Both Basal and Glucose-Induced Insulin Secretion in INS-1 832/13 Cells.

    PubMed

    Salunkhe, Vishal A; Elvstam, Olof; Eliasson, Lena; Wendt, Anna

    2016-01-01

    Rosuvastatin is a member of the statin family. Like the other statins it is prescribed to lower cholesterol levels and thereby reduce the risk of cardiovascular events. Rosuvastatin lowers the cholesterol levels by inhibiting the key enzyme 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMG-CoA reductase) in the cholesterol producing mevalonate pathway. It has been recognized that apart from their beneficial lipid lowering effects, statins also exhibit diabetogenic properties. The molecular mechanisms behind these remain unresolved. To investigate the effects of rosuvastatin on insulin secretion, we treated INS-1 832/13 cells with varying doses (20 nM to 20 μM) of rosuvastatin for 48 h. At concentrations of 2 μM and above basal insulin secretion was significantly increased. Using diazoxide we could determine that rosuvastatin did not increase basal insulin secretion by corrupting the KATP channels. Glucose-induced insulin secretion on the other hand seemed to be affected differently at different rosuvastatin concentrations. Rosuvastatin treatment (20 μM) for 24-48 h inhibited voltage-gated Ca(2+) channels, which lead to reduced depolarization-induced exocytosis of insulin-containing granules. At lower concentrations of rosuvastatin (≤ 2 μM) the stimulus-secretion coupling pathway was intact downstream of the KATP channels as assessed by the patch clamp technique. However, a reduction in glucose-induced insulin secretion could be observed with rosuvastatin concentrations as low as 200 nM. The inhibitory effects of rosuvastatin on glucose-induced insulin secretion could be reversed with mevalonate, but not squalene, indicating that rosuvastatin affects insulin secretion through its effects on the mevalonate pathway, but not through the reduction of cholesterol biosynthesis. Taken together, these data suggest that rosuvastatin has the potential to increase basal insulin secretion and reduce glucose-induced insulin secretion. The latter is possibly an unavoidable

  10. Early life stress affects cerebral glucose metabolism in adult rhesus monkeys (Macaca mulatta).

    PubMed

    Parr, Lisa A; Boudreau, Matthew; Hecht, Erin; Winslow, James T; Nemeroff, Charles B; Sánchez, Mar M

    2012-01-01

    Early life stress (ELS) is a risk factor for anxiety, mood disorders and alterations in stress responses. Less is known about the long-term neurobiological impact of ELS. We used [(18)F]-fluorodeoxyglucose Positron Emission Tomography (FDG-PET) to assess neural responses to a moderate stress test in adult monkeys that experienced ELS as infants. Both groups of monkeys showed hypothalamic-pituitary-adrenal (HPA) axis stress-induced activations and cardiac arousal in response to the stressor. A whole brain analysis detected significantly greater regional cerebral glucose metabolism (rCGM) in superior temporal sulcus, putamen, thalamus, and inferotemporal cortex of ELS animals compared to controls. Region of interest (ROI) analyses performed in areas identified as vulnerable to ELS showed greater activity in the orbitofrontal cortex of ELS compared to control monkeys, but greater hippocampal activity in the control compared to ELS monkeys. Together, these results suggest hyperactivity in emotional and sensory processing regions of adult monkeys with ELS, and greater activity in stress-regulatory areas in the controls. Despite these neural responses, no group differences were detected in neuroendocrine, autonomic or behavioral responses, except for a trend towards increased stillness in the ELS monkeys. Together, these data suggest hypervigilance in the ELS monkeys in the absence of immediate danger. PMID:22682736

  11. Response expectancies affect the acquisition and display of behavioral tolerance to alcohol.

    PubMed

    Sdao-Jarvie, K; Vogel-Sprott, M

    1991-01-01

    Two experiments demonstrated that a learned expectation of a favourable consequence for drug-compensatory performance enhanced behavioral tolerance to alcohol, and when the expectancy was trained, the subsequent display of tolerance depended upon its consequence. Both experiments involved each of four groups of six male social drinkers each, who drank 0.62 g/kg alcohol on four sessions, and a placebo on a fifth session. Experiment 1 provided two groups with the opportunity to learn the response expectancy by performing a motor task under alcohol with either an informative consequence (IO) or information plus money contingent upon drug-compensatory performance (MI). Two control groups performed with either no outcome (N), or with money for compensatory performance but no information about earnings until the experiment concluded (MO). The effects of learning history were evident on sessions 4 and 5 when the same consequence was contingent upon the performance of all groups. Compared to controls, the groups that had received response expectancy training (MI and IO) displayed significantly more alcohol tolerance and greater compensatory facilitation of performance under placebo. In Experiment 2, all groups received the same response expectancy training, and the effect of the consequence of compensatory performance was demonstrated during subsequent test sessions 4 and 5. An informative consequence (MI or IO) enhanced tolerance and the compensatory response to placebo, whereas performance with no response contingent information (N or MO), revealed little tolerance or compensatory response to placebo. Theoretical and practical implications of the findings were discussed. PMID:1781926

  12. Salt tolerance and stress level affect plant biomass-density relationships and neighbor effects

    NASA Astrophysics Data System (ADS)

    Yu, Zhenxing; Chen, Wenwen; Zhang, Qian; Yang, Haishui; Tang, Jianjun; Weiner, Jacob; Chen, Xin

    2014-07-01

    It has been shown that plant biomass-density relationships are altered under extreme or stressed conditions. We do not know whether variation in biomass-density relationships is a direct result of stress tolerance or occurs via changes in plant-plant interactions. Here, we evaluated biomass-density relationships and neighbor effects in six plant species that differ in salt tolerance in a salt marsh, and conducted a literature review of biomass-density relationship under higher and lower stress levels. Our field study showed that both neighbor effects and the exponent of the biomass-density relationship (α) varied among plant species with different degrees of salt tolerance. There was a positive relationship between neighbor effects (measured as relative interaction index) and α-value among the tested species. The literature review showed that α and its variation increased under higher stress. Our results indicate that plant species with different salinity tolerance differ in the direction and strength of neighbor effects, resulting in variation in biomass-density relationships. Our results support the hypothesis that differences in biomass-density relationships among species are not due to differences in stress tolerance alone, they are mediated by changes in plant-plant interactions.

  13. A sucrose transporter-interacting protein disulphide isomerase affects redox homeostasis and links sucrose partitioning with abiotic stress tolerance.

    PubMed

    Eggert, Erik; Obata, Toshihiro; Gerstenberger, Anne; Gier, Konstanze; Brandt, Tobias; Fernie, Alisdair R; Schulze, Waltraud; Kühn, Christina

    2016-06-01

    Sucrose accumulation in leaves in response to various abiotic stresses suggests a specific role of this disaccharide for stress tolerance and adaptation. The high-affinity transporter StSUT1 undergoes substrate-induced endocytosis presenting the question as to whether altered sucrose accumulation in leaves in response to stresses is also related to enhanced endocytosis or altered activity of the sucrose transporter. StSUT1 is known to interact with several stress-inducible proteins; here we investigated whether one of the interacting candidates, StPDI1, affects its subcellular localization in response to stress: StPDI1 expression is induced by ER-stress and salt. Both proteins, StSUT1 and StPDI1, were found in the detergent resistant membrane (DRM) fraction, and this might affect internalization. Knockdown of StPDI1 expression severely affects abiotic stress tolerance of transgenic potato plants. Analysis of these plants does not reveal modified subcellular localization or endocytosis of StSUT1, but rather a disturbed redox homeostasis, reduced detoxification of reactive oxygen species and effects on primary metabolism. Parallel observations with other StSUT1-interacting proteins are discussed. The redox status in leaves seems to be linked to the sugar status in response to various stress stimuli and to play a role in stress tolerance. PMID:26670204

  14. Genetic manipulation of polyphosphate metabolism affects cadmium tolerance in Escherichia coli

    SciTech Connect

    Keasling, J.D.; Hupf, G.A.

    1996-02-01

    Microorganisms have evolved several active heavy metal tolerance mechanisms: exclusion, excretion, sequestration, and transformation. They also have passive tolerance mechanisms, and it has been suggested that one such mechanism is intracellular chelation by long chain anionic polymers of phosphate called polyphosphate (polyP). To circumvent precipitation of metal phosphate complexes into the medium and limitation of phosphates, this study genetically munibulated the polyP level in Escherichia coli and examined the effect of the resulting polyP level on cell growth during exposure to heavy metals.

  15. Vagotomy Affects the Development of Oral Tolerance and Increases Susceptibility to Develop Colitis Independently of α-7 Nicotinic Receptor

    PubMed Central

    Di Giovangiulio, Martina; Bosmans, Goele; Meroni, Elisa; Stakenborg, Nathalie; Florens, Morgane; Farro, Giovanna; Gomez-Pinilla, Pedro J; Matteoli, Gianluca; Boeckxstaens, Guy E

    2016-01-01

    Vagotomy (VGX) increases the susceptibility to develop colitis suggesting a crucial role for the cholinergic anti-inflammatory pathway in the regulation of the immune responses. Since oral tolerance and the generation of regulatory T cells (Tregs) are crucial to preserve mucosal immune homeostasis, we studied the effect of vagotomy and the involvement of α7 nicotinic receptors (α7nAChR) at the steady state and during colitis. Therefore, the development of both oral tolerance and colitis (induced by dextran sulfate sodium (DSS) or via T cell transfer) was studied in vagotomized mice and in α7nAChR-/- mice. VGX, but not α7nAChR deficiency, prevented oral tolerance establishment. This effect was associated with reduced Treg conversion in the lamina propria and mesenteric lymphnodes. To the same extent, vagotomized mice, but not α7nAChR-/- mice, developed a more severe DSS colitis compared with control mice treated with DSS, associated with a decreased number of colonic Tregs. However, neither VGX nor absence of α7nAChR in recipient mice affected colitis development in the T cell transfer model. In line, deficiency of α7nAChR exclusively in T cells did not influence the development of colitis induced by T cell transfer. Our results indicate a key role for the vagal intestinal innervation in the development of oral tolerance and colitis, most likely by modulating induction of Tregs independently of α7nAChR. PMID:27341335

  16. Effects of sugar-sweetened beverage intake on the development of type 2 diabetes mellitus in subjects with impaired glucose tolerance: the Mihama diabetes prevention study.

    PubMed

    Teshima, Nobuko; Shimo, Miho; Miyazawa, Kae; Konegawa, Sachi; Matsumoto, Aki; Onishi, Yuki; Sasaki, Ryoma; Suzuki, Toshinari; Yano, Yutaka; Matsumoto, Kazutaka; Yamada, Tomomi; Gabazza, Esteban Cesar; Takei, Yoshiyuki; Sumida, Yasuhiro

    2015-01-01

    In Japan, the incidence of type 2 diabetes mellitus (T2DM) is increasing for several reasons, including increased consumption of sugar-sweetened beverages (SSBs). However, whether SSBs cause T2DM by excess of energy production resulting in obesity remains unclear. Therefore, the present study was designed to evaluate the effects of SSB intake on the development of T2DM in subjects with impaired glucose tolerance (IGT). Ninety-three subjects (30 males and 63 females) with IGT aged 40-69 y and residing in the Mihama district (southern Mie Prefecture, Japan) were included in the study. The mean observational period was 3.6 y. All subjects underwent the 75-g oral glucose tolerance test (OGTT) and completed a lifestyle questionnaire survey related to SSB intake. OGTT results and SSB intake were evaluated before and after the observational period. In addition, the correlation between SSB intake and development of T2DM was investigated. Of the 93 subjects, 20 (21.5%) developed T2DM (T2DM group) and demonstrated a significantly high SSB intake compared with the group that did not develop the disease (non-T2DM group). The odds ratio for the incidence of T2DM based on SSB intake was 3.26 (95% confidence interval, 1.17-9.06). The body mass index (BMI; kg/m(2)) and the homeostasis model assessment for insulin resistance (HOMA-R) values was significantly higher in the T2DM group than in the non-T2DM group, while the insulinogenic indices were significantly lower in the former than in the latter group. The sum of insulin secretion levels during OGTT was not significantly different between groups. SSB intake correlated with the predisposition for developing T2DM, possibly by influencing body weight, insulin resistance, and the ability of the pancreatic beta cells to effectively compensate for the insulin resistance. PMID:25994135

  17. Oligosaccharin and ABA synergistically affect the acquisition of freezing tolerance in winter wheat.

    PubMed

    Zabotin, Alexey I; Barisheva, Tatyana S; Trofimova, Oksana I; Toroschina, Tatyana E; Larskaya, Irina A; Zabotina, Olga A

    2009-09-01

    In this paper, we continue our studies of the previously discovered [O.A. Zabotina, D.A. Ayupova, O.N. Larskaya, O.N. Nikolaeva, G.I. Petrovicheva, A.I. Zabotin, Physiologically active oligosaccharides, accumulating in the roots of winter wheat during adaptation to low temperature, Russian Journal of Plant Physiology 45 (1998) 262] oligosaccharin (physiologically active oligosaccharide) GXAG, which stimulates the acquisition of freezing tolerance in winter varieties of Triticum aestivum L. The transient accumulation of GXAG in the tissues of winter wheat correlates with the temporal activation of cell wall glycosidases during the first hours of cold acclimation (2 degrees C). This finding suggests that the oligosaccharin is liberated as a result of the intensification of hemicellulose turnover. At low concentrations, GXAG initiates the acquisition of freezing tolerance in winter plants, in a manner similar to ABA, even at room temperature. The resultant effect of ABA and GXAG on the freezing tolerance of winter wheat depends on the sequence of pre-treatments with these two factors. When seedlings are pre-treated with GXAG a few hours before treatment with ABA, the effect is synergistic, and its impact depends on the duration of pre-treatment with GXAG. When ABA is applied first, the resultant effect on freezing tolerance is additive. The results obtained here lead to the conclusion that oligosaccharin, accumulating during the first hours of cold acclimation, functions as a partner of ABA during the initiation of freezing tolerance acquisition in winter plants. We hypothesize that GXAG increases cell receptivity to ABA signaling. PMID:19467881

  18. Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice.

    PubMed

    Park, Jae-Hyung; Choi, Yoon Jung; Kim, Yong Woon; Kim, Sang Pyo; Cho, Ho-Chan; Ahn, Shinbyoung; Bae, Ki-Cheor; Im, Seung-Soon; Bae, Jae-Hoon; Song, Dae-Kyu

    2013-08-01

    Green tea extract (GTE) is regarded to be effective against obesity and type 2 diabetes, but definitive evidences have not been proven. Based on the assumption that the gallated catechins (GCs) in GTE attenuate intestinal glucose and lipid absorption, while enhancing insulin resistance when GCs are present in the circulation through inhibiting cellular glucose uptake in various tissues, this study attempted to block the intestinal absorption of GCs and prolong their residence time in the lumen. We then observed whether GTE containing the nonabsorbable GCs could ameliorate body weight (BW) gain and glucose intolerance in db/db and high-fat diet mice. Inhibition of the intestinal absorption of GCs was accomplished by co-administering the nontoxic polymer polyethylene glycol-3350 (PEG). C57BLKS/J db/db and high-fat diet C57BL/6 mice were treated for 4 weeks with drugs as follows: GTE, PEG, GTE+PEG, voglibose, or pioglitazone. GTE mixed with meals did not have any ameliorating effects on BW gain and glucose intolerance. However, the administration of GTE plus PEG significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite. The effect was comparable to the effects of an α-glucosidase inhibitor and a peroxisome proliferator-activated receptor-γ/α agonist. These results indicate that prolonging the action of GCs of GTE in the intestinal lumen and blocking their entry into the circulation may allow GTE to be used as a prevention and treatment for both obesity and obesity-induced type 2 diabetes.

  19. High prevalence of diabetes mellitus and impaired glucose tolerance in liver cancer patients: A hospital based study of 4610 patients with benign tumors or specific cancers

    PubMed Central

    Roujun, Chen; Yanhua, Yi; Bixun, Li

    2016-01-01

    Objective: The prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were hypothesised to be different among different tumor patients. This study aimed to study the association between the prevalence of DM, IGT and IFG and liver cancer, colorectal cancer, breast cancer, cervical cancer, nasopharyngeal cancer and benign tumor. Methods:  A hospital based retrospective study was conducted on 4610 patients admitted to the Internal Medical Department of the Affiliated Tumor Hospital of Guangxi Medical University, China. Logistic regression was used to examine the association between gender, age group, ethnicity , cancer types or benign tumors and prevalence of DM, IFG, IGT. Results: Among 4610 patients, there were 1000 liver cancer patients, 373 breast cancer patients, 415 nasopharyngeal cancer patients, 230 cervical cancer patients, 405 colorectal cancer patients, and 2187 benign tumor patients. The prevalence of DM and IGT in liver cancer patients was 14.7% and 22.1%, respectively. The prevalence of DM and IGT was 13.8% and 20%, respectively, in colorectal cancer patients, significantly higher than that of benign cancers. After adjusting for gender, age group, and ethnicity, the prevalence of DM and IGT in liver cancers patients was 1.29 times (CI :1.12-1.66) and 1.49 times (CI :1.20-1.86) higher than that of benign tumors, respectively. Conclusion: There was a high prevalence of DM and IGT in liver cancer patients.

  20. Disruption of Tsc2 in pancreatic beta cells induces beta cell mass expansion and improved glucose tolerance in a TORC1-dependent manner.

    PubMed

    Rachdi, Latif; Balcazar, Norman; Osorio-Duque, Fernando; Elghazi, Lynda; Weiss, Aaron; Gould, Aaron; Chang-Chen, Karen J; Gambello, Michael J; Bernal-Mizrachi, Ernesto

    2008-07-01

    Regulation of pancreatic beta cell mass and function is a major determinant for the development of diabetes. Growth factors and nutrients are important regulators of beta cell mass and function. The signaling pathways by which these growth signals modulate these processes have not been completely elucidated. Tsc2 is an attractive candidate to modulate these processes, because it is a converging point for growth factor and nutrient signals. In these experiments, we generated mice with conditional deletion of Tsc2 in beta cells (betaTsc2(-/-)). These mice exhibited decreased glucose levels and hyperinsulinemia in the fasting and fed state. Improved glucose tolerance in these mice was observed as early as 4 weeks of age and was still present in 52-week-old mice. Deletion of Tsc2 in beta cells induced expansion of beta cell mass by increased proliferation and cell size. Rapamycin treatment reversed the metabolic changes in betaTsc2(-/-) mice by induction of insulin resistance and reduction of beta cell mass. The reduction of beta cell mass in betaTsc2(-/-) mice by inhibition of the mTOR/Raptor (TORC1) complex with rapamycin treatment suggests that TORC1 mediates proliferative and growth signals induced by deletion of Tsc2 in beta cells. These studies uncover a critical role for the Tsc2/mTOR pathway in regulation of beta cell mass and carbohydrate metabolism in vivo.

  1. High prevalence of diabetes mellitus and impaired glucose tolerance in liver cancer patients: A hospital based study of 4610 patients with benign tumors or specific cancers

    PubMed Central

    Roujun, Chen; Yanhua, Yi; Bixun, Li

    2016-01-01

    Objective: The prevalence of diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were hypothesised to be different among different tumor patients. This study aimed to study the association between the prevalence of DM, IGT and IFG and liver cancer, colorectal cancer, breast cancer, cervical cancer, nasopharyngeal cancer and benign tumor. Methods:  A hospital based retrospective study was conducted on 4610 patients admitted to the Internal Medical Department of the Affiliated Tumor Hospital of Guangxi Medical University, China. Logistic regression was used to examine the association between gender, age group, ethnicity , cancer types or benign tumors and prevalence of DM, IFG, IGT. Results: Among 4610 patients, there were 1000 liver cancer patients, 373 breast cancer patients, 415 nasopharyngeal cancer patients, 230 cervical cancer patients, 405 colorectal cancer patients, and 2187 benign tumor patients. The prevalence of DM and IGT in liver cancer patients was 14.7% and 22.1%, respectively. The prevalence of DM and IGT was 13.8% and 20%, respectively, in colorectal cancer patients, significantly higher than that of benign cancers. After adjusting for gender, age group, and ethnicity, the prevalence of DM and IGT in liver cancers patients was 1.29 times (CI :1.12-1.66) and 1.49 times (CI :1.20-1.86) higher than that of benign tumors, respectively. Conclusion: There was a high prevalence of DM and IGT in liver cancer patients. PMID:27610222

  2. Atorvastatin delays the glucose clearance rate in hypercholesterolemic rabbits.

    PubMed

    Cheng, Daxin; Wang, Yanli; Gao, Shoucui; Wang, Xiaojing; Sun, Wentao; Bai, Liang; Cheng, Gong; Chu, Yonglie; Zhao, Sihai; Liu, Enqi

    2015-05-01

    The administration of statin might increase the risk of new-onset diabetes in hypercholesterolemic patients based on the recent clinical evidence. However, the causal relationship must be clarified and confirmed in animal experiments. Therefore, we mimicked hypercholesterolemia by feeding rabbits a high-cholesterol diet (HCD) and performed 16 weeks of atorvastatin administration to investigate the effect of statin on glucose metabolism. The intravenous glucose tolerance test showed that plasma glucose levels in the statin-treated rabbits were consistently higher and that there was a slower rate of glucose clearance from the blood than in HCD rabbits. The incremental area under the curve for glucose in the statin-treated rabbits was also significantly larger than in the HCD rabbits. However, there was no significant difference between the two groups in the intravenous insulin tolerance test. The glucose-lowering ability of exogenous insulin was not impaired by statin treatment in hypercholesterolemic rabbits. The administration of a single dose of statin did not affect glucose metabolism in normal rabbits. The statin also significantly increased the levels of high-density lipoprotein cholesterol, alanine aminotransferase and aspartate transaminase and decreased plasma levels of total cholesterol, triglycerides and low-density lipoprotein cholesterol in the hypercholesterolemic rabbits, whereas it did not affect plasma levels of glucose and insulin. The current results showed that atorvastatin treatment resulted in a significant delay of glucose clearance in hypercholesterolemic rabbits, and this rabbit model could be suitable for studying the effects of statin on glucose metabolism.

  3. Long-term effects of dietary fiber on glucose tolerance and gastric emptying in noninsulin-dependent diabetic patients.

    PubMed

    Ray, T K; Mansell, K M; Knight, L C; Malmud, L S; Owen, O E; Boden, G

    1983-03-01

    Effects of long-term (2 months) supplementation of diet with 20 g of guar gum and 10 g of wheat bran on metabolic control was studied in 12 obese, poorly controlled noninsulin-dependent diabetic patients. Addition of fiber reduced urinary excretion of glucose from 30.5 +/- 6 to 8.3 +/- 2 g/24 h, (p less than 0.025), fasting plasma glucose concentration from 301 +/- 24 to 184 +/- 15 mg/dl (p less than 0.025), and plasma cholesterol concentration from 277 +/- 24 to 193 +/- 9 mg/dl (p less than 0.025). No significant changes were observed in the patients weight and serum concentrations of triglycerides, high-density lipoproteins, free fatty acids, and insulin. Addition of fiber also delayed gastric emptying of liquids and solids. This effect became statistically significant 60 and 90 min after intake of a test meal for liquids and solids, respectively. We conclude that addition of guar and bran to the diet resulted in long-term improvement of metabolic control in these patients and that delayed gastric emptying may be one of the mechanisms responsible for this beneficial effect. PMID:6299089

  4. Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

    PubMed

    Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

    2016-01-01

    This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20 mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24 h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24 h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2 h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200 mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants.

  5. Suppression of PCD-related genes affects salt tolerance in Arabidopsis.

    PubMed

    Bahieldin, Ahmed; Alqarni, Dhafer A M; Atef, Ahmed; Gadalla, Nour O; Al-matary, Mohammed; Edris, Sherif; Al-Kordy, Magdy A; Makki, Rania M; Al-Doss, Abdullah A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; El-Domyati, Fotouh M

    2016-01-01

    This work aims at examining a natural exciting phenomenon suggesting that suppression of genes inducing programmed cell death (PCD) might confer tolerance against abiotic stresses in plants. PCD-related genes were induced in tobacco under oxalic acid (OA) treatment (20 mM), and plant cells were characterized to confirm the incidence of PCD. The results indicated that PCD was triggered 24 h after the exposure to OA. Then, RNAs were extracted from tobacco cells 0, 2, 6, 12 and 24 h after treatment for deep sequencing. RNA-Seq analyses were done with a special emphasis to clusters whose PCD-related genes were upregulated after 2 h of OA exposure. Accordingly, 23 tobacco PCD-related genes were knocked down via virus-induced gene silencing (VIGS), whereas our results indicated the influence of five of them on inducing or suppressing PCD. Knockout T-DNA insertion mutants of these five genes in Arabidopsis were tested under salt stress (0, 100, 150, and 200 mM NaCl), and the results indicated that a mutant of an antiapoptotic gene, namely Bax Inhibitor-1 (BI-1), whose VIGS induced PCD in tobacco, was salt sensitive, while a mutant of an apoptotic gene, namely mildew resistance locus O (Mlo), whose VIGS suppressed PCD, was salt tolerant as compared to the WT (Col) control. These data support our hypothesis that retarding PCD-inducing genes can result in higher levels of salt tolerance, while retarding PCD-suppressing genes can result in lower levels of salt tolerance in plants. PMID:27052474

  6. Point mutation of H3/H4 histones affects acetic acid tolerance in Saccharomyces cerevisiae.

    PubMed

    Liu, Xiangyong; Zhang, Xiaohua; Zhang, Zhaojie

    2014-10-10

    The molecular mechanism of acetic acid tolerance in yeast remains unclear despite of its importance for efficient cellulosic ethanol production. In this study, we examined the effects of histone H3/H4 point mutations on yeast acetic acid tolerance by comprehensively screening a histone H3/H4 mutant library. A total of 24 histone H3/H4 mutants (six acetic acid resistant and 18 sensitive) were identified. Compared to the wild-type strain, the histone acetic acid-resistant mutants exhibited improved ethanol fermentation performance under acetic acid stress. Genome-wide transcriptome analysis revealed that changes in the gene expression in the acetic acid-resistant mutants H3 K37A and H4 K16Q were mainly related to energy production, antioxidative stress. Our results provide novel insights into yeast acetic acid tolerance on the basis of histone, and suggest a novel approach to improve ethanol production by altering the histone H3/H4 sequences.

  7. Deletion of GPR40 Impairs Glucose-Induced Insulin Secretion In Vivo in Mice Without Affecting Intracellular Fuel Metabolism in Islets

    SciTech Connect

    Alquier, Thierry; Peyot, Marie-Line; Latour, M. G.; Kebede, Melkam; Sorensen, Christina M.; Gesta, Stephane; Kahn, C. R.; Smith, Richard D.; Jetton, Thomas L.; Metz, Thomas O.; Prentki, Marc; Poitout, Vincent J.

    2009-11-01

    The G protein-coupled receptor GPR40 mediates fatty-acid potentiation of glucose-stimulated insulin secretion, but its contribution to insulin secretion in vivo and mechanisms of action remain uncertain. This study was aimed to ascertain whether GPR40 controls insulin secretion in vivo and modulates intracellular fuel metabolism in islets. We observed that glucose- and arginine-stimulated insulin secretion, assessed by hyperglycemic clamps, was decreased by approximately 60% in GPR40 knock-out (KO) fasted and fed mice, without changes in insulin sensitivity assessed by hyperinsulinemic-euglycemic clamps. Glucose and palmitate metabolism were not affected by GPR40 deletion. Lipid profiling revealed a similar increase in triglyceride and decrease in lysophosphatidylethanolamine species in WT and KO islets in response to palmitate. These results demonstrate that GPR40 regulates insulin secretion in vivo not only in response to fatty acids but also to glucose and arginine, without altering intracellular fuel metabolism.

  8. Abnormal glucose tolerance and insulin resistance in polycystic ovary syndrome amongst the Taiwanese population- not correlated with insulin receptor substrate-1 Gly972Arg/Ala513Pro polymorphism

    PubMed Central

    Lin, Ta-Chin; Yen, Jui-Mei; Gong, Kum-Bing; Kuo, Tsung-Cheng; Ku, Dong-Chi; Liang, Shu-Fen; Wu, Ming-Jiuan

    2006-01-01

    Background Insulin resistance and glucose dysmetabolism in polycystic ovary syndrome (PCOS) are related with the polymorphisms in the genes encoding the insulin receptor substrate (IRS) proteins, especially Gly972Arg/Ala513Pro polymorphism being reported to be associated with type-2 diabetes and PCOS. We intended to assess the prevalence of abnormal glucose tolerance (AGT) and insulin resistance in Taiwanese PCOS women. We also tried to assess whether the particular identity of Gly972Arg/Ala513Pro polymorphic alleles of the IRS-1 gene mutation can be used as an appropriate diagnostic indicator for PCOS. Methods We designed a prospective clinical study. Forty-seven Taiwanese Hoklo and Hakka women, diagnosed with PCOS were enrolled in this study as were forty-five healthy Hoklo and Hakka women as the control group. Insulin resistance was evaluated with fasting insulin, fasting glucose/insulin ratio, and homeostasis model assessment index for insulin resistance (HOMAIR). The genomic DNA of the subjects was amplified by PCR and digested by restriction fragmented length polymorphism (RFLP) with Bst N1 used for codon 972 and Dra III for codon 513. Results AGT was found in 46.8% of these PCOS patients and was significantly related to high insulin resistance rather than the low insulin resistance. Those patients with either insulin resistance or AGT comprised the majority of PCOS affected patients (AGT + fasting insulin ≥17: 83%, AGT + glucose/insulin ratio ≥6.5: 85.1%, AGT + HOMAIR ≥ 2: 87.2%, and AGT + HOMAIR ≥ 3.8: 72.3%). None of the tested samples revealed any polymorphism due to the absence of any Dra III recognition site or any Bst N1 recognition site in the amplified PCR fragment digested by restriction fragmented length polymorphism. Conclusion There is significantly high prevalence of AGT and insulin resistance in PCOS women, but Gly972Arg and Ala513Pro polymorphic alleles of IRS-1 are rare and are not associated with the elevated risk of PCOS amongst

  9. OsDREB2A, a rice transcription factor, significantly affects salt tolerance in transgenic soybean.

    PubMed

    Zhang, Xiu-Xiang; Tang, Yu-Juan; Ma, Qi-Bin; Yang, Cun-Yi; Mu, Ying-Hui; Suo, Hai-Cui; Luo, Lai-Hui; Nian, Hai

    2013-01-01

    The dehydration responsive element binding (DREB) transcription factors play an important role in regulating stress-related genes. OsDREB2A, a member of the DREBP subfamily of AP2/ERF transcription factors in rice (Oryza sativa), is involved in the abiotic stress response. OsDREB2A expression is induced by drought, low-temperature and salt stresses. Here, we report the ability of OsDREB2A to regulate high-salt response in transgenic soybean. Overexpressing OsDREB2A in soybeans enhanced salt tolerance by accumulating osmolytes, such as soluble sugars and free proline, and improving the expression levels of some stress-responsive transcription factors and key genes. The phenotypic characterization of transgenic soybean were significantly better than those of wild-type (WT). Electrophoresis mobility shift assay (EMSA) revealed that the OsDREB2A can bind to the DRE core element in vitro. These results indicate that OsDREB2A may participate in abiotic stress by directly binding with DRE element to regulate the expression of downstream genes. Overexpression of OsDREB2A in soybean might be used to improve tolerance to salt stress.

  10. Effect of amiloride, or amiloride plus hydrochlorothiazide, versus hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3): a parallel-group, double-blind randomised phase 4 trial

    PubMed Central

    Brown, Morris J; Williams, Bryan; Morant, Steve V; Webb, David J; Caulfield, Mark J; Cruickshank, J Kennedy; Ford, Ian; McInnes, Gordon; Sever, Peter; Salsbury, Jackie; Mackenzie, Isla S; Padmanabhan, Sandosh; MacDonald, Thomas M

    2016-01-01

    Summary Background Potassium depletion by thiazide diuretics is associated with a rise in blood glucose. We assessed whether addition or substitution of a potassium-sparing diuretic, amiloride, to treatment with a thiazide can prevent glucose intolerance and improve blood pressure control. Methods We did a parallel-group, randomised, double-blind trial in 11 secondary and two primary care sites in the UK. Eligible patients were aged 18–80 years; had clinic systolic blood pressure of 140 mm Hg or higher and home systolic blood pressure of 130 mmHg or higher on permitted background drugs of angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β blockers, calcium-channel blockers, or direct renin inhibitors (previously untreated patients were also eligible in specific circumstances); and had at least one component of the metabolic syndrome in addition to hypertension. Patients with known diabetes were excluded. Patients were randomly assigned (1:1:1) to 24 weeks of daily oral treatment with starting doses of 10 mg amiloride, 25 mg hydrochlorothiazide, or 5 mg amiloride plus 12·5 mg hydrochlorothiazide; all doses were doubled after 12 weeks. Random assignment was done via a central computer system. Both participants and investigators were masked to assignment. Our hierarchical primary endpoints, assessed on a modified intention-to-treat basis at 12 and 24 weeks, were the differences from baseline in blood glucose measured 2 h after a 75 g oral glucose tolerance test (OGTT), compared first between the hydrochlorothiazide and amiloride groups, and then between the hydrochlorothiazide and combination groups. A key secondary endpoint was change in home systolic blood pressure at 12 and 24 weeks. This trial is registered with ClinicalTrials.gov, number NCT00797862, and the MHRA, Eudract number 2009-010068-41, and is now complete. Findings Between Nov 18, 2009, and Dec 15, 2014, 145 patients were randomly assigned to amiloride, 146 to

  11. Involvement of glucagon-like peptide 1 in the glucose homeostasis regulation in obese and pituitary-dependent hyperadrenocorticism affected dogs.

    PubMed

    Miceli, D D; Cabrera Blatter, M F; Gallelli, M F; Pignataro, O P; Castillo, V A

    2014-10-01

    The incretin glucagon-like peptide 1 (GLP-1) enhances insulin secretion. The aim of this study was to assess GLP-1, glucose and insulin concentrations, Homeostatic Model Assessment (HOMA insulin sensitivity and HOMA β-cell function) in dogs with pituitary-dependent hyperadrenocorticism (PDH), and compare these values with those in normal and obese dogs. The Oral Glucose Tolerance Test was performed and the glucose, GLP-1 and insulin concentrations were evaluated at baseline, and after 15, 30, 60 and 120 minutes. Both basal concentration and those corresponding to the subsequent times, for glucose, GLP-1 and insulin, were statistically elevated in PDH dogs compared to the other groups. Insulin followed a similar behaviour together with variations of GLP-1. HOMA insulin sensitivity was statistically decreased and HOMA β-cell function increased in dogs with PDH. The higher concentrations of GLP-1 in PDH could play an important role in the impairment of pancreatic β-cells thus predisposing to diabetes mellitus.

  12. Effects of liraglutide and sibutramine on food intake, palatability, body weight and glucose tolerance in the gubra DIO-rats

    PubMed Central

    Hansen, Gitte; Jelsing, Jacob; Vrang, Niels

    2012-01-01

    Aim: To validate the gubra DIO-rats as a useful animal model of human obesity. Methods: The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 μg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d. Results: Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubra-diet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion. Conclusion: This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference. PMID:22301859

  13. The Preventive Effect of Zuogui Wan on Offspring Rats' Impaired Glucose Tolerance Whose Mothers Had Gestational Diabetes Mellitus

    PubMed Central

    Feng, Qianjin; Niu, Xin; Xu, Kaixia; Wang, Yingli; Wang, Jinlong; Mao, Yingqiu; Gao, Shuangrong

    2016-01-01

    In this experiment, we used streptozotocin (STZ) to establish a model of gestational diabetes mellitus (GDM) rats, where Zuogui Wan was given to GDM rats. After pregnancy, offspring rats were divided into 4 groups: control group, high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group. Rats in high fat and sugar as the control group, GDM group, and Zuogui Wan GDM group were fed with high fat and sugar diet. Rats in control group were fed the basic diet. The means of 2hPG were higher than 7.8 mmol·L−1 and lower than 11.1 mmol·L−1 on the rats of GDM group on week 15, and IGT models were successful. Body weight, abdominal fat weight, the ratio of abdominal fat weight and body weight, fasting plasma glucose, 2hPG, insulin, leptin, total cholesterol, and low density lipoprotein (LDL) of Zuogui Wan GDM group were significantly lower than GDM group. The level of adiponectin in Zuogui Wan GDM group was significantly higher than GDM group. And we concluded that giving Zuogui Wan to GDM rats can have a preventive effect on the offsprings' IGT induced by high fat and sugar diet. PMID:27034700

  14. Inhibition of Small Maf Function in Pancreatic β-Cells Improves Glucose Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin Secretion.

    PubMed

    Nomoto, Hiroshi; Kondo, Takuma; Miyoshi, Hideaki; Nakamura, Akinobu; Hida, Yoko; Yamashita, Ken-ichiro; Sharma, Arun J; Atsumi, Tatsuya

    2015-10-01

    The large-Maf transcription factor v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) has been found to be crucial for insulin transcription and synthesis and for pancreatic β-cell function and maturation. However, insights about the effects of small Maf factors on β-cells are limited. Our goal was to elucidate the function of small-Maf factors on β-cells using an animal model of endogenous small-Maf dysfunction. Transgenic (Tg) mice with β-cell-specific expression of dominant-negative MafK (DN-MafK) experiments, which can suppress the function of all endogenous small-Mafs, were fed a high-fat diet, and their in vivo phenotypes were evaluated. Phenotypic analysis, glucose tolerance tests, morphologic examination of β-cells, and islet experiments were performed. DN-MafK-expressed MIN6 cells were also used for in vitro analysis. The results showed that DN-MafK expression inhibited endogenous small-Maf binding to insulin promoter while increasing MafA binding. DN-MafK Tg mice under high-fat diet conditions showed improved glucose metabolism compared with control mice via incremental insulin secretion, without causing changes in insulin sensitivity or MafA expression. Moreover, up-regulation of insulin and glucokinase gene expression was observed both in vivo and in vitro under DN-MafK expression. We concluded that endogenous small-Maf factors negatively regulates β-cell function by competing for MafA binding, and thus, the inhibition of small-Maf activity can improve β-cell function. PMID:25763640

  15. Prevalence of and factors influencing impaired glucose tolerance among hepatitis B carriers: a nationwide cross-sectional study in the Republic of Korea.

    PubMed

    Park, Boyoung; Jung, Kyu-Won; Oh, Chang-Mo; Choi, Kui Son; Suh, Mina; Jun, Jae Kwan

    2014-10-01

    Diabetes is associated with a poor prognosis for liver disease, particularly in chronic hepatitis carriers. We investigated the prevalence of factors associated with impaired glucose tolerance (IGT) including diabetes and impaired fasting glucose (IFG) among individuals with hepatitis B virus (HBV) infection.We used data from the Korean National Health and Nutrition Examination Survey, a nationwide cross-sectional survey conducted between 2007 and 2011. Sociodemographic information was collected using a structured questionnaire. The HBV surface antigen, liver enzymes, and lipid profile were measured from blood samples.IFG was found in 18.1% of HBV carriers and 19.3% of noncarriers (P = 0.25). Diabetes was observed in 10.0% of HBV carriers and 12.2% of noncarriers (P = 0.08). Lower level of educational attainment was associated with a higher prevalence of IGT: high school education (odds ratio [OR] = 1.94 [95% confidence interval (CI) 1.14-3.29] and less than a high school education (OR = 3.20 [95% CI, 1.66-6.15] vs more than or equal to a college education. Elevated alanine transaminase and triglyceride by 10 were associated with increased risk of IGT (OR = 1.10 [95% CI, 1.01-1.20] and OR = 1.04 [95% CI, 1.01-1.07], respectively). Being a man and older in age were associated with a higher prevalence of IGT, and individuals with a low body mass index were at lower risk for IGT.Given the synergistic effect of diabetes and HBV infection on liver disease prognosis, we recommend targeted IGT screening and follow-up for HBV carriers. These efforts should include health policies and intervention programs aimed at reducing educational disparities and encouraging early control of elevated liver enzymes or lipid profiles.

  16. Endurance exercise training effects on body fatness, VO2max, HDL-C subfractions, and glucose tolerance are influenced by a PLIN haplotype in older Caucasians.

    PubMed

    Jenkins, Nathan T; McKenzie, Jennifer A; Damcott, Coleen M; Witkowski, Sarah; Hagberg, James M

    2010-03-01

    Perilipins are lipid droplet-coating proteins that regulate intracellular lipolysis in adipocytes. A haplotype of two perilipin gene (PLIN) single nucleotide polymorphisms, 13041A>G and 14995A>T, has been previously associated with obesity risk. Furthermore, the available data indicate that this association may be modified by sex. We hypothesized that this haplotype would associate with body fatness, aerobic fitness, and a number of cardiovascular (CV) risk factor phenotypes before and after a 6-mo endurance exercise training program in sedentary older Caucasians. The major haplotype group (13041A/14995A; n = 57) had significantly lower body mass index (BMI) and body fatness compared with noncarriers of the AA haplotype (n = 44) before the training intervention. Training improved body composition in both groups, but fatness remained higher in noncarriers than AA carriers after training. This fat retention in noncarriers blunted their maximal oxygen uptake (Vo(2 max)) adaptation to training. Female noncarriers had substantially higher concentrations of several conventionally and NMR-measured HDL-C subfractions than male noncarriers before and after training, but only minimal differences were found between the sexes in the AA haplotype group. Haplotype group differences in baseline and after-training responses to an oral glucose tolerance test (OGTT) also differed by sex, as noncarrier men had the highest baseline area under the insulin curve (insulin AUC), but were the only group to significantly improve insulin AUC with training. The insulin sensitivity index and plasma glucose responses to the OGTT were more favorable in AA carriers than noncarriers before and after training. Overall, our findings suggest that PLIN variation explains some of the interindividual differences in the response of obesity and CV phenotypes to exercise training. Furthermore, these data contribute to the growing understanding of PLIN as a candidate gene for human obesity and the

  17. Metabolic Syndrome Components and Their Response to Lifestyle and Metformin Interventions are Associated with Differences in Diabetes Risk in Persons with Impaired Glucose Tolerance

    PubMed Central

    Florez, Hermes; Temprosa, Marinella G; Orchard, Trevor J; Mather, Kieren J; Marcovina, Santica M; Barrett-Connor, Elizabeth; Horton, Edward; Saudek, Christopher; Pi-Sunyer, Xavier F; Ratner, Robert E; Goldberg, Ronald B

    2013-01-01

    Aims To determine the association of metabolic syndrome (MetS) and its components with diabetes risk in participants with impaired glucose tolerance (IGT), and whether intervention-related changes in MetS lead to differences in diabetes incidence. Methods We used the NCEP/ATP III revised MetS definition at baseline and intervention-related changes of its components to predict incident diabetes using Cox models in 3234 Diabetes Prevention Program (DPP) participants with IGT over an average follow-up of 3.2 years. Results In an intention-to-treat analysis, the demographic-adjusted hazard ratios (95%CI) for diabetes in those with MetS (versus no MetS) at baseline were 1.7(1.3-2.3), 1.7(1.2-2.3), and 2.0(1.3-3.0) for placebo, metformin, and lifestyle groups, respectively. Higher levels of fasting plasma glucose and triglycerides at baseline were independently associated with increased risk of diabetes. Greater waist circumference (WC) was associated with higher risk in placebo and lifestyle groups, but not in the metformin group. In a multivariate model, favorable changes in WC (placebo and lifestyle) and HDLc (placebo and metformin) contributed to reduced diabetes risk. Conclusions MetS and some of its components are associated with increased diabetes incidence in persons with IGT in a manner that differed according to DPP intervention. After hyperglycemia, the most predictive factors for diabetes were baseline hypertriglyceridemia and both baseline and lifestyle-associated changes in waist circumference. Targeting these cardio-metabolic risk factors may help to assess the benefits of interventions that reduce diabetes incidence. PMID:24118860

  18. Allocation, stress tolerance and carbon transport in plants: how does phloem physiology affect plant ecology?

    PubMed

    Savage, Jessica A; Clearwater, Michael J; Haines, Dustin F; Klein, Tamir; Mencuccini, Maurizio; Sevanto, Sanna; Turgeon, Robert; Zhang, Cankui

    2016-04-01

    Despite the crucial role of carbon transport in whole plant physiology and its impact on plant-environment interactions and ecosystem function, relatively little research has tried to examine how phloem physiology impacts plant ecology. In this review, we highlight several areas of active research where inquiry into phloem physiology has increased our understanding of whole plant function and ecological processes. We consider how xylem-phloem interactions impact plant drought tolerance and reproduction, how phloem transport influences carbon allocation in trees and carbon cycling in ecosystems and how phloem function mediates plant relations with insects, pests, microbes and symbiotes. We argue that in spite of challenges that exist in studying phloem physiology, it is critical that we consider the role of this dynamic vascular system when examining the relationship between plants and their biotic and abiotic environment. PMID:26147312

  19. Allocation, stress tolerance and carbon transport in plants: how does phloem physiology affect plant ecology?

    PubMed

    Savage, Jessica A; Clearwater, Michael J; Haines, Dustin F; Klein, Tamir; Mencuccini, Maurizio; Sevanto, Sanna; Turgeon, Robert; Zhang, Cankui

    2016-04-01

    Despite the crucial role of carbon transport in whole plant physiology and its impact on plant-environment interactions and ecosystem function, relatively little research has tried to examine how phloem physiology impacts plant ecology. In this review, we highlight several areas of active research where inquiry into phloem physiology has increased our understanding of whole plant function and ecological processes. We consider how xylem-phloem interactions impact plant drought tolerance and reproduction, how phloem transport influences carbon allocation in trees and carbon cycling in ecosystems and how phloem function mediates plant relations with insects, pests, microbes and symbiotes. We argue that in spite of challenges that exist in studying phloem physiology, it is critical that we consider the role of this dynamic vascular system when examining the relationship between plants and their biotic and abiotic environment.

  20. Power posing: brief nonverbal displays affect neuroendocrine levels and risk tolerance.

    PubMed

    Carney, Dana R; Cuddy, Amy J C; Yap, Andy J

    2010-10-01

    Humans and other animals express power through open, expansive postures, and they express powerlessness through closed, contractive postures. But can these postures actually cause power? The results of this study confirmed our prediction that posing in high-power nonverbal displays (as opposed to low-power nonverbal displays) would cause neuroendocrine and behavioral changes for both male and female participants: High-power posers experienced elevations in testosterone, decreases in cortisol, and increased feelings of power and tolerance for risk; low-power posers exhibited the opposite pattern. In short, posing in displays of power caused advantaged and adaptive psychological, physiological, and behavioral changes, and these findings suggest that embodiment extends beyond mere thinking and feeling, to physiology and subsequent behavioral choices. That a person can, by assuming two simple 1-min poses, embody power and instantly become more powerful has real-world, actionable implications. PMID:20855902

  1. Inequity Aversion Negatively Affects Tolerance and Contact-Seeking Behaviours towards Partner and Experimenter.

    PubMed

    Brucks, Désirée; Essler, Jennifer L; Marshall-Pescini, Sarah; Range, Friederike

    2016-01-01

    Inequity aversion has been proposed to act as a limiting factor for cooperation, thus preventing subjects from disadvantageous cooperative interactions. While a recent study revealed that also dogs show some sensitivity to inequity, the underlying mechanisms of this behaviour are still unclear. The aim of the current study was threefold: 1) to replicate the study by Range et al. (2009, PNAS, 106, 340-345); 2) to investigate the emotional mechanisms involved in the inequity response by measuring the heart rate and 3) to explore the link between inequity aversion and cooperation in terms of behaviours shown towards the partner dog and towards the experimenter who caused the inequity. Dog tested in dyads were alternately asked to give their paw and were either equally or unequally rewarded by the experimenter. After each social test condition, we conducted food tolerance tests and free interaction tests in which the subjects' social behaviour towards the partner and the experimenter were observed. As in the previous study, subjects refused to continue giving their paw when only the partner was rewarded, but not when both dogs were rewarded with rewards of different quality. Although subjects did not react to this quality inequity during the test, we did find reduced durations of food sharing in the subsequent tolerance test, indicating that dogs perceived the inequity but were not able to react to it in the test context. Moreover, subjects avoided their partner and the experimenter more during the free interaction time following unequal compared to equal treatment. Despite the clear behavioural reactions to inequity, we could not detect any changes in heart rate. Results suggest that inequity aversion might in fact be mediated by simple emotional mechanisms: sharing a negative experience, like inequity, might reduce future cooperation by decreasing the likelihood of proximity being maintained between partners. PMID:27081852

  2. Cadmium-dependent oxygen limitation affects temperature tolerance in eastern oysters (Crassostrea virginica Gmelin).

    PubMed

    Lannig, Gisela; Cherkasov, Anton S; Pörtner, Hans-O; Bock, Christian; Sokolova, Inna M

    2008-04-01

    Marine ectotherms, including oysters are exposed to variable environmental conditions in coastal shallow waters and estuaries. In the light of global climate change, additional stressors like pollution might pose higher risk to populations. On the basis of the concept of oxygen- and capacity-limited thermal tolerance in aquatic ectotherms (40), we show that a persistent pollutant, cadmium, can have detrimental effects on oysters (Crassostrea virginica). During acute warming from 20 to 28 degrees C (4 degrees C/48 h) standard metabolic rate (SMR) rose in control and cadmium-exposed (50 microg Cd2+/l) animals, with a consistently higher SMR in Cd-exposed oysters. Additionally, Cd-exposed oysters showed a stronger temperature-dependent decrease in hemolymph oxygen partial pressures. This observation indicates that the effect of temperature on aerobic metabolism was exacerbated due to the additional Cd stress. The oxygen delivery systems could not provide enough oxygen to cover Cd-induced elevated metabolic demands at high temperatures. Interestingly, cardiac performance (measured as the heart rate and hemolymph supply to tissues) rose to a similar extent in control and Cd-exposed oysters with warming indicating that cardiac output was unable to compensate for elevated energy demand in Cd-exposed oysters. Together with the literature data on metal-induced reduction of ventilatory capacity, these findings suggest that synergistic effects of elevated temperatures and cadmium exposure led to oxygen limitation by impaired performance in oxygen supply through ventilation and circulation. Overall, cadmium exposure resulted in progressive hypoxemia in oysters at high temperatures, suggesting that the thermal tolerance window is narrowed in marine ectotherms inhabiting polluted areas compared with pristine environments. PMID:18272660

  3. Cadmium-dependent oxygen limitation affects temperature tolerance in eastern oysters (Crassostrea virginica Gmelin).

    PubMed

    Lannig, Gisela; Cherkasov, Anton S; Pörtner, Hans-O; Bock, Christian; Sokolova, Inna M

    2008-04-01

    Marine ectotherms, including oysters are exposed to variable environmental conditions in coastal shallow waters and estuaries. In the light of global climate change, additional stressors like pollution might pose higher risk to populations. On the basis of the concept of oxygen- and capacity-limited thermal tolerance in aquatic ectotherms (40), we show that a persistent pollutant, cadmium, can have detrimental effects on oysters (Crassostrea virginica). During acute warming from 20 to 28 degrees C (4 degrees C/48 h) standard metabolic rate (SMR) rose in control and cadmium-exposed (50 microg Cd2+/l) animals, with a consistently higher SMR in Cd-exposed oysters. Additionally, Cd-exposed oysters showed a stronger temperature-dependent decrease in hemolymph oxygen partial pressures. This observation indicates that the effect of temperature on aerobic metabolism was exacerbated due to the additional Cd stress. The oxygen delivery systems could not provide enough oxygen to cover Cd-induced elevated metabolic demands at high temperatures. Interestingly, cardiac performance (measured as the heart rate and hemolymph supply to tissues) rose to a similar extent in control and Cd-exposed oysters with warming indicating that cardiac output was unable to compensate for elevated energy demand in Cd-exposed oysters. Together with the literature data on metal-induced reduction of ventilatory capacity, these findings suggest that synergistic effects of elevated temperatures and cadmium exposure led to oxygen limitation by impaired performance in oxygen supply through ventilation and circulation. Overall, cadmium exposure resulted in progressive hypoxemia in oysters at high temperatures, suggesting that the thermal tolerance window is narrowed in marine ectotherms inhabiting polluted areas compared with pristine environments.

  4. Thermal tolerance affects mutualist attendance in an ant-plant protection mutualism

    PubMed Central

    Fitzpatrick, Ginny; Lanan, Michele C.; Bronstein, Judith L.

    2014-01-01

    Mutualism is an often-complex interaction among multiple species, each of which may respond differently to abiotic conditions. The effects of temperature on the formation, dissolution, and success of these and other species interactions remain poorly understood. We studied the thermal ecology of the mutualism between the cactus Ferocactus wislizeni and its ant defenders (Forelius pruinosus, Crematogaster opuntiae, Solenopsis aurea, and Solenopsis xyloni) in the Sonoran Desert, USA. The ants are attracted to extrafloral nectar produced by the plants and in exchange protect the plants from herbivores; there is a hierarchy of mutualist effectiveness based on aggression toward herbivores. We determined the relationship between temperature and ant activity on plants, the thermal tolerance of each ant species, and ant activity in relation to the thermal environment of plants. Temperature played a role in determining which species interact as mutualists. Three of the four ant species abandoned the plants during the hottest part of the day (up to 40°C), returning when surface temperature began to decrease in the afternoon. The least effective ant mutualist, F. pruinosus, had a significantly higher critical thermal maximum than the other three species, was active across the entire range of plant surface temperatures observed (13.8-57.0°C), and visited plants that reached the highest temperatures. F. pruinosus occupied some plants full-time and invaded plants occupied by more dominant species when those species were thermally excluded. Combining data on thermal tolerance and mutualist effectiveness provides a potentially powerful tool for predicting the effects of temperature on mutualisms and mutualistic species. PMID:25012597

  5. Inequity Aversion Negatively Affects Tolerance and Contact-Seeking Behaviours towards Partner and Experimenter

    PubMed Central

    Brucks, Désirée; Essler, Jennifer L.; Marshall-Pescini, Sarah; Range, Friederike

    2016-01-01

    Inequity aversion has been proposed to act as a limiting factor for cooperation, thus preventing subjects from disadvantageous cooperative interactions. While a recent study revealed that also dogs show some sensitivity to inequity, the underlying mechanisms of this behaviour are still unclear. The aim of the current study was threefold: 1) to replicate the study by Range et al. (2009, PNAS, 106, 340–345); 2) to investigate the emotional mechanisms involved in the inequity response by measuring the heart rate and 3) to explore the link between inequity aversion and cooperation in terms of behaviours shown towards the partner dog and towards the experimenter who caused the inequity. Dog tested in dyads were alternately asked to give their paw and were either equally or unequally rewarded by the experimenter. After each social test condition, we conducted food tolerance tests and free interaction tests in which the subjects’ social behaviour towards the partner and the experimenter were observed. As in the previous study, subjects refused to continue giving their paw when only the partner was rewarded, but not when both dogs were rewarded with rewards of different quality. Although subjects did not react to this quality inequity during the test, we did find reduced durations of food sharing in the subsequent tolerance test, indicating that dogs perceived the inequity but were not able to react to it in the test context. Moreover, subjects avoided their partner and the experimenter more during the free interaction time following unequal compared to equal treatment. Despite the clear behavioural reactions to inequity, we could not detect any changes in heart rate. Results suggest that inequity aversion might in fact be mediated by simple emotional mechanisms: sharing a negative experience, like inequity, might reduce future cooperation by decreasing the likelihood of proximity being maintained between partners. PMID:27081852

  6. Glucose-6-phosphate dehydrogenase and alternative oxidase are involved in the cross tolerance of highland barley to salt stress and UV-B radiation.

    PubMed

    Zhao, Chengzhou; Wang, Xiaomin; Wang, Xiaoyu; Wu, Kunlun; Li, Ping; Chang, Ning; Wang, Jianfeng; Wang, Feng; Li, Jiaolong; Bi, Yurong

    2015-06-01

    In this study, a new mechanism involving glucose-6-phosphate dehydrogenase (G6PDH) and alternative pathways (AP) in salt pretreatment-induced tolerance of highland barley to UV-B radiation was investigated. When highland barley was exposed to UV-B radiation, the G6PDH activity decreased but the AP capacity increased. In contrast, under UV-B+NaCl treatment, the G6PDH activity was restored to the control level and the maximal AP capacity and antioxidant enzyme activities were reached. Glucosamine (Glucm, an inhibitor of G6PDH) obviously inhibited the G6PDH activity in highland barley under UV-B + NaCl treatment and a similar pattern was observed in reduced glutathione (GSH) and ascorbic acid (Asc) contents. Similarly, salicylhydroxamic acid (SHAM, an inhibitor of AOX) significantly reduced the AP capacity in highland barley under UV-B + NaCl treatment. The UV-B-induced hydrogen peroxide (H2O2) accumulation was also followed. Further studies indicated that non-functioning of G6PDH or AP under UV-B+NaCl + Glucm or UV-B + NaCl + SHAM treatment also caused damages in photosynthesis and stomatal movement. Western blot analysis confirmed that the alternative oxidase (AOX) and G6PDH were dependent each other in cross tolerance to UV-B and salt. The inhibition of AP or G6PDH activity resulted in a significant accumulation or reduction of NADPH content, respectively, under UV-B+NaCl treatment in highland barley leaves. Taken together, our results indicate that AP and G6PDH mutually regulate and maintain photosynthesis and stomata movement in the cross adaptation of highland barley seedlings to UV-B and salt by modulating redox homeostasis and NADPH content.

  7. 29 CFR 1952.8 - Variations, tolerances, and exemptions affecting the national defense.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) APPROVED STATE PLANS FOR ENFORCEMENT OF... affecting the national defense. (a) The power of the Secretary of Labor under section 16 of the Act...

  8. Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia

    PubMed Central

    Eik, W.; Marcon, S.S.; Krupek, T.; Previdelli, I.T.S.; Pereira, O.C.N.; Silva, M.A.R.C.P.; Bazotte, R.B.

    2016-01-01

    We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia

  9. Association of Waist Circumference and Body Fat Weight with Insulin Resistance in Male Subjects with Normal Body Mass Index and Normal Glucose Tolerance.

    PubMed

    Sasaki, Ryoma; Yano, Yutaka; Yasuma, Taro; Onishi, Yuki; Suzuki, Toshinari; Maruyama-Furuta, Noriko; Gabazza, Esteban C; Sumida, Yasuhiro; Takei, Yoshiyuki

    2016-01-01

    Objective We investigated the relationship of the waist circumference (WC) and body fat weight (BF) with insulin resistance in subjects with normal body mass index (BMI) and normal glucose tolerance (NGT) during a routine medical check-up. Methods We categorized 167 male subjects in three groups as follows: a group with normal BMI but high WC (normal-BMI/high-WC group; 22≤BMI<25 kg/m(2), waist ≥85 cm; n=31), a group with normal BMI and normal WC (normal-BMI/normal-WC group, waist <85 cm; n=68), and a group with low normal BMI and normal WC (low normal-BMI/normal-WC group; 18.5≤BMI<22 kg/m(2) and waist<85 cm; n=68). We measured the plasma glucose and serum insulin levels before glucose loading and after 30 and 120 minutes and calculated several indexes of insulin secretion and sensitivity. Results Subjects from the normal-BMI/high-WC group showed significantly decreased Matsuda index and increased homeostasis model assessment for insulin resistance (HOMA-IR) compared with normal-BMI/normal-WC group. Univariate regression analyses showed significant correlation of HOMA-IR with WC (r=0.39) and BF (r=0.37). Matsuda index was significantly correlated with WC (r=-0.39) and BF (r=-0.47). The multiple regression analysis showed that the BF is significantly correlated with HOMA-IR (p<0.05) and Masuda index (p<0.005) among the clinical variables and with HOMA-IR (p<0.05) and Masuda index (p<0.0001) among the anthropometric variables but not with WC in either analysis. Conclusion Decreased Matsuda index and increased HOMA-IR were observed in subjects from the normal-BMI/high-WC group. Multivariate analysis showed that BF is associated with decreased Matsuda index and increased HOMA-IR and that WC is not associated with either factors. PMID:27250047

  10. Blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in patients with symptoms suggesting reactive hypoglycemia.

    PubMed

    Eik, W; Marcon, S S; Krupek, T; Previdelli, I T S; Pereira, O C N; Silva, M A R C P; Bazotte, R B

    2016-07-11

    We evaluated the impact of postprandial glycemia on blood levels of pro-inflammatory and anti-inflammatory cytokines during an oral glucose tolerance test in non-diabetic patients with symptoms suggesting reactive hypoglycemia. Eleven patients with clinical symptoms suggesting reactive hypoglycemia received an oral glucose solution (75 g) Blood was collected at 0 (baseline), 30, 60, 120 and 180 min after glucose ingestion and the plasma concentrations of interferon-α (IFN-α), interferon-γ (IFN-γ), interleukin-1 receptor antagonist (IL-1RA), interleukin 2 (IL-2), interleukin-2 receptor (IL-2R), interleukin 4 (IL-4), interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin-12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), IFN-γ inducible protein 10 (IP-10), monocyte chemotactic protein 1 (MCP1), monokine induced by IFN-γ (MIG), macrophage inflammatory protein-1α (MIP-1α), interleukin-1β (IL-1β), colony stimulating factor (G-CSF), granulocyte-macrophage CSF (GM-CSF), basic fibroblast growth factor (FGF-basic), eotaxin, tumor necrosis factor α (TNFα), epidermal growth factor (EGF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), macrophage inflammatory protein-1α (MIP-1α), and 1β (MIP-1β) were evaluated. Overall, glycemic levels increased, reached its maximum at 30 min (phase 1), returned to baseline levels at 120 min (phase 2), followed by a mild hypoglycemia at 180 min (phase 3). During phase 1, cytokine blood levels were maintained. However, we observed a synchronous fall (P<0.05) in the concentrations of pro-inflammatory (IL-15, IL-17, MCP-1) and anti-inflammatory cytokines (FGF-basic, IL-13, IL-1RA) during phase 2. Furthermore, a simultaneous rise (P<0.05) of pro-inflammatory (IL-2, IL-5, IL-17) and anti-inflammatory cytokines (IL-4, IL-1RA, IL-2R, IL-13, FGF-basic) occurred during phase 3. Thus, mild acute hypoglycemia but not a physiological increase of glycemia

  11. MATLAB-implemented estimation procedure for model-based assessment of hepatic insulin degradation from standard intravenous glucose tolerance test data.

    PubMed

    Di Nardo, Francesco; Mengoni, Michele; Morettini, Micaela

    2013-05-01

    Present study provides a novel MATLAB-based parameter estimation procedure for individual assessment of hepatic insulin degradation (HID) process from standard frequently-sampled intravenous glucose tolerance test (FSIGTT) data. Direct access to the source code, offered by MATLAB, enabled us to design an optimization procedure based on the alternating use of Gauss-Newton's and Levenberg-Marquardt's algorithms, which assures the full convergence of the process and the containment of computational time. Reliability was tested by direct comparison with the application, in eighteen non-diabetic subjects, of well-known kinetic analysis software package SAAM II, and by application on different data. Agreement between MATLAB and SAAM II was warranted by intraclass correlation coefficients ≥0.73; no significant differences between corresponding mean parameter estimates and prediction of HID rate; and consistent residual analysis. Moreover, MATLAB optimization procedure resulted in a significant 51% reduction of CV% for the worst-estimated parameter by SAAM II and in maintaining all model-parameter CV% <20%. In conclusion, our MATLAB-based procedure was suggested as a suitable tool for the individual assessment of HID process.

  12. Decreased thioredoxin-1 and increased HSP90 expression in skeletal muscle in subjects with type 2 diabetes or impaired glucose tolerance.

    PubMed

    Venojärvi, M; Korkmaz, A; Aunola, S; Hällsten, K; Virtanen, K; Marniemi, J; Halonen, J-P; Hänninen, O; Nuutila, P; Atalay, M

    2014-01-01

    In diabetes, the endogenous defence systems are overwhelmed, causing various types of stress in tissues. In this study, newly diagnosed or diet-treated type 2 diabetics (T2D) (n = 10) were compared with subjects with impaired glucose tolerance (IGT) (n = 8). In both groups, at resting conditions, blood samples were drawn for assessing metabolic indices and skeletal muscle samples (m. vastus lateralis) were taken for the measurements of cellular defence markers: thioredoxin-1 (TRX-1) and stress proteins HSP72, HSP90. The protein level of TRX-1 was 36.1% lower (P = 0.031) and HSP90 was 380% higher (P < 0.001) in the T2D than in the IGT subjects, with no significant changes in HSP72. However, after the adjustment of both analyses with HOMA-IR only HSP90 difference remained significant. In conclusion, level of TRX-1 in skeletal muscle tissue was lower while that of HSP90 was higher in T2D than in IGT subjects. This may impair antioxidant defence and lead to disruptions of protein homoeostasis and redox regulation of cellular defences. Because HSP90 may be involved in sustaining functional insulin signalling pathway in type 2 diabetic muscles and higher HSP90 levels can be a consequence of type 2 diabetes, our results are potentially important for the diabetes research. PMID:24689038

  13. High root temperature affects the tolerance to high light intensity in Spathiphyllum plants.

    PubMed

    Soto, Adriana; Hernández, Laura; Quiles, María José

    2014-10-01

    Spathiphyllum wallisii plants were sensitive to temperature stress under high illumination, although the susceptibility of leaves to stress may be modified by root temperature. Leaves showed higher tolerance to high illumination, in both cold and heat conditions, when the roots were cooled, probably because the chloroplast were protected by excess excitation energy dissipation mechanisms such as cyclic electron transport. When the roots were cooled both the activity of electron donation by NADPH and ferredoxin to plastoquinone and the amount of PGR5 polypeptide, an essential component of cyclic electron flow around PSI, increased. However, when the stems were heated or cooled under high illumination, but the roots were heated, the quantum yield of PSII decreased considerably and neither the electron donation activity by NADPH and ferredoxin to plastoquinone nor the amount of PGR5 polypeptide increased. In such conditions, the cyclic electron flow cannot be enhanced by high light and PSII is damaged as a result of insufficient dissipation of excess light energy. Additionally, the damage to PSII induced the increase in both chlororespiratory enzymes, NDH complex and PTOX.

  14. Overexpression of the rice AKT1 potassium channel affects potassium nutrition and rice drought tolerance

    PubMed Central

    Ahmad, Izhar; Mian, Afaq; Maathuis, Frans J. M.

    2016-01-01

    Potassium (K+) is the most important cationic nutrient for all living organisms and has roles in most aspects of plant physiology. To assess the impact of one of the main K+ uptake components, the K+ inward rectifying channel AKT1, we characterized both loss of function and overexpression of OsAKT1 in rice. In many conditions, AKT1 expression correlated with K+ uptake and tissue K+ levels. No salinity-related growth phenotype was observed for either loss or gain of function mutants. However, a correlation between AKT1 expression and root Na+ when the external Na/K ratio was high suggests that there may be a role for AKT1 in Na+ uptake in such conditions. In contrast to findings with Arabidopsis thaliana, we did not detect any change in growth of AKT1 loss of function mutants in the presence of NH4 +. Nevertheless, NH4 +-dependent inhibition was detected during K+ uptake assays in loss of function and wild type plants, depending on pre-growth conditions. The most prominent result of OsAKT1 overexpression was a reduction in sensitivity to osmotic/drought stress in transgenic plants: the data suggest that AKT1 overexpression improved rice osmotic and drought stress tolerance by increasing tissue levels of K+, especially in the root. PMID:26969743

  15. Failure of human and mouse leptin to affect insulin, glucagon and somatostatin secretion by the perfused rat pancreas at physiological glucose concentration.

    PubMed

    Leclercq-Meyer, V; Malaisse, W J

    1998-06-25

    In isolated perfused pancreas from normal rats, a rise in d-glucose concentration from 3.3 to 8.3 mM provoked a rapid phasic stimulation of both insulin and somatostatin secretion and rapid fall in glucagon output, these changes being reversed when the concentration of the hexose was brought back to its initial low level. In the presence of 8.3 mM d-glucose, the administration of either human or mouse leptin (10 nM in both cases) for 15 min failed to affect significantly the perfusion pressure and release of the three hormones. It is concluded that leptin does not exert any major immediate and direct effect upon pancreatic insulin, glucagon and somatostatin secretion, at least at the physiological concentration of d-glucose normally found in the plasma of fed rats. PMID:9723892

  16. Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

    PubMed

    Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

    2015-08-01

    Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation. PMID:25421565

  17. Deficiency of PdxR in Streptococcus mutans affects vitamin B6 metabolism, acid tolerance response and biofilm formation.

    PubMed

    Liao, S; Bitoun, J P; Nguyen, A H; Bozner, D; Yao, X; Wen, Z T

    2015-08-01

    Streptococcus mutans, a key etiological agent of the human dental caries, lives primarily on the tooth surface in tenacious biofilms. The SMU864 locus, designated pdxR, is predicted to encode a member of the novel MocR/GabR family proteins, which are featured with a winged helix DNA-binding N-terminal domain and a C-terminal domain highly homologous to the pyridoxal phosphate-dependent aspartate aminotransferases. A pdxR-deficient mutant, TW296, was constructed using allelic exchange. PdxR deficiency in S. mutans had little effect on cell morphology and growth when grown in brain heart infusion. However, when compared with its parent strain, UA159, the PdxR-deficient mutant displayed major defects in acid tolerance response and formed significantly fewer biofilms (P < 0.01). When analyzed by real-time polymerase chain reaction, PdxR deficiency was found to drastically reduce expression of an apparent operon encoding a pyridoxal kinase (SMU865) and a pyridoxal permease (SMU866) of the salvage pathway of vitamin B6 biosynthesis. In addition, PdxR deficiency also altered the expression of genes for ClpL protease, glucosyltransferase B and adhesin SpaP, which are known to play important roles in stress tolerance and biofilm formation. Consistently, PdxR-deficiency affected the growth of the deficient mutant when grown in defined medium with and without vitamin B6 . Further studies revealed that although S. mutans is known to require vitamin B6 to grow in defined medium, B6 vitamers, especially pyridoxal, were strongly inhibitory at millimolar concentrations, against S. mutans growth and biofilm formation. Our results suggest that PdxR in S. mutans plays an important role in regulation of vitamin B6 metabolism, acid tolerance response and biofilm formation.

  18. Salinity affects production and salt tolerance of dimorphic seeds of Suaeda salsa.

    PubMed

    Wang, Fengxia; Xu, Yan-Ge; Wang, Shuai; Shi, Weiwei; Liu, Ranran; Feng, Gu; Song, Jie

    2015-10-01

    The effect of salinity on brown seeds/black seeds ratio, seed weight, endogenous hormone concentrations, and germination of brown and black seeds in the euhalophyte Suaeda salsa was investigated. The brown seeds/black seeds ratio, seed weight of brown and black seeds and the content of protein increased at a concentration of 500 mM NaCl compared to low salt conditions (1 mM NaCl). The germination percentage and germination index of brown seeds from plants cultured in 500 mM NaCl were higher than those cultured in 1 mM NaCl, but it was not true for black seeds. The concentrations of IAA (indole-3-acetic acid), ZR (free zeatin riboside) and ABA (abscisic acid) in brown seeds were much greater than those in black seeds, but there were no differences in the level of GAs (gibberellic acid including GA1 and GA3) regardless of the degree of salinity. Salinity during plant culture increased the concentration of GAs, but salinity had no effect on the concentrations of the other three endogenous hormones in brown seeds. Salinity had no effect on the concentration of IAA but increased the concentrations of the other three endogenous hormones in black seeds. Accumulation of endogenous hormones at different concentrations of NaCl during plant growth may be related to seed development and to salt tolerance of brown and black S. salsa seeds. These characteristics may help the species to ensure seedling establishment and population succession in variable saline environments. PMID:26184090

  19. Salinity affects production and salt tolerance of dimorphic seeds of Suaeda salsa.

    PubMed

    Wang, Fengxia; Xu, Yan-Ge; Wang, Shuai; Shi, Weiwei; Liu, Ranran; Feng, Gu; Song, Jie

    2015-10-01

    The effect of salinity on brown seeds/black seeds ratio, seed weight, endogenous hormone concentrations, and germination of brown and black seeds in the euhalophyte Suaeda salsa was investigated. The brown seeds/black seeds ratio, seed weight of brown and black seeds and the content of protein increased at a concentration of 500 mM NaCl compared to low salt conditions (1 mM NaCl). The germination percentage and germination index of brown seeds from plants cultured in 500 mM NaCl were higher than those cultured in 1 mM NaCl, but it was not true for black seeds. The concentrations of IAA (indole-3-acetic acid), ZR (free zeatin riboside) and ABA (abscisic acid) in brown seeds were much greater than those in black seeds, but there were no differences in the level of GAs (gibberellic acid including GA1 and GA3) regardless of the degree of salinity. Salinity during plant culture increased the concentration of GAs, but salinity had no effect on the concentrations of the other three endogenous hormones in brown seeds. Salinity had no effect on the concentration of IAA but increased the concentrations of the other three endogenous hormones in black seeds. Accumulation of endogenous hormones at different concentrations of NaCl during plant growth may be related to seed development and to salt tolerance of brown and black S. salsa seeds. These characteristics may help the species to ensure seedling establishment and population succession in variable saline environments.

  20. Glucose levels affect LL-37 expression in monocyte-derived macrophages altering the Mycobacterium tuberculosis intracellular growth control.

    PubMed

    Montoya-Rosales, Alejandra; Castro-Garcia, Pamela; Torres-Juarez, Flor; Enciso-Moreno, Jose Antonio; Rivas-Santiago, Bruno

    2016-08-01

    Diabetes mellitus (DM)-2 patients have an increased susceptibility to develop pulmonary tuberculosis; this is partly due to the impairment of the innate immunity because of their higher glucose concentrations. In the present study, we determined the effect of the glucose concentrations in the LL-37 expression in infected and non-infected macrophages. Our results showed that the increasing glucose concentrations correlates with the low cathelicidin expression in non-infected cells, however in Mycobacterium tuberculosis infected cells, LL-37 expression was substantially increased in higher glucose concentrations, nevertheless the mycobacterial burden also increased, this phenomena can be associated with the cathelicidin immunomodulatory activity. Further evaluation for LL-37 needs to be done to determine whether this peptide can be used as a biomarker of tuberculosis progression in DM2 patients.

  1. The Impact of Vitamin D Supplementation on Post-Partum Glucose Tolerance and Insulin Resistance in Gestational Diabetes: A Randomized Controlled Trial

    PubMed Central

    Valizadeh, Majid; Piri, Zahra; Mohammadian, Farnaz; Kamali, Koorosh; Amir Moghadami, Hamid Reza

    2016-01-01

    Background Hypovitaminosis D has been associated with the development of gestational diabetes mellitus (GDM) in many observational studies. Objectives We report the first study of the impact of prenatal vitamin D supplementation on postpartum dysglycemia in GDM patients in a randomized clinical trial. Patients and Methods Women with GDM at 12 - 32 weeks of gestation were assigned randomly to either the intervention group (in which serum 25-hydroxy vitamin D [25OHD] levels were measured immediately, n = 48) or the control group (in which the serum was stored and assayed at 6 - 12 weeks post-partum, n = 48). Participants with initial serum 25OHD < 30 ng/mL in the intervention group were instructed to take a total of 700,000 IU vitamin D3 during pregnancy. The primary outcomes were fasting plasma glucose (FPG), insulin, 2-h post 75 g glucose load plasma glucose (2-hPLG), homeostasis model assessment of insulin resistance (HOMA-IR), HbA1C, and 25 OHD at 6 - 12 weeks after delivery. Results The mean ± SD of serum 25OHD in the intervention group raised dramatically from 14.6 ± 6.3 to 32.4 ± 14.4 ng/mL, whereas no significant change occurred in the control group (from 17.7 ± 6.1 to 19.3 ± 9.6 ng/mL, P < 0.001). Thirteen participants developed dysglycemia in each group. Mean FPG, 2-hPLG, and HOMA-IR were not significantly different between the groups. There was no significant difference between the groups for maternal and neonatal outcomes. Conclusions Although the high vitamin D supplementation dose in the present study (compared to the 400 IU/day dose usually recommended for pregnancy) safely increases the serum 25OHD, in GDM cases, the higher dose does not affect the plasma glucose level or insulin resistance at short term follow-up after delivery. PMID:27679649

  2. Children's and adolescents' tolerance for divergent beliefs: exploring the cognitive and affective dimensions of moral conviction in our youth.

    PubMed

    Wright, Jennifer C

    2012-11-01

    Moral conviction predicts interpersonal tolerance in adults, but its role in children and adolescents is not as well understood. This study measured moral conviction for a variety of issues along two separate dimensions - cognitive and affective - in children and adolescents (4th-12th grade). Results showed that, like adults, when children and adolescents view an issue as moral, this is strongly predictive of both age groups' discomfort with divergent beliefs. But only for adolescents, and not children, did moral conviction play a role in that discomfort, as had previously been found with adults. The context in which the divergent beliefs were encountered also mattered, but more for adolescents than for children - both groups were most comfortable with divergent beliefs when they were encountered in distal relations. PMID:23039329

  3. GOLDEN 2-LIKE transcription factors for chloroplast development affect ozone tolerance through the regulation of stomatal movement

    PubMed Central

    Nagatoshi, Yukari; Mitsuda, Nobutaka; Hayashi, Maki; Inoue, Shin-ichiro; Okuma, Eiji; Kubo, Akihiro; Murata, Yoshiyuki; Seo, Mitsunori; Saji, Hikaru; Kinoshita, Toshinori; Ohme-Takagi, Masaru

    2016-01-01

    Stomatal movements regulate gas exchange, thus directly affecting the efficiency of photosynthesis and the sensitivity of plants to air pollutants such as ozone. The GARP family transcription factors GOLDEN 2-LIKE1 (GLK1) and GLK2 have known functions in chloroplast development. Here, we show that Arabidopsis thaliana (A. thaliana) plants expressing the chimeric repressors for GLK1 and -2 (GLK1/2-SRDX) exhibited a closed-stomata phenotype and strong tolerance to ozone. By contrast, plants that overexpress GLK1/2 exhibited an open-stomata phenotype and higher sensitivity to ozone. The plants expressing GLK1-SRDX had reduced expression of the genes for inwardly rectifying K+ (K+in) channels and reduced K+in channel activity. Abscisic acid treatment did not affect the stomatal phenotype of 35S:GLK1/2-SRDX plants or the transcriptional activity for K+in channel gene, indicating that GLK1/2 act independently of abscisic acid signaling. Our results indicate that GLK1/2 positively regulate the expression of genes for K+in channels and promote stomatal opening. Because the chimeric GLK1-SRDX repressor driven by a guard cell-specific promoter induced a closed-stomata phenotype without affecting chloroplast development in mesophyll cells, modulating GLK1/2 activity may provide an effective tool to control stomatal movements and thus to confer resistance to air pollutants. PMID:27035938

  4. GOLDEN 2-LIKE transcription factors for chloroplast development affect ozone tolerance through the regulation of stomatal movement.

    PubMed

    Nagatoshi, Yukari; Mitsuda, Nobutaka; Hayashi, Maki; Inoue, Shin-Ichiro; Okuma, Eiji; Kubo, Akihiro; Murata, Yoshiyuki; Seo, Mitsunori; Saji, Hikaru; Kinoshita, Toshinori; Ohme-Takagi, Masaru

    2016-04-12

    Stomatal movements regulate gas exchange, thus directly affecting the efficiency of photosynthesis and the sensitivity of plants to air pollutants such as ozone. The GARP family transcription factors GOLDEN 2-LIKE1 (GLK1) and GLK2 have known functions in chloroplast development. Here, we show that Arabidopsis thaliana (A. thaliana) plants expressing the chimeric repressors for GLK1 and -2 (GLK1/2-SRDX) exhibited a closed-stomata phenotype and strong tolerance to ozone. By contrast, plants that overexpress GLK1/2 exhibited an open-stomata phenotype and higher sensitivity to ozone. The plants expressing GLK1-SRDX had reduced expression of the genes for inwardly rectifying K(+) (K(+) in) channels and reduced K(+) in channel activity. Abscisic acid treatment did not affect the stomatal phenotype of 35S:GLK1/2-SRDX plants or the transcriptional activity for K(+) in channel gene, indicating that GLK1/2 act independently of abscisic acid signaling. Our results indicate that GLK1/2 positively regulate the expression of genes for K(+) in channels and promote stomatal opening. Because the chimeric GLK1-SRDX repressor driven by a guard cell-specific promoter induced a closed-stomata phenotype without affecting chloroplast development in mesophyll cells, modulating GLK1/2 activity may provide an effective tool to control stomatal movements and thus to confer resistance to air pollutants. PMID:27035938

  5. Chromium picolinate positively influences the glucose transporter system via affecting cholesterol homeostasis in adipocytes cultured under hyperglycemic diabetic conditions

    PubMed Central

    Pattar, Guruprasad R.; Tackett, Lixuan; Liu, Ping; Elmendorf, Jeffrey S.

    2008-01-01

    Since trivalent chromium (Cr3+) enhances glucose metabolism, interest in the use of Cr3+as a therapy for type 2 diabetes has grown in the mainstream medical community. Moreover, accumulating evidence suggests that Cr3+ may also benefit cardiovascular disease (CVD) and atypical depression. We have found that cholesterol, a lipid implicated in both CVD and neurodegenerative disorders, also influences cellular glucose uptake. A recent study in our laboratory shows that exposure of 3T3-L1 adipocytes to chromium picolinate (CrPic, 10 nM) induces a loss of plasma membrane cholesterol. Concomitantly, accumulation of intracellularly sequestered glucose transporter GLUT4 at the plasma membrane was dependent on the CrPic-induced cholesterol loss. Since CrPic supplementation has the greatest benefit on glucose metabolism in hyperglycemic insulin-resistant individuals, we asked here if the CrPic effect on cells was glucose-dependent. We found that GLUT4 redistribution in cells treated with CrPic occurs only in cells cultured under high glucose (25 mM) conditions that resemble the diabetic-state, and not in cells cultured under non-diabetic (5.5 mM glucose) conditions. Examination of the effect of CrPic on proteins involved in cholesterol homeostasis revealed that the activity of sterol regulatory element-binding protein (SREBP), a membrane-bound transcription factor ultimately responsible for controlling cellular cholesterol balance, was upregulated by CrPic. In addition, ABCA1, a major player in mediating cholesterol efflux was decreased, consistent with SREBP transcriptional repression of the ABCA1 gene. Although the exact mechanism of Cr3+-induced cholesterol loss remains to be determined, these cellular responses highlight a novel and significant effect of chromium on cholesterol homeostasis. Furthermore, these findings provide an important clue to our understanding of how chromium supplementation might benefit hypercholesterolemia-associated disorders. PMID:16870493

  6. Glycemic increase induced by intravenous glucose infusion fails to affect hunger, appetite, or satiety following breakfast in healthy men.

    PubMed

    Schultes, Bernd; Panknin, Ann-Kristin; Hallschmid, Manfred; Jauch-Chara, Kamila; Wilms, Britta; de Courbière, Felix; Lehnert, Hendrik; Schmid, Sebastian M

    2016-10-01

    Meal-dependent fluctuations of blood glucose and corresponding endocrine signals such as insulin are thought to provide important regulatory input for central nervous processing of hunger and satiety. Since food intake also triggers the release of numerous gastrointestinal signals, the specific contribution of changes in blood glucose to appetite regulation in humans has remained unclear. Here we tested the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety. In a single blind, counter-balanced crossover study 15 healthy young men participated in two experimental conditions on two separate days. 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, was intravenously infused over a 1-h period followed by a 1-h observation period. One hour before start of the respective infusion subjects had a light breakfast (284 kcal). Blood glucose and serum insulin concentrations as well as self-rated feelings of hunger, appetite, satiety, and fullness were assessed during the entire experiment. Glucose as compared to saline infusion markedly increased glucose and insulin concentrations (peak glucose level: 9.7 ± 0.8 vs. 5.3 ± 0.3 mmol/l; t(14) = -5.159, p < 0.001; peak insulin level: 370.4 ± 66.5 vs. 109.6 ± 21.5 pmol/l; t(14) = 4.563, p < 0.001) followed by a sharp decline in glycaemia to a nadir of 3.0 ± 0.2 mmol/l (vs. 3.9 ± 0.1 mmol/l at the corresponding time in the control condition; t(14) = -3.972, p = 0.001) after stopping the infusion. Despite this wide glycemic fluctuation in the glucose infusion condition subjective feelings of hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment. These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety.

  7. Glycemic increase induced by intravenous glucose infusion fails to affect hunger, appetite, or satiety following breakfast in healthy men.

    PubMed

    Schultes, Bernd; Panknin, Ann-Kristin; Hallschmid, Manfred; Jauch-Chara, Kamila; Wilms, Britta; de Courbière, Felix; Lehnert, Hendrik; Schmid, Sebastian M

    2016-10-01

    Meal-dependent fluctuations of blood glucose and corresponding endocrine signals such as insulin are thought to provide important regulatory input for central nervous processing of hunger and satiety. Since food intake also triggers the release of numerous gastrointestinal signals, the specific contribution of changes in blood glucose to appetite regulation in humans has remained unclear. Here we tested the hypothesis that inducing glycemic fluctuations by intravenous glucose infusion is associated with concurrent changes in hunger, appetite, and satiety. In a single blind, counter-balanced crossover study 15 healthy young men participated in two experimental conditions on two separate days. 500 ml of a solution containing 50 g glucose or 0.9% saline, respectively, was intravenously infused over a 1-h period followed by a 1-h observation period. One hour before start of the respective infusion subjects had a light breakfast (284 kcal). Blood glucose and serum insulin concentrations as well as self-rated feelings of hunger, appetite, satiety, and fullness were assessed during the entire experiment. Glucose as compared to saline infusion markedly increased glucose and insulin concentrations (peak glucose level: 9.7 ± 0.8 vs. 5.3 ± 0.3 mmol/l; t(14) = -5.159, p < 0.001; peak insulin level: 370.4 ± 66.5 vs. 109.6 ± 21.5 pmol/l; t(14) = 4.563, p < 0.001) followed by a sharp decline in glycaemia to a nadir of 3.0 ± 0.2 mmol/l (vs. 3.9 ± 0.1 mmol/l at the corresponding time in the control condition; t(14) = -3.972, p = 0.001) after stopping the infusion. Despite this wide glycemic fluctuation in the glucose infusion condition subjective feelings of hunger, appetite satiety, and fullness did not differ from the control condition throughout the experiment. These findings clearly speak against the notion that fluctuations in glycemia and also insulinemia represent major signals in the short-term regulation of hunger and satiety. PMID

  8. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics

    PubMed Central

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  9. The oral glucose tolerance test for the diagnosis of diabetes mellitus in patients during acute coronary syndrome hospitalization: a meta-analysis of diagnostic test accuracy

    PubMed Central

    2012-01-01

    Background The appropriateness of the routine performance of an oral glucose tolerance test (OGTT) to screen for diabetes mellitus (DM) during acute coronary syndrome hospitalization is still under debate. Methods A systematic search of databases (MEDLINE [1985 to March 2012], EMBASE [1985 to March 2012]) was conducted. All prospective cohort studies assessing the accuracy or reproducibility of an OGTT in ACS or non-ACS individuals were included. A bivariate model was used to calculate the pooled sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR). Heterogeneity was explored using subgroup analysis and meta-regression. Results Fifteen studies with 8,027 participants were included (10 ACS and 5 non-ACS studies). The pooled results on SEN, SPE, PLR, NLR, and DOR were 0.70 (95% CI, 0.60-0.78), 0.91 (95% CI, 0.86-0.94), 7.6 (95% CI, 4.9-11.7), 0.33 (95% CI, 0.25-0.45), and 23 (95% CI, 12–41), respectively. The OGTT has a slightly lower SPE in diagnosing DM in ACS than in non-ACS patients (0.86 [95% CI 0.81-0.92] versus 0.95 [95% CI 0.93-0.98], p<0.01), while the SEN values are comparable (0.71 [95% CI 0.60-0.82] versus 0.67 [95% CI 0.54-0.81], p=0.43). After adjusting the interval between repeated tests and age, the meta-regression did not show a difference in DOR between ACS and non-ACS studies. Conclusions Despite the discrepancy in the interval between the two OGTTs, performing an OGTT in patients with ACS provides accuracy that is similar to that in in non-ACS patients. It is reasonable to screen patients hospitalized for ACS for previously undiagnosed DM using an OGTT. PMID:23270530

  10. Amino Acid and Biogenic Amine Profile Deviations in an Oral Glucose Tolerance Test: A Comparison between Healthy and Hyperlipidaemia Individuals Based on Targeted Metabolomics.

    PubMed

    Li, Qi; Gu, Wenbo; Ma, Xuan; Liu, Yuxin; Jiang, Lidan; Feng, Rennan; Liu, Liyan

    2016-01-01

    Hyperlipidemia (HLP) is characterized by a disturbance in lipid metabolism and is a primary risk factor for the development of insulin resistance (IR) and a well-established risk factor for cardiovascular disease and atherosclerosis. The aim of this work was to investigate the changes in postprandial amino acid and biogenic amine profiles provoked by an oral glucose tolerance test (OGTT) in HLP patients using targeted metabolomics. We used ultra-high-performance liquid chromatography-triple quadrupole mass spectrometry to analyze the serum amino acid and biogenic amine profiles of 35 control and 35 HLP subjects during an OGTT. The amino acid and biogenic amine profiles from 30 HLP subjects were detected as independent samples to validate the changes in the metabolites. There were differences in the amino acid and biogenic amine profiles between the HLP individuals and the healthy controls at baseline and after the OGTT. The per cent changes of 13 metabolites from fasting to the 2 h samples during the OGTT in the HLP patients were significantly different from those of the healthy controls. The lipid parameters were associated with the changes in valine, isoleucine, creatine, creatinine, dimethylglycine, asparagine, serine, and tyrosine (all p < 0.05) during the OGTT in the HLP group. The postprandial changes in isoleucine and γ-aminobutyric acid (GABA) during the OGTT were positively associated with the homeostasis model assessment of insulin resistance (HOMA-IR; all p < 0.05) in the HLP group. Elevated oxidative stress and disordered energy metabolism during OGTTs are important characteristics of metabolic perturbations in HLP. Our findings offer new insights into the complex physiological regulation of metabolism during the OGTT in HLP. PMID:27338465

  11. Effects of Sodium Butyrate and Its Synthetic Amide Derivative on Liver Inflammation and Glucose Tolerance in an Animal Model of Steatosis Induced by High Fat Diet

    PubMed Central

    Mattace Raso, Giuseppina; Simeoli, Raffaele; Russo, Roberto; Iacono, Anna; Santoro, Anna; Paciello, Orlando; Ferrante, Maria Carmela; Canani, Roberto Berni; Calignano, Antonio; Meli, Rosaria

    2013-01-01

    Background & Aims Nonalcoholic fatty liver disease (NAFLD) is the most common form of chronic liver disease. Insulin resistance (IR) appears to be critical in its pathogenesis. We evaluated the effects of sodium butyrate (butyrate) and its synthetic derivative N-(1-carbamoyl-2-phenyl-ethyl) butyramide (FBA) in a rat model of insulin resistance and steatosis induced by high-fat diet (HFD). Methods After weaning, young male Sprague-Dawley rats were divided into 4 groups receiving different diets for 6 weeks: 1. control group (standard diet); 2. HFD; 3. HFD plus butyrate (20 mg/kg/die) and 4. HFD plus FBA (42.5 mg/Kg/die, the equimolecular dose of butyrate). Liver tissues of the rats were analyzed by Western blot and real-time PCR. Insulin resistance, liver inflammation and Toll-like pattern modifications were determined. Results Evaluation of these two preparations of butyrate showed a reduction of liver steatosis and inflammation in HFD fed animals. The compounds showed a similar potency in the normalisation of several variables, such as transaminases, homeostasis model assessment for insulin resistance index, and glucose tolerance. Both treatments significantly reduced hepatic TNF-α expression and restored GLUTs and PPARs, either in liver or adipose tissue. Finally, FBA showed a higher potency in reducing pro-inflammatory parameters in the liver, via suppression of Toll-like receptors and NF-κB activation. Conclusions Our results demonstrated a protective effect of butyrate in limiting molecular events underlying the onset of IR and NAFLD, suggesting a potential clinical relevance for this substance. In particular, its derivative, FBA, could represent an alternative therapeutic option to sodium butyrate, sharing a comparable efficacy, but a better palatability and compliance. PMID:23861927

  12. Higher serum uric acid level increases risk of prehypertension in subjects with normal glucose tolerance, but not pre-diabetes and diabetes.

    PubMed

    Wu, I-H; Wu, J-S; Sun, Z-J; Lu, F-H; Chang, C-S; Chang, C-J; Yang, Y-C

    2016-08-01

    Although the association between serum uric acid (SUA) levels and prehypertension has been reported in previous studies, it is unknown whether their relationship is similar in subjects with diabetes, pre-diabetes and normal glucose tolerance (NGT). This study thus aimed to investigate the relationship between SUA and prehypertension in subjects with different glycemic status, including NGT, pre-diabetes and diabetes. A total of 12 010 participants were included after excluding subjects with blood pressure ⩾140/90 mm Hg, history of hypertension, leukaemia, lymphoma, hypothyroidism, medication for hypertension and hyperuricemia and missing data. Subjects were divided into four groups based on SUA quartiles (male Q1: ⩽345.0, Q2: 345.0-392.6, Q3: 392.6-440.2, Q4: ⩾440.2 μmol l(-1) and female Q1: ⩽249.8, Q2: 249.8-285.5, Q3: 285.5-333.1, Q4: ⩾333.1 μmol l(-1)). Diabetes, pre-diabetes and NGT were assessed according to the 2010 American Diabetes Association diagnostic criteria. Normotension and prehypertension were defined according to the JNC-7 (The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) criteria. The SUA was significantly higher in prehypertensive subjects as compared with normotensive subjects. SUA, as a continuous variable, was positively associated with prehypertension in subjects with NGT but not pre-diabetes and diabetes. Besides, NGT subjects with the highest quartile of SUA exhibited a higher risk of prehypertension after adjustment for other confounding factors. In pre-diabetes and diabetes groups, none of SUA quartiles was significantly related to prehypertension. SUA was significantly associated with an increased risk of prehypertension in subjects with NGT but insignificantly in subjects with pre-diabetes and diabetes. PMID:26911534

  13. Dietary amylose-amylopectin starch content affects glucose and lipid metabolism in adipocytes of normal and diabetic rats.

    PubMed

    Kabir, M; Rizkalla, S W; Champ, M; Luo, J; Boillot, J; Bruzzo, F; Slama, G

    1998-01-01

    The aim of this study was to evaluate the effects of the chronic consumption of two starches, characterized by different glycemic indices and amylose-amylopectin content, on glucose metabolism in rat epididymal adipocytes. The two chosen starches were from mung bean (32% amylose) and cornstarch (0.5% amylose). The alpha-amylase digestibility was higher for the waxy cornstarch than that of the mung bean starch (60 +/- 4 vs. 45 +/- 3%, mean +/- SEM, respectively). The glycemic index of the waxy cornstarch diet (575 g starch /kg diet) was higher than that of the mung bean starch diet (107 +/- 7 vs. 67 +/- 5%, P < 0.01) when measured in vivo in two groups of normal rats (n = 9). In a subsequent study, normal and diabetic (streptozotocin-injected on d 2 of life) male Sprague-Dawley rats (18 per group) consumed a diet containing 575 g starch/kg diet as either waxy cornstarch or mung bean starch. After 3 wk, food intake, epididymal fat pad weights, and plasma glucose, insulin and triglyceride concentrations did not differ between diet groups. Adipocyte diameter was smaller in rats that consumed mung bean starch compared with those that consumed the waxy cornstarch diet (P < 0.01). The mung bean diet increased maximal insulin-stimulated 14C-glucose oxidation (% of basal values, P < 0. 05). In contrast, incorporation of 14C-glucose into total lipids was significantly lower in rats that consumed the mung bean diet (P < 0. 05). We conclude that in both normal and diabetic rats, the chronic replacement of a high glycemic index starch by a low glycemic index one in a mixed diet increases insulin-stimulated glucose oxidation, decreases glucose incorporation into total lipids and decreases epididymal adipocyte diameter. Thus, the type of starch mixed into the diet has important metabolic consequences at the cellular level in both normal and diabetic rats.

  14. Experience with the high-intensity sweetener saccharin impairs glucose homeostasis and GLP-1 release in rats.

    PubMed

    Swithers, Susan E; Laboy, Alycia F; Clark, Kiely; Cooper, Stephanie; Davidson, T L

    2012-07-15

    Previous work from our lab has demonstrated that experience with high-intensity sweeteners in rats leads to increased food intake, body weight gain and adiposity, along with diminished caloric compensation and decreased thermic effect of food. These changes may occur as a result of interfering with learned relations between the sweet taste of food and the caloric or nutritive consequences of consuming those foods. The present experiments determined whether experience with the high-intensity sweetener saccharin versus the caloric sweetener glucose affected blood glucose homeostasis. The results demonstrated that during oral glucose tolerance tests, blood glucose levels were more elevated in animals that had previously consumed the saccharin-sweetened supplements. In contrast, during glucose tolerance tests when a glucose solution was delivered directly into the stomach, no differences in blood glucose levels between the groups were observed. Differences in oral glucose tolerance responses were not accompanied by differences in insulin release; insulin release was similar in animals previously exposed to saccharin and those previously exposed to glucose. However, release of GLP-1 in response to an oral glucose tolerance test, but not to glucose tolerance tests delivered by gavage, was significantly lower in saccharin-exposed animals compared to glucose-exposed animals. Differences in both blood glucose and GLP-1 release in saccharin animals were rapid and transient, and suggest that one mechanism by which exposure to high-intensity sweeteners that interfere with a predictive relation between sweet tastes and calories may impair energy balance is by suppressing GLP-1 release, which could alter glucose homeostasis and reduce satiety.

  15. Glucose intolerance states in women with the polycystic ovary syndrome.

    PubMed

    Pasquali, R; Gambineri, A

    2013-09-01

    The polycystic ovary syndrome (PCOS), the most common hyperandrogenic disorder affecting 4-7% of women, is often associated with metabolic alterations, chiefly insulin resistance and obesity. Based on available scientific evidence, PCOS should be regarded as an independent risk for the development of glucose intolerance states. This short review summarizes the available literature on the prevalence and incidence of impaired glucose tolerance and Type 2 diabetes in this disorder. In addition, some insights on potential factors responsible for individual susceptibility are discussed. Targeted intervention studies focused on prevention and treatment of glucose intolerance states in PCOS are warranted.

  16. Behavioral Self-Regulation in Adolescents with Type 1 Diabetes: Negative Affectivity and Blood Glucose Symptom Perception.

    ERIC Educational Resources Information Center

    Wiebe, Deborah J.; And Others

    1994-01-01

    Adolescents who were more internally focused were more able to discern which symptoms actually covaried with blood glucose (BG) fluctuations; those with higher trait anxiety tended to misattribute non-diabetes-related symptoms to BG levels. Interactions suggested those who both attend to internal physical sensations and experience-heightened…

  17. High dose flaxseed oil supplementation may affect fasting blood serum glucose management in human type 2 diabetics.

    PubMed

    Barre, Douglas E; Mizier-Barre, Kazimiera A; Griscti, Odette; Hafez, Kevin

    2008-01-01

    Type 2 diabetes is characterized partially by elevated fasting blood serum glucose and insulin concentrations and the percentage of hemoglobin as HbA1c. It was hypothesized that each of blood glucose and its co-factors insulin and HbA1c and would show a more favorable profile as the result of flaxseed oil supplementation. Patients were recruited at random from a population pool responding to a recruitment advertisement in the local newspaper and 2 area physicians. Completing the trial were 10 flaxseed oil males, 8 flaxseed oil females, 8 safflower (placebo) oil males and 6 safflower oil females. Patients visited on two pre-treatment occasions each three months apart (visits 1 and 2). At visit 2 subjects were randomly assigned in double blind fashion and in equal gender numbers to take flaxseed oil or safflower oil for three further months until visit 3. Oil consumption in both groups was approximately 10 g/d. ALA intake in the intervention group was approximately 5.5 g/d. Power was 0.80 to see a difference of 1 mmol of glucose /L using 12 subjects per group with a p < 0.05. Flaxseed oil had no impact on fasting blood serum glucose, insulin or HbA1c levels. It is concluded that high doses of flaxseed oil have no effect on glycemic control in type 2 diabetics.

  18. Chronic sleep disturbance impairs glucose homeostasis in rats.

    PubMed

    Barf, R Paulien; Meerlo, Peter; Scheurink, Anton J W

    2010-01-01

    Epidemiological studies have shown an association between short or disrupted sleep and an increased risk for metabolic disorders. To assess a possible causal relationship, we examined the effects of experimental sleep disturbance on glucose regulation in Wistar rats under controlled laboratory conditions. Three groups of animals were used: a sleep restriction group (RS), a group subjected to moderate sleep disturbance without restriction of sleep time (DS), and a home cage control group. To establish changes in glucose regulation, animals were subjected to intravenous glucose tolerance tests (IVGTTs) before and after 1 or 8 days of sleep restriction or disturbance. Data show that both RS and DS reduce body weight without affecting food intake and also lead to hyperglycemia and decreased insulin levels during an IVGTT. Acute sleep disturbance also caused hyperglycemia during an IVGTT, yet, without affecting the insulin response. In conclusion, both moderate and severe disturbances of sleep markedly affect glucose homeostasis and body weight control. PMID:20339560

  19. Pollution-induced community tolerance to non-steroidal anti-inflammatory drugs (NSAIDs) in fluvial biofilm communities affected by WWTP effluents.

    PubMed

    Corcoll, Natàlia; Acuña, Vicenç; Barceló, Damià; Casellas, Maria; Guasch, Helena; Huerta, Belinda; Petrovic, Mira; Ponsatí, Lidia; Rodríguez-Mozaz, Sara; Sabater, Sergi

    2014-10-01

    We assessed the tolerance acquired by stream biofilms to two non-steroidal anti-inflammatory-drugs (NSAIDs), ibuprofen and diclofenac. Biofilms came from a stream system receiving the effluent of a wastewater treatment plant (WWTP). The response of biofilms from a non-polluted site (upstream the WWTP) was compared to that of others downstream with relevant and decreasing levels of NSAIDs. Experiments performed in the laboratory following the pollution-induced community tolerance (PICT) approach determined that both algae and microbial communities from biofilms of the sites exposed at the highest concentrations of ibuprofen and diclofenac acquired tolerance to the mixture of these NSAIDs occurring at the sites. It was also observed that the chronic pollution by the WWTP effluent affected the microbial metabolic profile, as well as the structure of the algal community. The low (at ng L(-1) level) but chronic inputs of pharmaceuticals to the river ecosystem result in tolerant communities of lower diversity and altered microbial metabolism.

  20. Enterovirus infection of human islets of Langerhans affects β-cell function resulting in disintegrated islets, decreased glucose stimulated insulin secretion and loss of Golgi structure

    PubMed Central

    Hodik, M; Skog, O; Lukinius, A; Isaza-Correa, J M; Kuipers, J; Giepmans, B N G; Frisk, G

    2016-01-01

    Aims/hypothesis In type 1 diabetes (T1D), most insulin-producing β cells are destroyed, but the trigger is unknown. One of the possible triggers is a virus infection and the aim of this study was to test if enterovirus infection affects glucose stimulated insulin secretion and the effect of virus replication on cellular macromolecules and organelles involved in insulin secretion. Methods Isolated human islets were infected with different strains of coxsackievirus B (CVB) virus and the glucose-stimulated insulin release (GSIS) was measured in a dynamic perifusion system. Classical morphological electron microscopy, large-scale electron microscopy, so-called nanotomy, and immunohistochemistry were used to study to what extent virus-infected β cells contained insulin, and real-time PCR was used to analyze virus induced changes of islet specific genes. Results In islets infected with CVB, GSIS was reduced in correlation with the degree of virus-induced islet disintegration. The expression of the gene encoding insulin was decreased in infected islets, whereas the expression of glucagon was not affected. Also, in islets that were somewhat disintegrated, there were uninfected β cells. Ultrastructural analysis revealed that virus particles and virus replication complexes were only present in β cells. There was a significant number of insulin granules remaining in the virus-infected β cells, despite decreased expression of insulin mRNA. In addition, no typical Golgi apparatus was detected in these cells. Exposure of islets to synthetic dsRNA potentiated glucose-stimulated insulin secretion. Conclusions/interpretation Glucose-stimulated insulin secretion; organelles involved in insulin secretion and gene expression were all affected by CVB replication in β cells. PMID:27547409

  1. The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired Glucose Tolerance

    PubMed Central

    Hsu, Tai-Hao; Lee, Chien-Hsing; Lin, Fang-Yi; Wasser, Solomon P.; Lo, Hui-Chen

    2014-01-01

    The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia and impaired immune function, is increasing worldwide. Progression from impaired glucose tolerance (IGT) to type 2 DM has recently become a target for early intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein, we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX) extracted from CM on the immunocyte responses. Male Wistar rats were injected with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected with saline and gavaged vehicle were used as controls. Two weeks later, peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of FB, CM, and GX significantly decreased blood glucose levels in the postprandial period and in oral glucose tolerance test, and partially reversed T-splenocytic proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the IGT-induced decreases in tumor necrosis factor-α production; GX significantly increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes; and CM and GX significantly reversed IGT-induced decrease in interferon-γ production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic polysaccharide GX of T. mesenterica may increase T-cell immunity via the elevation of proinflammatory and T-helper cytokine production in rats with impaired glucose tolerance. PMID:24872934

  2. Changes in the salinity tolerance of sweet pepper plants as affected by nitrogen form and high CO2 concentration.

    PubMed

    Piñero, María C; Pérez-Jiménez, Margarita; López-Marín, Josefa; Del Amor, Francisco M

    2016-08-01

    The assimilation and availability of nitrogen in its different forms can significantly affect the response of primary productivity under the current atmospheric alteration and soil degradation. An elevated CO2 concentration (e[CO2]) triggers changes in the efficiency and efficacy of photosynthetic processes, water use and product yield, the plant response to stress being altered with respect to ambient CO2 conditions (a[CO2]). Additionally, NH4(+) has been related to improved plant responses to stress, considering both energy efficiency in N-assimilation and the overcoming of the inhibition of photorespiration at e[CO2]. Therefore, the aim of this work was to determine the response of sweet pepper plants (Capsicum annuum L.) receiving an additional supply of NH4(+) (90/10 NO3(-)/NH4(+)) to salinity stress (60mM NaCl) under a[CO2] (400μmolmol(-1)) or e[CO2] (800μmolmol(-1)). Salt-stressed plants grown at e[CO2] showed DW accumulation similar to that of the non-stressed plants at a[CO2]. The supply of NH4(+) reduced growth at e[CO2] when salinity was imposed. Moreover, NH4(+) differentially affected the stomatal conductance and water use efficiency and the leaf Cl(-), K(+), and Na(+) concentrations, but the extent of the effects was influenced by the [CO2]. An antioxidant-related response was prompted by salinity, the total phenolics and proline concentrations being reduced by NH4(+) at e[CO2]. Our results show that the effect of NH4(+) on plant salinity tolerance should be globally re-evaluated as e[CO2] can significantly alter the response, when compared with previous studies at a[CO2].

  3. Changes in the salinity tolerance of sweet pepper plants as affected by nitrogen form and high CO2 concentration.

    PubMed

    Piñero, María C; Pérez-Jiménez, Margarita; López-Marín, Josefa; Del Amor, Francisco M

    2016-08-01

    The assimilation and availability of nitrogen in its different forms can significantly affect the response of primary productivity under the current atmospheric alteration and soil degradation. An elevated CO2 concentration (e[CO2]) triggers changes in the efficiency and efficacy of photosynthetic processes, water use and product yield, the plant response to stress being altered with respect to ambient CO2 conditions (a[CO2]). Additionally, NH4(+) has been related to improved plant responses to stress, considering both energy efficiency in N-assimilation and the overcoming of the inhibition of photorespiration at e[CO2]. Therefore, the aim of this work was to determine the response of sweet pepper plants (Capsicum annuum L.) receiving an additional supply of NH4(+) (90/10 NO3(-)/NH4(+)) to salinity stress (60mM NaCl) under a[CO2] (400μmolmol(-1)) or e[CO2] (800μmolmol(-1)). Salt-stressed plants grown at e[CO2] showed DW accumulation similar to that of the non-stressed plants at a[CO2]. The supply of NH4(+) reduced growth at e[CO2] when salinity was imposed. Moreover, NH4(+) differentially affected the stomatal conductance and water use efficiency and the leaf Cl(-), K(+), and Na(+) concentrations, but the extent of the effects was influenced by the [CO2]. An antioxidant-related response was prompted by salinity, the total phenolics and proline concentrations being reduced by NH4(+) at e[CO2]. Our results show that the effect of NH4(+) on plant salinity tolerance should be globally re-evaluated as e[CO2] can significantly alter the response, when compared with previous studies at a[CO2]. PMID:27317970

  4. Linking cytoarchitecture to metabolism: sarcolemma-associated plectin affects glucose uptake by destabilizing microtubule networks in mdx myofibers

    PubMed Central

    2013-01-01

    Background Duchenne muscular dystrophy (DMD) is one of the most frequent forms of muscular disorders. It is caused by the absence of dystrophin, a core component of the sarcolemma-associated junctional complex that links the cytoskeleton to the extracellular matrix. We showed previously that plectin 1f (P1f), one of the major muscle-expressed isoforms of the cytoskeletal linker protein plectin, accumulates at the sarcolemma of DMD patients as well as of mdx mice, a widely studied animal model for DMD. Based on plectin’s dual role as structural protein and scaffolding platform for signaling molecules, we speculated that the dystrophic phenotype observed after loss of dystrophin was caused, at least to some extent, by excess plectin. Thus, we hypothesized that elimination of plectin expression in mdx skeletal muscle, while probably resulting in an overall more severe phenotype, may lead to a partial phenotype rescue. In particular, we wanted to assess whether excess sarcolemmal plectin contributes to the dysregulation of sugar metabolism in mdx myofibers. Methods We generated plectin/dystrophin double deficient (dKO) mice by breeding mdx with conditional striated muscle-restricted plectin knockout (cKO) mice. The phenotype of these mice was comparatively analyzed with that of mdx, cKO, and wild-type mice, focusing on structural integrity and dysregulation of glucose metabolism. Results We show that the accumulation of plectin at the sarcolemma of mdx muscle fibers hardly compensated for their loss of structural integrity. Instead, it led to an additional metabolic deficit by impairing glucose uptake. While dKO mice suffered from an overall more severe form of muscular dystrophy compared to mdx or plectin-deficient mice, sarcolemmal integrity as well as glucose uptake of their myofibers were restored to normal levels upon ablation of plectin. Furthermore, microtubule (MT) networks in intact dKO myofibers, including subsarcolemmal areas, were found to be more robust

  5. The contribution of cardiorespiratory fitness and visceral fat to risk factors in Japanese patients with impaired glucose tolerance and type 2 diabetes mellitus.

    PubMed

    Nagano, M; Kai, Y; Zou, B; Hatayama, T; Suwa, M; Sasaki, H; Kumagai, S

    2004-05-01

    It is still unclear as to how cardiorespiratory fitness and visceral fat accumulation contribute to coronary heart disease (CHD) risk factors in patients with diabetes mellitus. The purpose of the present study was to investigate whether cardiorespiratory fitness contributes to such risk factors independently of visceral fat accumulation. Two hundred Japanese patients (137 men and 63 women, aged 22 to 81 years) with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (type 2 DM) without any intervention and pharmacological therapy participated in a cross-sectional study. The levels of fasting insulin, triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and resting blood pressure were assessed. Maximal oxygen uptake (V.o(2max)), an index of cardiorespiratory fitness, was predicted by a graded exercise test using a cycle ergometer. Visceral fat area (VFA) was measured by computed tomography scan. The criteria for abnormalities of the risk factors were determined according to the standard values for Japanese. All subjects were divided equally into the following 3 groups according to their fitness level: low-fit (V.o(2max) < 32 mL/kg/min in men, V.o(2max) < 26 mL/kg/min in women), mid-fit (32 < or = V.o(2max) < 36 in men, 26 < or = V.o(2max) < 30 in women), and high-fit (V.o(2max) > or = 36 in men, V.o(2max) > or = 30 in women). The association between fitness level and the prevalence of abnormal values for these parameters was analyzed by a multiple logistic regression model adjusted for age and VFA. The odds ratio (OR) and 95% confidence interval (CI) for the prevalence of hyperinsulinemia were significantly lower in the mid-fit (OR = 0.35, 95% CI, 0.16 to 0.78) and in the high-fit groups (OR = 0.40, 95% CI, 0.16 to 0.98) compared with the low-fit group. In addition, ORs for the prevalence of low HDL-C in the mid-fit and high-fit groups were significantly lower (OR = 0.35, 95% CI, 0.14 to 0.86; and OR = 0.19; 95% CI, 0

  6. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation.

    PubMed

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

    2015-03-01

    Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans

  7. Amino acid and glucose metabolism in fed-batch CHO cell culture affects antibody production and glycosylation.

    PubMed

    Fan, Yuzhou; Jimenez Del Val, Ioscani; Müller, Christian; Wagtberg Sen, Jette; Rasmussen, Søren Kofoed; Kontoravdi, Cleo; Weilguny, Dietmar; Andersen, Mikael Rørdam

    2015-03-01

    Fed-batch Chinese hamster ovary (CHO) cell culture is the most commonly used process for IgG production in the biopharmaceutical industry. Amino acid and glucose consumption, cell growth, metabolism, antibody titer, and N-glycosylation patterns are always the major concerns during upstream process optimization, especially media optimization. Gaining knowledge on their interrelations could provide insight for obtaining higher immunoglobulin G (IgG) titer and better controlling glycosylation-related product quality. In this work, different fed-batch processes with two chemically defined proprietary media and feeds were studied using two IgG-producing cell lines. Our results indicate that the balance of glucose and amino acid concentration in the culture is important for cell growth, IgG titer and N-glycosylation. Accordingly, the ideal fate of glucose and amino acids in the culture could be mainly towards energy and recombinant product, respectively. Accumulation of by-products such as NH4(+) and lactate as a consequence of unbalanced nutrient supply to cell activities inhibits cell growth. The levels of Leu and Arg in the culture, which relate to cell growth and IgG productivity, need to be well controlled. Amino acids with the highest consumption rates correlate with the most abundant amino acids present in the produced IgG, and thus require sufficient availability during culture. Case-by-case analysis is necessary for understanding the effect of media and process optimization on glycosylation. We found that in certain cases the presence of Man5 glycan can be linked to limitation of UDP-GlcNAc biosynthesis as a result of insufficient extracellular Gln. However, under different culture conditions, high Man5 levels can also result from low α-1,3-mannosyl-glycoprotein 2-β-N-acetylglucosaminyltransferase (GnTI) and UDP-GlcNAc transporter activities, which may be attributed to high level of NH4+ in the cell culture. Furthermore, galactosylation of the mAb Fc glycans