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Sample records for 100-g glucose tolerance

  1. 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)

  2. Glucose tolerance test - non-pregnant

    MedlinePlus

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

  3. Glucose tolerance and insulin response to glucose load in body builders.

    PubMed

    Szczypaczewska, M; Nazar, K; Kaciuba-Uscilko, H

    1989-02-01

    To find out to what extent body composition affects glucose tolerance, blood glucose (BG) and insulin (IRI) responses to a 100-g oral glucose tolerance test (OGTT) were compared in 10 male body builders, 11 untrained lean control subjects, and 11 mildly obese men, all of similar age (19-35 years). In comparison with the remaining two groups, the body builders had the lowest percentage of fat, although their lean body mass (LBM) in absolute terms did not differ from that in obese subjects. Both BG and IRI concentrations during the OGTT were the lowest in body builders, medium in controls, and the highest in obese men. The differences in glucose tolerance between the groups were also demonstrated by comparison of the subjects' BG levels during the OGTT with the respective mean BG values obtained in a reference group of 42 healthy nonobese men aged from 20 to 55 years. The data indicate that body builders show better glucose tolerance and improved insulin action in comparison with untrained, nonobese subjects of similar age and body weight. Lean body mass in absolute terms cannot, however, be considered as a sole determinant of the insulin action in the body since in mildly obese subjects glucose tolerance was considerably reduced in spite of the fact that their LBM was similar to that in body builders. Either muscle hypertrophy or reduced adiposity may account for the beneficial effects of body building on glucose metabolism.

  4. Meal related glucose monitoring is a method of diagnosing glucose intolerance in pregnancies with high probability of gestational diabetes but normal glucose tolerance by oral glucose tolerance test.

    PubMed

    John, Mathew; Gopinath, Deepa

    2013-06-01

    Gestational diabetes mellitus diagnosed by classical oral glucose tolerance test can result in fetal complications like macrosomia and polyhydramnios. Guidelines exist on management of patients diagnose by abnormal oral glucose tolerance test with diet modification followed by insulin. Even patients with abnormal oral glucose tolerance test maintaining apparently normal blood sugars with diet are advised insulin if there is accelerated fetal growth. But patients with normal oral glucose tolerance test can present with macrosomia and polyhydramnios. These patients are labelled as not having gestational diabetes mellitus and are followed up with repeat oral glucose tolerance test. We hypothesise that these patients may have an altered placental threshold to glucose or abnormal sensitivity of fetal tissues to glucose. Meal related glucose monitoring in these patients can identify minor abnormalities in glucose disturbance and should be treated to targets similar to physiological levels of glucose in non pregnant adults.

  5. Glucose tolerance during pregnancy in Asian women.

    PubMed

    Samanta, A; Burden, M L; Burden, A C; Jones, G R

    1989-08-01

    The present study was aimed at examining differences in gestational diabetes mellitus (GDM) between two ethnic populations (immigrant Asians and indigenous White Caucasians) residing in Leicester, U.K. The study was divided into two parts: to determine the prevalence of GDM and to determine the level at which glycaemia may impose a risk to the mother and the foetus. Of a total of 12,005 pregnancies (4561 Asian and 7444 White Caucasian), over a 3-year period, 314 (6.8%) Asian and 504 (6.7%) White Caucasian were given a 75-g oral glucose tolerance test (OGTT) at 28-32 weeks for indications of 'large for date' pregnancies, hydramnios, glycosuria, a history of previous abortions, stillbirths, congenital abnormalities or glucose intolerance, and family history of diabetes. Abnormal glucose tolerance (AGT) was taken as a 2-h venous plasma glucose greater than or equal to 7.8 mmol/l which reverted to normal when formally tested during the puerperium (WHO criteria, 1985). AGT was found in 1.38% Asian and 0.87% White Caucasian pregnancies (P less than 0.01). This was further divided into impaired glucose tolerance (IGT) (2-h value 7.8-11.1 mmol/l) and gestational diabetes mellitus (GDM) (2-h value greater than or equal to 11.1 mmol/l). IGT was found in 1.2% Asian and 0.84% White Caucasian pregnancies (P less than 0.01), and GDM in 0.18% and 0.02% respectively (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Amino acid mixture acutely improves the glucose tolerance of healthy overweight adults.

    PubMed

    Wang, Bei; Kammer, Lynne M; Ding, Zhenping; Lassiter, David G; Hwang, Jungyun; Nelson, Jeffrey L; Ivy, John L

    2012-01-01

    Certain amino acids have been reported to influence carbohydrate metabolism and blood glucose clearance, as well as improve the glucose tolerance in animal models. We hypothesized that an amino acid mixture consisting of isoleucine and 4 additional amino acids would improve the glucose response of healthy overweight men and women to an oral glucose tolerance test (OGTT). Twenty-two overweight healthy subjects completed 2 OGTTs after consuming 2 different test beverages. The amino acid mixture beverage (CHO/AA) consisted of 0.088 g cystine 2HCl, 0.043 g methionine, 0.086 g valine, 12.094 g isoleucine, 0.084 g leucine, and 100 g dextrose. The control beverage (CHO) consisted of 100 g dextrose only. Venous blood samples were drawn 10 minutes before the start of ingesting the drinks and 15, 30, 60, 120, and 180 minutes after the completion of the drinks. During the OGTT, the plasma glucose response for the CHO/AA treatment was significantly lower than that of the CHO treatment (P < .01), as was the plasma glucose area under the curve (CHO/AA 806 ± 31 mmol/L·3 hours vs CHO 942 ± 40 mmol/L·3 hours). Differences in plasma glucose between treatments occurred at 30, 60, 120, and 180 minutes after supplement ingestion. Plasma glucagon during the CHO/AA treatment was significantly higher than during the CHO treatment. However, there were no significant differences in plasma insulin or C-peptide responses between treatments. These results suggest that the amino acid mixture lowers the glucose response to an OGTT in healthy overweight subjects in an insulin-independent manner.

  7. Improvement in glucose tolerance due to Momordica charantia (karela).

    PubMed Central

    Leatherdale, B A; Panesar, R K; Singh, G; Atkins, T W; Bailey, C J; Bignell, A H

    1981-01-01

    The effect of karela (Momordica charantia), a fruit indigenous to South America and Asia, on glucose and insulin concentrations was studied in nine non-insulin-dependent diabetics and six non-diabetic laboratory rats. A water-soluble extract of the fruits significantly reduced blood glucose concentrations during a 50 g oral glucose tolerance test in the diabetics and after force-feeding in the rats. Fried karela fruits consumed as a daily supplement to the diet produced a small but significant improvement in glucose tolerance. Improvement in glucose tolerance was not associated with an increase in serum insulin responses. These results show that karela improves glucose tolerance in diabetes. Doctors supervising Asian diabetics should be aware of the fruit's hypoglycaemic properties. PMID:6786635

  8. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

    PubMed Central

    Knudsen, Sine H.; Karstoft, Kristian; Pedersen, Bente K.; van Hall, Gerrit; Solomon, Thomas P. J.

    2014-01-01

    Abstract We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty‐four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m2, P > 0.05) underwent a 180‐min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6‐2H2]glucose and ingestion of [U‐13C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials, plasma glucose concentrations and kinetics, insulin, C‐peptide, and glucagon were measured. Rates (mg kg−1 min−1) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; RaOGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, RaOGTT, and Rd (all P < 0.0001) in all groups with a tendency for a greater (~20%) peak RaOGTT value in NGT subjects when compared to IGT and T2D subjects. Accordingly, following exercise, the plasma glucose concentration during the OGTT was increased in NGT subjects (P < 0.05), while unchanged in subjects with IGT and T2D. In conclusion, while a single bout of moderate‐intensity exercise increased the postprandial glucose response in NGT subjects, glucose tolerance following exercise was preserved in the two hyperglycemic groups. Thus, postprandial plasma glucose responses immediately following exercise are dependent on the underlying degree of glycemic control. PMID:25168869

  9. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    PubMed

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 <11.1 mmol/L), and none with diabetes. Using the continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and <11.1 mmol/L (IGT) in 9 children (69%) and >11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of <2.7 mmol/L (hypoglycemia). No glycemic abnormality was detected using HbA1C (5.7 ± 0.3%). 11/13 patients had HOMA values >2.6 and QUICKI values <0.35 denoting insulin resistance. Beta cell mass percent (B %) = 200 ± 94.8% and insulin sensitivity values (IS)=50.4 ± 45.5% denoted insulin resistance with hyper-insulinaemia and preserved beta cell mass. In obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  10. A study of the effect of diet on glycosylated haemoglobin and albumin levels and glucose tolerance in normal subjects.

    PubMed

    Ryle, A J; Davie, S; Gould, B J; Yudkin, J S

    1990-12-01

    As factors other than the degree of glucose tolerance or ambient blood glucose may determine glycosylated haemoglobin levels, we have investigated the effects of dietary glucose and soluble fibre supplementation on glucose tolerance, glycosylated haemoglobin and glycosylated albumin in non-diabetic subjects. Eleven non-diabetic subjects (7 M, 4 F; age 26.5 +/- 6.5 (+/- SD) yr; BMI 21.6 +/- 3.1 kg m-2) followed a high-soluble-fibre (5 g guar gum thrice daily)/low-glucose diet, or a low-soluble-fibre/high-glucose (500 ml glucose drink providing 100 g glucose per day) diet, each for 6 weeks, in randomized order. A 75 g oral glucose tolerance test was performed at recruitment and after each diet period, and fasting blood was assayed for glycosylated albumin by affinity chromatography, and glycosylated haemoglobin by four different methods. Adherence to guar and glucose supplementation was assessed at 89.5 +/- 7.5% and 97.1 +/- 3.5%, respectively. There was no significant effect of either diet on mean fasting, 1-h or 2-h plasma glucose concentration, or glycosylated haemoglobin levels by any assay. Glycosylated albumin was 1.71 +/- 0.35% at entry, fell to 1.33 +/- 0.30% (p less than 0.01) with high-fibre and rose to 1.95 +/- 0.23% (p less than 0.02) after a high-glucose diet. Insulin, total- and HDL-cholesterol and triglyceride levels were unaffected by either diet. A high-glucose diet increases, and a high-soluble-fibre diet decreases, levels of glycosylated albumin without effects on glucose tolerance or glycosylated haemoglobin.

  11. An amino acid mixture improves glucose tolerance and lowers insulin resistance in the obese Zucker rat.

    PubMed

    Bernard, Jeffrey R; Liao, Yi-Hung; Ding, Zhenping; Hara, Daisuke; Kleinert, Maximilian; Nelson, Jeffrey L; Ivy, John L

    2013-07-01

    The purpose of this investigation was to test an amino acid mixture on glucose tolerance in obese Zucker rats [experiment (Exp)-1] and determine whether differences in blood glucose were associated with alterations in muscle glucose uptake [experiment (Exp)-2]. Exp-1 rats were gavaged with either carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1), carbohydrate plus amino acid mixture with increased leucine concentration (OB-AA-2) or water (OB-PLA). The glucose response in OB-AA-1 and OB-AA-2 were similar, and both were lower compared to OB-CHO. This effect of the amino acid mixtures did not appear to be solely attributable to an increase in plasma insulin. Rats in Exp-2 were gavaged with carbohydrate (OB-CHO), carbohydrate plus amino acid mixture (OB-AA-1) or water (OB-PLA). Lean Zuckers were gavaged with carbohydrate (LN-CHO). Fifteen minutes after gavage, a radiolabeled glucose analog was infused through a catheter previously implanted in the right jugular vein. Blood glucose was significantly lower in OB-AA-1 compared to OB-CHO while the insulin responses were similar. Glucose uptake was greater in OB-AA-1 compared with OB-CHO, and similar to that in LN-CHO in red gastrocnemius muscle (5.15 ± 0.29, 3.8 ± 0.27, 5.18 ± 0.34 µmol/100 g/min, respectively). Western blot analysis showed that Akt substrate of 160 kDa (AS160) phosphorylation was enhanced for OB-AA-1 and LN-CHO compared to OB-CHO. These findings suggest that an amino acid mixture improves glucose tolerance in an insulin resistant model and that these improvements are associated with an increase in skeletal muscle glucose uptake possibly due to improved intracellular signaling.

  12. Impaired glucose tolerance in patients with amyotrophic lateral sclerosis.

    PubMed

    Pradat, Pierre-Francois; Bruneteau, Gaelle; Gordon, Paul H; Dupuis, Luc; Bonnefont-Rousselot, Dominique; Simon, Dominique; Salachas, Francois; Corcia, Philippe; Frochot, Vincent; Lacorte, Jean-Marc; Jardel, Claude; Coussieu, Christiane; Le Forestier, Nadine; Lacomblez, Lucette; Loeffler, Jean-Philippe; Meininger, Vincent

    2010-01-01

    Our objectives were to analyse carbohydrate metabolism in a series of ALS patients and to examine potential association with parameters of lipid metabolism and clinical features. Glucose tolerance was assessed by the oral glucose tolerance test in 21 non-diabetic ALS patients and compared with 21 age- and sex-matched normal subjects. Lipids and lactate/pyruvate ratio, levels of pro-inflammatory cytokines (tumour necrosis factor-alpha and interleukin-6) and adipocytokines (leptin and adiponectin) were also measured in ALS patients. Mann-Whitney U-tests analysed continuous data and Fisher's exact tests assessed categorical data. Blood glucose determined 120 min after the glucose bolus was significantly higher in patients with ALS (7.41 mmol/l+/-1.68) compared to controls (6.05+/-1.44, p=0.006). ALS patients with impaired glucose tolerance (IGT) according to WHO criteria (n=7, 33%) were more likely to have elevated free fatty acids (FFA) levels compared to patients with normal glucose tolerance (0.77 nmol/l+/-0.30 vs. 0.57+/-0.19, p=0.04). IGT was not associated with disease duration or severity. In conclusion, patients with ALS show abnormal glucose tolerance that could be associated with increased FFA levels, a key determinant of insulin resistance. The origin of glucose homeostasis abnormalities in ALS may be multifactorial and deserves further investigation.

  13. New insulin sensitivity index from the oral glucose tolerance test.

    PubMed

    Kazama, Youichiro; Takamura, Toshinari; Sakurai, Masaru; Shindo, Hisakazu; Ohkubo, Eizho; Aida, Kaoru; Harii, Norikazu; Taki, Katsumi; Kaneshige, Masahiro; Tanaka, Shoichiro; Shimura, Hiroki; Endo, Toyoshi; Kobayashi, Tetsuro

    2008-01-01

    A new insulin sensitivity index was devised on the basis of an autoregressive model and its validity was investigated. Using data from the 75-g oral glucose tolerance test (OGTT), 115 subjects were divided into 3 groups: 40 with normal glucose tolerance, 34 with impaired glucose tolerance, and 41 with type 2 diabetes mellitus. The new insulin sensitivity index: oral glucose insulin sensitivity index (GSI) was calculated from five sets of plasma glucose and insulin levels obtained at 0, 30, 60, 90 and 120 min during OGTT using a formula based on an autoregressive model. Forty-three of the 115 subjects were examined for insulin sensitivity index (ISI) by euglycemic hyperinsulinemic clamp. GSI decreased in the order of normal glucose tolerance group>impaired glucose tolerance group>diabetic group. There was a significant correlation between GSI and the ISI derived from euglycemic hyperinsulinemic clamp study data in all 43 subjects who underwent both tests (r=0.72; P<0.0001). The ISI calculated by previous methods poorly correlated with the ISIs obtained by euglycemic hyperinsulinemic clamp study. In conclusion, this new insulin sensitivity index based on the data obtained from OGTT using an autoregressive model is comparable to an insulin sensitivity index by euglycemic hyperinsulinemic clamp technique and may be superior to previous indexes that have been devised to determine insulin sensitivity from OGTT data.

  14. An integrated glucose-insulin model to describe oral glucose tolerance test data in type 2 diabetics.

    PubMed

    Jauslin, Petra M; Silber, Hanna E; Frey, Nicolas; Gieschke, Ronald; Simonsson, Ulrika S H; Jorga, Karin; Karlsson, Mats O

    2007-10-01

    An integrated model for the glucose-insulin system describing oral glucose tolerance test data was developed, extending on a previously introduced model for intravenous glucose provocations. Model extensions comprised the description of glucose absorption by a chain of transit compartments with a mean transit time of 35 minutes, a bioavailability of 80%, and a representation of the incretin effect, expressed as a direct effect of the glucose absorption rate on insulin secretion. The ability of the model to predict the incretin effect was assessed by simulating the observed difference in insulin response following an oral glucose tolerance test compared with an isoglycemic glucose infusion mimicking an oral glucose tolerance test profile. The extension of the integrated glucose-insulin model to gain information from oral glucose tolerance test data considerably expands its range of applications because the oral glucose tolerance test is one of the most common glucose challenge experiments for assessing the efficacy of hypoglycemic agents in clinical drug development.

  15. Evaluation of Oral Glucose Tolerance Test in Children With Epilepsy.

    PubMed

    Varlamis, Sotirios; Vavatsi, Norma; Pavlou, Evangelos; Kotsis, Vasileios; Spilioti, Martha; Kavga, Maria; Varlamis, George; Sotiriadou, Foteini; Agakidou, Eleni; Voutoufianakis, Spyridon; Evangeliou, Athanasios E

    2013-11-01

    Glucose metabolism of children with drug-resistant epilepsy, controlled by antiepileptic drugs epilepsy, and first-time nonfebrile seizures was studied through the performance of an oral glucose tolerance test and through insulin, C-peptide, and glycosylated hemoglobin measurements. In the refractory epilepsy group, there were more abnormal oral glucose tolerance test results (62.07%) in comparison to the controlled epilepsy group (25%) and the group of first-time seizures (21.21%). There was a significant difference between the group of refractory epilepsy and every other group concerning the abnormality of the oral glucose tolerance test (P < .05). The mean values of insulin, HbA1c, and C-peptide levels were normal for all groups. The results of the present study suggest that there is a distinction of refractory epilepsies from the drug-controlled ones and the first-induced seizures relating to their metabolic profile, regardless of the type of seizures.

  16. 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.

  17. Acute effects of nicorandil on glucose tolerance in subjects with borderline fasting blood glucose levels.

    PubMed

    Boes, U; Wallner, S; Wascher, T C

    2001-02-15

    The acute effect of the anti-ischemic potassium channel opener nicorandil on glucose tolerance and post-challenge insulin levels was investigated in 11 subjects (6 males and 5 females, age 59 +/- 2 years) with borderline fasting blood glucose in a single blinded randomised study. All participants were submitted to two oral glucose tolerance tests in randomised order, once without any premedication and once 30 minutes after oral administration of 20 mg nicorandil. This single dose of nicorandil significantly increased blood glucose levels at 120 minutes (173 +/- 16 vs. 150 +/- 11 mg/dl, p < 0.05 by ANOVA) and 180 minutes (106 +/- 11 vs. 88 +/- 7 mg/dl, p < 0.05 by ANOVA) after ingestion of 75 mg of glucose. Serum insulin levels were not significantly altered. In conclusion we suggest that controlled studies in patients with coronary artery disease should be performed to investigate whether long term treatment with nicorandil increases progression rates from impaired glucose tolerance to type-II diabetes and/or from normal to impaired glucose tolerance with a possibly negative impact on the course of cardiovascular disease in comparison to conventional anti-anginal drugs.

  18. Pregnane X receptor agonists impair postprandial glucose tolerance.

    PubMed

    Rysä, J; Buler, M; Savolainen, M J; Ruskoaho, H; Hakkola, J; Hukkanen, J

    2013-06-01

    We conducted a randomized, open, placebo-controlled crossover trial to investigate the effects of the pregnane X receptor (PXR) agonist rifampin on an oral glucose tolerance test (OGTT) in 12 healthy volunteers. The subjects were administered 600 mg rifampin or placebo once daily for 7 days, and OGTT was performed on the eighth day. The mean incremental glucose and insulin areas under the plasma concentration-time curves (AUC(incr)) increased by 192% (P = 0.008) and 45% (P = 0.031), respectively. The fasting glucose, insulin, and C-peptide, and the homeostasis model assessment for insulin resistance, were not affected. The glucose AUC(incr) during OGTT was significantly increased in rats after 4-day treatment with pregnenolone 16α-carbonitrile (PCN), an agonist of the rat PXR. The hepatic level of glucose transporter 2 (Glut2) mRNA was downregulated by PCN. In conclusion, both human and rat PXR agonists elicited postprandial hyperglycemia, suggesting a detrimental role of PXR activation on glucose tolerance.

  19. 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.

  20. Lactation Intensity and Postpartum Maternal Glucose Tolerance and Insulin Resistance in Women With Recent GDM

    PubMed Central

    Gunderson, Erica P.; Hedderson, Monique M.; Chiang, Vicky; Crites, Yvonne; Walton, David; Azevedo, Robert A.; Fox, Gary; Elmasian, Cathie; Young, Stephen; Salvador, Nora; Lum, Michael; Quesenberry, Charles P.; Lo, Joan C.; Sternfeld, Barbara; Ferrara, Assiamira; Selby, Joseph V.

    2012-01-01

    OBJECTIVE To examine the association between breastfeeding intensity in relation to maternal blood glucose and insulin and glucose intolerance based on the postpartum 2-h 75-g oral glucose tolerance test (OGTT) results at 6–9 weeks after a pregnancy with gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS We selected 522 participants enrolled into the Study of Women, Infant Feeding, and Type 2 Diabetes (SWIFT), a prospective observational cohort study of Kaiser Permanente Northern California members diagnosed with GDM using the 3-h 100-g OGTT by the Carpenter and Coustan criteria. Women were classified as normal, prediabetes, or diabetes according to American Diabetes Association criteria based on the postpartum 2-h 75-g OGTT results. RESULTS Compared with exclusive or mostly formula feeding (>17 oz formula per 24 h), exclusive breastfeeding and mostly breastfeeding (≤6 oz formula per 24 h) groups, respectively, had lower adjusted mean (95% CI) group differences in fasting plasma glucose (mg/dL) of −4.3 (−7.4 to −1.3) and −5.0 (−8.5 to −1.4), in fasting insulin (μU/mL) of −6.3 (−10.1 to −2.4) and −7.5 (−11.9 to −3.0), and in 2-h insulin of −21.4 (−41.0 to −1.7) and −36.5 (−59.3 to −13.7) (all P < 0.05). Exclusive or mostly breastfeeding groups had lower prevalence of diabetes or prediabetes (P = 0.02). CONCLUSIONS Higher intensity of lactation was associated with improved fasting glucose and lower insulin levels at 6–9 weeks’ postpartum. Lactation may have favorable effects on glucose metabolism and insulin sensitivity that may reduce diabetes risk after GDM pregnancy. PMID:22011407

  1. Correspondence of continuous interstitial glucose measurement against arterialised and capillary glucose following an oral glucose tolerance test in healthy volunteers.

    PubMed

    Dye, Louise; Mansfield, Michael; Lasikiewicz, Nicola; Mahawish, Lena; Schnell, Rainer; Talbot, Duncan; Chauhan, Hitesh; Croden, Fiona; Lawton, Clare

    2010-01-01

    The aim of the present study was to validate the Glucoday continuous interstitial ambulatory glucose-monitoring device (AGD) against plasma glucose measured from arterialised venous (AV) and glucose from capillary whole blood (finger prick, FP) in non-diabetic subjects in response to an oral glucose tolerance test. Fifteen healthy overweight men (age 30-49 years, BMI 26-31 kg/m2) participated. Glucose levels were measured before, during and after consumption of an oral 75 g glucose load using twelve FP samples and forty-four 1 ml AV blood samples during 180 min. Interstitial glucose was measured via the AGD. Three venous samples for fasting insulin were taken to estimate insulin resistance. Profiles of AGD, AV and FP glucose were generated for each participant. Glucose values for each minute of the measurement period were interpolated using a locally weighted scatterplot smoother. Data were compared using Bland-Altman plots that showed good correspondence between all pairs of measurements. Concordance between the three methods was 0.8771 (Kendall's W, n 15, P < 0.001). Concordance was greater between AV and FP (W = 0.9696) than AGD and AV (W = 0.8770) or AGD and FP (W = 0.8764). Analysis of time to peak glucose indicated that AGD measures lagged approximately 15 min behind FP and AV measures. Percent body fat was significantly correlated with time to peak glucose levels for each measure, while BMI and estimated insulin resistance (homeostatic model assessment, HOMA) were not. In conclusion, AGD shows good correspondence with FP and AV glucose measures in response to a glucose load with a 15 min time lag. Taking this into account, AGD has potential application in nutrition and behaviour studies.

  2. [Effects of coca chewing on the glucose tolerance test].

    PubMed

    Galarza Guzmán, M; Peñaloza Imaña, R; Echalar Afcha, L; Aguilar Valerio, M; Spielvogel, H; Sauvain, M

    1997-01-01

    The effects of coca chewing on the glucose tolerance test were measured. The subjects were 14 habitual coca chewers and 14 non-chewers. All were of Aymara ancestry and came from a rural community from the "Altiplano" close to the city of La Paz. The coca users chewed coca leaves during 3 1/2 hours of the test. The non-chewers showed a significant hypoglycemia at 120 minutes of the test. This effect was not observed in the coca chewers. The hormonal counter-regulation response to hypoglycemia worked perfectly in non-chewers, since glucose levels reached normal values at 180 minutes of the test. These results suggest that coca chewers, at high altitude do not present hypoglycemia, due to an antagonic action of coca metabolites on insulin; allowing a greater availability of glucose in the organism. This would have a positive effect on metabolism in an environment of hypobaric hypoxia, known to lead to situations of hypoglycemia.

  3. Sodium salicylate restores the impaired insulin response to glucose and improves glucose tolerance in heroin addicts.

    PubMed

    Giugliano, D; Quatraro, A; Consoli, G; Stante, A; Simeone, V; Ceriello, A; Paolisso, G; Torella, R

    1987-01-01

    Plasma glucose, insulin, C-peptide, glucagon and growth hormone responses to intravenous glucose were evaluated in 10 heroin addicts in the basal state and during an infusion of sodium salicylate, an inhibitor of endogenous prostaglandin synthesis. Ten normal subjects, matched for age, sex and weight served as controls. In the basal state, the heroin addicts had markedly reduced insulin responses to intravenous glucose and low glucose disappearance rates (p less than 0.01 vs controls). The infusion of sodium salicylate caused a striking increase of the acute insulin response to intravenous glucose (from 14.5 +/- 4 microU/ml to 88 +/- 11 microU/ml, p less than 0.001) and restored to normal the reduced glucose tolerance (KG from 1.10 +/- 0.1% min-1 to 2.04 +/- 0.19% min-1). Hypoglycemic values were found in all addicts at the end of the test during salicylate infusion. Indomethacin pretreatment in five additional addicts also caused normalization of the impaired insulin responses to the intravenous glucose challenge and restored to normal the reduced glucose disappearance rate. Plasma glucagon and growth hormone levels were normally suppressed by glucose in addicts in basal conditions; sodium salicylate infusion completely overturned these hormonal responses which became positive in the first 15 min following the glucose challenge. These results demonstrate that the two prostaglandin synthesis inhibitors can restore the impaired B-cell response to glucose in heroin addicts to normal, indicating that this response is not lost but is inhibited by heroin itself or by other substances, perhaps by the endogenous prostaglandins.

  4. 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

  5. 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.

  6. An integrated glucose-insulin model to describe oral glucose tolerance test data in healthy volunteers.

    PubMed

    Silber, Hanna E; Frey, Nicolas; Karlsson, Mats O

    2010-03-01

    The extension of the previously developed integrated models for glucose and insulin (IGI) to include the oral glucose tolerance test (OGTT) in healthy volunteers could be valuable to better understand the differences between healthy individuals and those with type 2 diabetes mellitus (T2DM). Data from an OGTT in 23 healthy volunteers were used. Analysis was based on the previously developed intravenous model with extensions for glucose absorption and incretin effect on insulin secretion. The need for additional structural components was evaluated. The model was evaluated by simulation and a bootstrap. Multiple glucose and insulin concentration peaks were observed in most individuals as well as hypoglycemic episodes in the second half of the experiment. The OGTT data were successfully described by the extended basic model. An additional control mechanism of insulin on glucose production improved the description of the data. The model showed good predictive properties, and parameters were estimated with good precision. In conclusion, a previously presented integrated model has been extended to describe glucose and insulin concentrations in healthy volunteers following an OGTT. The characterization of the differences between the healthy and diabetic stages in the IGI model could potentially be used to extrapolate drug effect from healthy volunteers to T2DM.

  7. Blood glucose rise after lactose tolerance testing in infants.

    PubMed

    Paige, D M; Mellits, E D; Chiu, F Y; Davis, L; Bayless, T M; Cordano, A

    1978-02-01

    Lactose tolerance tests are used clinically to screen children and infants. It is assumed that absorption of a lactose challenge in infants would occur in a predictable pattern prior to weaning. Twenty-one infants from 3 to 12 months of age were studied. The maximum blood glucose rise over fasting levels ranged from 11.0 to 62.0 mg/100 ml; the mean was 32.6 mg/100 ml. Six infants had a maximum rise of less than 20 mg/100 ml. Eleven infants (52%) had a maximum rise of greater than 30 mg/100 ml. Signs of intolerance were not noted in any subject. Weight and length were normally disturbed. Results indicate the variance in glucose rise existing within a population of infants growing normally and consuming milk. Gastric emptying, digestion, and absorption may influence the blood glucose rise after a lactose test. Established glucose levels used as an index to lactose absorption in older children and adults may not accurately reflect lactase activity in infants.

  8. [Flat curves of oral glucose tolerance tests (author's transl)].

    PubMed

    Slama, G; Tchobroutsky, G

    1980-04-26

    Patients are often referred to diabetologists on account of a flat curve of oral glucose tolerance test. This abnormality, however, is virtually never associated with a serious metabolic disorder and in any case, it never points to a disease that cannot be diagnosed by questioning or by straightforward clinical examination, nor confirmed by a more specific laboratory test. The curve may be flat for technical reasons (e.g. rejection of the glucose administered, timing of blood withdrawals and assays), for physiological reasons (differences between venous and arteriolo-capillary blood), or for pathological reasons (interaction with drugs, pituitary, thyroid or adrenal insufficiency, digestive malabsorption) but it never implies organic hypoglycaemia nor diabetes mellitus.

  9. Glucose and insulin tolerance throughout the menstrual cycle.

    PubMed

    Fioretti, P; Genazzani, A R; Felber, J P; Facchini, V; Onano, A M; Romagnino, S; Facchinetti, F; Piras, G L

    1975-03-01

    On the basis of the behaviour during menstrual cycle of the pituitary hormones plasma levels, the Authors have studied during the different periods of the cycle (follicular, ovulatory and luteal) the effects of OGTT and ITT's on the plasma levels of Glucose, insulin, HGH and Cortisol. Significantly lower levels of IRI, HGH and Cortisol were found in follicular phase compared to ovulatory period and luteal phase except for Cortisol in luteal phase. A slightly higher glucose tolerance was found in follicular phase as well as a reduced hypoglicemia under insulin load. Reduced HGH response to ITT was found in follicular phase as well as a reduced Cortisol response compared to the results observed in ovulatory and luteal phase. These data sustain the concept that hormonal variations occurring in an ovulatory cycle are also capable of modifying the woman's body response to various stimuli such as OGTT and ITT.

  10. Chronic Manganism: Preliminary Observations on Glucose Tolerance and Serum Proteins

    PubMed Central

    Hassanein, M.; Ghaleb, H. A.; Haroun, E. A.; Hegazy, M. R.; Khayyal, M. A. H.

    1966-01-01

    An intravenous glucose tolerance test was carried out in 11 patients with chronic manganese poisoning. Prolonged reactionary hypoglycaemia was observed. The underlying mechanism is discussed. It may be due to a disturbance of the hypothalamo-pituitary-adrenal axis. In seven of these patients total serum proteins were estimated and were separated electrophoretically. The albumin: globulin ratios were lower in patients than in controls. There were significant reductions in serum albumin concentrations and increases in concentrations of α1 and β globulins. PMID:5904101

  11. Effects of celiac superior mesenteric ganglionectomy on glucose homeostasis and hormonal changes during oral glucose tolerance testing in rats.

    PubMed

    Kumakura, Atsushi; Shikuma, Junpei; Ogihara, Norikazu; Eiki, Jun-ichi; Kanazawa, Masao; Notoya, Yōko; Kikuchi, Masatoshi; Odawara, Masato

    2013-01-01

    The liver plays an important role in maintaining glucose homeostasis in the body. In the prandial state, some of the glucose which is absorbed by the gastrointestinal tract is converted into glycogen and stored in the liver. In contrast, the liver produces glucose by glycogenolysis and gluconeogenesis while fasting. Thus, the liver contributes to maintaining blood glucose level within normoglycemic range. Glycogenesis and glycogenolysis are regulated by various mechanisms including hormones, the sympathetic and parasympathetic nervous systems and the hepatic glucose content. In this study, we examined a rat model in which the celiac superior mesenteric ganglion (CSMG) was resected. We attempted to elucidate how the celiac sympathetic nervous system is involved in regulating glucose homeostasis by assessing the effects of CSMG resection on glucose excursion during an oral glucose tolerance test, and by examining hepatic glycogen content and hepatic glycogen phosphorylase (GP) activity. On the oral glucose tolerance test, CSMG-resected rats demonstrated improved glucose tolerance and significantly increased GP activity compared with sham-operated rats, whereas there were no significant differences in insulin, glucagon or catecholamine levels between the 2 groups. These results suggest that the celiac sympathetic nervous system is involved in regulating the rate of glycogen consumption through GP activity. In conclusion, the examined rat model showed that the celiac sympathetic nervous system regulates hepatic glucose metabolism in conjunction with vagal nerve innervations and is a critical component in the maintenance of blood glucose homeostasis.

  12. Native fructose extracted from apple improves glucose tolerance in mice.

    PubMed

    Dray, C; Colom, A; Guigné, C; Legonidec, S; Guibert, A; Ouarne, F; Valet, P

    2009-12-01

    Fructose is one of the most abundant monosaccharide in nature. It is also the sweetest naturally occurring carbohydrate. Since decades, fructose used for food preparations is not provided by fruit or vegetable but by a chemical process of starch or inulin conversion. We processed a new method of fructose extraction from apple and investigated the acute and long term effect of this carbohydrate on glucose metabolism in C57Bl6/j mice. By using the glycemic index (GI), we have shown that one of the sugars obtained from apple, FructiLight, has a very low impact on glycemic and insulin response during acute treatment compared to other sugars. This carbohydrate, essentially constituted by fructose, has also beneficial properties when administrated for long term treatment. Indeed, as two other sugars extracted from apple (FructiSweetApple and FructiSweet67), FructiLight exposure during 21 weeks in beverage has promoted an enhancement of glucose tolerance compared to glucose treatment without affecting food intake and weight. All these results indicate that apple-extracted sugars and more precisely fructose from these fruits could be a promising way to produce new food and sweet beverages.

  13. 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

  14. Biomarkers in Fasting Serum to Estimate Glucose Tolerance, Insulin Sensitivity, and Insulin Secretion

    PubMed Central

    Goldfine, Allison B.; Gerwien, Robert W.; Kolberg, Janice A.; O’Shea, Sheila; Hamren, Sarah; Hein, Glenn P.; Xu, Xiaomei M.; Patti, Mary Elizabeth

    2014-01-01

    BACKGROUND Biomarkers for estimating reduced glucose tolerance, insulin sensitivity, or impaired insulin secretion would be clinically useful, since these physiologic measures are important in the pathogenesis of type 2 diabetes mellitus. METHODS We conducted a cross-sectional study in which 94 individuals, of whom 84 had 1 or more risk factors and 10 had no known risk factors for diabetes, underwent oral glucose tolerance testing. We measured 34 protein biomarkers associated with diabetes risk in 250-μL fasting serum samples. We applied multiple regression selection techniques to identify the most informative biomarkers and develop multivariate models to estimate glucose tolerance, insulin sensitivity, and insulin secretion. The ability of the glucose tolerance model to discriminate between diabetic individuals and those with impaired or normal glucose tolerance was evaluated by area under the ROC curve (AUC) analysis. RESULTS Of the at-risk participants, 25 (30%) were found to have impaired glucose tolerance, and 11 (13%) diabetes. Using molecular counting technology, we assessed multiple biomarkers with high accuracy in small volume samples. Multivariate biomarker models derived from fasting samples correlated strongly with 2-h postload glucose tolerance (R2 = 0.45, P < 0.0001), composite insulin sensitivity index (R2 = 0.91, P < 0.0001), and insulin secretion (R2 = 0.45, P < 0.0001). Additionally, the glucose tolerance model provided strong discrimination between diabetes vs impaired or normal glucose tolerance (AUC 0.89) and between diabetes and impaired glucose tolerance vs normal tolerance (AUC 0.78). CONCLUSIONS Biomarkers in fasting blood samples may be useful in estimating glucose tolerance, insulin sensitivity, and insulin secretion. PMID:21149503

  15. 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.

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

    PubMed Central

    Adams, Jessica M.; Fagel, Brian; Lam, Daniel D.; Qi, Nathan; Rubinstein, Marcelo

    2016-01-01

    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

  17. 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.

  18. 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.

  19. 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.

  20. Hepatic portal vein denervation impairs oral glucose tolerance but not exenatide's effect on glycemia.

    PubMed

    Ionut, Viorica; Castro, Ana Valeria B; Woolcott, Orison O; Stefanovski, Darko; Iyer, Malini S; Broussard, Josiane L; Burch, Miguel; Elazary, Ram; Kolka, Cathryn M; Mkrtchyan, Hasmik; Bediako, Isaac Asare; Bergman, Richard N

    2014-10-15

    The hepatoportal area is an important glucohomeostatic metabolic sensor, sensing hypoglycemia, hyperglycemia, and hormones such as glucagon-like peptide-1 (GLP-1). We have reported previously that activation of hepatoportal sensors by intraportal infusion of glucose and GLP-1 or by subcutaneous administration of GLP-1 receptor activator exenatide and of intraportal glucose improved glycemia independent of corresponding changes in pancreatic hormones. It is not clear whether this effect is mediated via the portal vein (PV) or by direct action on the liver itself. To test whether receptors in the PV mediate exenatide's beneficial effect on glucose tolerance, we performed 1) paired oral glucose tolerance tests (OGTT) with and without exenatide and 2) intravenous glucose tolerance tests before and after PV denervation in canines. Denervation of the portal vein affected oral glucose tolerance; post-denervation (POST-DEN) OGTT glucose and insulin AUC were 50% higher than before denervation (P = 0.01). However, portal denervation did not impair exenatide's effect to improve oral glucose tolerance (exenatide effect: 48 ± 12 mmol·l⁻¹·min before vs. 64 ± 26 mmol·l⁻¹·min after, P = 0.67). There were no changes in insulin sensitivity or secretion during IVGTTs. Portal vein sensing might play a role in controlling oral glucose tolerance during physiological conditions but not in pharmacological activation of GLP-1 receptors by exenatide.

  1. Intragastric administration of allyl isothiocyanate reduces hyperglycemia in intraperitoneal glucose tolerance test (IPGTT) by enhancing blood glucose consumption in mice.

    PubMed

    Mori, Noriyuki; Kurata, Manami; Yamazaki, Hanae; Hosokawa, Hiroshi; Nadamoto, Tomonori; Inoue, Kazuo; Fushiki, Tohru

    2013-01-01

    We investigated the effects of allyl isothiocyanate (AITC) on the blood glucose levels of mice using an intraperitoneal glucose tolerance test. The intragastric administration of 25 mg/kg body weight AITC reduced the increase in blood glucose level after 2 g/kg body weight glucose was given intraperitoneally, compared with that of control mice. To elucidate the mechanism responsible for the reduction, respiratory gas analysis employing (13)C-labeled glucose was performed. The intragastrically administering AITC increased (13)CO2 emission, compared to vehicle, after intraperitoneal administration of (13)C-labeled glucose. This indicated that AITC increased the utilization of exogenously administered glucose, which was excessive glucose in the blood. To examine whether transient receptor potential (TRP) channels mediated this reduction in the blood glucose levels, we used TRPA1 and TRPV1 knockout (KO) mice. Intragastrically administering AITC reduced the increase in the blood glucose level in TRPA1 KO mice but not in TRPV1 KO mice. These findings suggest that dietary AITC might reduce the increases in blood glucose levels by increasing the utilization of excessive glucose in the blood by activating TRPV1.

  2. Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats.

    PubMed

    Marchionne, Elizabeth M; Diamond-Stanic, Maggie K; Prasonnarong, Mujalin; Henriksen, Erik J

    2012-01-01

    We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker (fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser(473) phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the

  3. Oral glucose tolerance and hormonal response in heroin-dependent males.

    PubMed

    Reed, J L; Ghodse, A H

    1973-06-09

    Tests on 12 heroin addicts showed that their response to a glucose load differed from that in normal controls. Though the fasting blood sugar was normal, the rise in blood glucose after a standard 50-g oral glucose tolerance test was delayed and the rise smaller than in the controls. The heroin addicts had high resting insulin levels and a delayed peak response to an oral glucose load, and their growth hormone response was also abnormal.

  4. Impaired glucose tolerance and metabolic syndrome in idiopathic neuropathy.

    PubMed

    Smith, A Gordon

    2012-05-01

    Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case-control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT-associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies.

  5. The effect of short-term dietary supplementation with glucose on gastric emptying of glucose and fructose and oral glucose tolerance in normal subjects.

    PubMed

    Horowitz, M; Cunningham, K M; Wishart, J M; Jones, K L; Read, N W

    1996-04-01

    Recent observations indicate that gastric emptying may be influenced by patterns of previous nutrient intake. The aims of this study were to determine the effects of a high glucose diet on gastric emptying of glucose and fructose, and the impact of any changes in gastric emptying on plasma concentrations of glucose, insulin and gastric inhibitory polypeptide in response to glucose and fructose loads. Gastric emptying of glucose and fructose (both 75 g dissolved in 350 ml water) were measured in seven normal volunteers on separate days while each was on a "standard' diet and an identical diet supplemented with 440 g/day of glucose for 4-7 days. Venous blood samples for measurement of plasma glucose, insulin and gastric inhibitory polypeptide levels were taken immediately before and for 180 min after ingestion of glucose and fructose loads. Dietary glucose supplementation accelerated gastric emptying of glucose (50% emptying time 82 +/- 8 vs 106 +/- 10 min, p = 0.004) and fructose (73 +/- 9 vs 106 +/- 9 min, p = 0.001). After ingestion of glucose, plasma concentrations of insulin (p < 0.05) and gastric inhibitory polypeptide (p < 0.05) were higher during the glucose-supplemented diet. In contrast, plasma glucose concentrations at 60 min and 75 min were lower (p < 0.05) on the glucose-supplemented diet. We conclude that short-term supplementation of the diet with glucose accelerates gastric emptying of glucose and fructose, presumably as a result of reduced feedback inhibition of gastric emptying from small intestinal luminal receptors. More rapid gastric emptying of glucose has a significant impact on glucose tolerance.

  6. Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice.

    PubMed

    Carlson, Scott; Prasain, Jeevan K; Peng, Ning; Dai, Yanying; Wyss, J Michael

    2014-01-01

    Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

  7. Acute and Chronic Kudzu Improves Plasma Glucose Tolerance in Non-Diabetic CD-1 Mice

    PubMed Central

    Carlson, Scott; Prasain, Jeevan K.; Peng, Ning; Dai, Yanying; Wyss, J. Michael

    2016-01-01

    Previous studies demonstrate that kudzu root extract and its major isoflavone (puerarin) improve glucose metabolism in animal models of insulin resistance and type 2 diabetes; however, these beneficial effects have not been investigated in normal glycemic mice. The present study investigates the effect of acute and chronic kudzu root extract supplementation on glucose tolerance in normoglycemic CD-1 mice. Male, adult CD-1 mice were fed a phytoestrogen-free diet containing 0.2% or 0.0% kudzu root extract for 6 weeks. Thereafter, they were acutely administered kudzu root extract (75 mg/kg BW; oral) or vehicle followed by a glucose challenge (2 g/kg BW; oral). In control fed mice, the acute glucose challenge increased blood glucose ~300% after 30 minutes, and acute kudzu root extract administration significantly blunted this response by ~50%. In mice chronically fed a kudzu-supplemented diet, glucose tolerance was improved, and acute treatment caused no additional improvement. Irrespective of treatment, all mice were normoglycemic at the start of each glucose challenge. Administration of insulin resulted in a larger decrease in blood glucose in chronic kudzu-supplemented compared to control mice. Co-administration of phloridzin (a specific inhibitor of SGLT-mediated glucose uptake), improved glucose tolerance in acutely kudzu-treated mice but had no significant effect on glucose tolerance in chronically treated mice. These results indicate that both acute and chronic administration of kudzu root extract improves glucose tolerance in a normal glycemic mouse strain and that the effects of chronic kudzu feeding may be mediated, in part, by enhanced insulin sensitivity (chronic) and inhibition of sodium dependent glucose transport.

  8. 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

  9. Glucose tolerance in depressed inpatients, under treatment with mirtazapine and in healthy controls.

    PubMed

    Hennings, J M; Ising, M; Grautoff, S; Himmerich, H; Pollmächer, T; Schaaf, L

    2010-02-01

    Impaired glucose tolerance and diabetes have been associated with depression, and antidepressant treatment is assumed to improve impaired glucose tolerance. However, antidepressant treatment is also considered as a risk factor for the development of diabetes. Reports about glucose tolerance under antidepressant treatment frequently lack appropriate control groups. We conducted the oral glucose tolerance test (OGTT) in 10 healthy controls selected from an epidemiological sample with a negative lifetime history of mental Axis I disorder. Controls were carefully matched to a sample of inpatients with major depression that participated in an OGTT before and after antidepressant treatment with mirtazapine. All participants underwent a standard OGTT protocol. In patients, a second (after 2 weeks) and a third (after 4-6 weeks) OGTT was performed under treatment with mirtazapine. Compared to healthy controls, we observed significantly impaired glucose tolerance in acutely depressed patients. Effect size calculation indicated a moderate to large effects on glucose and insulin concentrations in response to an OGTT. Although glucose tolerance improved under mirtazapine treatment, insulin sensitivity was still impaired and remained significantly lower in patients compared to controls.

  10. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans

    PubMed Central

    Morris, Christopher J.; Yang, Jessica N.; Garcia, Joanna I.; Myers, Samantha; Bozzi, Isadora; Wang, Wei; Buxton, Orfeu M.; Shea, Steven A.; Scheer, Frank A. J. L.

    2015-01-01

    Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show—by using two 8-d laboratory protocols—in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers. PMID:25870289

  11. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans.

    PubMed

    Morris, Christopher J; Yang, Jessica N; Garcia, Joanna I; Myers, Samantha; Bozzi, Isadora; Wang, Wei; Buxton, Orfeu M; Shea, Steven A; Scheer, Frank A J L

    2015-04-28

    Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show--by using two 8-d laboratory protocols--in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.

  12. 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.

  13. The impact of low and no-caloric sweeteners on glucose absorption, incretin secretion and glucose tolerance.

    PubMed

    Chan, Catherine B; Hashemi, Zohre; Subhan, Fatheema Begum

    2017-04-13

    The consumption of non-nutritive, low or no-calorie sweeteners (LCS) is increasing globally. Previously thought to be physiologically inert, there is a growing body of evidence that LCS not only provide a sweet taste but may also elicit metabolic effects in the gastrointestinal tract. This review provides a brief overview of the chemical and receptor-binding properties and effects on chemosensation of different LCS but focuses on the extent to which LCS stimulates glucose transport, incretin and insulin secretion, and effects on glucose tolerance. Aspartame and sucralose both bind to a similar region of the sweet receptor. For sucralose, the data are contradictory regarding effects on glucose tolerance in humans and may depend on the food or beverage matrix and the duration of administration, as suggested by longer-term rodent studies. For aspartame, there are fewer data. On the other hand, acesulfame-potassium (Ace-K) and saccharin have similar binding characteristics to each other but, while Ace-K may increase incretin secretion and glucose responses in humans, there are no data on saccharin except in rats, which show impaired glucose tolerance after chronic administration. Additional research, particularly of the effects of chronic consumption, is needed to provide concrete evidence for beneficial or detrimental effects of LCS on blood glucose regulation in humans.

  14. FFA2 Contribution to Gestational Glucose Tolerance Is Not Disrupted by Antibiotics

    PubMed Central

    Li, Xiaoran; Fisch, Robert; Bughara, Moneb; Wicksteed, Barton; Kovatcheva-Datchary, Petia; Layden, Brian T.

    2016-01-01

    During the insulin resistant phase of pregnancy, the mRNA expression of free fatty acid 2 receptor (Ffar2) is upregulated and as we recently reported, this receptor contributes to insulin secretion and pancreatic beta cell mass expansion in order to maintain normal glucose homeostasis during pregnancy. As impaired gestational glucose levels can affect metabolic health of offspring, we aimed to explore the role of maternal Ffar2 expression during pregnancy on the metabolic health of offspring and also the effects of antibiotics, which have been shown to disrupt gut microbiota fermentative activity (the source of the FFA2 ligands) on gestational glucose homeostasis. We found that maternal Ffar2 expression and impaired glucose tolerance during pregnancy had no effect on the growth rates, ad lib glucose and glucose tolerance in the offspring between 3 and 6 weeks of age. To disrupt short chain fatty acid production, we chronically treated WT mice and Ffar2-/- mice with broad range antibiotics and further compared their glucose tolerance prior to pregnancy and at gestational day 15, and also quantified cecum and plasma SCFAs. We found that during pregnancy antibiotic treatment reduced the levels of SCFAs in the cecum of the mice, but resulted in elevated levels of plasma SCFAs and altered concentrations of individual SCFAs. Along with these changes, gestational glucose tolerance in WT mice, but not Ffar2-/- mice improved while on antibiotics. Additional data showed that gestational glucose tolerance worsened in Ffar2-/- mice during a second pregnancy. Together, these results indicate that antibiotic treatment alone is inadequate to deplete plasma SCFA concentrations, and that modulation of gut microbiota by antibiotics does not disrupt the contribution of FFA2 to gestational glucose tolerance. PMID:27959892

  15. Serum high-molecular weight adiponectin decreases abruptly after an oral glucose load in subjects with normal glucose tolerance or impaired fasting glucose, but not those with impaired glucose tolerance or diabetes mellitus.

    PubMed

    Ozeki, Noriyuki; Hara, Kenji; Yatsuka, Chikako; Nakano, Tomoki; Matsumoto, Sachiko; Suetsugu, Mariko; Nakamachi, Takafumi; Takebayashi, Kohzo; Inukai, Toshihiko; Haruki, Kohsuke; Aso, Yoshimasa

    2009-10-01

    Adiponectin exists in the blood as 3 forms, which are a trimer, a hexamer, and a high-molecular weight (HMW) form. We investigated whether circulating HMW adiponectin levels were altered by oral glucose or fat ingestion. Forty male subjects underwent a 75-g oral glucose loading test (OGTT), and 11 healthy subjects (5 women and 6 men) received a fat loading test. Serum levels of HMW and total adiponectin were measured during the OGTT and the fat loading test. The fat loading test was performed for at least 8 hours. Among the 40 male subjects, 11 had normal glucose tolerance (NGT), 9 had impaired fasting glucose (IFG), 11 had impaired glucose tolerance, and 9 had diabetes mellitus (DM). In all 40 subjects, the serum total adiponectin level did not change significantly, whereas serum HMW adiponectin decreased significantly after a glucose load and reached 92.2% of the basal level at 120 minutes after the OGTT (P < .01). The HMW to total adiponectin ratio decreased significantly from 0.47 +/- 0.15 at baseline to 0.43 +/- 0.13 at 120 minutes after a glucose load (P < .05). Serum HMW adiponectin measured at 120 minutes after the OGTT decreased significantly to 86.0% and 85.6% of the basal level in subjects with NGT or IFG, respectively (both P < .01). In subjects with impaired glucose tolerance or DM, however, serum HMW adiponectin did not change. The area under the curve for insulin at 30 minutes after a glucose load during the OGTT was significantly larger in subjects with NGT or IFG than in those with DM (P < .05). In addition, the insulinogenic index (DeltaI(0-30)/DeltaG(0-30)) was significantly higher in subjects with NGT or IFG than in those with DM (P < .001). Percentage changes in serum HMW adiponectin of the baseline at 120 minutes correlated negatively with those in serum insulin (r = -0.468, P = .0023), but not plasma glucose, of the baseline at 30 minutes in 40 subjects. On the other hand, serum triglycerides increased significantly after an oral fat load in

  16. Effect of acacia polyphenol on glucose homeostasis in subjects with impaired glucose tolerance: A randomized multicenter feeding trial

    PubMed Central

    OGAWA, SOSUKE; MATSUMAE, TOMOYUKI; KATAOKA, TAKESHI; YAZAKI, YOSHIKAZU; YAMAGUCHI, HIDEYO

    2013-01-01

    Numerous in vitro and animal studies, as well as clinical trials have indicated that plant-derived polyphenols exert beneficial effects on glucose intolerance or type 2 diabetes. This clinical study aimed to investigate the effects of acacia polyphenol (AP) on glucose and insulin responses to an oral glucose tolerance test (OGTT) in non-diabetic subjects with impaired glucose tolerance (IGT). A randomized, double-blind, placebo-controlled trial was conducted in a total of 34 enrolled subjects. The subjects were randomly assigned to the AP-containing dietary supplement (AP supplement; in a daily dose of 250 mg as AP; n=17) or placebo (n=17) and the intervention was continued for 8 weeks. Prior to the start of the intervention (baseline) and after 4 and 8 weeks of intervention, plasma glucose and insulin were measured during a two-hour OGTT. Compared with the baseline, plasma glucose and insulin levels at 90 and/or 120 min, as well as the total area under the curve values during the OGTT (AUC0→2h) for glucose and insulin, were significantly reduced in the AP group, but not in the placebo group after intervention for 8 weeks. The decline from baseline in plasma glucose and insulin at 90 or 120 min of the OGTT for the AP group was significantly greater compared with that of the placebo group after 8 weeks of intervention. No AP supplement-related adverse side-effects nor any abnormal changes in routine laboratory tests and anthropometric parameters were observed throughout the study period. The AP supplement may have the potential to improve glucose homeostasis in subjects with IGT. PMID:23837032

  17. Simulation of oral glucose tolerance tests and the corresponding isoglycemic intravenous glucose infusion studies for calculation of the incretin effect.

    PubMed

    Kim, Myeungseon; Oh, Tae Jung; Lee, Jung Chan; Choi, Karam; Kim, Min Young; Kim, Hee Chan; Cho, Young Min; Kim, Sungwan

    2014-03-01

    The incretin effect, which is a unique stimulus of insulin secretion in response to oral ingestion of nutrients, is calculated by the difference in insulin secretory responses from an oral glucose tolerance test (OGTT) and a corresponding isoglycemic intravenous glucose infusion (IIGI) study. The OGTT model of this study, which is individualized by fitting the glucose profiles during an OGTT, was developed to predict the glucose profile during an IIGI study in the same subject. Also, the model predicts the insulin and incretin profiles during both studies. The incretin effect, estimated by simulation, was compared with that measured by physiologic studies from eight human subjects with normal glucose tolerance, and the result exhibited a good correlation (r > 0.8); the incretin effect from the simulation was 56.5% ± 10.6% while the one from the measured data was 52.5% ± 19.6%. In conclusion, the parameters of the OGTT model have been successfully estimated to predict the profiles of both OGTTs and IIGI studies. Therefore, with glucose data from the OGTT alone, this model could control and predict the physiologic responses, including insulin secretion during OGTTs and IIGI studies, which could eventually eliminate the need for complex and cumbersome IIGI studies in incretin research.

  18. 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.

  19. Sexual dimorphism of hyperglycemia and glucose tolerance in Wistar fatty rats.

    PubMed

    Kava, R A; West, D B; Lukasik, V A; Greenwood, M R

    1989-02-01

    Obese and lean male and female Wistar fatty rats were fed a high-sucrose (68% of calories) diet from 5 to 22 wk of age. Obese males, but not obese females, developed hyperglycemia in the fed state and were more glucose intolerant during an intragastric glucose tolerance test than obese females. Lean Wistar fatty rats did not become hyperglycemic on the sucrose diet. Obese males also showed a smaller insulin response during the glucose tolerance test than did obese females. The Wistar fatty rat is a sexually dimorphic model of non-insulin-dependent diabetes mellitus in which the male but not the female obese rats become diabetic. The diabetic condition and impaired glucose tolerance in the obese male Wistar fatty rat may be related to impaired pancreatic insulin release and peripheral insulin resistance.

  20. Orally administered glucagon-like peptide-1 affects glucose homeostasis following an oral glucose tolerance test in healthy male subjects.

    PubMed

    Steinert, R E; Poller, B; Castelli, M C; Friedman, K; Huber, A R; Drewe, J; Beglinger, C

    2009-12-01

    Glucagon-like peptide-1 (GLP-1) exerts several effects on glucose homeostasis and reduces food intake. After its release from intestinal L cells, GLP-1 is subject to (i) rapid breakdown by dipeptidyl peptidase IV and (ii) high liver extraction. The highest concentrations of GLP-1 are found in the splanchnic blood rather than in the systemic circulation. An oral delivery system would mimic endogenous secretion. Here we investigated the pharmacokinetic/pharmacodynamic (PK/PD) effects of a single dose (2 mg) of oral GLP-1 administered prior to an oral glucose tolerance test (OGTT) in 16 healthy males. GLP-1 was rapidly absorbed from the gut, leading to tenfold higher plasma concentrations compared with controls. The PD profile was consistent with reported pharmacology; GLP-1 significantly stimulated basal insulin release (P < 0.027), with marked effects on glucose levels. The postprandial glucose peak was delayed with GLP-1, suggesting an effect on gastric emptying.

  1. Intestinal transit of a glucose bolus and incretin kinetics: a mathematical model with application to the oral glucose tolerance test.

    PubMed

    Salinari, Serenella; Bertuzzi, Alessandro; Mingrone, Geltrude

    2011-06-01

    The rate of appearance (R(a)) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the R(a) time course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the R(a) profile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated (r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose R(a) measurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense.

  2. [Dynamics of erythrocyte hexokinase activity during glucose tolerance test in children with hereditary diabetes mellitus].

    PubMed

    Ignatiuk, T E; Ermolenko, R I

    1979-01-01

    In determining the changes in hexokinase activity in erythrocytes during the glucose tolerance test in children with heredity aggravated by diabetes mellitus in comparison with such in apparently healthy children it was shown that in latent diabets the enzyme activity failed to alter during the whold period of study (on fasting stomach, 30, 60 and 180 minutes after glucose load), and increased 60 minutes after glucose load in potential diabetes, but to a lesser extent than in the control group. Changes of erythrocyte hexokinase response to glucose administration could serve as an auxiliary criterion for determination of the degree of risk in children with threatening diabetes.

  3. 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.

  4. Senescence marker protein-30/gluconolactonase deletion worsens glucose tolerance through impairment of acute insulin secretion.

    PubMed

    Hasegawa, Goji; Yamasaki, Masahiro; Kadono, Mayuko; Tanaka, Muhei; Asano, Mai; Senmaru, Takafumi; Kondo, Yoshitaka; Fukui, Michiaki; Obayashi, Hiroshi; Maruyama, Naoki; Nakamura, Naoto; Ishigami, Akihito

    2010-02-01

    Senescence marker protein-30 (SMP30) is an androgen-independent factor that decreases with age. We recently identified SMP30 as the lactone-hydrolyzing enzyme gluconolactonase (GNL), which is involved in vitamin C biosynthesis in animal species. To examine whether the age-related decrease in SMP30/GNL has effects on glucose homeostasis, we used SMP30/GNL knockout (KO) mice treated with L-ascorbic acid. In an ip glucose tolerance test at 15 wk of age, blood glucose levels in SMP30/GNL KO mice were significantly increased by 25% at 30 min after glucose administration compared with wild-type (WT) mice. Insulin levels in SMP30/GNL KO mice were significantly decreased by 37% at 30 min after glucose compared with WT mice. Interestingly, an insulin tolerance test showed a greater glucose-lowering effect in SMP30/GNL KO mice. High-fat diet feeding severely worsened glucose tolerance in both WT and SMP30/GNL KO mice. Morphometric analysis revealed no differences in the degree of high-fat diet-induced compensatory increase in beta-cell mass and proliferation. In the static incubation study of islets, insulin secretion in response to 20 mm glucose or KCl was significantly decreased in SMP30/GNL KO mice. On the other hand, islet ATP content at 20 mm in SMP30/GNL KO mice was similar to that in WT mice. Collectively, these data indicate that impairment of the early phase of insulin secretion due to dysfunction of the distal portion of the secretion pathway underlies glucose intolerance in SMP30/GNL KO mice. Decreased SMP30/GNL may contribute to the worsening of glucose tolerance that occurs in normal aging.

  5. Glucose tolerance of 2- to 5-yr-old offspring of diabetic mothers.

    PubMed

    Buinauskiene, Jurate; Baliutaviciene, Dalia; Zalinkevicius, Rimas

    2004-09-01

    The aim of this study was to determine the prevalence of and some risk factors for impaired glucose tolerance (IGT) in 2- to 5-yr-old offspring of diabetic mothers (ODM). The glucose tolerance of 51 offspring born to women with pregnancies complicated by diabetes (type 1) and of 109 children of the control group was analyzed. Our results showed that the fasting glycemia of ODM was similar, when compared to the controls, but 2 h after the glucose loading the glycemia of ODM was significantly higher than that in the control group (5.47 +/- 1.79 mmol/L vs. 4.86 +/- 1.13 mmol/L). Normal glucose tolerance was found in 68.6% of ODM and 86.2% of controls; IGT was found in 17.6% of ODM and 4.6% of controls. Children with macrosomia at birth or overweight at 2-5 yr had IGT at 2-5 yr more often than children with normal weight at birth or normal weight at 2-5 yr. A significant, though relatively low, positive correlation was found between the duration of breastfeeding and fasting glycemia (r=0.241, p <0.01), and positive correlation was found between the duration of breastfeeding and glycemia 2 h after glucose loading (r=0.458, p=0.002) in the offspring of diabetic mothers. In conclusion, the average glycemia of ODM after glucose loading was higher than that in the control group. Macrosomia after birth, overweight, and obesity in childhood had a significant influence on the glucose tolerance of the ODM. The results of the oral glucose tolerance test correlated with the length of breastfeeding.

  6. Pulsatile insulin secretion, impaired glucose tolerance and type 2 diabetes

    PubMed Central

    Satin, Leslie S.; Butler, Peter C.; Ha, Joon; Sherman, Arthur S.

    2015-01-01

    Type 2 diabetes (T2DM) results when increases in beta cell function and/or mass cannot compensate for rising insulin resistance. Numerous studies have documented the longitudinal changes in metabolism that occur during the development of glucose intolerance and lead to T2DM. However, the role of changes in insulin secretion, both amount and temporal pattern has been understudied. Most of the insulin secreted from pancreatic beta cells of the pancreas is released in a pulsatile pattern, which is disrupted in T2DM. Here we review the evidence that changes in beta cell pulsatility occur during the progression from glucose intolerance to T2DM in humans, and contribute significantly to the etiology of the disease. We review the evidence that insulin pulsatility improves the efficacy of secreted insulin on its targets, particularly hepatic glucose production, but also examine evidence that pulsatility alters or is altered by changes in peripheral glucose uptake. Finally, we summarize our current understanding of the biophysical mechanisms responsible for oscillatory insulin secretion. Understanding how insulin pulsatility contributes to normal glucose homeostasis and is altered in metabolic disease states may help improve the treatment of T2DM. PMID:25637831

  7. Response of incretins (GIP and GLP-1) to an oral glucose load in female and male subjects with normal glucose tolerance.

    PubMed

    Matsuo, Toshihiro; Kusunoki, Yoshiki; Katsuno, Tomoyuki; Ikawa, Takashi; Akagami, Takafumi; Murai, Kazuki; Miuchi, Masayuki; Miyagawa, Jun-ichiro; Namba, Mitsuyoshi

    2014-11-01

    The aim of this study was to analyze the blood glucose profile and the response of incretins in healthy young subjects by the 75 g oral glucose tolerance test (OGTT). We first reported that plasma glucose and GIP levels were higher in males during the early phase of the OGTT.

  8. Effect of pro- and antioxidants on insulin sensitivity and glucose tolerance.

    PubMed

    Volchegorskii, I A; Rassokhina, L M; Miroshnichenko, I Yu; Mester, K M; Novoselov, P N; Astakhova, T V

    2011-01-01

    We studied the correlation between the effect of α-lipoic acid, emoxipin, reamberin, and mexidol on LPO in vitro and the action of these drugs on insulin sensitivity and tolerance to glucose load in vivo. It was found that the preparations producing prooxidant effect in vitro (α-lipoic acid and reamberin) are characterized by pronounced insulin-potentiating activity, but only slightly increase (α-lipoic acid) or even decrease (reamberin) tolerance to glucose load. 3-Hydroxypyridine derivatives (emoxipin and mexidol) producing an antioxidant effect in vitro increase glucose tolerance, but exhibit relatively weak insulin-potentiating activity. These results suggest that differential use of the studied drugs in patients with diabetes mellitus depending on the type of the disease and individual insulin requirement is a promising trend in medical studies.

  9. Glucose tolerance female-specific QTL mapped in collaborative cross mice.

    PubMed

    Abu-Toamih Atamni, Hanifa J; Ziner, Yaron; Mott, Richard; Wolf, Lior; Iraqi, Fuad A

    2017-02-01

    Type-2 diabetes (T2D) is a complex metabolic disease characterized by impaired glucose tolerance. Despite environmental high risk factors, host genetic background is a strong component of T2D development. Herein, novel highly genetically diverse strains of collaborative cross (CC) lines from mice were assessed to map quantitative trait loci (QTL) associated with variations of glucose-tolerance response. In total, 501 mice of 58 CC lines were maintained on high-fat (42 % fat) diet for 12 weeks. Thereafter, an intraperitoneal glucose tolerance test (IPGTT) was performed for 180 min. Subsequently, the values of Area under curve for the glucose at zero and 180 min (AUC0-180), were measured, and used for QTL mapping. Heritability and coefficient of variations in glucose tolerance (CVg) were calculated. One-way analysis of variation was significant (P < 0.001) for AUC0-180 between the CC lines as well between both sexes. Despite Significant variations for both sexes, QTL analysis was significant, only for females, reporting a significant female-sex-dependent QTL (~2.5 Mbp) associated with IPGTT AUC0-180 trait, located on Chromosome 8 (32-34.5 Mbp, containing 51 genes). Gene browse revealed QTL for body weight/size, genes involved in immune system, and two main protein-coding genes involved in the Glucose homeostasis, Mboat4 and Leprotl1. Heritability and coefficient of genetic variance (CVg) were 0.49 and 0.31 for females, while for males, these values 0.34 and 0.22, respectively. Our findings demonstrate the roles of genetic factors controlling glucose tolerance, which significantly differ between sexes requiring independent studies for females and males toward T2D prevention and therapy.

  10. 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

  11. Dietary trimethylamine N-oxide exacerbates impaired glucose tolerance in mice fed a high fat diet.

    PubMed

    Gao, Xiang; Liu, Xiaofang; Xu, Jie; Xue, Changhu; Xue, Yong; Wang, Yuming

    2014-10-01

    Trimethylamine N-oxide (TMAO) is an oxidation product of trimethylamine (TMA) and is present in many aquatic foods. Here, we investigated the effects of TMAO on glucose tolerance in high fat diet (HFD)-fed mice. Male C57BL/6 mice were randomly assigned to the control, high fat (HF), and TMAO groups. The HF group was fed a diet containing 25% fat, and the TMAO group was fed the HFD plus 0.2% TMAO for 4 weeks. After 3 weeks of feeding, oral glucose tolerance tests were performed. Dietary TMAO increased fasting insulin levels and homeostasis model assessment-estimated insulin resistance (HOMA-IR) and exacerbated the impaired glucose tolerance in HFD-fed mice. These effects were associated with the expression of genes related to the insulin signal pathway, glycogen synthesis, gluconeogenesis and glucose transport in liver. mRNA levels of the pro-inflammatory cytokine MCP-1 increased significantly and of the anti-inflammatory cytokine IL-10 greatly decreased in adipose tissue. Our results suggest that dietary TMAO exacerbates impaired glucose tolerance, obstructs the hepatic insulin signaling pathway, and causes adipose tissue inflammation in mice fed a high fat diet.

  12. Imparied glucose tolerance in long-term lithium-treated patients.

    PubMed

    Müller-Oerlinghausen, B; Passoth, P M; Poser, W; Pudel, V

    1979-01-01

    The oral glucose tolerance test (oGTT) was performed twice in patients under long-term lithium treatment. Blood glucose and plasma insulin were determined. The oGTT results were evaluated by three criteria (Köbberling-Creutzfeldt, WHO, and Epidemiological Study Group of the European Diabetes Association) and were compared to two representative reference studies from normal populations. The frequency of impaired glucose tolerance in the patients was three times higher than expected on the basis of the studies on normal populations. The variability of the oGTT curves between the first and second tests as well as the steepness of the time-course of the 'insulinogenic index' suggested mild disturbances of carbohydrate metabolism (mild diabetes) in some of the patients. It is considered unlikely that the impairment of glucose tolerance in the patients was a direct pharmacological effect of lithium salts. The possible role of age, sex, manic-depressive disease, additional medication, and particularly obesity in the effects of long-term lithium treatment on glucose tolerance is discussed. The authors suggest that the oGTT should be carried out periodically in long-term, lithium-treated patients over the age of 40 years in order to detect abnormalities in their carbohydrate metabolism.

  13. Improved tolerance to sequential glucose loading (Staub-Traugott effect): size and mechanisms.

    PubMed

    Bonuccelli, Sandra; Muscelli, Elza; Gastaldelli, Amalia; Barsotti, Elisabetta; Astiarraga, Brenno D; Holst, Jens J; Mari, Andrea; Ferrannini, Ele

    2009-08-01

    Improved glucose tolerance to sequential glucose loading (Staub-Traugott effect) is an important determinant of day-to-day glycemic exposure. Its mechanisms have not been clearly established. We recruited 17 healthy volunteers to receive two sequential oral glucose tolerance tests (OGTTs), at time 0 min and 180 min (Study I). The protocol was repeated on a separate day (Study II) except that plasma glucose was clamped at 8.3 mmol/l between 60 and 180 min. beta-Cell function was analyzed by mathematical modeling of C-peptide concentrations. In a subgroup, glucose kinetics were measured by a triple-tracer technique (infusion of [6,6-(2)H(2)]glucose and labeling of the 2 glucose loads with [1-(2)H]glucose and [U-(13)C]glucose). In both Studies I and II, the plasma glucose response to the second OGTT equaled 84 +/- 2% (P = 0.003) of the response to the first OGTT. Absolute insulin secretion was lower (37.8 +/- 4.3 vs. 42.8 +/- 5.1 nmol/m(2), P = 0.02), but glucose potentiation (i.e., higher secretion at the same glycemia) was stronger (1.08 +/- 0.02- vs. 0.92 +/- 0.02-fold, P = 0.006), the increment being higher in Study II (+36 +/- 5%) than Study I (+19 +/- 6%, P < 0.05). In pooled data, a higher glucose area during the first OGTT was associated with a higher potentiation during the second OGTT (rho=0.60, P = 0.002). Neither insulin clearance nor glucose clearance differed between loads, and appearance of glucose over 3 h totalled 60 +/- 6 g for the first load and 52 +/- 5 g for the second load (P = not significant). Fasting endogenous glucose production [13.3 +/- 0.6 micromol x min(-1) x kg fat-free mass (FFM)(-1)] averaged 6.0 +/- 3.8 micromol x min(-1) x kg FFM(-1) between 0 and 180 min and 1.7 +/- 2.6 between 180 and 360 min (P < 0.03). Glucose potentiation and stronger suppression of endogenous glucose release are the main mechanisms underlying the Staub-Traugott effect.

  14. Vitamin D status and resistance exercise training independently affect glucose tolerance in older adults.

    PubMed

    Kobza, Vanessa M; Fleet, James C; Zhou, Jing; Conley, Travis B; Peacock, Munro; IglayReger, Heidi B; DePalma, Glen; Campbell, Wayne W

    2013-05-01

    We assessed the influence of serum 25-hydroxyvitamin D (25[OH]D) and parathyroid hormone (PTH) concentrations on oral glucose tolerance, body composition, and muscle strength in older, nondiabetic adults who performed resistance exercise training (RT) while consuming diets with either 0.9 or 1.2 g protein kg(-1) d(-1). We hypothesized that individuals with insufficient 25(OH)D and/or high PTH would have less improvement in glucose tolerance after 12 weeks of RT compared with individuals with sufficient 25(OH)D and lower PTH. Sixteen men and 19 women (aged 61 ± 8 years; range, 50-80 years; body mass index, 26.3 ± 3.6 kg/m(2)) performed RT 3 times/wk for 12 weeks, with oral glucose tolerance tests done at baseline and postintervention. Protein intake did not influence the responses described below. Plasma glucose area under the curve (P = .02) and 2-hour plasma glucose concentration (P = .03) were higher for vitamin D-insufficient subjects (25[OH]D <50 nmol/L, n = 7) vs vitamin D-sufficient subjects (25[OH]D ≥50 nmol/L, n = 28). These differences remained significant after adjustment for age and body mass index. Resistance exercise training reduced fat mass (mean ± SD, -6% ± 7%; P < .001) and increased lean body mass (2% ± 3%, P < .001) and whole-body muscle strength (32% ± 17%, P < .001) in these weight-stable subjects but did not affect 25(OH)D or PTH concentrations. Oral glucose tolerance improved after RT (-10% ± 16% in glucose area under the curve and -21% ± 40% in 2-hour glucose, P = .001), but baseline 25(OH)D and PTH did not influence these RT-induced changes. These findings indicate that vitamin D status and RT independently affect glucose tolerance, and a training-induced improvement in glucose tolerance does not offset the negative effect of insufficient vitamin D status in older, nondiabetic adults.

  15. Spontaneous hyperglycemia and impaired glucose tolerance in athymic nude BALB/c mice.

    PubMed

    Zeidler, A; Tosco, C; Kumar, D; Slavin, B; Parker, J

    1982-09-01

    Basal plasma glucose, glucose tolerance, and insulin secretion were investigated in young and mature athymic nude BALB/c mice and in age-matched controls. Basal plasma glucose levels in male athymic nude mice were similar to those of controls at 1, 3, and 4 wk of age. At 6, 8, and 12 wk of age, male athymic nudes had significantly higher basal plasma glucose levels when compared with controls (P less than 0.01). Plasma immunoreactive insulin concentrations were similar in athymic nudes and controls at 1 wk of age, but at 3 wk of age and subsequently at 6, 8, and 12 wk athymic nude mice had significantly decreased insulin levels when compared with their age-matched controls (P less than 0.05). We found impaired glucose tolerance in male athymic nude mice at all age groups when compared with both female athymic nudes and control BALB/c mice. The discovery of a spontaneous diabetic syndrome (hyperglycemia, impaired glucose tolerance, and decreased insulin secretion) in a colony of athymic nude mice may provide an excellent model for studying the genetics and interactions between the immune and endocrine systems.

  16. Heritability of metabolic response to the intravenous glucose tolerance test in German Holstein Friesian bulls.

    PubMed

    Pieper, Laura; Staufenbiel, Rudolf; Christ, Jana; Panicke, Lothar; Müller, Uwe; Brockmann, Gudrun A

    2016-09-01

    Selection for improved health and welfare in farm animals is of increasing interest worldwide. Peripartum energy balance is a key factor for pathogenesis of diseases in dairy cows. The intravenous glucose tolerance test (ivGTT) can be used to study the metabolic response to a glucose stimulus. The aim of this study was to estimate heritability of ivGTT traits in German Holstein bulls. A total of 541 Holstein bulls aged 7 to 17 mo from 2 breeding stations were subjected to the ivGTT. Serum glucose concentrations were measured at 0, 7, 14, 21, 28, 35, 42, 49, 56, and 63 min relative to glucose infusion. The maximum increase in blood glucose concentration, glucose area equivalent, and blood glucose half-life period were calculated. Heritabilities were estimated using a univariate animal model including station-year-season and age as fixed effects, and animal additive genetic and residual as random effects. The estimated heritabilities were 0.19 for fasting glucose concentration, 0.43 for glucose area equivalent, 0.40 for glucose half-life period, 0.14 for the peak glucose concentration, and 0.12 for the maximum increase of blood glucose concentration. Correlations between ivGTT traits and breeding values for milk yield and composition were not found. The results indicate that heritability for response to glucose is high, which warrants further investigation of this trait for genetic improvement of metabolic disorders. Research is necessary to determine the target levels of ivGTT traits and potential associations between ivGTT traits in breeding bulls and periparturient diseases in their offspring.

  17. Assessment of circulating betatrophin concentrations in lean glucose-tolerant women with polycystic ovary syndrome.

    PubMed

    Erol, Onur; Özel, Mustafa Kemal; Ellidağ, Hamit Yaşar; Toptaş, Tayfun; Derbent, Aysel Uysal; Yılmaz, Necat

    2017-03-20

    The aims of the current study were to investigate the betatrophin levels in lean glucose-tolerant women with polycystic ovary syndrome (PCOS), and to explore the relationships between these levels and antropometric, hormonal and metabolic parameters. The study population consisted of 50 lean (body mass index [BMI] < 25 kg/m(2)) women diagnosed with PCOS using the Rotterdam criteria, and 60 age- and BMI-matched healthy controls without any features of clinical or biochemical hyperandrogenism. Before recruitment, glucose tolerance was evaluated in all of the subjects using the 2-h 75 g oral glucose-tolerance test, and only those exhibiting normal glucose tolerance were enrolled. Serum betatrophin levels were significantly higher in women with PCOS (median 322.3; range 44.7-1989.3 ng/L) compared to the controls (median 199.9; range 6.2-1912.9 ng/L; p = .005). In the control group, no significant correlation was evident between betatrophin levels and clinical or biochemical parameters. In the PCOS group, betatrophin levels were positively correlated with prolactin levels (r = .286, p = .046) and negatively correlated with BMI (r = -.283, p = .049), waist/hip ratio (r = -.324, p = .023), and low-density lipoprotein cholesterol levels (r = -.385, p = .006). Impact statement What is already known on this subject: Several studies have suggested that primary alteration in beta-cell function is a pathophysiological feature of PCOS, and insulin resistance is the most significant predictor of beta-cell dysfunction independent of obesity. Betatrophin is a circulating protein that is primarily expressed in the liver in humans. Early experimental investigations demonstrated that overexpression of betatrophin significantly promoted pancreatic beta-cell proliferation, insulin production and improved glucose tolerance. Few studies have investigated the association between PCOS and betatrophin. However, in contrast to our study, the

  18. Physicochemical characteristics of polysaccharide conjugates prepared from fresh tea leaves and their improving impaired glucose tolerance.

    PubMed

    Chen, Xiaoqiang; Fang, Yapeng; Nishinari, Katsuyoshi; We, Heng; Sun, Chaochao; Li, Jianrong; Jiang, Yongwen

    2014-11-04

    Hot-water extracts were prepared from fresh tea leaves and fractionated by DEAE-cellulose DE-52 column chromatography to yield one unexplored polysaccharide-conjugate fraction TPC-L (tea polysaccharide conjugates). Chemical components, molecular weight and its distribution, water vapor sorption properties, zeta potentials and optical characteristics of TPC-L were investigated. As compared with injured cell group, the two dosages of TPC-L (150 and 300 μg/mL) were discovered to possess remarkably protective effect on human umbilical vein endothelial cells against impairments induced by high glucose in a dose-dependent manner (p < 0.05, p < 0.001, respectively). Compared with group NC (normal control), the ingestion of 40 mg/kg of TPC-L could significantly reduce blood glucose levels of normal mice ingesting starch, and significant difference of AUC (area under the curve of blood glucose) and ΔAUC (p < 0.05, p < 0.01) at the postprandial time point of 0.5 and 1.0 h were observed. The three dosages of TPC-L (10, 40 and 160 mg/kg) did not significantly lower postprandial blood glucose levels of normal mice ingesting glucose. TPC-L could improve starch tolerance to prevent impaired glucose tolerance (IGT) from developing into diabetes as well as protective effects on HUVE cells against impairments induced by high glucose It was suggested that TPC-L improved IGT through its capability of inhibition on digestive enzymes.

  19. Dietary nitrate improves glucose tolerance and lipid profile in an animal model of hyperglycemia.

    PubMed

    Khalifi, Saeedeh; Rahimipour, Ali; Jeddi, Sajad; Ghanbari, Mahboubeh; Kazerouni, Faranak; Ghasemi, Asghar

    2015-01-30

    Reduction in nitric oxide (NO) production and bioavailability contribute to the pathogenesis of type 2 diabetes. Administration of nitrate has strong NO-like outcomes in both animals and humans. In this study, we examined the effects of dietary nitrate on glucose tolerance and lipid profile in type 2 diabetic rats. Type 2 diabetes was induced by injection of streptozotocin and nicotinamide. Thirty-two male Wistar rats were divided into 4 groups: controls (C), control+nitrate (CN), diabetes (D), and diabetes+nitrate (DN). For 8 weeks, the CN and DN groups consumed sodium nitrate (100 mg/L in drinking water) while the C and D groups consumed tap water. Serum nitrate+nitrite (NOx), glucose, lipid profile, total antioxidant capacity (TAC), and catalase (CAT) activity were measured before and at the end of the study. Systolic blood pressure (SBP) was measured every 10 days. Intravenous glucose tolerance test (IVGTT) was performed at the end of the study. Serum NOx decreased in diabetic rats and dietary nitrate restored it to normal values. Increases in serum glucose levels was significantly lower in the DN group compared to the D group (24.1% vs. 90.2%; p < 0.05). Nitrate therapy in diabetic rats significantly improved lipid profile, glucose tolerance (AUC: 20264 ± 659 vs. 17923 ± 523; p < 0.05 for D and DN groups respectively) and restored elevated SBP to normal values. Diabetic rats had lower TAC and CAT activity and dietary nitrate restored these to normal status. In conclusion, dietary nitrate prevented increase in SBP and serum glucose, improved glucose tolerance and restored dyslipidemia in an animal model of hyperglycemia.

  20. High prevalence of undiagnosed diabetes and abnormal glucose tolerance in the Iranian urban population: Tehran Lipid and Glucose Study

    PubMed Central

    Hadaegh, Farzad; Bozorgmanesh, Mohammad Reza; Ghasemi, Asghar; Harati, Hadi; Saadat, Navid; Azizi, Fereidoun

    2008-01-01

    Background To estimate the prevalence of diagnosed and undiagnosed diabetes mellitus, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and combined IFG/IGT in a large urban Iranian population aged ≥ 20 years. Methods The study population included 9,489 participants of the Tehran Lipid and Glucose Study with full relevant clinical data. Age-standardized prevalence of diabetes and glucose intolerance categories were reported according to the 2003 American Diabetes Association definitions. Age-adjusted logistic regression models were used to estimate the numbers needed to screen (NNTS) to find one person with undiagnosed diabetes. Results The prevalence of diagnosed and undiagnosed diabetes, isolated IFG, isolated IGT, and combined IFG/IGT were 8.1%, 5.1%, 8.7%, 5.4% and 4.0% in men and 10%, 4.7%, 6.3%, 7.6%, and 4.5% in women respectively. Participants with undiagnosed diabetes had higher age, body mass index (BMI), waist circumference, systolic and diastolic blood pressures, triglycerides (all p values <0.001) and lower HDL-cholesterol (only in women, p < 0.01) compared to normoglycemic subjects. Undiagnosed diabetes was associated with family history of diabetes, increased BMI (≥ 25 kg/m2), abdominal obesity, hypertriglyceridemia, hypertension and low HDL-cholesterol levels. Among men, a combination of increased BMI, hypertension, and family history of diabetes led to a NNTS of 1.6 (95% CI: 1.57–1.71) and among women a combination of family history of diabetes and abdominal obesity, yielded a NNTS of 2.2 (95% CI: 2.1–2.4). Conclusion In conclusion, about one third of Tehranian adults had disturbed glucose tolerance or diabetes. One- third of total cases with diabetes were undiagnosed. Screening individuals with BMI ≥ 25 kg/m2 (men), hypertension (men), abdominal obesity (women) and family history of diabetes may be more efficient. PMID:18501007

  1. Using 100G Network Technology in Support of Petascale Science

    NASA Technical Reports Server (NTRS)

    Gary, James P.

    2011-01-01

    NASA in collaboration with a number of partners conducted a set of individual experiments and demonstrations during SC 10 that collectively were titled "Using 100G Network Technology in Support of Petascale Science". The partners included the iCAIR, Internet2, LAC, MAX, National LambdaRail (NLR), NOAA and SCinet Research Sandbox (SRS) as well as the vendors Ciena, Cisco, ColorChip, cPacket, Extreme Networks, Fusion-io, HP and Panduit who most generously allowed some of their leading edge 40G/100G optical transport, Ethernet switch and Internet Protocol router equipment and file server technologies to be involved. The experiments and demonstrations featured different vendor-provided 40G/100G network technology solutions for full-duplex 40G and 100G LAN data flows across SRS-deployed single-node fiber-pairs among the Exhibit Booths of NASA, the National Center for Data lining, NOAA and the SCinet Network Operations Center, as well as between the NASA Exhibit Booth in New Orleans and the Starlight Communications Exchange facility in Chicago across special SC 10- only 80- and 100-Gbps wide area network links provisioned respectively by the NLR and Internet2, then on to GSFC across a 40-Gbps link. provisioned by the Mid-Atlantic Crossroads. The networks and vendor equipment were load-stressed by sets of NASA/GSFC High End Computer Network Team-built, relatively inexpensive, net-test-workstations that are capable of demonstrating greater than 100Gbps uni-directional nuttcp-enabled memory-to-memory data transfers, greater than 80-Gbps aggregate--bidirectional memory-to-memory data transfers, and near 40-Gbps uni-directional disk-to-disk file copying. This paper will summarize the background context, key accomplishments and some significances of these experiments and demonstrations.

  2. 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.

  3. Impaired glucose tolerance in midlife and longitudinal changes in brain function during aging.

    PubMed

    Thambisetty, Madhav; Beason-Held, Lori L; An, Yang; Kraut, Michael; Metter, Jeffrey; Egan, Josephine; Ferrucci, Luigi; O'Brien, Richard; Resnick, Susan M

    2013-10-01

    We investigated whether individuals with impaired glucose tolerance (IGT) in midlife subsequently show regionally specific longitudinal changes in regional cerebral blood flow (rCBF) relative to those with normal glucose tolerance (NGT). Sixty-four cognitively normal participants in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent serial (15)O-water positron emission tomography scans (age at first scan, 69.6 ± 7.5 years) and oral glucose tolerance tests 12 years earlier (age at first oral glucose tolerance test, 57.2 ± 11.1 years). Using voxel-based analysis, we compared changes in rCBF over an 8-year period between 15 participants with IGT in midlife and 49 with NGT. Significant differences were observed in longitudinal change in rCBF between the IGT and NGT groups. The predominant pattern was greater rCBF decline in the IGT group in the frontal, parietal, and temporal cortices. Some brain regions in the frontal and temporal cortices also showed greater longitudinal increments in rCBF in the IGT group. Our findings suggest that IGT in midlife is associated with subsequent longitudinal changes in brain function during aging even in cognitively normal older individuals.

  4. 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…

  5. U. S. Army Aviation Epidemiology Data Registry: Army Aviators with Diabetes Mellitus and Impaired Glucose Tolerance

    DTIC Science & Technology

    1994-03-01

    glucose tolerance (IGT), diabetes mellitus (DM), use of oral hypoglycemic agents, or use of insulin for the period 1988 to 1992. The paper reviewed the...incidence and prevalence of diabetes mellitus in Army aviators. The study tabulated the incidence and age-specific annual rates of diabetes mellitus and

  6. Clofibrate-induced reduction of plasma branched-chain amino acid concentrations impairs glucose tolerance in rats.

    PubMed

    Kadota, Yoshihiro; Kazama, Shunsuke; Bajotto, Gustavo; Kitaura, Yasuyuki; Shimomura, Yoshiharu

    2012-05-01

    It has been reported that branched-chain amino acid (BCAA) administration stimulates glucose uptake into muscles and whole body glucose oxidation in rats. The authors examined the effect of decreased plasma BCAA concentrations induced by clofibrate treatment on glucose tolerance in rats. Since clofibrate, a drug for hyperlipidemia (high serum triglyceride concentration), is a potent inhibitor of the branched-chain α-keto acid dehydrogenase kinase, clofibrate treatment (0.2 g/kg body weight) activated the hepatic branched-chain α-keto acid dehydrogenase complex, resulting in decreased plasma BCAA concentrations by 30% to 50% from the normal level. An intraperitoneal glucose tolerance test was conducted after clofibrate administration, and the results showed that peak plasma glucose concentration and the area under the curve of glucose concentration during the intraperitoneal glucose tolerance test were significantly higher in clofibrate-treated rats than in control rats. This impaired glucose tolerance in the clofibrate-treated rats was ameliorated by administration of BCAAs (0.45 g/kg body weight, leucine:isoleucine:valine = 2:1:1), which kept plasma BCAA concentrations at normal levels during the intraperitoneal glucose tolerance test. These results suggest that plasma BCAAs play an important role in maintaining normal glucose tolerance in rats.

  7. Glucose tolerance and pancreatic hormones in thyroidectomized and thyroid hormone-injected cockerels.

    PubMed

    Klandorf, H

    1988-02-01

    The effect of surgical thyroidectomy and of T4/T3 injections on basal and glucose-induced concentrations of plasma insulin and glucagon has been investigated in 20-week-old domestic chickens. Birds injected daily (im) for 2 weeks with T4/T3 (50 micrograms/day) had marginally lower fasting glucose concentrations whereas thyroidectomy had no effect. Glucose tolerance to an intravenous injection of glucose (0.5 g/kg) was impaired in T4/T3 injected animals although the peak hyperglycemia was identical with sham-operated animals. This was associated with significantly reduced basal and glucose-induced insulin concentrations. However, fasting plasma glucagon concentrations were significantly elevated in this group as was the magnitude of the glucose-induced suppression of glucagon release 10 min after injection (48% decline vs 34% in sham-operated animals). Basal concentrations of plasma insulin were markedly elevated in thyroidectomized animals and were associated with only mildly depressed plasma glucagon levels. The absolute concentrations of plasma insulin remained higher in the thyroidectomized birds as compared with those of sham-operated or T4/T3 injected animals after the glucose challenge, although within 30 min after glucose injection they had significantly declined below preinjection levels. This was associated both with significantly reduced plasma glucose concentrations 30 min after injection and the lowest absolute levels of plasma glucagon. The rebound in plasma glucagon in sham-operated animals in response to the rapid decline in glucose concentrations was not as pronounced in either thyroidectomized or T4/T3 injected animals. In conclusion these studies illustrate the secretory dynamics of avian pancreatic endocrine islets in response to both absolute glucose levels and glucose requirements as affected by the thyroid state of the bird.

  8. Comparison of the effects of fetal hypothyroidism on glucose tolerance in male and female rat offspring.

    PubMed

    Bagheripuor, Fatemeh; Ghanbari, Mahboubeh; Zahediasl, Saleh; Ghasemi, Asghar

    2015-03-01

    Thyroid hormones are vital for survival of mammalian species and play critical roles in growth, development, and metabolism. Both fetal hypothyroidism and sex can affect carbohydrate metabolism during adult life. This study aims to assess carbohydrate metabolism in male and female offspring born from mothers who were hypothyroid during pregnancy. Pregnant rats were divided into two groups; the controls consumed water and the hypothyroid group received water containing 0.025 % 6-propyl-2-thiouracial throughout gestation. The intravenous glucose tolerance test (0.5 g/kg glucose) was carried out in 3-month-old offspring. Findings showed that compared to controls, male fetal hypothyroid rats during adulthood had glucose intolerance (area under the curve: 446.4 ± 9.7 vs. 486.4 ± 8.8, p < 0.01 in control and fetal hypothyroid groups, respectively) whereas females had improved glucose tolerance (478.1 ± 7.0 vs. 455.9 ± 8.5, p < 0.01). In conclusion, sex could modulate the effects of fetal hypothyroidism on glucose tolerance in rats.

  9. 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.

  10. Distinguishing between persistent and transient impaired glucose tolerance using a prediction model.

    PubMed

    Bourn, D M; Williams, S M; Mann, J I

    1992-10-01

    Screening for impaired glucose tolerance (IGT) and Type 2 (non-insulin dependent) diabetes was carried out in 777 people and those with high blood glucose levels completed three 2-h oral glucose tolerance tests (OGTT). Blood lipid levels, fasting and 2-h insulin levels, body mass index, and blood pressure were also measured and family history of Type 2 diabetes recorded. Fifty people were identified with IGT and of these 21 were found to have persistent IGT and 29 transient IGT. A model including the variables body mass index, fasting and 2-h insulin levels, fasting triglycerides and family history of Type 2 diabetes was developed using the Speigelhalter-Knill-Jones weighting method to predict subjects with persistent IGT. This model could be useful in identifying people with persistent IGT and therefore eliminate the need for repeat OGTTs which are time consuming and expensive.

  11. Distribution of fasting plasma glucose and prevalence of impaired fasting glucose, impaired glucose tolerance and type 2 diabetes in the Mexican paediatric population.

    PubMed

    Guerrero-Romero, Fernando; Violante, Rafael; Rodríguez-Morán, Martha

    2009-07-01

    Published data on the distribution of fasting plasma glucose (FPG) in children are scarce. We therefore set out to examine the distribution of FPG and determine the prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and type 2 diabetes (T2-DM) in Mexican children aged 6-18 years in a community-based cross-sectional study. A total of 1534 apparently healthy children were randomly enrolled and underwent an oral glucose tolerance test. IFG was defined by an FPG value between >or=100 and <126 mg/dL, IGT by glucose concentration 2-h post-load between >or=140 and <200 mg/dL, and T2-DM by glucose concentration 2-h post-load >or=200 mg/dL. The FPG level at the 75(th) percentile of distribution was 98.0, 100.0 and 99.0 mg/dL for children aged 6-9, 10-14 and 15-18 years, respectively; the 95(th) percentile of FPG was greater than 100 mg/dL for all the age strata. In the population overall, the prevalences of IFG, IGT, and T2-DM were 18.3%, 5.2% and 0.6%, respectively. Among obese children and adolescents, the prevalences of IFG, IGT, IFG + IGT and T2-DM were 19.1%, 5.7%, 2.5% and 1.3%. Our study shows a high prevalence of prediabetes and is the first that reports the distribution of FPG in Mexican children and adolescents.

  12. Diabetes mellitus and impaired glucose tolerance are underdiagnosed in intensive care units

    PubMed Central

    Ladeira, Renata Teixeira; Simioni, Ana Cinthia Marques; Bafi, Antonio Tonete; Nascente, Ana Paula Metran; Freitas, Flavio Geraldo Resende; Machado, Flávia Ribeiro

    2012-01-01

    Objective To evaluate the presence of diabetes mellitus and impaired glucose tolerance in intensive care unit inpatients. Methods The study included patients in post-surgical care for elective and emergency surgery and excluded those patients with known diabetes mellitus. To diagnose prior serum glucose level disorders, we considered the value of glycated hemoglobin (HbA1c) at the time of admission, classifying the patients as normal (<5.7%), glucose intolerant (5.7-6.4%) or diabetic (>6.4%). During the first 3 days of the patient's hospital stay, glycemic control and clinical complications were assessed. Mortality was monitored for 28 days. For the statistical analyses, chi-square, ANOVA, student's t, Kruskal-Wallis or Mann Whitney tests were used. Results Thirty patients were included in the present study, 53% of whom were women; the patients had a mean age of 53.4±19.7 years and an APACHE II score of 13.6±6.6. The majority of patients were admitted for severe sepsis or septic shock followed by post-operative care for elective surgery, oncological surgery, multiple traumas and emergency surgery. When classifying these patients according to HbA1c, despite the absence of a prior history of diabetes mellitus, only 13.3% had a normal HbA1c level, 23.3% had levels compatible with the diagnosis of diabetes mellitus and 63.3% had levels compatible with impaired glucose tolerance. We found a significant association between the diagnosis of diabetes mellitus or impaired glucose tolerance and the use of vasoactive drugs (p=0.04). Conclusion A high prevalence of undiagnosed diabetes mellitus and impaired glucose tolerance was observed in inpatients at a general intensive care unit. PMID:23917931

  13. Chromium status and glucose tolerance in Saudi men with and without coronary artery disease.

    PubMed

    Alissa, Eman M; Bahjri, Suhad M; Ahmed, Waqar H; Al-Ama, Nabeel; Ferns, Gordon A A

    2009-12-01

    Chromium deficiency is associated with impaired glucose tolerance (IGT) and dyslipidemia. Hence, the objective of the current study was to investigate chromium status among Saudi men with and without established cardiovascular disease (CVD) and its relationship to glucose tolerance, lipid profile and other established CVD risk factors. We measured serum and urine chromium concentrations, fasted lipid profile, plasma glucose, and serum lipid peroxide in 130 Saudi men with an established history of myocardial infarction and 130 age-matched controls without established CVD. Patients with established CVD had higher serum triglycerides (p < 0.05) and plasma glucose (p < 0.0001) and lower serum and urinary chromium concentrations (p < 0.0001) than controls. Serum chromium was inversely correlated with plasma glucose among cases and controls (r = -0.189, p < 0.05 and r = -0.354, p < 0.00001, respectively). Plasma glucose (OR 1.127, CI 1.0-1.269, p < 0.05), serum chromium (OR 0.99, CI 0.985-0.995, p < 0.0001), and urinary chromium (OR 0.988, CI 0.981-0.995, p < 0.001) were independently associated with the presence of established coronary disease applying this model. While chromium metabolism appears to be altered in individuals with CVD, it is unclear whether chromium supplementation would be effective in CVD prevention among patients with IGT. This would need to be tested in long-term outcome trials.

  14. Oral glucose tolerance test reduces arterial baroreflex sensitivity in older adults.

    PubMed

    Madden, Kenneth M; Tedder, Gale; Lockhart, Chris; Meneilly, Graydon S

    2008-03-01

    Although postprandial decreases in blood pressure are a common cause of syncope in the older adult population, the postprandial effects of the oral glucose tolerance test on blood pressure and the arterial baroreflex remain poorly characterized in older adults. Therefore, arterial blood pressure and the arterial baroreflex were studied in 19 healthy older adults (mean age 71.7 +/- 1.1 years) who were given a standardized oral glucose load (75 g) or an isovolumetric sham drink during 2 separate sessions. All measures were taken for 120 min after treatment. Baroreflex function was assessed by using the spontaneous baroreflex method (baroreflex sensitivity, BRS). Subjects demonstrated a decrease in BRS after oral glucose that was not seen in the placebo session (two-way analysis of variance, p = 0.04). There was no significant change in systolic, mean, or diastolic blood pressure; together with a drop in BRS, this resulted in a significant tachycardia post glucose (two-way analysis of variance, p < 0.001). We conclude that healthy older adults can successfully maintain blood pressure during an oral glucose tolerance test despite a decrease in arterial BRS. Decreased BRS resulted in a tachycardic response to glucose.

  15. Effect of glycemia on plasma incretins and the incretin effect during oral glucose tolerance test.

    PubMed

    Salehi, Marzieh; Aulinger, Benedict; D'Alessio, David A

    2012-11-01

    The incretin effect, reflecting the enhancement of postprandial insulin secretion by factors including the intestinal hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide, increases in proportion to meal size. However, it is unknown whether the incretin effect is dependent on ambient glucose. The goal of this study was to determine the effect of plasma glycemia on the incretin effect. Thirteen healthy subjects consumed 50 g oral glucose solution mixed with d-xylose during fixed hyperglycemia at 8 and 10.5 mmol/L, on 3 separate days, twice at lower glycemia (LOW) and once at higher values (HIGH). The relative increase in insulin release after glucose ingestion at fixed hyperglycemia, a surrogate for the incretin effect, was similar among all three studies. The GLP-1 response to oral glucose was significantly lower at higher plasma glycemia, as was the appearance of d-xylose after the meal. Between the two LOW studies, the reproducibility of insulin release in response to intravenous glucose alone and intravenous plus ingested glucose was similar. These findings indicate that the incretin contribution to postprandial insulin release is independent of glycemia in healthy individuals, despite differences in GLP-1 secretion. The incretin effect is a reproducible trait among humans with normal glucose tolerance.

  16. Effect of Helicteres isora root extracts on glucose tolerance in glucose-induced hyperglycemic rats.

    PubMed

    Venkatesh, Sama; Dayanand Reddy, G; Reddy, Y S R; Sathyavathy, D; Madhava Reddy, B

    2004-06-01

    The ethanol, ethyl acetate and butanol extracts of Helicteres isora root showed significant oral hypoglycemic activity on glucose loaded rats at a dose of 250 mg/kg. The butanol extract showed maximum antihyperglycemic activity and effect being comparable to that of glibenclamide.

  17. The Rockwell SR-100G reactor turboelectric space power system

    NASA Technical Reports Server (NTRS)

    Anderson, R. V.

    1985-01-01

    During FY 1982 and 1983, Rockwell International performed system and subsystem studies for space reactor power systems. These studies drew on the expertise gained from the design and flight of the SNAP-10A space nuclear reactor system. These studies, performed for the SP-100 Program, culminated in the selection of a reactor-turboelectric (gas Brayton) system for the SP-100 application; this system is called the SR-100G. This paper describes the features of the system and provides references where more detailed information can be obtained.

  18. Prevention of diabetes and cardiovascular disease in patients with impaired glucose tolerance: rationale and design of the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial.

    PubMed

    Califf, Robert M; Boolell, Mitradev; Haffner, Steven M; Bethel, M Angelyn; McMurray, John; Duggal, Anil; Holman, Rury R

    2008-10-01

    Patients with impaired glucose tolerance (IGT) have increased risk for developing type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Lifestyle modification and medication can prevent or delay progression to diabetes (PD), but whether such interventions also reduce the risk of CVD has not been rigorously tested. The Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is a multinational, randomized, double-blind, 2 x 2 factorial trial in subjects with IGT (on a screening oral glucose tolerance test [OGTT]) aged > or = 50 years with known CVD or aged > or = 55 years with > or = 1 CVD risk factor. Enrollment began in January 2002 and was completed January 2004, with 9,518 patients randomized to receive 1 of 4 possible treatment combinations as follows: nateglinide with valsartan, nateglinide with valsartan-placebo, nateglinide-placebo with valsartan, or nateglinide-placebo with valsartan-placebo. All subjects are participating in a clinic-based and telephone-based lifestyle intervention aimed at reducing weight and dietary fat and increasing physical activity. The 3 coprimary end points are new onset of T2DM, a "core" composite of major cardiovascular events (death, myocardial infarction, stroke, or hospitalization for heart failure), and an "extended" composite including the components of the core composite plus coronary revascularization and hospitalization for unstable angina. The study was designed to evaluate whether reducing postprandial hyperglycemia, blockade of the renin-angiotensin-aldosterone system, or both interventions reduce the risk of T2DM or cardiovascular events in patients with IGT.

  19. 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.

  20. The role of ranitidine infusion on glucose, insulin and C-peptide serum levels induced by oral glucose tolerance test in healthy subjects.

    PubMed

    Gentile, S; Marmo, R; Costume, A; Orlando, C; D'Alessandro, R; De Bellis, G; Porcellini, M; Coltorti, M

    1986-01-01

    In 9 healthy subjects we evaluated the effect of a constant ranitidine infusion (100 mg) on glucose (mg/dl), insulin (microU/ml) and C-peptide (ng/ml) serum levels promoted by oral glucose tolerance test (75 g). Ranitidine significantly increased the area under concentration/time curves for glucose and insulin but not that of C-peptide. Our data indicate that ranitidine does not affect pancreatic insulin release nor peripheral glucose utilization and are consistent with the hypothesis that ranitidine influences the hepatic clearance of glucose and insulin both of which undergo high first-pass liver extraction.

  1. 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.

  2. 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

  3. Gut microbiota modulation with norfloxacin and ampicillin enhances glucose tolerance in mice.

    PubMed

    Membrez, Mathieu; Blancher, Florence; Jaquet, Muriel; Bibiloni, Rodrigo; Cani, Patrice D; Burcelin, Rémy G; Corthesy, Irène; Macé, Katherine; Chou, Chieh Jason

    2008-07-01

    Recent data suggest that the gut microbiota plays a significant role in fat accumulation. However, it is not clear whether gut microbiota is involved in the pathophysiology of type 2 diabetes. To assess this issue, we modulated gut microbiota via antibiotics administration in two different mouse models with insulin resistance. Results from dose-determination studies showed that a combination of norfloxacin and ampicillin, at a dose of 1 g/L, maximally suppressed the numbers of cecal aerobic and anaerobic bacteria in ob/ob mice. After a 2-wk intervention with the antibiotic combination, both ob/ob and diet-induced obese and insulin-resistant mice showed a significant improvement in fasting glycemia and oral glucose tolerance. The improved glycemic control was independent of food intake or adiposity because pair-fed ob/ob mice were as glucose intolerant as the control ob/ob mice. Reduced liver triglycerides and increased liver glycogen correlated with improved glucose tolerance in the treated mice. Concomitant reduction of plasma lipopolysaccharides and increase of adiponectin further supported the antidiabetic effects of the antibiotic treatment in ob/ob mice. In summary, modulation of gut microbiota ameliorated glucose tolerance of mice by altering the expression of hepatic and intestinal genes involved in inflammation and metabolism, and by changing the hormonal, inflammatory, and metabolic status of the host.

  4. The study of serum vitamin d and insulin resistance in chinese populations with normal glucose tolerance.

    PubMed

    Ding, Lin; Wang, Congcong; Ma, Heliang; Tian, Yuling; Lu, Yong; Pang, Shuguang

    2014-01-01

    Objectives. The aim of this study was to investigate the relationship between serum vitamin D and insulin resistance in Chinese subjects without diabetes mellitus. Methods. Serum 25(OH)D was measured in 897 individuals with normal glucose tolerance (NGT). Oral glucose tolerance tests (OGTTs) were conducted to exclude cases with diabetes, impaired fasting glucose (IFG), and impaired glucose tolerance (IGT). Metabolic parameters were measured and compared between the highest and lowest 25(OH)D quartiles. The relationship between serum 25(OH)D and homeostatic model assessment-insulin resistance (HOMA-IR) was analyzed. Results. Indexes, such as HOMA-IR, FINS, and SBP, were negatively correlated with serum 25(OH)D concentrations. Compared with the lowest quartile, individuals in the highest group had decreased Lg (HOMA-IR), Lg (FINS), and SBP. Pearson correlation analyses showed that serum 25(OH)D was negatively associated with age, BMI, Lg (HOMA-IR), and Lg (FINS). Multivariate linear regression analysis confirmed the negative correlation of Lg (HOMA-IR) and 25(OH)D. Conclusions. This study showed that serum 25(OH)D could be regarded as an independent predictor of insulin resistance for subjects without diabetes mellitus in China. Adequate vitamin D supplementation may improve multiple metabolic disturbances.

  5. 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.

  6. The effect of low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test.

    PubMed

    Kamau, R K; Maina, F W; Kigondu, C; Mati, J K

    1990-08-01

    The effect of a low-oestrogen combined pill, progestogen-only pill and medroxyprogesterone acetate on oral glucose tolerance test was studied in 29, 30 and 9 indigenous Kenyan women respectively. Glucose tolerance test was performed before treatment was started and then after 1,3 and 6 months in microgynon users. The mean areas under the glucose curves were also significantly elevated. Significant increase in blood glucose values were noted only at 30 minutes after 6 months of use of the progestogen-only oral contraceptive but the mean blood glucose values were higher than in the control after 1,3 and 6 months of use. However, the mean values of the areas under the glucose curves were significantly elevated after 1,3, and 6 months of use. Medroxyprogesterone acetate users showed significantly lower fasting blood glucose values at 60 and 90 minutes after 1 month of use, after which the blood glucose values returned to the pre-treatment values. The mean values of the glucose curve areas showed no significant change. It is concluded that both microgynon and minipill cause relative impairment of glucose tolerance test as early as after 1 month of use. Medroxyprogesterone acetate does not impair oral glucose tolerance for at least the first 6 months of use. The implications of these findings are discussed.

  7. 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.

  8. 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

  9. High prevalence of abnormal circadian blood pressure regulation and impaired glucose tolerance in adults with hypopituitarism.

    PubMed

    Krzyzanowska, K; Schnack, C; Mittermayer, F; Kopp, H P; Hofer, M; Kann, T; Schernthaner, G

    2005-09-01

    Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.

  10. Abnormal antioxidant status in impaired glucose tolerance and non-insulin-dependent diabetes mellitus.

    PubMed

    Vijayalingam, S; Parthiban, A; Shanmugasundaram, K R; Mohan, V

    1996-08-01

    A total of 105 subjects with impaired glucose tolerance were classified into two groups, 51 subjects with plasma glucose > 11.1 mmol l-1 in one of the blood samplings during OGTT, but at 2 h being less than < 11.1 mmol l-1 were classified as early hyperglycaemics. Fifty-four cases were classified as true IGT, with fasting plasma glucose < 7.8 mmol l-1 and post plasma glucose level between 7.8 and 11.1 mmol l-1. Age and sex matched groups of normals (healthy adults) and NIDDM cases without symptomatic secondary complications were also included in the study. Lipid peroxidation (LPO) product in plasma, erythrocyte, and erythrocyte cell membrane were found to be significantly elevated (p < 0.001) in IGT, early hyperglycaemia and diabetes mellitus while glycosylated haemoglobin was also higher. Antioxidant enzymes superoxide dismutase and catalase were significantly lower in red blood cells obtained from IGT and early hyperglycaemic groups. They were closer to the levels showed in NIDDM confirming that antioxidant deficiency is already present in subjects classified as impaired glucose tolerant. Among the antioxidant scavengers, reduced glutathione (GSH) and ascorbic acid are reduced by 15% and 20% in IGT and NIDDM, respectively. We conclude that antioxidant status is poor in both IGT and NIDDM, suggesting an overlap of frank diabetic state in those classified as IGT. It is possible that antioxidant therapy might retard progression from IGT to NIDDM.

  11. [Insulin response and NEFA behavior in volunteers with a flat response to oral glucose tolerance test].

    PubMed

    Viviani, G; Cordera, R; Maiello, M; De Micheli, A; Odetti, P; Corsi, L; Boeri, D; Prando, R

    1979-07-15

    The insulin response and the NEFA behaviour of 7 lean and 8 obese subjects with a flat response to an oral glucose tolerance test have been studied. A flat response has been defined as one in which the maximum glycemic increase and the area of increase does not exceed 32 mg% and 18 mg% respectively. The insulin response and the NEFA behaviour were similar both in lean and in obese subjects to controls with normal O.G.T.T. The glucose/I.R.I. ratios were increased. A possible physiopathological interpretation is proposed.

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

    PubMed

    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.

  13. Assessment of Insulin Resistance in Subjects with Normal Glucose Tolerance, Hyperinsulinemia with Normal Blood Glucose Tolerance, Impaired Glucose Tolerance, and Newly Diagnosed Type 2 Diabetes (Prediabetes Insulin Resistance Research)

    PubMed Central

    Yang, Guang; Li, Chunlin; Gong, Yanping; Fang, Fusheng; Tian, Hui; Li, Jian; Cheng, Xiaoling

    2016-01-01

    Aim. To evaluate the differences in insulin resistance (IR) among subjects with normal glucose tolerance (NGT), hyperinsulinemia with NGT (HINS), impaired glucose tolerance (IGT), and newly diagnosed type 2 diabetes mellitus (T2DM). Methods. 5 NGT, 25 HINS, 25 IGT, and 25 T2DM subjects participated in this research. The hyperinsulinemic-euglycemic clamp technique (HECT) was performed in all of them to evaluate IR levels. The relative factors influencing IR were evaluated. The simple insulin sensitivity indices were calculated, and the correlation between each index and the M value was analyzed. Results. The M values of NGT, HINS, IGT, and T2DM groups were 11.88 ± 2.93 mg·kg−1·min−1, 6.23 ± 1.73 mg·kg−1·min−1, 6.37 ± 2.12 mg·kg−1·min−1, and 6.19 ± 1.89 mg·kg−1·min−1, respectively. M values in HINS, IGT, and T2DM groups were lower than those in the NGT group (P = 0.005); however, the differences among the HINS, IGT, and T2DM groups were not statistically significant (P = 0.835). The independent factors influencing the M value were waistline and fasting insulin level (FINS). The simple insulin sensitivity indices, especially Matsuda and Gutt index, were significantly associated with the M value (P < 0.01). Conclusion. IR existed in the HINS, IGT, and T2DM groups, and IR levels were consistent in the three groups. The independent factors influencing IR were waistline and FINS. PMID:26770991

  14. 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

  15. 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.

  16. Risk of impaired glucose tolerance in normal weight hirsute women during four years observation.

    PubMed

    Andries, Magdalene; Glintborg, Dorte; Andersen, Marianne

    2010-08-01

    Hirsutism is a common disorder affecting 5-20% of women in reproductive age. Only limited follow-up data exist regarding the prognosis for glucose tolerance and metabolic risk factors in hirsutism. Sixty-nine Caucasian hirsute women underwent a clinical examination and an oral glucose tolerance test (OGTT) during 1997-2002 (baseline) and during 2003-2004 (re-evaluation). The observation period was (median; range) 4 (2-7) years. During re-evaluation, body mass index (BMI) was 24.9 (22.4-29.0) kg/m(2) and total Ferriman-Gallwey score was 10 (7-15) (median; 25-75% quartile). The women had unchanged BMI compared to baseline but increased fasting and 2 hour glucose levels. Impaired OGTT outcome during follow-up was seen in 14/66 (21.2%) women, 5/66 (7.6%) developed diabetes. Women who took oral contraceptives had a significantly decreased area under the curve (AUC) for insulin during follow-up, whereas AUC glucose levels increased. The present data supported a high risk of diabetes in only moderately overweight hirsute women.

  17. 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

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

    PubMed

    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.

  19. How Tom Moon's research highlighted the question of glucose tolerance in carnivorous fish.

    PubMed

    Polakof, S; Panserat, S

    2016-09-01

    Fifteen years ago, Tom Moon wrote a review on this journal in order to propose some explanations to the exacerbated glycaemic response after a glucose load or a carbohydrate meal intake observed in fish, the so-called intolerance to glucose. Before, but in most of cases after this paper, several laboratories worldwide started to make important efforts in order to better understand this strange phenotype observed in fish and that so far seemed to belong to diabetic humans only. Tom had been worked on fish metabolism for at least 30years when he proposed that mini-review and the paths opened by him in 2001 were followed by tens of fish researchers, making this paper a breaking point on the field. Fifteen years later, we propose not only to have a look to the answers given to the questions rose in that paper, but also to summarize how his career over all these years impacted the domain of glucose metabolism in fish. In the review, we will show how Tom Moon analysed at different levels (from genes up to the whole organism), using distinct experimental tools (cells, hormone or glucose injection, pumps, drugs) the questions of glucose metabolism, tolerance and nutrition in fish species.

  20. A novel test for IGT utilizing metabolite markers of glucose tolerance.

    PubMed

    Cobb, Jeff; Eckhart, Andrea; Perichon, Regis; Wulff, Jacob; Mitchell, Matthew; Adam, Klaus-Peter; Wolfert, Robert; Button, Eric; Lawton, Kay; Elverson, Robert; Carr, Bernadette; Sinnott, Margaret; Ferrannini, Ele

    2015-01-01

    The oral glucose tolerance test (OGTT) is the only method to diagnose patients having impaired glucose tolerance (IGT), but its use has diminished considerably in recent years. Metabolomic profiling studies have identified a number of metabolites whose fasting levels are associated with dysglycemia and type 2 diabetes. These metabolites may serve as the basis of an alternative test for IGT. Using the stable isotope dilution technique, quantitative assays were developed for 23 candidate biomarker metabolites. These metabolites were measured in fasting plasma samples taken just prior to an OGTT from 1623 nondiabetic subjects: 955 from the Relationship between Insulin Sensitivity and Cardiovascular Disease Study (RISC Study; 11.7% IGT) and 668 subjects from the Diabetes Mellitus and Vascular Health Initiative (DMVhi) cohort from the DEXLIFE project (11.8% IGT). The associations between metabolites, anthropometric, and metabolic parameters and 2hPG values were assessed by Pearson correlation coefficients and Random Forest classification analysis to rank variables for their ability to distinguish IGT from normal glucose tolerance (NGT). Multivariate logistic regression models for estimating risk of IGT were developed and evaluated using AUCs calculated from the corresponding ROC curves. A model based on the fasting plasma levels of glucose, α-hydroxybutyric acid, β-hydroxybutyric acid, 4-methyl-2-oxopentanoic acid, linoleoylglycerophosphocholine, oleic acid, serine and vitamin B5 was optimized in the RISC cohort (AUC = 0.82) and validated in the DMVhi cohort (AUC = 0.83). A novel, all-metabolite-based test is shown to be a discriminate marker of IGT. It requires only a single fasted blood draw and may serve as a more convenient surrogate for the OGTT or as a means of identifying subjects likely to be IGT.

  1. Effect of nematode Trichinella infection on glucose tolerance and status of macrophage in obese mice.

    PubMed

    Okada, Hideyuki; Ikeda, Takahide; Kajita, Kazuo; Mori, Ichiro; Hanamoto, Takayuki; Fujioka, Kei; Yamauchi, Masahiro; Usui, Taro; Takahashi, Noriko; Kitada, Yoshihiko; Taguchi, Koichiro; Uno, Yoshihiro; Morita, Hiroyuki; Wu, Zhiliang; Nagano, Isao; Takahashi, Yuzo; Kudo, Takuya; Furuya, Kazuki; Yamada, Takahiro; Ishizuka, Tatsuo

    2013-01-01

    We investigated the effect of Trichinella infection on glucose tolerance and (pro- or anti-inflammatory) macrophage status in adipose tissue. Ob/ob mice and high fat-fed mice (obesity model) and C57/BL mice (control mice) were orally infected with (infected group) or without (uninfected group) 400 Trichinella per mouse. Four weeks later, the mice were subjected to investigation, which showed that fasting plasma glucose levels decreased in the infected group of C57/BL and ob/ob mice. Glucose tolerance, evaluated with intraperitoneal GTT, improved in the infected group of ob/ob mice and high fat-fed mice compared with the uninfected groups. Additional assay included anti-inflammatory macrophage (M2) markers and pro-inflammatory macrophage (M1) markers, with the aim to explore the effect of Trichinella infection on adipose tissue inflammation, since our previous study identified anti-inflammatory substances in secreted proteins by Trichinella. The result showed that mRNA levels of M2 markers, such as CD206, arginase and IL-10, increased, whereas M1 markers, such as CD11c, iNOS and IL-6, decreased in the stromal vascular fraction (SVF) isolated from epididymal fat in ob/ob mice. Residential macrophages obtained from the peritoneal lavage exhibited lower M1 markers and higher M2 markers levels in the infected group than in the uninfected group. Trichinella infection increases the ratio of M2/M1 systemically, which results in an improvement in pro-inflammatory state in adipose tissue and amelioration of glucose tolerance in obese mice.

  2. 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

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

    PubMed

    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

    2016-03-14

    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-(13)C]-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.

  4. Changes of the plasma metabolome during an oral glucose tolerance test: is there more than glucose to look at?

    PubMed

    Zhao, Xinjie; Peter, Andreas; Fritsche, Jens; Elcnerova, Michaela; Fritsche, Andreas; Häring, Hans-Ulrich; Schleicher, Erwin D; Xu, Guowang; Lehmann, Rainer

    2009-02-01

    The oral glucose tolerance test (oGTT) is a common tool to provoke a metabolic challenge for scientific purposes, as well as for diagnostic reasons, to monitor the kinetics of glucose and insulin. Here, we aimed to follow the variety of physiological changes of the whole metabolic pattern in plasma during an oGTT in healthy subjects in a nontargeted reversed-phase ultra performance liquid chromatography coupled to electrospray ionization quadrupole time of flight mass spectrometric metabolomics approach. We detected 11,500 metabolite ion masses/individual. Applying multivariate data analysis, four major groups of metabolites have been detected as the most discriminating oGTT biomarkers: free fatty acids (FFA), acylcarnitines, bile acids, and lysophosphatidylcholines. We found in detail 1) a strong decrease of all saturated and monounsaturated FFA studied during the oGTT; 2) a significant faster decline of palmitoleate (C16:1) and oleate (C18:1) FFA levels than their saturated counterparts; 3) a strong relative increase of polyunsaturated fatty acids in the fatty acid pattern at 120 min; and 4) a clear decrease in plasma C10:0, C12:0, and C14:1 acylcarnitine levels. These data reflect the switch from beta-oxidation to glycolysis and fat storage during the oGTT. Moreover, the bile acids glycocholic acid, glycochenodeoxycholic acid, and glycodeoxycholic acid were highly discriminative, showing a biphasic kinetic with a maximum of a 4.5- to 6-fold increase at 30 min after glucose ingestion, a significant decrease over the next 60 min followed by an increase until the end of the oGTT. Lysophosphatidylcholines were also increased significantly. The findings of our metabolomics study reveal detailed insights in the complex physiological regulation of the metabolism during an oGTT offering novel perspectives of this widely used procedure.

  5. Big Data over a 100G network at Fermilab

    SciTech Connect

    Garzoglio, Gabriele; Mhashilkar, Parag; Kim, Hyunwoo; Dykstra, Dave; Slyz, Marko

    2014-06-11

    As the need for Big Data in science becomes ever more relevant, networks around the world are upgrading their infrastructure to support high-speed interconnections. To support its mission, the high-energy physics community as a pioneer in Big Data has always been relying on the Fermi National Accelerator Laboratory to be at the forefront of storage and data movement. This need was reiterated in recent years with the data-taking rate of the major LHC experiments reaching tens of petabytes per year. At Fermilab, this resulted regularly in peaks of data movement on the Wide area network (WAN) in and out of the laboratory of about 30 Gbit/s and on the Local are network (LAN) between storage and computational farms of 160 Gbit/s. To address these ever increasing needs, as of this year Fermilab is connected to the Energy Sciences Network (ESnet) through a 100 Gb/s link. To understand the optimal system-and application-level configuration to interface computational systems with the new highspeed interconnect, Fermilab has deployed a Network Research & Development facility connected to the ESnet 100G Testbed. For the past two years, the High Throughput Data Program (HTDP) has been using the Testbed to identify gaps in data movement middleware [5] when transferring data at these high-speeds. The program has published evaluations of technologies typically used in High Energy Physics, such as GridFTP [4], XrootD [9], and Squid [8]. Furthermore, this work presents the new R&D facility and the continuation of the evaluation program.

  6. Big Data over a 100G network at Fermilab

    DOE PAGES

    Garzoglio, Gabriele; Mhashilkar, Parag; Kim, Hyunwoo; ...

    2014-06-11

    As the need for Big Data in science becomes ever more relevant, networks around the world are upgrading their infrastructure to support high-speed interconnections. To support its mission, the high-energy physics community as a pioneer in Big Data has always been relying on the Fermi National Accelerator Laboratory to be at the forefront of storage and data movement. This need was reiterated in recent years with the data-taking rate of the major LHC experiments reaching tens of petabytes per year. At Fermilab, this resulted regularly in peaks of data movement on the Wide area network (WAN) in and out ofmore » the laboratory of about 30 Gbit/s and on the Local are network (LAN) between storage and computational farms of 160 Gbit/s. To address these ever increasing needs, as of this year Fermilab is connected to the Energy Sciences Network (ESnet) through a 100 Gb/s link. To understand the optimal system-and application-level configuration to interface computational systems with the new highspeed interconnect, Fermilab has deployed a Network Research & Development facility connected to the ESnet 100G Testbed. For the past two years, the High Throughput Data Program (HTDP) has been using the Testbed to identify gaps in data movement middleware [5] when transferring data at these high-speeds. The program has published evaluations of technologies typically used in High Energy Physics, such as GridFTP [4], XrootD [9], and Squid [8]. Furthermore, this work presents the new R&D facility and the continuation of the evaluation program.« less

  7. Big Data Over a 100G Network at Fermilab

    NASA Astrophysics Data System (ADS)

    Garzoglio, Gabriele; Mhashilkar, Parag; Kim, Hyunwoo; Dykstra, Dave; Slyz, Marko

    2014-06-01

    As the need for Big Data in science becomes ever more relevant, networks around the world are upgrading their infrastructure to support high-speed interconnections. To support its mission, the high-energy physics community as a pioneer in Big Data has always been relying on the Fermi National Accelerator Laboratory to be at the forefront of storage and data movement. This need was reiterated in recent years with the data-taking rate of the major LHC experiments reaching tens of petabytes per year. At Fermilab, this resulted regularly in peaks of data movement on the Wide area network (WAN) in and out of the laboratory of about 30 Gbit/s and on the Local are network (LAN) between storage and computational farms of 160 Gbit/s. To address these ever increasing needs, as of this year Fermilab is connected to the Energy Sciences Network (ESnet) through a 100 Gb/s link. To understand the optimal system-and application-level configuration to interface computational systems with the new highspeed interconnect, Fermilab has deployed a Network Research & Development facility connected to the ESnet 100G Testbed. For the past two years, the High Throughput Data Program (HTDP) has been using the Testbed to identify gaps in data movement middleware [5] when transferring data at these high-speeds. The program has published evaluations of technologies typically used in High Energy Physics, such as GridFTP [4], XrootD [9], and Squid [8]. This work presents the new R&D facility and the continuation of the evaluation program.

  8. Monitoring changes in the scattering properties of mouse skin with optical coherence tomography during an in vivo glucose tolerance test

    NASA Astrophysics Data System (ADS)

    Kinnunen, M.; Tausta, S.; Myllylä, R.; Vainio, S.

    2007-05-01

    A non-invasive glucose monitoring technique would make evaluation of blood glucose values easier and more convenient. This would help diabetic patients to control their blood glucose values more regularly. A few years ago optical coherence tomography (OCT) was proposed as a non-invasive sensor for monitoring changes in blood glucose concentration. The method is based on monitoring glucose-induced changes in the scattering properties of the target. This article describes how OCT was used to monitor changes in the scattering properties of mouse skin during an in vivo glucose tolerance test. The results show that OCT has the potential to register glucose-induced changes in the optical properties of the sample. However, a commercial OCT device with a probe designed for imaging is not very suitable for non-invasive monitoring of glucose-induced changes in scattering. The problems confronted in this study, possibly originating from the small size of the animals, are discussed in the article.

  9. Effect of malnutrition during the first year of life on adult plasma insulin and glucose tolerance.

    PubMed

    González-Barranco, J; Ríos-Torres, J M; Castillo-Martínez, L; López-Alvarenga, J C; Aguilar-Salinas, C A; Bouchard, C; Deprès, J P; Tremblay, A

    2003-08-01

    There is evidence linking intrauterine growth retardation with increased cardiovascular risk and diabetes mellitus (DM) later in life. However, little is known about the association between malnutrition during the first year of life and metabolic abnormalities in adulthood. The objective of this study was to assess the effect of documented malnutrition during the first year of life on glucose tolerance, plasma insulin, lipid profile, and blood pressure in early adulthood, as well as to assess the interaction between body mass index (BMI) and malnutrition on these variables. A study group of young men with a documented history of malnutrition during their first year of life was recruited from 4 pediatric hospitals in Mexico City and compared with a control group. Subjects included were 52 men, aged 20.2 +/- 3.6 years, with a mean birth weight of 3.0 +/- 0.7 kg and documented malnutrition in their first year of life; controls were 50 men, aged 23.3 +/- 1.8 years, with a mean birth weight of 3.2 +/- 0.5 kg. Insulin and glucose concentrations, fasting and in response to an oral glucose load, plasma lipids, blood pressure, and an insulin sensitivity index (ISI) were measured. The areas under the curves of glucose (AUCG) and insulin (AUCI) were significantly higher in cases (P =.012 and <.002, respectively), independent of birth weight, BMI, or age. BMI was significantly associated with fasting plasma insulin (FPI), AUCI, ISI, triglyceride, and high-density lipoprotein (HDL)-cholesterol concentrations in cases, but not in controls. These data suggest that early malnutrition in extrauterine life, independently of birth weight, has an adverse effect on insulin metabolism and glucose tolerance in young men, and it worsens as body mass increases even within the normal range of BMI. Therefore, it is advisable to prevent obesity in individuals exposed to early malnutrition.

  10. Impaired glucose tolerance in pediatric burn patients at discharge from the acute hospital stay.

    PubMed

    Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Barr, David; Herndon, David N

    2010-01-01

    Hyperglycemia, secondary to the hypermetabolic stress response, is a common occurrence after thermal injury. This stress response has been documented to persist up to 9 months postburn. The purpose of this study was to measure insulin sensitivity in severely burned children before discharge when wounds are 95% healed. Twenty-four children, aged 4 to 17 years, with burns > or = 40% TBSA underwent a 2-hour oral glucose tolerance test before discharge from the acute pediatric burn unit. Plasma glucose and insulin levels as well as the Homeostasis Model Assessment for Insulin Resistance (HOMAIR) were compared with published oral glucose tolerance test data from healthy, nonburned children. There was a significant difference between severely burned children and nonburned, healthy children with respect to the HOMAIR. Severely burned children had a HOMAIR of 3.53 +/- 1.62 compared with the value in nonburned, healthy children of 1.28 +/- 0.16 (P < .05). Insulin resistance secondary to the hypermetabolic stress response persists in severely burned children when burn wounds are at least 95% healed. The results of this study warrant future investigations into therapeutic options for the burned child during the rehabilitative phase of their care after injury.

  11. Serum concentrations of vitamins A and E in impaired glucose tolerance.

    PubMed

    Tavridou, A; Unwin, N C; Laker, M F; White, M; Alberti, K G

    1997-10-31

    Serum concentrations of vitamins A and E were measured in 32 subjects with impaired glucose tolerance (IGT) and 148 subjects with normal glucose tolerance using reversed-phase high-performance liquid chromatography. Fasting glucose, insulin and lipid concentrations were also measured. Serum vitamin A concentrations were higher in subjects with IGT 2.5 (1.1-3.4) vs. 2.1 (1.4-3.2) mumol/l [median (2.5-97.5 percentiles)] (P = 0.002), the difference remaining significant after adjustment for triglycerides (P = 0.028). There was a univariate association between vitamin A levels and insulin resistance (r = 0.164; P = 0.02) and in multivariate logistic regression analysis the relative risk of subjects with high vitamin A concentrations having IGT was 3.8 (P = 0.002). There were no differences in serum vitamin E concentrations between the groups. These data suggest that higher vitamin A concentrations found in non-insulin-dependent diabetes pre-date the onset of diabetes. Further studies are required to confirm this finding and to investigate the possibility of a role for vitamin A in the aetiology of diabetes and IGT.

  12. Effect of transcutaneous auricular vagus nerve stimulation on impaired glucose tolerance: a pilot randomized study

    PubMed Central

    2014-01-01

    Background Impaired glucose tolerance (IGT) is a pre-diabetic state of hyperglycemia that is associated with insulin resistance, increased risk of type II diabetes, and cardiovascular pathology. Recently, investigators hypothesized that decreased vagus nerve activity may be the underlying mechanism of metabolic syndrome including obesity, elevated glucose levels, and high blood pressure. Methods In this pilot randomized clinical trial, we compared the efficacy of transcutaneous auricular vagus nerve stimulation (taVNS) and sham taVNS on patients with IGT. 72 participants with IGT were single-blinded and were randomly allocated by computer-generated envelope to either taVNS or sham taVNS treatment groups. In addition, 30 IGT adults were recruited as a control population and not assigned treatment so as to monitor the natural fluctuation of glucose tolerance in IGT patients. All treatments were self-administered by the patients at home after training at the hospital. Patients were instructed to fill in a patient diary booklet each day to describe any side effects after each treatment. The treatment period was 12 weeks in duration. Baseline comparison between treatment and control group showed no difference in weight, BMI, or measures of systolic blood pressure, diastolic blood pressure, fasting plasma glucose (FPG), 2-hour plasma glucose (2hPG), or glycosylated hemoglobin (HbAlc). Results 100 participants completed the study and were included in data analysis. Two female patients (one in the taVNS group, one in the sham taVNS group) dropped out of the study due to stimulation-evoked dizziness. The symptoms were relieved after stopping treatment. Compared with sham taVNS, taVNS significantly reduced the two-hour glucose tolerance (F(2) = 5.79, p = 0.004). In addition, we found that taVNS significantly decreased (F(1) = 4.21, p = 0.044) systolic blood pressure over time compared with sham taVNS. Compared with the no-treatment control group, patients

  13. 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.

  14. 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.

  15. Effects of an oral glucose tolerance test on the myogenic response in healthy individuals.

    PubMed

    Lott, Mary E J; Hogeman, Cynthia; Herr, Michael; Gabbay, Robert; Sinoway, Lawrence I

    2007-01-01

    The myogenic response, the inherent ability of blood vessels to rapidly respond to changes in transmural pressure, is involved in local blood flow autoregulation. Animal studies suggest that both acute hyperglycemia and hyperinsulinemia may impair myogenic vasoconstriction. The purpose of this study was to examine the effects of an oral glucose load on brachial mean blood velocity (MBV) during increases in forearm transmural pressure in humans. Eight healthy men and women (38 +/- 5 yr) underwent an oral glucose tolerance test (OGTT). MBV (in cm/s; Doppler ultrasound) responses to a rise in forearm transmural pressure (arm tank suction, -50 mmHg) were studied before and every 30 min for 120 min during the OGTT. Before the start of the OGTT, MBV was lower than baseline values 30 and 60 s after the application of negative pressure. This suggests that myogenic constriction was present. During the OGTT, blood glucose rose from 88 +/- 2 to 120 +/- 6 mg/dl (P < 0.05) and insulin rose from 14 +/- 1 to 101 +/- 32 microU/ml (P < 0.05). Glucose loading attenuated the reduction in MBV with arm suction (Delta-0.73 +/- 0.14 vs. Delta-1.67 +/- 0.43 cm/s and Delta-1.07 +/- 0.14 vs. Delta-2.38 +/- 0.54 cm/s, respectively, during 30 and 60 s of suction postglucose compared with preglucose values; all P < 0.05). We observed no such time effect for myogenic responses during a sham OGTT. In an additional 5 subjects, glucose loading had no effect on brachial diameters with the application of negative pressure. Oral glucose loading leads to attenuated myogenic vasoconstriction in healthy individuals. The role that this diminished postglucose reactivity plays in mediating postprandial hypotension and/or orthostasis needs to be further explored.

  16. SIRT1 enhances glucose tolerance by potentiating brown adipose tissue function

    PubMed Central

    Boutant, Marie; Joffraud, Magali; Kulkarni, Sameer S.; García-Casarrubios, Ester; García-Roves, Pablo M.; Ratajczak, Joanna; Fernández-Marcos, Pablo J.; Valverde, Angela M.; Serrano, Manuel; Cantó, Carles

    2014-01-01

    Objective SIRT1 has been proposed to be a key signaling node linking changes in energy metabolism to transcriptional adaptations. Although SIRT1 overexpression is protective against diverse metabolic complications, especially in response to high-fat diets, studies aiming to understand the etiology of such benefits are scarce. Here, we aimed to identify the key tissues and mechanisms implicated in the beneficial effects of SIRT1 on glucose homeostasis. Methods We have used a mouse model of moderate SIRT1 overexpression, under the control of its natural promoter, to evaluate glucose homeostasis and thoroughly characterize how different tissues could influence insulin sensitivity. Results Mice with moderate overexpression of SIRT1 exhibit better glucose tolerance and insulin sensitivity even on a low fat diet. Euglycemic-hyperinsulinemic clamps and in-depth tissue analyses revealed that enhanced insulin sensitivity was achieved through a higher brown adipose tissue activity and was fully reversed by housing the mice at thermoneutrality. SIRT1 did not influence brown adipocyte differentiation, but dramatically enhanced the metabolic transcriptional responses to β3-adrenergic stimuli in differentiated adipocytes. Conclusions Our work demonstrates that SIRT1 improves glucose homeostasis by enhancing BAT function. This is not consequent to an alteration in the brown adipocyte differentiation process, but as a result of potentiating the response to β3-adrenergic stimuli. PMID:25685699

  17. Glucose tolerance and lipid-lipoprotein levels in middle-aged powerlifters.

    PubMed

    Hurley, B F; Hagberg, J M; Seals, D R; Ehsani, A A; Goldberg, A P; Holloszy, J O

    1987-02-01

    The purpose of this study was to obtain information regarding the effects of a form of strength training (powerlifting) on certain coronary artery disease (CAD) risk factors in middle-aged men. The risk factors studied were the plasma lipid-lipoprotein profile, glucose tolerance and plasma insulin levels, all of which have been shown to be favourably influenced by endurance training in middle-aged and older men. Five elite powerlifters (52 +/- 9 years) were compared to distance runners and sedentary controls of similar age with whom they were matched in terms of body fatness as estimated from skin-fold thickness measurements. The powerlifters had a significantly (P less than 0.01) lower HDL cholesterol (HDL-C) level (34 +/- 4 mg/100 ml) than the sedentary controls (48 +/- 12 mg/100 ml) and runners (54 +/- 8 mg/100 ml). The total cholesterol to HDL-C ratio, a good indicator of CAD risk, was 41% higher in the powerlifters than in the controls, and 57% higher than in the runners (both P less than 0.01). The total area under the glucose tolerance curve during an oral glucose tolerance test (OGTT) for the powerlifters was 74% higher than for the sedentary controls (P less than 0.05) and 229% higher than for runners (P less than 0.01). Similarly, the total area under the OGTT insulin curve for the powerlifters was 68% higher than for sedentary controls and 332% higher than for the runners (P less than 0.001). These findings suggest that middle-aged powerlifters, in marked contrast to endurance athletes, have an increased risk of developing CAD.

  18. Selective slow wave sleep but not rapid eye movement sleep suppression impairs morning glucose tolerance in healthy men.

    PubMed

    Herzog, Nina; Jauch-Chara, Kamila; Hyzy, Franziska; Richter, Annekatrin; Friedrich, Alexia; Benedict, Christian; Oltmanns, Kerstin M

    2013-10-01

    Shortened nocturnal sleep impairs morning glucose tolerance. The underlying mechanism of this effect is supposed to involve a reduced fraction of slow wave sleep (SWS). However, it remains unanswered if impaired glucose tolerance occurs due to specific SWS reduction or a general disturbance of sleep. Sixteen healthy men participated in three experimental conditions in a crossover design: SWS suppression, rapid eye movement (REM)-sleep disturbance, and regular sleep. Selective sleep stage disturbance was performed by means of an acoustic tone (532Hz) with gradually rising sound intensity. Blood concentrations of glucoregulatory parameters were measured upon an oral glucose tolerance test the next morning. Our data show that morning plasma glucose and serum insulin responses were significantly increased after selective SWS suppression. Moreover, SWS suppression reduced postprandial insulin sensitivity up to 20%, as determined by Matsuda Index. Contrastingly, disturbed REM-sleep did not affect glucose homeostasis. We conclude that specifically SWS reduction is critically involved in the impairment of glucose tolerance associated with disturbed sleep. Therefore, glucose metabolism in subjects predisposed to reduced SWS (e.g. depression, aging, obstructive sleep apnea, pharmacological treatment) should be thoroughly monitored.

  19. Genome shuffling enhanced ε-poly-L-lysine production by improving glucose tolerance of Streptomyces graminearus.

    PubMed

    Li, Shu; Li, Feng; Chen, Xu-Sheng; Wang, Liang; Xu, Jian; Tang, Lei; Mao, Zhong-Gui

    2012-01-01

    The productivity of ε-poly-L: -lysine (ε-PL) in currently reported wild-type strains is low. Here we improved glucose tolerance of a Streptomyces graminearus strain LS-B1 by genome shuffling while simultaneously enhancing the ε-PL productivity. The starting population was generated by ultraviolet irradiation and nitrosoguanidine mutagenesis and then subjected for recursive protoplast fusion. The positive colonies from library, created by fusing the inactivated protoplasts were screened on agar plates containing different concentrations of glucose. Characterization of all recombinants and wild-type strain in shake-flask fermentation indicated the compatibility of two phenotypes of glucose tolerance and ε-PL yield enhancement. The best performing recombinant, F3-4, was isolated after three rounds of genome shuffling, whose ε-PL production was about 88% higher than that of the parent strain. In batch fermentation test, the ε-PL concentration was obtained as 2.4 g/L by F3-4 compared with 1.6 g/L of wild type. Fed-batch fermentation by F3-4 was carried out and the ε-PL production accumulated to 13.5 g/L when initial glucose concentration was improved from 50 to 85 g/L. Enzyme activities of hexokinase, pyruvate kinase, and citrate synthase revealed that the glycolytic pathway and tricarboxylic acid circle way in F3-4 were more active than those in wild type, which was a possible reason for enhanced ε-PL production.

  20. Neuregulin improves response to glucose tolerance test in control and diabetic rats.

    PubMed

    López-Soldado, Iliana; Niisuke, Katrin; Veiga, Catarina; Adrover, Anna; Manzano, Anna; Martínez-Redondo, Vicente; Camps, Marta; Bartrons, Ramon; Zorzano, Antonio; Gumà, Anna

    2016-03-15

    Neuregulin (NRG) is an EGF-related growth factor that binds to the tyrosine kinase receptors ErbB3 and ErbB4, thus inducing tissue development and muscle glucose utilization during contraction. Here, we analyzed whether NRG has systemic effects regulating glycemia in control and type 2 diabetic rats. To this end, recombinant NRG (rNRG) was injected into Zucker diabetic fatty (ZDF) rats and their respective lean littermates 15 min before a glucose tolerance test (GTT) was performed. rNRG enhanced glucose tolerance without promoting the activation of the insulin receptor (IR) or insulin receptor substrates (IRS) in muscle and liver. However, in control rats, rNRG induced the phosphorylation of protein kinase B (PKB) and glycogen synthase kinase-3 (GSK-3) in liver but not in muscle. In liver, rNRG increased ErbB3 tyrosine phosphorylation and its binding to phosphatidylinositol 3-kinase (PI3K), thus indicating that rNRG activates the ErbB3/PI3K/PKB signaling pathway. rNRG increased glycogen content in liver but not in muscle. rNRG also increased the content of fructose-2,6-bisphosphate (Fru-2,6-P2), an activator of hepatic glycolysis, and lactate in liver but not in muscle. Increases in lactate were abrogated by wortmannin, a PI3K inhibitor, in incubated hepatocytes. The liver of ZDF rats showed a reduced content of ErbB3 receptors, entailing a minor stimulation of the rNRG-induced PKB/GSK-3 cascade and resulting in unaltered hepatic glycogen content. Nonetheless, rNRG increased hepatic Fru-2,6-P2 and augmented lactate both in liver and in plasma of diabetic rats. As a whole, rNRG improved response to the GTT in both control and diabetic rats by enhancing hepatic glucose utilization.

  1. Acute postexercise effects of concentric and eccentric exercise on glucose tolerance.

    PubMed

    Cook, Matthew David; Myers, Stephen David; Kelly, John Stephen Michael; Willems, Mark Elisabeth Theodorus

    2015-02-01

    Impaired glucose tolerance was shown to be present 48 hr following muscle-damaging eccentric exercise. We examined the acute effect of concentric and muscle-damaging eccentric exercise, matched for intensity, on the responses to a 2-hr 75-g oral glucose tolerance test (OGTT). Ten men (27 ± 9 years, 178 ± 7 cm, 75 ± 11 kg, VO₂max: 52.3 ± 7.3 ml · kg⁻¹ · min⁻¹) underwent three OGTTs after an overnight 12 hr fast: rest (control), 40-min (5 × 8-min with 2-min interbout rest) of concentric (level running, 0%, CON) or eccentric exercise (downhill running, -12%, ECC). Running intensity was matched at 60% of maximal metabolic equivalent. Maximal isometric force of m. quadriceps femoris of both legs was measured before and after the running protocols. Downhill running speed was higher (level: 9.7 ± 2.1, downhill: 13.8 ± 3.2 km · hr⁻¹, p < .01). Running protocols had similar VO₂max (p = .59), heart rates (p = .20) and respiratory exchange ratio values (p = .74) indicating matched intensity and metabolic demands. Downhill running resulted in higher isometric force deficits (level: 3.0 ± 6.7, downhill: 17.1 ± 7.3%, p < .01). During OGTTs, area-under-the-curve for plasma glucose (control: 724 ± 97, CON: 710 ± 77, ECC: 726 ± 72 mmol · L⁻¹ · 120 min, p = .86) and insulin (control: 24995 ± 11229, CON: 23319 ± 10417, ECC: 21842 ± 10171 pmol · L⁻¹ · 120 min, p = .48), peak glucose (control: 8.1 ± 1.3, CON: 7.7 ± 1.2, ECC: 7.7 ± 1.1 mmol · L⁻¹, p = .63) and peak insulin levels (control: 361 ± 188, CON: 322 ± 179, ECC: 299 ± 152 pmol · L⁻¹, p = .30) were similar. It was concluded that glucose tolerance and the insulin response to an OGTT were not changed immediately by muscle-damaging eccentric exercise.

  2. Glucose Tolerance and Insulin Resistance in Indian Children: Relationship to Infant feeding Pattern

    PubMed Central

    Veena, SR; Krishnaveni, GV; Wills, AK; Hill, JC; Karat, SC; Fall, CHD

    2011-01-01

    Aims/hypothesis Our objective was to examine whether longer duration of breast-feeding and later introduction of complementary foods are associated with lower glucose concentrations and insulin resistance (IR-HOMA) in Indian children. Methods Breast-feeding duration (6 categories from <3 to ≥18 months) and age at introduction of complementary foods (4 categories from <4 to ≥6 months) were recorded at 1, 2 and 3 year follow-up of 568 children from a birth cohort in Mysore, India. At 5- and 9.5-years of age 518 children were assessed for glucose tolerance and IR-HOMA. Results All the children were initially breast-fed; 90% were breast-fed for ≥6 months and 56.7% started complementary foods at or before the age of 4 months. Each category increase in breast-feeding duration was associated with lower fasting insulin concentration (β=−0.05 pmol/L (95% CI: −0.10, −0.004); P=0.03) and IR-HOMA (β=−0.05 (95% CI: −0.10, −0.001); P=0.046) at 5-years, adjusted for the child’s sex, age, current BMI, socio-economic status, parent’s education, rural/urban residence, birthweight and maternal gestational diabetes status. Longer duration of breastfeeding was associated with higher 120-minute glucose concentration at 5-years (β=0.08 mmol/L (95% CI: 0.001, 0.15; P=0.03) but lower 120-minute glucose concentration at 9.5-years (β=−0.09 (95% CI: −0.16, −0.03; P=0.006). Age at starting complementary foods was unrelated to the children’s glucose tolerance and IR-HOMA. Conclusions/interpretation Within this cohort, in which prolonged breast-feeding was the norm, there was evidence of a protective effect of longer duration of breast-feeding against glucose intolerance at 9.5-years. At 5-years longer duration of breast-feeding was associated with lower IR-HOMA. PMID:21773682

  3. Defective liver disposal of free fatty acids in patients with impaired glucose tolerance.

    PubMed

    Iozzo, Patricia; Turpeinen, Anu K; Takala, Teemu; Oikonen, Vesa; Bergman, Jörgen; Grönroos, Tove; Ferrannini, Ele; Nuutila, Pirjo; Knuuti, Juhani

    2004-07-01

    The liver exchanges high fluxes of glucose and free fatty acids (FFA) and is one main site of their reciprocal regulation. Acute exposure to hyperglycemia and hyperinsulinemia has been shown to reduce splanchnic beta-oxidation in healthy humans. We investigated whether a spontaneous condition of chronic mild hyperglycemia and hyperinsulinemia affects liver FFA uptake. Hepatic FFA influx rate constant (LKi) was measured after a 12-15-h fast in 10 patients with impaired glucose tolerance (IGT) and eight control subjects using positron emission tomography in combination with the long-chain FFA analog 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Compared with controls, IGT patients had higher serum insulin, glucose, and triglyceride levels (1.71 +/- 0.24 vs. 0.59 +/- 0.06 mmol/liter, P < 0.001), lower high-density lipoprotein (1.04 +/- 0.11 vs. 1.42 +/- 0.13 mmol/liter, P < 0.05), and similar FFA levels (0.59 +/- 0.06 vs. 0.56 +/- 0.05 mmol/liter(-1), P = not significant). LKi was significantly reduced in IGT (0.288 +/- 0.014 min(-1)) compared with control subjects (0.341 +/- 0.014 min(-1), P < 0.02). LKi was negatively correlated with plasma glucose (r = 0.51, P < 0.03), glycosylated hemoglobin (r = 0.55, P < 0.02), and blood lactate levels (r = 0.52, P < 0.03). We conclude that, in IGT patients, the ability of the liver to extract FFA from the circulation appears to be impaired. The reciprocal relationship between hepatic FFA extraction and glucose/lactate flux may derive from intrahepatic substrate competition.

  4. Optimization of the intravenous glucose tolerance test in T2DM patients using optimal experimental design.

    PubMed

    Silber, Hanna E; Nyberg, Joakim; Hooker, Andrew C; Karlsson, Mats O

    2009-06-01

    Intravenous glucose tolerance test (IVGTT) provocations are informative, but complex and laborious, for studying the glucose-insulin system. The objective of this study was to evaluate, through optimal design methodology, the possibilities of more informative and/or less laborious study design of the insulin modified IVGTT in type 2 diabetic patients. A previously developed model for glucose and insulin regulation was implemented in the optimal design software PopED 2.0. The following aspects of the study design of the insulin modified IVGTT were evaluated; (1) glucose dose, (2) insulin infusion, (3) combination of (1) and (2), (4) sampling times, (5) exclusion of labeled glucose. Constraints were incorporated to avoid prolonged hyper- and/or hypoglycemia and a reduced design was used to decrease run times. Design efficiency was calculated as a measure of the improvement with an optimal design compared to the basic design. The results showed that the design of the insulin modified IVGTT could be substantially improved by the use of an optimized design compared to the standard design and that it was possible to use a reduced number of samples. Optimization of sample times gave the largest improvement followed by insulin dose. The results further showed that it was possible to reduce the total sample time with only a minor loss in efficiency. Simulations confirmed the predictions from PopED. The predicted uncertainty of parameter estimates (CV) was low in all tested cases, despite the reduction in the number of samples/subject. The best design had a predicted average CV of parameter estimates of 19.5%. We conclude that improvement can be made to the design of the insulin modified IVGTT and that the most important design factor was the placement of sample times followed by the use of an optimal insulin dose. This paper illustrates how complex provocation experiments can be improved by sequential modeling and optimal design.

  5. [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.

  6. Urinary C peptide creatinine ratio in pregnant women with normal glucose tolerance and type 1 diabetes: evidence for insulin secretion

    PubMed Central

    Markoska, Ankica; Valaiyapathi, Rajalakshmi; Thorn, Chloe; Dornhorst, Anne

    2017-01-01

    Hypothesis In pregnancy, urinary C peptide creatinine ratio (UCPCR) reflects endogenous insulin secretion in women with normal glucose tolerance and type 1 diabetes. Research design and methods UCPCR and serum C peptide were measured in 90 glucose-tolerant women at 0 and 120 min during a 75 g oral glucose tolerance test (OGTT) at 28 weeks of gestation. UCPCR was measured in 2 samples obtained over 10 weeks apart in 7 pregnant women with longstanding type 1 diabetes. Results UCPCROGTT and serum C peptideOGTT of glucose-tolerant women were significantly correlated at 0 and 120 min (rs0.675, 0.541 respectively, p<0.0001). All 7 pregnant women with type 1 diabetes had detectable first sample UCPCR (median (range) 49 (6–1038) pmol/mmol) that rose in 6 women by 477 (29–1491) pmol/mmol. Conclusions Detectable UCPCR in pregnant women with normal glucose tolerance and type 1 diabetes is likely to reflect endogenous insulin secretion and hence β-cell activity. PMID:28090333

  7. Diagnosing Impaired Glucose Tolerance Using Direct Infusion Mass Spectrometry of Blood Plasma

    PubMed Central

    Lokhov, Petr G.; Trifonova, Oxana P.; Maslov, Dmitry L.; Balashova, Elena E.; Archakov, Alexander I.; Shestakova, Ekaterina A.; Shestakova, Marina V.; Dedov, Ivan I.

    2014-01-01

    The goal of this study was to evaluate the capacity for mass spectrometry of blood plasma to diagnose impaired glucose tolerance (IGT). For this study, blood plasma samples from control subjects (n = 30) and patients with IGT (n = 20) were treated with methanol and low molecular weight fraction were then analyzed by direct infusion mass spectrometry. A total of 51 metabolite ions strongly associated with IGT were detected. The area under a receiver operating characteristic (ROC) curve (AUC) for diagnosing IGT that was based on an analysis of all these metabolites was 0.93 (accuracy 90%, specificity 90%, and sensitivity 90%). The associated reproducibility was 85%. The metabolites identified were also consistent with risk factors previously associated with the development of diabetes. Thus, direct infusion mass spectrometry of blood plasma metabolites represents a rapid, single-step, and reproducible method for the analysis of metabolites. Moreover, this method has the potential to serve as a prototype for clinical analyses that could replace the currently used glucose tolerance test with a more patient-friendly assay. PMID:25202985

  8. Diagnosing impaired glucose tolerance using direct infusion mass spectrometry of blood plasma.

    PubMed

    Lokhov, Petr G; Trifonova, Oxana P; Maslov, Dmitry L; Balashova, Elena E; Archakov, Alexander I; Shestakova, Ekaterina A; Shestakova, Marina V; Dedov, Ivan I

    2014-01-01

    The goal of this study was to evaluate the capacity for mass spectrometry of blood plasma to diagnose impaired glucose tolerance (IGT). For this study, blood plasma samples from control subjects (n = 30) and patients with IGT (n = 20) were treated with methanol and low molecular weight fraction were then analyzed by direct infusion mass spectrometry. A total of 51 metabolite ions strongly associated with IGT were detected. The area under a receiver operating characteristic (ROC) curve (AUC) for diagnosing IGT that was based on an analysis of all these metabolites was 0.93 (accuracy 90%, specificity 90%, and sensitivity 90%). The associated reproducibility was 85%. The metabolites identified were also consistent with risk factors previously associated with the development of diabetes. Thus, direct infusion mass spectrometry of blood plasma metabolites represents a rapid, single-step, and reproducible method for the analysis of metabolites. Moreover, this method has the potential to serve as a prototype for clinical analyses that could replace the currently used glucose tolerance test with a more patient-friendly assay.

  9. 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

  10. Glucose tolerance in mice exposed to light–dark stimulus patterns mirroring dayshift and rotating shift schedules

    PubMed Central

    Figueiro, Mariana G.; Radetsky, Leora; Plitnick, Barbara; Rea, Mark S.

    2017-01-01

    Glucose tolerance was measured in (nocturnal) mice exposed to light–dark stimulus patterns simulating those that (diurnal) humans would experience while working dayshift (DSS) and 2 rotating night shift patterns (1 rotating night shift per week [RSS1] and 3 rotating night shifts per week [RSS3]). Oral glucose tolerance tests were administered at the same time and light phase during the third week of each experimental session. In contrast to the RSS1 and RSS3 conditions, glucose levels reduced more quickly for the DSS condition. Glucose area-under-the-curve measured for the DSS condition was also significantly less than that for the RSS1 and RSS3 conditions. Circadian disruption for the 3 light–dark patterns was quantified using phasor magnitude based on the 24-h light–dark patterns and their associated activity–rest patterns. Circadian disruption for mice in the DSS condition was significantly less than that for the RSS1 and RSS3 conditions. This study extends previous studies showing that even 1 night of shift work decreases glucose tolerance and that circadian disruption is linked to glucose tolerance in mice. PMID:28079162

  11. New-onset diabetes after transplantation--role of oral glucose tolerance test for diagnosis and study of risk factors.

    PubMed

    Sahay, Manisha; Sahay, Rakesh K; Narayan, Girish

    2013-09-01

    To determine the role of the oral glucose tolerance test in the early detection of new-onset diabetes after transplantation (NODAT) and to compare the various risk factors and insulin kinetics in the transplant patients, we studied 41 live-related renal allograft recipients who were not diabetic before transplantation. Immunosuppression included triple drug therapy (cyclosporine, azathioprine and steroids) and rejection episodes were treated with methyl prednisolone (30 mg/kg IV × 3 days). All the study patients were subjected to an oral glucose tolerance test (OGTT) at Day 90 post-transplant and classified as having normal glucose tolerance (NGT), impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and NODAT as per the World Health Organization guidelines. Insulin levels were also determined at 0, ½ hour, 1 hour and 2 hours during OGTT. NODAT was noted in 29.2% of the study patients, IFG in 4.8% of the study patients and NGT in 65.8% of the study patients. All the groups had normal fasting plasma glucose, but higher than normal insulin levels, suggesting insulin resistance. The patients with overt NODAT had, in addition, low fasting insulin (insulin secretory defect). OGTT may be used for the early detection of NODAT. Although insulin resistance is detected in the majority of post-transplant patients, NODAT also reveals also an insulin secretory defect.

  12. Obese mice on a high-fat alternate-day fasting regimen lose weight and improve glucose tolerance.

    PubMed

    Joslin, P M N; Bell, R K; Swoap, S J

    2016-06-08

    Alternate-day fasting (ADF) causes body weight (BW) loss in humans and rodents. However, it is not clear that ADF while maintaining a high-fat (HF) diet results in weight loss and the accompanying improvement in control of circulating glucose. We tested the hypotheses that a high-fat ADF protocol in obese mice would result in (i) BW loss, (ii) improved glucose control, (iii) fluctuating phenotypes on 'fasted' days when compared to 'fed' days and (iv) induction of torpor on 'fasted days'. We evaluated the physiological effects of ADF in diet-induced obese mice for BW, heart rate (HR), body temperature (Tb ), glucose tolerance, insulin responsiveness, blood parameters (leptin, insulin, free fatty acids) and hepatic gene expression. Diet-induced obese male C57BL/6J mice lost one-third of their pre-diet BW while on an ADF diet for 10 weeks consisting of HF food. The ADF protocol improved glucose tolerance and insulin sensitivity, although mice on a fast day were less glucose tolerant than the same mice on a fed day. ADF mice on a fast day had low circulating insulin, but had an enhanced response to an insulin-assisted glucose tolerance test, suggesting the impaired glucose tolerance may be a result of insufficient insulin production. On fed days, ADF mice were the warmest, had a high HR and displayed hepatic gene expression and circulating leptin that closely mimicked that of mice fed an ad lib HF diet. ADF mice never entered torpor as assessed by HR and Tb . However, on fast days, they were the coolest, had the slowest HR, and displayed hepatic gene expression and circulating leptin that closely mimicked that of Chow-Fed mice. Collectively, the ADF regimen with a HF diet in obese mice results in weight loss, improved blood glucose control, and daily fluctuations in selected physiological and biochemical parameters in the mouse.

  13. 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.

  14. An oral lipid challenge and acute intake of caffeinated coffee additively decrease glucose tolerance in healthy men.

    PubMed

    Beaudoin, Marie-Soleil; Robinson, Lindsay E; Graham, Terry E

    2011-04-01

    Lipid-induced insulin resistance has been investigated primarily with i.v. infusions, and caffeine-induced insulin resistance, with alkaloid caffeine. The effects of orally consumed lipids and coffee have not been established and to our knowledge have never been simultaneously investigated. The goals of this study were to determine whether an oral lipid challenge and caffeinated coffee would disrupt glucose homeostasis and to characterize their respective incretin responses. It was hypothesized that oral ingestion of saturated lipids would impair glucose tolerance and that caffeinated coffee would further hinder glucose management. Ten young, healthy males participated in 5 trials in a randomized, cross-over design. At time 0 h, they underwent an oral fat tolerance test (OFTT: 1 g lipid/kg body weight) or consumed water, followed 5 h later by caffeinated (5 mg/kg) coffee, decaffeinated coffee, or water. At 6 h, volunteers underwent an oral glucose tolerance test (OGTT). Consumption of the OFTT increased glucose concentrations (P < 0.05) after a subsequent OGTT. At 7 h, caffeinated coffee produced the highest glucose concentrations (P < 0.05). Glucagon-like peptide-1 active (GLP-1a) and glucose-dependent insulinotropic polypeptide (GIP) were both increased for up to 6 h in all OFTT trials (P < 0.05). Compared to all other treatments, caffeinated and decaffeinated coffee produced higher GLP-1a response at 6.25 h (P < 0.05), whereas only caffeinated coffee increased GIP secretion (P < 0.05). These results show that oral consumption of lipids and caffeinated coffee can independently and additively decrease glucose tolerance. Incretin hormones could explain at least in part this impaired glucose homeostasis.

  15. 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

  16. 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.

  17. Diacylglycerol kinase ϵ deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.

    PubMed

    Mannerås-Holm, Louise; Schönke, Milena; Brozinick, Joseph T; Vetterli, Laurène; Bui, Hai-Hoang; Sanders, Philip; Nascimento, Emmani B M; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2017-02-28

    Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of DAG into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε deficient (KO) and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGKε KO mice, which was paradoxically associated with increased glucose tolerance. While skeletal muscle insulin sensitivity was unaltered, whole body respiratory exchange ratio was reduced, and abundance of mitochondrial markers was increased, indicating a greater reliance on fat oxidation and intracellular lipid metabolism in DGKε KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGKε KO mice may undergo rapid turnover due to increased mitochondrial function and lipid oxidation, rather than storage, which in turn may preserve insulin sensitivity. In conclusion, DGKε plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle.

  18. Changes in the serum composition of free-fatty acids during an intravenous glucose tolerance test.

    PubMed

    Soriguer, Federico; García-Serrano, Sara; García-Almeida, Jose M; Garrido-Sánchez, Lourdes; García-Arnés, Juan; Tinahones, Francisco J; Cardona, Isabel; Rivas-Marín, Jose; Gallego-Perales, Jose L; García-Fuentes, Eduardo

    2009-01-01

    Recent studies suggest that measuring the free-fatty acids (FFA) during an intravenous glucose tolerance test (IVGTT) may provide information about the metabolic associations between serum FFA and carbohydrate and insulin metabolism. We evaluated the FFA profile during an IVGTT and determined whether this test changes the composition and concentration of FFA. An IVGTT was given to 38 severely obese persons before and 7 months after undergoing bariatric surgery and also to 12 healthy, nonobese persons. The concentration and composition of the FFA were studied at different times during the test. The concentration of FFA fell significantly faster during the IVGTT in the controls and in the severely obese persons with normal-fasting glucose (NFG) than in the severely obese persons with impaired-fasting glucose (IFG) or type 2 diabetes mellitus (T2DM) (P < 0.05). Significant differences were found in the time to minimum serum concentrations of FFA (control = NFG < IFG < T2DM) (P < 0.001). These variables improved after bariatric surgery in the three groups. The percentage of monounsaturated and n-6 polyunsaturated FFA in the control subjects and in the obese persons, both before and after surgery, decreased significantly during the IVGTT. In conclusion, during an IVGTT, severely obese persons with IFG or T2DM experienced a lower fall in the FFA than the severely obese persons with NFG and the controls, becoming normal after bariatric surgery.

  19. 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.

  20. The role of physical activity in the management of impaired glucose tolerance: a systematic review

    PubMed Central

    Khunti, K.; Bull, F.; Gorely, T.; Davies, M. J.

    2007-01-01

    Although physical activity is widely reported to reduce the risk of type 2 diabetes in individuals with prediabetes, few studies have examined this issue independently of other lifestyle modifications. The aim of this review is to conduct a systematic review of controlled trials to determine the independent effect of exercise on glucose levels and risk of type 2 diabetes in people with prediabetes (IGT and/or IFG). A detailed search of MEDLINE (1966–2006) and EMBASE (1980–2006) found 279 potentially relevant studies, eight of which met the inclusion criteria for this review. All eight studies were controlled trials in individuals with impaired glucose tolerance. Seven studies used a multi-component lifestyle intervention that included exercise, diet and weight loss goals and one used a structured exercise training intervention. Four studies used the incidence of diabetes over the course of the study as an outcome variable and four relied on 2-h plasma glucose as an outcome measure. In the four studies that measured the incidence of diabetes as an outcome, the risk of diabetes was reduced by approximately 50% (range 42–63%); as these studies reported only small changes in physical activity levels, the reduced risk of diabetes is likely to be attributable to factors other than physical activity. In the remaining four studies, only one reported significant improvements in 2-h plasma glucose even though all but one reported small to moderate increases in maximal oxygen uptake. These results indicate that the contribution of physical activity independent of dietary or weight loss changes to the prevention of type 2 diabetes in people with prediabetes is equivocal. PMID:17415549

  1. Exhaled breath condensate pH decreases following oral glucose tolerance test.

    PubMed

    Bikov, Andras; Pako, Judit; Montvai, David; Kovacs, Dorottya; Koller, Zsofia; Losonczy, Gyorgy; Horvath, Ildiko

    2015-12-15

    Exhaled breath condensate (EBC) pH is a widely measured non-invasive marker of airway acidity. However, some methodological aspects have not been thoroughly investigated. The aim of the study was to determine the effect of oral glucose tolerance test (OGTT) on EBC pH in attempt to better standardize its measurement. Seventeen healthy subjects (24  ±  2 years, 6 men, 11 women) participated in the study. EBC collection and capillary blood glucose measurements were performed before as well as 0, 30, 60 and 120 min after a standardized OGTT test. The rate of respiratory droplet dilution and pH were evaluated in EBC. Blood glucose significantly increased at 30 min and maintained elevation after 60 and 120 min following OGTT. Compared to baseline (7.99  ±  0.25) EBC pH significantly decreased immediately after OGTT (7.41  ±  0.47); this drop sustained over 30 (7.44  ±  0.72) and 60 min (7.62  ±  0.44) without a significant difference at 120 min (7.78  ±  0.26). No change was observed in the rate of respiratory droplet dilution. There was no relationship between blood glucose and EBC pH values. Sugar intake may significantly decrease EBC pH. This effect needs to be considered when performing EBC pH studies. Further experiments are also warranted to investigate the effect of diet on other exhaled biomarkers.

  2. Evidence that the oral glucose-tolerance test does not provide a uniform stimulus to pancreatic islets in pregnancy.

    PubMed

    de Leacy, E A; Cowley, D M

    1989-07-01

    Fifty consecutive pregnant patients referred for a glucose-tolerance test were classified on the basis of increasing (n = 20) or decreasing (n = 28) hematocrit after an oral 75-g glucose load. (The hematocrit did not change in the other two patients.) Patients with increasing hematocrit, a response previously seen in patients with the dumping syndrome, showed significantly flatter increases in glucose concentrations in plasma after the load. The mean decrease in the concentration of phosphate in plasma, measured as an index of glucose uptake by cells, was significantly less (P less than 0.05) 2 h after the load in the group with flatter glucose responses, suggesting that the flat response is ascribable to poor glucose absorption rather than to an exaggerated insulin response. These results indicate that the oral glucose-tolerance test stresses the pancreatic islets differently in different pregnant subjects, owing to individual variations in the gastrointestinal handling of the glucose load. Consequently, patients may give a "normal" result who might otherwise become hyperglycemic after normal meals. We suggest that alternative screening procedures be investigated to assess pregnant patients postprandially.

  3. Determinants of Glycated Hemoglobin in Subjects With Impaired Glucose Tolerance: Subanalysis of the Japan Diabetes Prevention Program

    PubMed Central

    Sakane, Naoki; Sato, Juichi; Tsushita, Kazuyo; Tsujii, Satoru; Kotani, Kazuhiko; Tominaga, Makoto; Kawazu, Shoji; Sato, Yuzo; Usui, Takeshi; Kamae, Isao; Yoshida, Toshihide; Kiyohara, Yutaka; Sato, Shigeaki; Tsuzaki, Kokoro; Nirengi, Shinsuke; Takahashi, Kaoru; Kuzuya, Hideshi; Group, JDPP Research

    2017-01-01

    Background Limited evidence is available about the relationship of lifestyle factors with glycated hemoglobin (HbA1c) in subjects with impaired glucose tolerance. The aim of study was to identify such determinant factors of HbA1c in subjects with impaired glucose tolerance. Methods This cross-sectional study included 121 men and 124 women with impaired glucose tolerance, who were diagnosed based on a 75-g oral glucose tolerance test. Demographic and biochemical parameters, including the body mass index (BMI), fasting plasma glucose (FPG), 2-h post-load glucose (2-h PG), and HbA1c, were measured. The pancreatic β-cell function and insulin resistance were assessed using homeostasis model assessment (HOMA-β). Dietary intake was assessed by a food frequency questionnaire. Results The levels of FPG, 2-h PG, and carbohydrate intake were correlated with the HbA1c level in men, while the FPG and 2-h PG levels were correlated with the HbA1c level in women. In multiple regression analyses, BMI, FPG, 2-h PG, and white rice intake were associated with HbA1c levels in men, while BMI, FPG, HOMA-β, and bread intake were associated with HbA1c levels in women. Conclusions The present findings suggest that a substantial portion of HbA1c may be composed of not only glycemic but also several lifestyle factors in men with impaired glucose tolerance. These factors can be taken into consideration as modifiable determinants in assessing the HbA1c level for the diagnosis and therapeutic monitoring of the disease course. PMID:28270897

  4. 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

  5. Skeletal muscle signaling associated with impaired glucose tolerance in spinal cord-injured men and the effects of contractile activity

    PubMed Central

    Yarar-Fisher, Ceren; Bickel, C. Scott; Windham, Samuel T.; McLain, Amie B.

    2013-01-01

    The mechanisms underlying poor glucose tolerance in persons with spinal cord injury (SCI), along with its improvement after several weeks of neuromuscular electrical stimulation-induced resistance exercise (NMES-RE) training, remain unclear, but presumably involve the affected skeletal musculature. We, therefore, investigated skeletal muscle signaling pathways associated with glucose transporter 4 (GLUT-4) translocation at rest and shortly after a single bout of NMES-RE in SCI (n = 12) vs. able-bodied (AB, n = 12) men. Subjects completed an oral glucose tolerance test during visit 1 and ≈90 NMES-RE isometric contractions of the quadriceps during visit 2. Muscle biopsies were collected before, and 10 and 60 min after, NMES-RE. We assessed transcript levels of GLUT-4 by quantitative PCR and protein levels of GLUT-4 and phosphorylated- and total AMP-activated protein kinase (AMPK)-α, CaMKII, Akt, and AS160 by immunoblotting. Impaired glucose tolerance in SCI was confirmed by higher (P < 0.05) plasma glucose concentrations than AB at all time points after glucose ingestion, despite equivalent insulin responses to the glucose load. GLUT-4 protein content was lower (P < 0.05) in SCI vs. AB at baseline. Main group effects revealed higher phosphorylation in SCI of AMPK-α, CaMKII, and Akt (P < 0.05), and Akt phosphorylation increased robustly (P < 0.05) following NMES-RE in SCI only. In SCI, low skeletal muscle GLUT-4 protein concentration may, in part, explain poor glucose tolerance, whereas heightened phosphorylation of relevant signaling proteins (AMPK-α, CaMKII) suggests a compensatory effort. Finally, it is encouraging to find (based on Akt) that SCI muscle remains both sensitive and responsive to mechanical loading (NMES-RE) even ≈22 yr after injury. PMID:23766505

  6. 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.

  7. Training in the fasted state improves glucose tolerance during fat-rich diet

    PubMed Central

    Van Proeyen, Karen; Szlufcik, Karolina; Nielens, Henri; Pelgrim, Koen; Deldicque, Louise; Hesselink, Matthijs; Van Veldhoven, Paul P; Hespel, Peter

    2010-01-01

    A fat-rich energy-dense diet is an important cause of insulin resistance. Stimulation of fat turnover in muscle cells during dietary fat challenge may contribute to maintenance of insulin sensitivity. Exercise in the fasted state markedly stimulates energy provision via fat oxidation. Therefore, we investigated whether exercise training in the fasted state is more potent than exercise in the fed state to rescue whole-body glucose tolerance and insulin sensitivity during a period of hyper-caloric fat-rich diet. Healthy male volunteers (18–25 y) received a hyper-caloric (∼+30% kcal day−1) fat-rich (50% of kcal) diet for 6 weeks. Some of the subjects performed endurance exercise training (4 days per week) in the fasted state (F; n = 10), whilst the others ingested carbohydrates before and during the training sessions (CHO; n = 10). The control group did not train (CON; n = 7). Body weight increased in CON (+3.0 ± 0.8 kg) and CHO (+1.4 ± 0.4 kg) (P < 0.01), but not in F (+0.7 ± 0.4 kg, P = 0.13). Compared with CON, F but not CHO enhanced whole-body glucose tolerance and the Matsuda insulin sensitivity index (P < 0.05). Muscle GLUT4 protein content was increased in F (+28%) compared with both CHO (P = 0.05) and CON (P < 0.05). Furthermore, only training in F elevated AMP-activated protein kinase α phosphorylation (+25%) as well as up-regulated fatty acid translocase/CD36 and carnitine palmitoyltransferase 1 mRNA levels compared with CON (∼+30%). High-fat diet increased intramyocellular lipid but not diacylglycerol and ceramide contents, either in the absence or presence of training. This study for the first time shows that fasted training is more potent than fed training to facilitate adaptations in muscle and to improve whole-body glucose tolerance and insulin sensitivity during hyper-caloric fat-rich diet. PMID:20837645

  8. Training in the fasted state improves glucose tolerance during fat-rich diet.

    PubMed

    Van Proeyen, Karen; Szlufcik, Karolina; Nielens, Henri; Pelgrim, Koen; Deldicque, Louise; Hesselink, Matthijs; Van Veldhoven, Paul P; Hespel, Peter

    2010-11-01

    A fat-rich energy-dense diet is an important cause of insulin resistance. Stimulation of fat turnover in muscle cells during dietary fat challenge may contribute to maintenance of insulin sensitivity. Exercise in the fasted state markedly stimulates energy provision via fat oxidation. Therefore, we investigated whether exercise training in the fasted state is more potent than exercise in the fed state to rescue whole-body glucose tolerance and insulin sensitivity during a period of hyper-caloric fat-rich diet. Healthy male volunteers (18-25 y) received a hyper-caloric (∼+30% kcal day(-1)) fat-rich (50% of kcal) diet for 6 weeks. Some of the subjects performed endurance exercise training (4 days per week) in the fasted state (F; n = 10), whilst the others ingested carbohydrates before and during the training sessions (CHO; n = 10). The control group did not train (CON; n = 7). Body weight increased in CON (+3.0 ± 0.8 kg) and CHO (+1.4 ± 0.4 kg) (P < 0.01), but not in F (+0.7 ± 0.4 kg, P = 0.13). Compared with CON, F but not CHO enhanced whole-body glucose tolerance and the Matsuda insulin sensitivity index (P < 0.05). Muscle GLUT4 protein content was increased in F (+28%) compared with both CHO (P = 0.05) and CON (P < 0.05). Furthermore, only training in F elevated AMP-activated protein kinase α phosphorylation (+25%) as well as up-regulated fatty acid translocase/CD36 and carnitine palmitoyltransferase 1 mRNA levels compared with CON (∼+30%). High-fat diet increased intramyocellular lipid but not diacylglycerol and ceramide contents, either in the absence or presence of training. This study for the first time shows that fasted training is more potent than fed training to facilitate adaptations in muscle and to improve whole-body glucose tolerance and insulin sensitivity during hyper-caloric fat-rich diet.

  9. Molecular cloning of glucose transporter 1 in grouper Epinephelus coioides and effects of an acute hyperglycemia stress on its expression and glucose tolerance.

    PubMed

    Liu, Hongyu; Dong, Xiaohui; Chi, Shuyan; Yang, Qihui; Zhang, Shuang; Chen, Liqiao; Tan, Beiping

    2017-02-01

    The glucose transporter family proteins play pivotal roles in glucose metabolism. In this study, we successfully cloned the orange spotted grouper (Epinephelus coioides) glucose transporter 1 (EcGlut1) gene (GenBank accession: JQ623903). The full-length EcGlut1 cDNA was 2126 bp with a 1476 bp ORF, a 437bp5'-UTR and 223bp3'-UTR. EcGlut1 is predicted to encode a 491 amino acid protein with a MW of 53.9 kDa, a pI of 8.66 and a Pfam domain. Bioinformatics analysis revealed that EcGlut1 was evolutionally conserved between fishes with 80-89 % amino acid identities. EcGlut1 was expressed predominantly in heart and liver and at lower levels in muscle, intestine, stomach and brain. We also investigated the effect of acute hyperglycemia stress on EcGlut1 expression. In glucose tolerance test, changes in EcGlut1 mRNA expression in response to glucose injection and glucose metabolism-related indictors were assessed at the same time. Glucose injection significantly suppressed EcGlut1 mRNA expression in liver at 12 h and in brain at 24 h postinjection (P < 0.05). EcGlut1 mRNA levels in heart were increased at 6 h (P < 0.05). Plasma glucose level increased significantly and reached its maximum at 3 h postinjection (P < 0.05). The spatiotemporal expression of EcGlut1 and glucose metabolism suggested that orange spotted grouper might rely on fat anabolism to reduce acute hyperglycemia stress and the delayed transcription of EcGlut1 gene might be one reason for glucose intolerance in E. coioides.

  10. Decreased senescence marker protein-30 could be a factor that contributes to the worsening of glucose tolerance in normal aging.

    PubMed

    Hasegawa, Goji

    2010-01-01

    In our recent paper, we proposed that senescence marker protein-30 (SMP30) could be a novel molecule which was involved in an impairment of β-cell function with aging. SMP30 knockout (KO) mice and wild-type (WT) mice were fed a standard diet (SD) or a high fat diet (HFD) for 8 weeks from 7 weeks of age. In an intraperitoneal glucose tolerance test at 15 weeks of age, blood glucose levels in SD-fed KO mice were significantly increased by 25% at 30 min after glucose administration compared to SD-fed WT mice. Insulin levels in SD-fed KO mice were significantly decreased by 37% at 30 min postglucose compared to SD-fed WT mice. Interestingly, an insulin tolerance test showed a greater glucose lowering effect in SD-fed KO mice. Morphometric analysis revealed no differences in the degree of HFD-induced compensatory increase in β-cell mass and proliferation. Collectively, these data indicate that impairment of the early phase of insulin secretion underlies glucose intolerance in KO mice. Decreased SMP30 may contribute to the worsening of glucose tolerance that occurs in normal aging.

  11. Effects of rumen-protected Capsicum oleoresin on productivity and responses to a glucose tolerance test in lactating dairy cows.

    PubMed

    Oh, J; Harper, M; Giallongo, F; Bravo, D M; Wall, E H; Hristov, A N

    2017-03-01

    The objective of this experiment was to investigate the effects of rumen-protected Capsicum oleoresin (RPC) supplementation on feed intake, milk yield and composition, nutrient utilization, fecal microbial ecology, and responses to a glucose tolerance test in lactating dairy cows. Nine multiparous Holstein cows were used in a replicated 3 × 3 Latin square design balanced for residual effects with three 28-d periods. Each period consisted of 14 d for adaptation and 14 d for data collection and sampling. Treatments were 0 (control), 100, and 200 mg of RPC/cow per day. They were mixed with a small portion of the total mixed ration and top-dressed. Glucose tolerance test was conducted once during each experimental period by intravenous administration of glucose at a rate of 0.3 g/kg of body weight. Dry matter intake was not affected by RPC. Milk yield tended to increase for RPC treatments compared to the control. Feed efficiency was linearly increased by RPC supplementation. Concentrations of fat, true protein, and lactose in milk were not affected by RPC. Apparent total-tract digestibility of dry matter, organic matter, and crude protein was linearly increased, and fecal nitrogen excretion was linearly decreased by RPC supplementation. Rumen-protected Capsicum oleoresin did not affect the composition of fecal bacteria. Glucose concentration in serum was not affected by RPC supplementation post glucose challenge. However, compared to the control, RPC decreased serum insulin concentration at 5, 10, and 40 min post glucose challenge. The area under the insulin concentration curve was also decreased 25% by RPC. Concentration of nonesterified fatty acids and β-hydroxybutyrate in serum were not affected by RPC following glucose administration. In this study, RPC tended to increase milk production and increased feed efficiency in dairy cows. In addition, RPC decreased serum insulin concentration during the glucose tolerance test, but glucose concentration was not affected

  12. A single dose of sodium nitrate does not improve oral glucose tolerance in patients with type 2 diabetes mellitus.

    PubMed

    Cermak, Naomi M; Hansen, Dominique; Kouw, Imre W K; van Dijk, Jan-Willem; Blackwell, Jamie R; Jones, Andrew M; Gibala, Martin J; van Loon, Luc J C

    2015-08-01

    Dietary nitrate (NO3(-)) supplementation has been proposed as an emerging treatment strategy for type 2 diabetes. We hypothesized that ingestion of a single bolus of dietary NO3(-) ingestion improves oral glucose tolerance in patients with type 2 diabetes. Seventeen men with type 2 diabetes (glycated hemoglobin, 7.3% ± 0.2%) participated in a randomized crossover experiment. The subjects ingested a glucose beverage 2.5 hours after consumption of either sodium NO3(-) (0.15 mmol NaNO3(-) · kg(-1)) or a placebo solution. Venous blood samples were collected before ingestion of the glucose beverage and every 30 minutes thereafter during a 2-hour period to assess postprandial plasma glucose and insulin concentrations. The results show that plasma NO3(-) and nitrite levels were increased after NaNO3(-) as opposed to placebo ingestion (treatment-effect, P = .001). Despite the elevated plasma NO3(-) and nitrite levels, ingestion of NaNO3(-) did not attenuate the postprandial rise in plasma glucose and insulin concentrations (time × treatment interaction, P = .41 for glucose, P = .93 for insulin). Despite the lack of effect on oral glucose tolerance, basal plasma glucose concentrations measured 2.5 hours after NaNO3(-) ingestion were lower when compared with the placebo treatment (7.5 ± 0.4 vs 8.3 ± 0.4 mmol/L, respectively; P = .04). We conclude that ingestion of a single dose of dietary NO3(-) does not improve subsequent oral glucose tolerance in patients with type 2 diabetes.

  13. Assessment of endothelial dysfunction in patients with impaired glucose tolerance during a cold pressor test.

    PubMed

    Smirnova, Elena; Podtaev, Sergey; Mizeva, Irina; Loran, Evgenia

    2013-11-01

    The objective of this study is to explore changes in microvascular tone during a contralateral cold pressor test and to compare the results obtained in healthy subjects and in patients with impaired glucose tolerance (IGT) and type 2 diabetes. Low-amplitude fluctuations of skin temperature in the appropriate frequency ranges were used as a characteristic for the mechanism for vascular tone regulation. In total, 13 adults with type 2 diabetes aged 40-67 years and 18 adults with IGT aged 31-60 years participated in this pilot study. The control group included 12 healthy men and women aged 39-60 years. The response to the cold pressor test in patients with type 2 diabetes and with IGT differs essentially from that of healthy subjects in the endothelial frequency range. Endothelial dysfunction occurs in the preclinical stage of diabetes and manifests, in particular, as a disturbance of the endothelial part of vascular tone regulation.

  14. 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

    2012-05-02

    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.

  15. Plaque Characteristics in Coronary Artery Disease Patients with Impaired Glucose Tolerance

    PubMed Central

    Suzuki, Keishi; Takano, Hitoshi; Kubota, Yoshiaki; Inui, Keisuke; Nakamura, Shunichi; Tokita, Yukichi; Kato, Koji; Asai, Kuniya; Shimizu, Wataru

    2016-01-01

    Background Impaired glucose tolerance (IGT) patients are known to have a high risk of cardiovascular events and their prognosis has been reported to be poor. The present study aimed to compare coronary plaque characteristics among coronary artery disease (CAD) patients with normal glucose tolerance (NGT), those with IGT, and those with diabetes mellitus (DM) by using optical coherence tomography (OCT). Methods The present study included 101 coronary artery disease patients (mean age, 67.9 ± 10.4 years; 82.4% male). OCT was performed for target and non-target vessels during percutaneous coronary intervention. The patients were divided into the following 3 groups: the NGT, IGT, and DM groups. Results A total of 136 non-target residual plaques were found in 101 patients (27, 30, and 44 in the NGT, IGT, and DM groups, respectively). The size of the lipid core expressed as the mean angle of the lipid arc was significantly greater in the IGT and DM groups than in the NGT group (163.0 ± 58.7°, 170.1 ± 59.3°, and 130.9 ± 37.7°, respectively, P < 0.05). The fibrous cap covering the lipid core was significantly thinner in the IGT group than in the NGT group (77.0 ± 23.4 μm vs. 105.6 ± 47.0 μm, P = 0.040). Conclusion The coronary plaques in CAD patients are more vulnerable when having IGT compared to those with NGT, and similar to those with DM. This finding may explain the high risk of cardiovascular events in CAD patients with IGT. PMID:27936195

  16. Autoreactive Human TCR Initiate Insulitis and Impaired Glucose Tolerance in HLA DR4 Transgenic Mice

    PubMed Central

    Gebe, John A.; Unrath, Kellee A.; Yue, Betty B.; Miyake, Tom; Falk, Ben A.; Nepom, Gerald T.

    2008-01-01

    A human TcR derived from an autoreactive T cell specific for GAD65, from a subject at high risk for autoimmune diabetes, was introduced into HLA-DR4 transgenic mice. The source of TCR was a CD4+ TH1+T cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2o/o/I-Abo/o/B6 background exhibited a CD4+ infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. These mice also exhibited a subclinical impaired tolerance to exogenously fed glucose as assayed by an intraperitoneal glucose tolerance test. T cells containing the GAD65/67 (555–567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1 percent of CD4+ T cells in Rag2 sufficient mice. Upon in vitro stimulation, GAD65/67 555–567 responsive T cells secrete IFN-γ, minimal IL2 and TNFα and no IL4, IL5, IL10, or IL17, consistent with a TH1 profile. These data demonstrate that CD4+ T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. The relatively slow progression and patchy insulitis are reminiscent of the chronic pre-clinical phase similar to a majority of human at-risk subjects, and models these indolent features of human T1D. PMID:17949947

  17. Platelet, monocyte and neutrophil activation and glucose tolerance in South African Mixed Ancestry individuals

    PubMed Central

    Davison, Glenda M.; Nkambule, Bongani B.; Mkandla, Zibusiso; Hon, Gloudina M.; Kengne, Andre P.; Erasmus, Rajiv T.; Matsha, Tandi E.

    2017-01-01

    Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14++ CD42b+ events and platelet neutrophil aggregates as CD16++ CD42b+ events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p ≤ 0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both p ≤ 0.003). In robust linear regressions adjusted for age and gender, known diabetes was significantly and positively associated with the percentage of monocytes expressing CD69 [beta 11.06 (p = 0.016)] and CD42b (PMAs) [19.51 (0.003)] as well as the percentage of neutrophils expressing CD69 [14.19 (<0.0001)] and CD42b [17.7 (0.001)]. We conclude that monitoring platelet activation in diagnosed diabetic patients may have a role in the management and risk stratification. PMID:28091589

  18. Impact of maternal chromium restriction on glucose tolerance, plasma insulin and oxidative stress in WNIN rat offspring.

    PubMed

    Padmavathi, Inagadapa J N; Rao, Kalashikam Rajender; Raghunath, Manchala

    2011-12-01

    Robust evidence suggests that nutritional insult during fetal development could program the offspring to glucose intolerance, impaired insulin response and insulin resistance (IR). Considering the importance of chromium (Cr) in maintaining carbohydrate metabolism, this study determined the effect of maternal Cr restriction (CrR) on glucose metabolism and plasma insulin in Wistar/NIN (WNIN) rat offspring and the associated biochemical and/or molecular mechanisms. Female, weanling WNIN rats received ad libitum for 12 weeks, a control diet or the same with 65% restriction of Cr and mated with control males. Some of the Cr-restricted dams were rehabilitated from conception or parturition and their pups weaned on to control diet. At the time of weaning, half of the Cr restricted offspring were rehabilitated to control diet while others continued on Cr-restricted diet. Maternal CrR increased fasting plasma glucose, fasting insulin, homeostasis model assessment of IR, and area under the curve of glucose and insulin during oral glucose tolerance test in the offspring. Expression and activity of rate-limiting enzymes of glucose metabolism were comparable among different groups and expression of genes involved in insulin secretion was increased albeit in male offspring whereas antioxidant enzyme activities were decreased in offspring of both genders. Rehabilitation, in general, corrected the changes albeit partially. Maternal dietary CrR induced IR, impaired glucose tolerance in WNIN rat offspring and was associated with increased oxidative stress, which may predispose them to type 2 diabetes in their later life.

  19. Impaired glucose tolerance in pediatric burn patients at discharge from the acute hospital stay

    PubMed Central

    Fram, Ricki Y.; Cree, Melanie G.; Wolfe, Robert R.; Barr, David; Herndon, David N.

    2013-01-01

    Objective Hyperglycemia, secondary to the hypermetabolic stress response, is a common occurrence after thermal injury. This stress response has been documented to persist up to 9 months post burn. The purpose of this study was to measure insulin sensitivity in severely burned children prior to discharge when wounds are 95% healed. Methods Twenty-four children, aged 4–17 years, with burns ≥ 40% total body surface area (TBSA) underwent a 2 hour oral glucose tolerance test (OGTT) prior to discharge from the acute pediatric burn unit. Plasma glucose and insulin levels, as well as the Homeostasis Model Assessment for Insulin Resistance (HOMAIR) were compared to published OGTT data from healthy, non-burned children. Results There was a significant difference between severely burned children and non-burned, healthy children with respect to the HOMAIR. Severely burned children had a HOMAIR of 3.53±1.62 compared to the value in non-burned healthy children was 1.28±0.16 (p<0.05). Conclusion Insulin resistance secondary to the hypermetabolic stress response persists in severely burned children when burn wounds are at least 95% healed. The results of this study warrant future investigations into therapeutic options for the burned child during the rehabilitative phase of their care after injury. PMID:20634704

  20. 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).

  1. Oral glucose tolerance test effects on endothelial inflammation markers in healthy subjects and diabetic patients.

    PubMed

    Derosa, G; D'Angelo, A; Salvadeo, S A T; Ferrari, I; Fogari, E; Gravina, A; Mereu, R; Palumbo, I; Maffioli, P; Randazzo, S; Cicero, A F G

    2010-01-01

    The aim of this study was to evaluate the effect of an oral glucose tolerance test (OGTT) on the level of endothelial dysfunction and vascular inflammation markers in healthy subjects (H) and diabetic overweight patients (D). We enrolled 256 healthy subjects and 274 type 2 diabetic patients. We evaluated blood glucose (BG), soluble intercellular adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), high-sensitivity C reactive protein (hsCRP), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble E-selectin (sE-selectin), and tumor necrosis factor-alpha (TNF-alpha) at baseline and after OGTT. We observed that BG, sICAM-1, IL-6, hs-CRP, sVCAM-1, sE-selectin, and TNF-alpha values were higher in D group than in H group. In a large sample of adult healthy subjects and type 2 diabetics we observed that both answer to an OGTT with a significant increase in biomarkers of systemic low-grade inflammation and endothelial dysfunction such as hsCRP, IL-6, TNF-alpha, sICAM-1, sVCAM-1, and sE-selectin. Type 2 diabetics experienced, however, a more significant increase in TNF-alpha, and sE-selectin.

  2. Modeling glucose and free fatty acid kinetics during insulin-modified intravenous glucose tolerance test in healthy humans: role of counterregulatory response.

    PubMed

    Thomaseth, Karl; Brehm, Attila; Pavan, Alessandra; Pacini, Giovanni; Roden, Michael

    2014-08-01

    Insulin administration during insulin-modified intravenous glucose tolerance test (IM-IVGTT) can induce transient hypoglycemia in healthy insulin-sensitive subjects. This triggers counterregulatory reflex (CRR) responses, which influence the kinetics of glucose and nonesterified fatty acids (NEFA), and undermines the accuracy of mathematical modeling methods that do not explicitly account for CRR. The aim of this study is to evaluate mathematical models of glucose and NEFA kinetics against experimental data in the presence or absence of CRR. Thirteen healthy nondiabetic subjects underwent a standard IM-IVGTT and a modified test (GC-IM-IVGTT) with a variable glucose infusion preventing hypoglycemia. While model predictions fit very well with glucose and NEFA data from GC-IM-IVGTT, they lagged behind observations from IM-IVGTT during recovery from hypoglycemia, independently of insulinemia, which did not differ significantly between protocols. A modification to the glucose minimal model, using the glucose concentration below a threshold as a signal for CRR, improves model predictions for both glucose and NEFA. The associated increase in endogenous glucose production correlates, among various CRR hormones, mainly with the dynamics of glucagon concentration. The modified minimal models introduce new parameters that quantify strength and duration of CRR following hypoglycemia. Although CRR represents an unwanted side-effect in IM-IVGTT occurring only in insulin-sensitive subjects, this study provides new insights leading to improved procedures for estimating insulin sensitivity from IM-IVGTT, which may also allow for assessing the individual capacity of recovery from hypoglycemic events in patients treated with insulin or insulin-releasing drugs.

  3. 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...

  4. 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

  5. Associations between maternal BMI as well as glucose tolerance and adverse pregnancy outcomes in women with polycystic ovary syndrome.

    PubMed

    Li, Ying-Ying; Ye, Su-Qi; Zhong, Zhuo-Hui; Xu, Qiong; Mai, Wei-Bi; Yin, Cai-Xin; Zhu, Zhi-Qin; He, Xiao-Qian; Xiao, Qing

    2017-04-01

    This retrospective, cohort study examined the association between maternal pre-pregnancy body mass index (BMI), independent of glucose tolerance and adverse pregnancy outcomes in women with polycystic ovary syndrome (PCOS), for which there are few previous studies. Medical records from 2012 to 2015 at Guangzhou Women and Children's Medical Center, China were reviewed for women previously diagnosed with PCOS with normal 2-h 75-g oral glucose tolerance test (OGTT) results (n = 1249). The separate and joint effects of maternal BMI and glucose levels on pregnancy outcomes were assessed. Maternal pre-pregnancy BMI was associated with hypertensive disorders of pregnancy (HDP) (OR: 1.22, 95% CI: 1.02-1.45), preterm birth (OR: 1.49, 95% CI: 1.08-2.17), and large for gestational age (LGA) (OR: 1.69, 95% CI: 1.16-2.20). Elevated fasting glucose and maternal pre-pregnancy BMI were jointly associated with increased risks of HDP, preterm birth, and LGA. Therefore, among women with PCOS and normal glucose tolerance, maternal pre-pregnancy BMI is an independent risk factor of adverse pregnancy outcomes.

  6. Increasing palmitic acid intake enhances milk production and prevents glucose-stimulated fatty acid disappearance without modifying systemic glucose tolerance in mid-lactation dairy cows.

    PubMed

    Mathews, A T; Rico, J E; Sprenkle, N T; Lock, A L; McFadden, J W

    2016-11-01

    Feeding saturated fatty acids may enhance milk yield in part by decreasing insulin sensitivity and shifting glucose utilization toward the mammary gland. Our objective was to evaluate the effects of palmitic acid (C16:0) on milk production and insulin sensitivity in cows. Twenty multiparous mid-lactation Holstein cows were enrolled in a study consisting of a 5-d covariate, 49-d treatment, and 14-d posttreatment period. All cows received a common sorghum silage-based diet and were randomly assigned to a diet containing no supplemental fat (control; n=10; 138±45d in milk) or C16:0 at 4% of ration DM (PALM; 98% C16:0; n=10; 136±44d in milk). Blood and milk were collected at routine intervals. Intravenous glucose tolerance tests (300mg/kg of body weight) were performed at d -1, 24, and 49 relative to start of treatment. Data were analyzed as repeated measures using a mixed model with fixed effects of treatment and time, and milk yield served as a covariate. The PALM treatment increased milk yield by wk 7. Furthermore, PALM increased milk fat yield and energy-corrected milk at wk 3 and 7. Changes in milk production occurred in parallel with enhanced energy intake. Increased milk fat yield during PALM treatment was due to increased C16:0 and C16:1 incorporation; PALM had no effect on concentration of milk components, BW, or body condition score. Two weeks posttreatment, energy-corrected milk and milk fat yield remained elevated in PALM-fed cows whereas yields of milk were similar between treatments. Increased milk fat yield after PALM treatment was due to increased de novo lipogenesis and uptake of preformed fatty acids. The basal concentration of nonesterified fatty acids (NEFA) in plasma increased by d 4, 6, and 8 of PALM treatment, a response not observed thereafter. Although PALM supplementation did not modify insulin, glucose, or triacylglycerol levels in plasma, total cholesterol in plasma was elevated by wk 3. Estimated insulin sensitivity was lower during the

  7. Effects of Oral Administration of Moringa oleifera Lam on Glucose Tolerance in Goto-Kakizaki and Wistar Rats

    PubMed Central

    Ndong, Moussa; Uehara, Mariko; Katsumata, Shin-ichi; Suzuki, Kazuharu

    2007-01-01

    Medicinal plants constitute an important source of potential therapeutic agents for diabetes. In the present study, we investigated the effects of Moringa oleifera (MO) Lam, Moringacea, on glucose tolerance in Wistar rats and Goto-Kakizaki (GK) rats, modeled type 2 diabetes. Major polyphenols in MO powder were quercetin glucosides, rutin, kaempferol glycosides and chlorogenic acids by HPLC analysis. As the results of glucose tolerance test, MO significantly decreased the blood glucose at 20, 30, 45and 60 min for GK rats and at 10, 30 and 45 min for Wistar rats (p<0.05) compared to the both controls after glucose administration. The area under the curve of changes in the blood glucose was significantly higher in the GK control group than in the GK plus MO group (p<0.05) in the periods 30–60 min and 60–120 min. Furthermore, MO significantly decreased stomach emptying in GK rats (p<0.05). The results indicated that MO has an ameliorating effect for glucose intolerance, and the effect might be mediated by quercetin-3-glucoside and fiber contents in MO leaf powder. The action of MO was greater in GK rats than in Wistar rats. PMID:18398501

  8. 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

  9. 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.

  10. Effects of basswood honey, honey-comparable glucose-fructose solution, and oral glucose tolerance test solution on serum insulin, glucose, and C-peptide concentrations in healthy subjects.

    PubMed

    Münstedt, Karsten; Sheybani, Babak; Hauenschild, Annette; Brüggmann, Dörthe; Bretzel, Reinhard G; Winter, Daniel

    2008-09-01

    Studies suggest that honey has less influence on serum glucose concentrations than monosaccharides and disaccharides. This study aimed to confirm these findings conclusively by comparing directly the effects of honey, an identical sugar solution, and oral glucose tolerance (OGT) test solution on serum glucose, insulin, and C-peptide values in healthy subjects. Twelve healthy men with a mean age of 27.7 years, a mean body mass index of 23.2 kg/m(2), and no history of metabolic disorders participated in the study. Subjects underwent OGT testing to establish values and exclude preclinical diabetes. One week later they were randomly assigned to basswood honey or a glucose-fructose solution (honey-comparable glucose-fructose solution). The following week subjects were given the other solution. All solutions contained 75 g of glucose. Serum glucose was measured before drinking test solutions and every 10 minutes for 120 minutes afterwards. C-peptide and insulin were measured at 60 and 120 minutes. Serum insulin and C-peptide values at 60 minutes were significantly lower for honey. The mean serum glucose concentration was also lower for honey, but direct comparisons at the various times showed no statistically significant differences between solutions. However, the area under the concentration-time profile for glucose response was lower for the honey than the honey-comparable glucose-fructose solution. Honey had less effect on serum glucose, C-peptide, and insulin values than the honey-comparable glucose-fructose solution. Further study to elucidate underlying mechanisms may be worthwhile, as may investigation of the implications of these findings for diabetic patients.

  11. Oral administration of corn zein hydrolysate stimulates GLP-1 and GIP secretion and improves glucose tolerance in male normal rats and Goto-Kakizaki rats.

    PubMed

    Higuchi, Noriyuki; Hira, Tohru; Yamada, Nao; Hara, Hiroshi

    2013-09-01

    We have previously demonstrated that ileal administration of the dietary protein hydrolysate prepared from corn zein (ZeinH) stimulated glucagon-like peptide-1 (GLP-1) secretion and attenuated hyperglycemia in rats. In this study, to examine whether oral administration of ZeinH improves glucose tolerance by stimulating GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) secretion, glucose tolerance tests were performed in normal Sprague-Dawley male rats and diabetic Goto-Kakizaki (GK) male rats. The test solution was gavaged before ip glucose injection in normal rats or gavaged together with glucose in GK rats. Blood samples were collected from the tail vein or by using the jugular catheter to measure glucose, insulin, GLP-1, and GIP levels. In the ip glucose tolerance test, oral administration of ZeinH (2 g/kg) significantly suppressed the glycemic response accompanied by an immediate increase in plasma GLP-1 and GIP levels in normal rats. In contrast, oral administration of another dietary peptide, meat hydrolysate, did not elicit a similar effect. The glucose-lowering effect of ZeinH was attenuated by a GLP-1 receptor antagonist or by a GIP receptor antagonist. Furthermore, oral ZeinH induced GLP-1 secretion and reduced glycemic response in GK rats under the oral glucose tolerance test. These results indicate that the oral administration of the dietary peptide ZeinH improves glucose tolerance in normal and diabetic rats by its incretin-releasing activity, namely, the incretinotropic effect.

  12. Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation

    PubMed Central

    Ren, Xingxing; Han, Tingting; Chen, Yawen; Qiu, Huiying; Wu, Peihong; Zheng, Jun; Wang, Lihua; Liu, Wei; Hu, Yaomin

    2017-01-01

    Aims To investigate the associations of dyslipidemia with insulin resistance and β cell function in individuals with normal glucose tolerance (NGT) and different categories of impaired glucose regulation (IGR). Methods 544 subjects (365 with dyslipidemia and/or IGR and 179 with normal lipid and glucose tolerance) were enrolled in the study. All subjects underwent oral glucose tolerance test (OGTT). HOMA-IR was used to evaluate insulin sensitivity. Disposition index (DI) was used to evaluate β cell function. Multiple linear regression analysis was performed to assess correlations among lipid profiles, insulin resistance and β cell function. Results Among subjects with NGT, those with dyslipidemia had higher level of HOMA-IR but lower level of DI. While among subjects with different categories of IGR, those with dyslipidemia and CGI had significantly decreased DI. No obvious differences of insulin resistance or β cell function were found in IFG or IGT subjects with or without dyslipidemia. TG and HDL-C were correlated with HOMA-IR (β = 0.79, p <0.001; β = -0.38, p = 0.027, respectively, compared with subjects in the low level groups). Moreover, TG and TC were negatively correlated with DI (β = -2.17, p = 0.013; β = -2.01, p = 0.034 respectively, compared with subjects in the low level groups) after adjusting for confounding parameters. Conclusions Dyslipidemia induces insulin resistance and impaired β cell response to insulin resistance in individuals with NGT. Furthermore, dyslipidemia diminishes β cell function in subjects with CGI. TG and HDL-C were correlated with insulin resistance, and TG, TC were negatively correlated with β cell response to insulin resistance in non-diabetic individuals. PMID:28199386

  13. Periodontal Infection, Impaired Fasting Glucose and Impaired Glucose Tolerance: Results from The Continuous National Health and Nutrition Examination Survey 2009–2010

    PubMed Central

    Arora, Nidhi; Papapanou, Panos N.; Rosenbaum, Michael; Jacobs, David R.; Desvarieux, Moïse; Demmer, Ryan T.

    2014-01-01

    Aim We investigated the relationship between periodontal disease, a clinical manifestation of periodontal infection, and prediabetes. Methods The National Health and Nutrition Examination Survey, 2009–2010 enrolled 1,165 diabetes-free adults (51% female) aged 30–80 years (mean ± SD=50±14) who received a full-mouth periodontal examination and an oral glucose tolerance test. Participants were classified as having none/mild, moderate or severe periodontitis and also according to mean probing depth≥2.19 mm or attachment loss≥1.78 mm, (respective 75th percentiles). Pre-diabetes was defined according to ADA criteria as either: i) impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). In multivariable logistic regression models, the odds of IFG and IGT were regressed on levels of periodontitis category. Results The odds ratios and 95% confidence intervals for having IGT among participants with moderate or severe periodontitis, relative to participants with none/mild periodontitis were 1.07[0.50,2.25] and 1.93[1.18,3.17], P=0.02. The ORs for having IFG were 1.14[0.74, 1.77] and 1.12[0.58, 2.18], P =0.84. PD≥75th percentile was related to a 105% increase in the odds of IGT: OR[95%CI] =2.05[1.24, 3.39], P=0.005. Conclusions Periodontal infection was positively associated with prevalent impaired glucose tolerance in a cross-sectional study among a nationally representative sample. PMID:24708451

  14. Adiponectin complexes composition in Japanese-Brazilians regarding their glucose tolerance status

    PubMed Central

    2013-01-01

    Background Adiponectin circulates in different multimer complexes comprised of low molecular weight trimeric form (LMW), hexamer of middle molecular weight (MMW) and high molecular weight multimers (HMW). In Japanese-Brazilians, a population with high prevalence of glucose metabolism disturbances, we examined the associations of total adiponectin and its multimers with diabetes mellitus. Methods Two study groups were examined: 26 patients with diabetes mellitus (DM,14 women and 12 men, aged 55.3 ± 8.6 years) and 27 age-matched control subjects with normal glucose tolerance (NGT,12 women and 15 men, aged 54.0 ± 9.2 years). Results We found no significant differences in total [NGT: 6.90 ug/ml (4.38-13.43); DM: 5.38 ug/ml (3.76-8.56), p = 0.35], MMW [NGT:2.34 ug/ml (1.38-3.25); DM: 1.80 ug/ml (1.18-2.84), p = 0.48] or LMW adiponectin [NGT: 2.07 ug/ml (1.45-3.48), DM: 2.93 ug/ml (1.78-3.99), p = 0.32] between groups. In contrast, HMW adiponectin levels were significantly lower in patients with DM [TGN: 2.39 ug/ml (1.20-4.75); DM: 1.04 ug/ml (0.42-1.60), p = 0.001]. A logistic regression analysis was done to identify independent associations with diabetes mellitus. The results showed that HOMA-IR and HMW adiponectin in women were independently associated with diabetes mellitus. Conclusion The current investigation demonstrates that in Japanese-Brazilians HMW adiponectin is selectively reduced in individuals with type 2 diabetes, while no differences were found in MMW and LMW adiponectin isoforms. PMID:23570346

  15. Impaired glucose tolerance (IGT) is not associated with disturbed homocysteine metabolism.

    PubMed

    Pixa, A; Pietzsch, J; Julius, U; Menschikowski, M; Hanefeld, M

    2000-01-01

    Elevated plasma total homocysteine (tHcy) has been suggested to be an additional risk factor for cardiovascular disease in subjects with impaired glucose tolerance (IGT) and Type 2 diabetes (T2D). In order to investigate whether an insulin resistant/chronic hyperinsulinemic situation in male diabetic and prediabetic subjects directly influences the tHcy metabolism, fasting tHcy and post-methionine load tHcy plasma levels (PML-tHcy) were determined in 15 men with IGT, 13 men with newly diagnosed T2D, and 16 normoglycemic controls (NGT). Fasting tHcy (IGT, 13.1 +/- 4.6; T2D, 12.8 +/- 4.0; NGT, 10.7 +/- 4.4 micromol/L) and PML-tHcy (IGT, 46.5 +/-17.39; T2D, 41.1 +/- 6.8; NGT, 38.0 +/- 9.7 micromol/L) showed no differences between the groups. Fasting tHcy and PML-tHcy correlated with fasting proinsulin (r = 0.395, p < 0.05; r = 0.386, p< 0.05) and creatinine (r = 0.489, p < 0.01; r = 0.339, p < 0.05), resp. Multiple regression analysis showed only a relationship between fasting tHcy and creatinine. No relationships have been found between fasting tHcy and PML-tHcy, resp., and indicators of an insulin resistant state, e.g., insulin and proinsulin, as well as serum cobalamin and folate concentrations. In conclusion, our data suggest that the degree of glucose intolerance has no direct impact on the metabolism of homocysteine. However, tHcy levels tend to be elevated with the development of nephropathy, indicating an association between tHcy and renal function in these subjects.

  16. A randomised study on the effects of fish protein supplement on glucose tolerance, lipids and body composition in overweight adults.

    PubMed

    Vikøren, Linn A; Nygård, Ottar K; Lied, Einar; Rostrup, Espen; Gudbrandsen, Oddrun A

    2013-02-28

    The popularity of high-protein diets for weight reduction is immense. However, the potential benefits from altering the source of dietary protein rather than the amount is scarcely investigated. In the present study, we examined the effects of fish protein supplement on glucose and lipid metabolism in overweight adults. A total of thirty-four overweight adults were randomised to 8 weeks' supplementation with fish protein or placebo tablets (controls). The intake of fish protein supplement was 3 g/d for the first 4 weeks and 6 g/d for the last 4 weeks. In this study, 8 weeks of fish protein supplementation resulted in lower values of fasting glucose (P< 0·05), 2 h postprandial glucose (P< 0·05) and glucose-area under the curve (AUC) (five measurements over 2 h, P< 0·05) after fish protein supplementation compared to controls. Glucose-AUC was decreased after 8 weeks with fish protein supplement compared to baseline (P< 0·05), concomitant with increased 30 min and decreased 90 min and 2 h insulin C-peptide level (P< 0·05), and reduced LDL-cholesterol (P< 0·05). Body muscle % was increased (P< 0·05) and body fat % was reduced (P< 0·05) after 4 weeks' supplementation. Physical activity and energy and macronutrients intake did not change during the course of the study. In conclusion, short-term daily supplementation with a low dose of fish protein may have beneficial effects on blood levels of glucose and LDL-cholesterol as well as glucose tolerance and body composition in overweight adults. The long-term effects of fish protein supplementation is of interest in the context of using more fish as a protein source in the diet, and the effects of inclusion of fish in the diet of individuals with low glucose tolerance should be evaluated.

  17. Growth hormone ameliorates adipose dysfunction during oxidative stress and inflammation and improves glucose tolerance in obese mice.

    PubMed

    Fukushima, M; Okamoto, Y; Katsumata, H; Ishikawa, M; Ishii, S; Okamoto, M; Minami, S

    2014-08-01

    Patients with adult growth hormone deficiency exhibit visceral fat accumulation, which gives rise to a cluster of metabolic disorders such as impaired glucose tolerance and dyslipidemia. Plasma growth hormone levels are lower in obese patients with metabolic syndrome than in healthy subjects. Here we examined the hypothesis that exogenous growth hormone administration regulates function of adipose tissue to improve glucose tolerance in diet-induced obese mice. Twelve-week-old obese male C57BL/6 J mice received bovine growth hormone daily for 6 weeks. In epididymal fat, growth hormone treatment antagonized diet-induced changes in the gene expression of adiponectin, leptin, and monocyte chemoattractant protein-1, and significantly increased the gene expression of interleukin-10 and CD206. Growth hormone also suppressed the accumulation of oxidative stress marker, thiobarbituric acid-reactive substances, in the epididymal fat and enhanced the gene expression of anti-oxidant enzymes. Moreover, growth hormone significantly restored glucose tolerance in obese mice. In cultured 3T3-L1 adipocytes, growth hormone prevented the decline in adiponectin gene expression in the presence of hydrogen peroxide. These results suggest that growth hormone administration ameliorates glucose intolerance in obese mice presumably by decreasing adipose mass, oxidative stress, and chronic inflammation in the visceral fat.

  18. 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.

  19. Factors associated with the glucose-lowering effect of vildagliptin identified from the results of the oral glucose tolerance test in Japanese patients with type 2 diabetes.

    PubMed

    Nakamura, Akinobu; Terauchi, Yasuo

    2013-01-01

    In order to investigate the factors contributing to the glucose-lowering effect of vildagliptin, we analyzed the results of the oral glucose tolerance test together with several clinical parameters in Japanese patients with type 2 diabetes before and after 24 weeks of treatment with vildagliptin. The data of the 13 patients who satisfactorily completed the follow-up examinations were included. After 24 weeks treatment with vildagliptin, the patients were classified into a responder group (69.2%) and a non-responder group (30.8%); the responders consisting of subjects whose HbA1c decreased following 24 weeks treatment with vildagliptin, and the non-responders consisting of subjects who did not show any significant decrease of HbA1c. There were no differences in baseline characteristics between the two groups before administration of vildagliptin. After 24 weeks of treatment, HbA1c was significantly reduced from 7.3 ± 0.5% to 6.7 ± 0.5% in the responder group (P = 0.0077), while it tended to rather increased from 7.1 ± 0.6% to 7.5 ± 0.7% in the non-responder group (P = 0.0679). Also, parameters reflecting the glucose-stimulated insulin secretion, such as the insulinogenic index and oral disposition index, were significantly higher in the responder group than in the non-responder group, whereas insulin sensitivity was similar between the two groups. These results suggest that the difference in the degree of improvement of the glucose tolerance between the responder group and non-responder group in this study could be associated with the effect of vildagliptin on the glucose-stimulated insulin secretion, but not on the insulin sensitivity.

  20. Male mice retain a metabolic memory of improved glucose tolerance induced during adult onset, short-term dietary restriction

    PubMed Central

    2012-01-01

    Background Chronic dietary restriction (DR) has been shown to have beneficial effects on glucose homeostasis and insulin sensitivity. These factors show rapid and robust improvements when rodents were crossed over from an ad libitum (AL) diet to DR in mid life. We aimed to determine whether the beneficial effects induced by short-term exposure to DR can be retained as a ‘metabolic memory’ when AL feeding is resumed (AL-DR-AL) and vice versa: whether the effects of long-term DR can be reversed by a period of AL feeding (DR-AL-DR). C57BL/6 male and female mice were used to examine sex differences (N = 10/sex/group). Mice were fed AL or DR from 3 until 15 months (baseline) and each dietary crossover lasted approximately 5 months. Results In females, body and fat mass were proportional to the changes in feeding regime and plasma insulin and glucose tolerance were unaffected by the crossovers. However, in male mice, glucose tolerance and plasma insulin levels were reversed within 6 to 12 weeks. When males returned to AL intake following 5 months DR (AL-DR-AL), body mass was maintained below baseline, proportional to changes in fat mass. Glucose tolerance was also significantly better compared to baseline. Conclusions Male mice retained a metabolic memory of 5 months of DR feeding in terms of reduced body mass and improved glucose tolerance. This implies that some of the beneficial effects induced by a period of DR in adult life may be beneficial, even when free feeding is resumed at least in males. However, under continuous DR, lifespan extension was more prominent in females than in males. PMID:24764509

  1. Pancreatic β-cell-specific ablation of TASK-1 channels augments glucose-stimulated calcium entry and insulin secretion, improving glucose tolerance.

    PubMed

    Dadi, Prasanna K; Vierra, Nicholas C; Jacobson, David A

    2014-10-01

    Calcium entry through voltage-dependent Ca(2+) channels (VDCCs) is required for pancreatic β-cell insulin secretion. The 2-pore-domain acid-sensitive potassium channel (TASK-1) regulates neuronal excitability and VDCC activation by hyperpolarizing the plasma membrane potential (Δψp); however, a role for pancreatic β-cell TASK-1 channels is unknown. Here we examined the influence of TASK-1 channel activity on the β-cell Δψp and insulin secretion during secretagogue stimulation. TASK-1 channels were found to be highly expressed in human and rodent islets and localized to the plasma membrane of β-cells. TASK-1-like currents of mouse and human β-cells were blocked by the potent TASK-1 channel inhibitor, A1899 (250nM). Although inhibition of TASK-1 currents did not influence the β-cell Δψp in the presence of low (2mM) glucose, A1899 significantly enhanced glucose-stimulated (14mM) Δψp depolarization of human and mouse β-cells. TASK-1 inhibition also resulted in greater secretagogue-stimulated Ca(2+) influx in both human and mouse islets. Moreover, conditional ablation of mouse β-cell TASK-1 channels reduced K2P currents, increased glucose-stimulated Δψp depolarization, and augmented secretagogue-stimulated Ca(2+) influx. The Δψp depolarization caused by TASK-1 inhibition resulted in a transient increase in glucose-stimulated mouse β-cell action potential (AP) firing frequency. However, secretagogue-stimulated β-cell AP duration eventually increased in the presence of A1899 as well as in β-cells without TASK-1, causing a decrease in AP firing frequency. Ablation or inhibition of mouse β-cell TASK-1 channels also significantly enhanced glucose-stimulated insulin secretion, which improved glucose tolerance. Conversely, TASK-1 ablation did not perturb β-cell Δψp, Ca(2+) influx, or insulin secretion under low-glucose conditions (2mM). These results reveal a glucose-dependent role for β-cell TASK-1 channels of limiting glucose-stimulated

  2. Insulin resistance in first-trimester pregnant women with pre-pregnant glucose tolerance and history of recurrent spontaneous abortion.

    PubMed

    Hong, Y; Xie, Q X; Chen, C Y; Yang, C; Li, Y Z; Chen, D M; Xie, M Q

    2013-01-01

    Insulin resistance (IR) has been reported to play an important role in recurrent spontaneous abortion (RSA) among patients with polycystic ovary syndrome (PCOS). However, scanted materials exist regarding the independent effect of IR on RSA. The aim of this study is to investigate the status of IR in first trimester pregnant patients with normal pre-pregnant glucose tolerance and history of RSA. This two-center case-control study enrolled totally 626 first trimester pregnant women including 161 patients with a history of recurrent spontaneous abortion, who were pre-pregnantly glucose-tolerant according to oral glucose tolerance test (OGTT), and 465 women with no history of abnormal pregnancies of any kind. Clinical, biochemical and hormonal parameters were simultaneously measured in all participants. Serum beta-HCG, estradiol, progesterone, fasting plasma glucose and fasting plasma insulin levels, as well, the calculated homeostasis model assessment of insulin resistance index (HOMA-IR), fasting plasma glucose/insulin ratio(G/I) and pregnancy outcome were analyzed and compared. Serum beta-HCG and progesterone were found to be significantly lower in RSA group compared to controls. Subjects in RSA group were found to have higher HOMA-IR and lower G/I ratio than those in control group. Serum beta-HCG and progesterone were negatively correlated with HOMA-IR, and positively with G/I ratio even after adjustment for BMI. The spontaneous abortion rate within first trimester pregnancy of RSA patients was significantly higher than that in controls. In conclusion, woman with recurrent spontaneous abortion and normal pre-pregnant glucose metabolism tends to be more insulin resistant during first trimester pregnancy than healthy controls, no matter whether she has PCOS or not. Insulin resistance might be one of the direct causes that lead to recurrent abortion.

  3. Randomized Pilot Study of Cabergoline, a Dopamine Receptor Agonist: Effects on Body Weight and Glucose Tolerance in Obese Adults

    PubMed Central

    Gibson, Charlisa D.; Karmally, Wahida; McMahon, Donald J.; Wardlaw, Sharon L.; Korner, Judith

    2011-01-01

    Aim Dopaminergic hypofunction and hyperprolactinemia have been implicated in the pathogenesis of obesity and glucose intolerance. The aim of this pilot study was to determine the efficacy of cabergoline, a dopamine receptor agonist, on body weight and glucose tolerance in obese non-diabetic persons with normal plasma prolactin levels. Materials and Methods This 16-week double blind, placebo-controlled pilot study randomized non- diabetic obese adults (BMI 30-42 kg/m2) to placebo or cabergoline (0.25 mg twice weekly for 4 weeks followed by 0.5 mg twice weekly for the next 12 weeks). Of 40 subjects enrolled, 29 completed 16 weeks: 16 randomized to placebo, 13 to cabergoline. All subjects were counseled on a 500 kcal/day calorie deficit diet. A 75 gm oral glucose tolerance test was performed at baseline and at 16 weeks. Results As expected, prolactin levels decreased after cabergoline (P<0.001). Weight loss was similar after placebo compared with cabergoline treatment: 1.0 vs 1.2% body weight, respectively. Fasting glucose levels did not differ between groups after treatment, however, 90 minute post-prandial glucose and insulin decreased in the cabergoline group only (P = 0.029). HOMA-IR increased by 40% after placebo, and 1.5% after cabergoline treatment. Conclusions This pilot study suggests that cabergoline therapy may improve glucose tolerance independent of weight loss, however, a larger, longer term study of dopamine receptor agonist therapy in obese individuals is warranted to confirm this finding. PMID:22074059

  4. 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

  5. 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

  6. Standing balance and trunk position sense in impaired glucose tolerance (IGT)-related peripheral neuropathy.

    PubMed

    Goldberg, Allon; Russell, James William; Alexander, Neil Burton

    2008-07-15

    Type 2 diabetes mellitus (T2DM) and pre-diabetes or impaired glucose tolerance (IGT) affect a large segment of the population. Peripheral neuropathy (PN) is a common complication of T2DM, leading to sensory and motor deficits. While T2DM-related PN often results in balance- and mobility-related dysfunction which manifests as gait instability and falls, little is known about balance capabilities in patients who have evidence of PN related to IGT (IGT-PN). We evaluated patients with IGT-PN on commonly-used clinical balance and mobility tests as well as a new test of trunk position sense and balance impairment, trunk repositioning errors (TREs). Eight participants aged 50-72 years with IGT-PN, and eight age- and gender-matched controls underwent balance, mobility and trunk repositioning accuracy tests at a university neurology clinic and mobility research laboratory. Compared to controls, IGT-PN participants had as much as twice the magnitude of TREs and stood approximately half as long on the single leg balance test. People with IGT-PN exhibit deficits in standing balance and trunk position sense. Furthermore, there was a significant association between performance on commonly-used clinical balance and mobility tests, and electrophysiological and clinical measures of neuropathy in IGT-PN participants. Because IGT-related neuropathy represents the earliest stage of diabetic neuropathy, deficits in IGT-PN participants highlight the importance of early screening in the dysglycemic process for neuropathy and associated balance deficits.

  7. The Impact of Abnormal Glucose Tolerance and Obesity on Fetal Growth

    PubMed Central

    Hill, David J.; Evers, Susan; Van Aarsen, Kristine; Yama, Brie; Yuan, Su; Campbell, M. Karen

    2015-01-01

    Objective. Factors linked with insulin resistance were examined for their association with large-for-gestational-age (LGA) infant birth weight and gestational diabetes. Study Design. Data came from a longitudinal cohort study of 2,305 subjects without overt diabetes, analyzed using multinomial logistic and linear regression. Results. High maternal BMI (OR = 1.53 (1.11, 2.12)), height (1.98 (1.62, 2.42)), antidepressant use (1.71 (1.20, 2.44)), pregnancy weight-gain exceeding 40 pounds (1.79 (1.25, 2.57)), and high blood sugar (2.68, (1.53, 5.27)) were all positively associated with LGA birth. Strikingly, the difference in risk from diagnosed and treated gestational diabetes compared to women with a single abnormal glucose tolerance test (but no diagnosis of gestational diabetes) was significant (OR = 0.65, p = 0.12 versus OR = 2.84, p < 0.01). When weight/length ratio was used instead, different factors were found to be significant. BMI and pregnancy weight-gain were found to influence the development of gestational diabetes, through an additive interaction. Conclusions. High prepregnancy BM, height, antidepressant use, pregnancy weight-gain exceeding 40 pounds, and high blood sugar were associated with LGA birth, but not necessarily infant weight/length ratio. An additive interaction between BMI and pregnancy weight-gain influenced gestational diabetes development. PMID:25977929

  8. Muscle-specific Deletion of Carnitine Acetyltransferase Compromises Glucose Tolerance and Metabolic Flexibility

    PubMed Central

    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.

    2012-01-01

    Summary 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

  9. Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naïve Type 2 Diabetes following Equivalent Weight Loss.

    PubMed

    Straznicky, Nora E; Grima, Mariee T; Sari, Carolina I; Lambert, Elisabeth A; Phillips, Sarah E; Eikelis, Nina; Mariani, Justin A; Kobayashi, Daisuke; Hering, Dagmara; Dixon, John B; Lambert, Gavin W

    2016-01-01

    Background and Purpose: Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n = 15), impaired glucose tolerant (IGT, n = 24), and newly-diagnosed T2D (n = 15) consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate) for 4-months. The three groups were matched for baseline age (56 ± 1 years), body mass index (BMI, 32.9 ± 0.7 kg/m(2)), and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography), spontaneous cardiac baroreflex sensitivity (BRS), and oral glucose tolerance test. Results: Weight loss averaged -7.5 ± 0.8, -8.1 ± 0.5, and -8.0 ± 0.9% of body weight in NGT, IGT, and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0-120) compared to NGT and IGT (group effect, P <0.001). Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group × time, P = 0.04). The magnitude of reduction in MSNA (-7 ± 3, -8 ± 4, -15 ± 4 burst/100 hb, respectively) and whole-body norepinephrine spillover rate (-28 ± 8, -18 ± 6, and -25 ± 7%, respectively), time effect both P <0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0-120 was independently associated with reduction in arterial norepinephrine concentration, whilst Δ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different

  10. Comparable Attenuation of Sympathetic Nervous System Activity in Obese Subjects with Normal Glucose Tolerance, Impaired Glucose Tolerance, and Treatment Naïve Type 2 Diabetes following Equivalent Weight Loss

    PubMed Central

    Straznicky, Nora E.; Grima, Mariee T.; Sari, Carolina I.; Lambert, Elisabeth A.; Phillips, Sarah E.; Eikelis, Nina; Mariani, Justin A.; Kobayashi, Daisuke; Hering, Dagmara; Dixon, John B.; Lambert, Gavin W.

    2016-01-01

    Background and Purpose: Elevated sympathetic nervous system (SNS) activity is a characteristic of obesity and type 2 diabetes (T2D) that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n = 15), impaired glucose tolerant (IGT, n = 24), and newly-diagnosed T2D (n = 15) consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate) for 4-months. The three groups were matched for baseline age (56 ± 1 years), body mass index (BMI, 32.9 ± 0.7 kg/m2), and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography), spontaneous cardiac baroreflex sensitivity (BRS), and oral glucose tolerance test. Results: Weight loss averaged −7.5 ± 0.8, −8.1 ± 0.5, and −8.0 ± 0.9% of body weight in NGT, IGT, and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0−120) compared to NGT and IGT (group effect, P <0.001). Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group × time, P = 0.04). The magnitude of reduction in MSNA (−7 ± 3, −8 ± 4, −15 ± 4 burst/100 hb, respectively) and whole-body norepinephrine spillover rate (−28 ± 8, −18 ± 6, and −25 ± 7%, respectively), time effect both P <0.001, did not differ between groups. After adjustment for age and change in body weight, Δ insulin AUC0−120 was independently associated with reduction in arterial norepinephrine concentration, whilst Δ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects

  11. Insulin resistance and lipid profile during an oral glucose tolerance test in women with and without gestational diabetes mellitus.

    PubMed

    Liang, Zx; Wu, Y; Zhu, Xy; Fang, Q; Chen, Dq

    2016-01-01

    We aimed to compare changes in insulin levels during an oral glucose tolerance test (OGTT) between women with normal glucose tolerance (NGT) during pregnancy and those with gestational diabetes mellitus (GDM). Overall, 105 pregnant women between 24 and 28 weeks' gestation, 50 with NGT and 55 with GDM according to NDDG standard, were enrolled into the study. The levels of fasting blood glucose, insulin, triglyceride (TG) and total cholesterol (TC) and the insulin levels, blood glucose levels at 1, 2 and 3 hours post oral glucose administration during an OGTT (5.8, 10.6, 9.2 and 8.1 mmol/L, respectively) were measured. Then, insulin resistance (IR) index was calculated. There was no significant difference in fasting, 3-h insulin levels and 3-h blood glucose levels between those with NGT and those with GDM (P > 0.05). However, 1-h and 2-h insulin levels, fasting and 1-h and 2-h blood glucose levels in women with GDM were significantly higher than those in the NGT group (P < 0.05). Fasting TC and TG levels in the GDM group were significantly higher than those with NGT (P = 0.031 and P = 0.025, respectively). Correlation analysis showed that TG and TC levels were positively correlated with homoeostasis model assessment-IR (HOMA-IR) (r = 0.67 and r = 0.78, respectively; P < 0.05). Our findings suggest that insulin sensitivity in women with GDM was significantly lower than that observed in those with NGT. Reducing IR and blood lipids in women with GDM could potentially improve maternal and foetal outcomes.

  12. Anti-CD3 antibody treatment induces hypoglycemia and super tolerance to glucose challenge in mice through enhancing glucose consumption by activated lymphocytes.

    PubMed

    Xia, Chang-Qing; Chernatynskaya, Anna V; Looney, Benjamin; Wan, Suigui; Clare-Salzler, Michael J

    2014-01-01

    Anti-CD3 antibody has been employed for various immune-mediated disorders. However, whether anti-CD3 administration leads to rapid metabolic alternation has not been well investigated. In the current study, we studied how anti-CD3 treatment affected blood glucose levels in mice. We found that anti-CD3 treatment induced immediate reduction of blood glucose after administration. Furthermore, a single dose of anti-CD3 treatment corrected hyperglycemia in all nonobese diabetic mice with recently diagnosed diabetes. This glucose-lowering effect was not attributable to major T cell produced cytokines. Of interest, when tested in a normal strain of mice (C57BL/6), the serum levels of C-peptide in anti-CD3 treated animals were significantly lower than control mice. Paradoxically, anti-CD3 treated animals were highly tolerant to exogenous glucose challenge. Additionally, we found that anti-CD3 treatment significantly induced activation of T and B cells in vitro and in vivo. Further studies demonstrated that anti-CD3 treatment lowered the glucose levels in T cell culture media and increased the intracellular transportation of 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2 deoxyglucose (2-NBDG) particularly in activated T and B cells. In addition, injection of anti-CD3 antibodies induced enhanced levels of Glut1 expression in spleen cells. This study suggests that anti-CD3 therapy-induced hypoglycemia likely results from increased glucose transportation and consumption by the activated lymphocytes.

  13. Serum 25-hydroxyvitamin D levels in subjects with reduced glucose tolerance and type 2 diabetes - the Tromsø OGTT-study.

    PubMed

    Hutchinson, Moira S; Figenschau, Yngve; Almås, Bjørg; Njølstad, Inger; Jorde, Rolf

    2011-09-01

    The relationships between vitamin D concentrations, hyperglycemia, and insulin resistance remain uncertain. During 2008 - 2010, an oral glucose tolerance test was performed in 3520 subjects from Tromsø, Norway. Serum 25-hydroxyvitamin D [25(OH)D] was measured in 1193 subjects with normal glucose tolerance, in 304 with isolated impaired fasting glucose, in 254 with isolated impaired glucose tolerance, in 139 with a combination of the two, and in 194 subjects with type 2 diabetes. Serum 25(OH)D did not differ between subjects with isolated impaired fasting glucose or impaired glucose tolerance, but was lower in all groups of deranged glucose metabolism as compared with normal subjects. These differences could not be explained by differences in intakes of vitamin D from cod liver oil or other supplements and remained statistically significant after adjustment for gender, age, body mass index, physical activity score, and month of examination. When the cohort was divided according to serum 25(OH)D quartiles, there was an improvement in all measures of glucose metabolism (fasting and 2-hour plasma glucose, serum insulin, HbA(1c)) and estimates of insulin resistance (QUICKI , HOMA-IR, ISI(0.120)) with increasing serum 25(OH)D quartile. However, interventional studies are needed to prove a causal relationship between vitamin D and glucose metabolism.

  14. Beyond glucose: metabolic shifts in responses to the effects of the oral glucose tolerance test and the high-fructose diet in rats.

    PubMed

    Lin, Shuhai; Yang, Zhu; Liu, Hongde; Tang, Leihan; Cai, Zongwei

    2011-05-01

    High-fructose diet-fed rats as one of the insulin resistant models was used widely for understanding the mechanisms of type 2 diabetes mellitus. Systems-level metabolic profiling of the rat model, however, has not been deciphered clearly. To address this issue, mass spectrometry-based metabolomics was employed to unlock the metabolic snapshots of the oral glucose tolerance test (oGTT) effect in either healthy or diabetic rats, as well as to delineate the metabolic signatures in tissues of rats fed with high-fructose diet. Several differentiating metabolites were highlighted to reveal the metabolic perturbation of the oGTT effects in healthy and diabetic rats, which involved amino acid biosynthesis, polyunsaturated fatty acids, phospholipids and purine metabolism. Surprisingly, the patterns of relationships for the metabolic phenotypes by using data mining revealed that glucose ingestion might induce the healthy group to display its trajectory towards diabetic status, while only a very slight influence was observed on the high-fructose diet-fed rats 120 min after glucose ingestion. The data treatment for liver, skeletal muscle and brain tissues suggested that oxidative stress, such as lipid peroxidation and the declined antioxidant, the elevated amino acids and the perturbation of fatty acids, were caused by the high-fructose diet in liver and skeletal muscle tissues. On the other hand, the up-regulation in purine biosynthesis and the decreased concentrations for amino acids were observed in the cerebral cortex and hippocampus tissues. Collectively, the obtained results might provide a new insight not only for the impairment of glucose tolerance but also for the dietary style in rats.

  15. Amantadine reduces glucagon and enhances insulin secretion throughout the oral glucose tolerance test: central plus peripheral nervous system mechanisms

    PubMed Central

    Lechin, Fuad; van der Dijs, Bertha; Pardey-Maldonado, Betty; Rivera, Jairo E; Lechin, Marcel E; Baez, Scarlet

    2009-01-01

    Objective The purpose of the trial was to examine the effects of amantadine, a N-methyl-D-aspartate (NMDA) antagonist, on the oral glucose tolerance test (OGTT) plus insulin, glucagon and neurotransmitters circulating levels. Previous findings showed that hyperinsulinism and type 2 diabetes are positively associated with neural sympathetic and adrenal sympathetic activities, respectively. These peripheral sympathetic branches depend on the pontine (A5-noradrenergic) and the rostral ventrolateral (C1-adrenergic) medullary nuclei. They are excited by glutamate axons which act at NMDA postsynaptic receptors. Research design and methods One OGTT plus placebo and one OGTT plus oral amantadine test were carried out two weeks apart in 15 caucasic normal voluntary humans. Noradrenaline, adrenaline, dopamine, plasma-free serotonin, platelet serotonin, glucose, glucagon, and insulin were measured throughout the 180-minute testing period. Results Maximal reductions of plasma glucose and glucagon plus exacerbated insulin rises were significantly greater throughout the oral glucose plus amantadine test than those registered throughout the oral glucose plus placebo challenge. The above findings were paralleled by greater than normal noradrenaline/adrenaline plasma ratio increases. In addition, maximal reductions of the platelet serotonin and plasma serotonin circulating values contrasted with the normal rises of these parameters, always registered during the glucose load plus placebo challenge. Conclusion This study supports the theory that amantadine might be a powerful antidiabetic tool and could be added to the therapeutic arsenal against type 2 diabetes. PMID:21437134

  16. Improving glucose tolerance by reducing weight gain in a polygenic obese mouse model: use of a high protein diet.

    PubMed

    Blair, A R; Strube, M L; Proietto, J; Andrikopoulos, S

    2015-03-01

    Diets to decrease body weight have limited success in achieving and importantly maintaining this weight loss long-term. It has recently been suggested that energy intake can be regulated by the amount of protein ingested, termed the protein leverage hypothesis. In this study, we determined whether a high protein diet would be effective in achieving and maintaining weight loss in a genetically obese model, the New Zealand Obese (NZO) mouse. NZO and C57BL/6J (C57) control mice were fed a high protein or chow diet for 5 weeks from weaning (3 weeks of age). Body weight and food intake were determined. Mice on the same diet were bred to produce offspring that were fed either a chow or high protein diet. Body weight, food intake, and glucose tolerance were determined. Feeding NZO and C57 mice a high protein diet for 5 weeks resulted in reduced food intake and consequently energy intake and body weight gain compared with mice on a chow diet. NZO mice fed a high protein diet showed a significant improvement in glucose tolerance compared with their chow-fed counterparts, while no difference was seen in C57 mice fed chow or protein diet. The offspring of NZO mice that were fed a high protein diet during gestation and weaning were also lighter and displayed improved glucose tolerance compared with chow fed animals. We conclude that a high protein diet is a reasonable strategy to reduce body weight gain and improve glucose tolerance in the NZO mouse, a polygenic model of obesity.

  17. Adult offspring of high-fat diet-fed dams can have normal glucose tolerance and body composition.

    PubMed

    Platt, K M; Charnigo, R J; Pearson, K J

    2014-06-01

    Maternal high-fat diet consumption and obesity have been shown to program long-term obesity and lead to impaired glucose tolerance in offspring. Many rodent studies, however, use non-purified, cereal-based diets as the control for purified high-fat diets. In this study, primiparous ICR mice were fed purified control diet (10-11 kcal% from fat of lard or butter origin) and lard (45 or 60 kcal% fat) or butter (32 or 60 kcal% fat)-based high-fat diets for 4 weeks before mating, throughout pregnancy, and for 2 weeks of nursing. Before mating, female mice fed the 32 and 60% butter-based high-fat diets exhibited impaired glucose tolerance but those females fed the lard-based diets showed normal glucose disposal following a glucose challenge. High-fat diet consumption by female mice of all groups decreased lean to fat mass ratios during the 4th week of diet treatment compared with those mice consuming the 10-11% fat diets. All females were bred to male mice and pregnancy and offspring outcomes were monitored. The body weight of pups born to 45% lard-fed dams was significantly increased before weaning, but only female offspring born to 32% butter-fed dams exhibited long-term body weight increases. Offspring glucose tolerance and body composition were measured for at least 1 year. Minimal, if any, differences were observed in the offspring parameters. These results suggest that many variables should be considered when designing future high-fat diet feeding and maternal obesity studies in mice.

  18. 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.

  19. 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.

  20. [The titration of double bonds in fatty acids of blood plasma in patients in testing of glucose tolerance].

    PubMed

    Titov, V N; Sazhina, N N; Evteeva, N M; Aripovskiĭ, A V; Tkhagalizhokova, E M

    2015-01-01

    The article deals with per oral glucose tolerance test applied to 20 patients with arterial hypertension. The blood plasma was analyzed to detect content of individual fatty acids, double bounds, glucose, insulin and metabolites of fatty acids. In patients with different resistance to insulin content of non-etherized fatty acids decreased approximatively up to 3 times. Without insulin resistance secretion of insulin in 2 hours after glucose load increased up to 3 times and content of individual fatty acids decreases in greater extent. Under insulin resistance secretion of insulin increases up to 8 times and decreasing of content of fatty acids is less expressed. The decrease in blood plasma of content of oleic and linoleic fatty acids and double bounds reflects effectiveness of effect of insulin--blockade of hydrolysis of triglycerides in subcutaneous adipocytes. The concentration of insulin positively correlates with initial content of palmitic fatty acid in the pool of lipids of blood plasma.

  1. Rare Sugar Syrup Containing d-Allulose but Not High-Fructose Corn Syrup Maintains Glucose Tolerance and Insulin Sensitivity Partly via Hepatic Glucokinase Translocation in Wistar Rats.

    PubMed

    Shintani, Tomoya; Yamada, Takako; Hayashi, Noriko; Iida, Tetsuo; Nagata, Yasuo; Ozaki, Nobuaki; Toyoda, Yukiyasu

    2017-03-09

    Ingestion of high-fructose corn syrup (HFCS) is associated with the risk of both diabetes and obesity. Rare sugar syrup (RSS) has been developed by alkaline isomerization of HFCS and has anti-obesity and anti-diabetic effects. However, the influence of RSS on glucose metabolism has not been explored. We investigated whether long-term administration of RSS maintains glucose tolerance and whether the underlying mechanism involves hepatic glucokinase translocation. Wistar rats were administered water, RSS, or HFCS in drinking water for 10 weeks and then evaluated for glucose tolerance, insulin tolerance, liver glycogen content, and subcellular distribution of liver glucokinase. RSS significantly suppressed body weight gain and abdominal fat mass (p < 0.05). The glucose tolerance test revealed significantly higher blood glucose levels in the HFCS group compared to the water group, whereas the RSS group had significantly lower blood glucose levels from 90 to 180 min (p < 0.05). At 30, 60, and 90 min, the levels of insulin in the RSS group were significantly lower than those in the water group (p < 0.05). The amount of hepatic glycogen was more than 3 times higher in the RSS group than that in the other groups. After glucose loading, the nuclear export of glucokinase was significantly increased in the RSS group compared to the water group. These results imply that RSS maintains glucose tolerance and insulin sensitivity, at least partly, by enhancing nuclear export of hepatic glucokinase.

  2. A novel extract of Gymnema sylvestre improves glucose tolerance in vivo and stimulates insulin secretion and synthesis in vitro.

    PubMed

    Al-Romaiyan, A; King, A J; Persaud, S J; Jones, P M

    2013-07-01

    Herbal medicines, especially plant-derived extracts, have been used to treat Type 2 diabetes mellitus (T2DM) for many centuries, and offer the potential of cheap and readily available alternatives to conventional pharmaceuticals in developing countries. Extracts of Gymnema sylvestre (GS) have anti-diabetic activities and have been used as a folk medicine in India for centuries. We have investigated the effects of a novel high molecular weight GS extract termed OSA® on glucose tolerance in insulin-resistant ob/ob mice, and on insulin secretion and synthesis by isolated mouse islets. Single administration of OSA® (500 mg/kg) to ob/ob mice 30 min before an intraperitoneal glucose load improved their abnormal glucose tolerance. In vitro studies indicated that OSA® (0.25 mg/ml) initiated rapid and reversible increases in insulin secretion from isolated mouse islets at substimulatory (2 mM) and stimulatory (20 mM) glucose concentrations. In addition, prolonged treatment (24-48 h) of mouse islets with OSA® elevated the expression of preproinsulin mRNA and maintained the total insulin content of mouse islets in the presence of stimulated insulin secretion. These effects of OSA® are consistent with its potential use as a therapy for the hyperglycemia associated with obesity-related T2DM.

  3. 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.

  4. [Diagnostic value of fasting glucose, fructosamine, and glycated haemoglobin HbA(1c) with regard to ADA 1997 and who 1998 criteria for detecting diabetes and other glucose tolerance abnormalities].

    PubMed

    Gołembiewska, Edyta

    2004-01-01

    New diagnostic criteria for diabetes mellitus proposed by the American Diabetes Association in 1997 and the World Heath Organization Consultation Report in 1998 recommend lowering of the fasting plasma glucose (FPG) to 7.0 mmol/L. This change in the diagnostic FPG cut-off point was based on the results of well-documented epidemiological studies showing that increased risk of microangiopathy starts at values closer to 7.0 than 7.8 mmol/L used in the past. To facilitate the diagnosis, ADA Expert Committee recommends using FPG as the main diagnostic tool and eliminating OGTT from routine clinical practice. In contrast to ADA, WHO Consultation Group strongly recommended keeping OGTT in routine use. Due to the inconvenience, poor reproducibility, non-physiological character and labour-intensiveness of OGTT, an alternative test has been sought. The aim of this study was to determine whether fasting capillary glucose (FCG) along with fructosamine and glycated haemoglobin (HbA(1c)) perform better for the detection of glucose tolerance abnormalities than FCG alone. OGTT was performed in 1528 patients. Serum fructosamine was determined in 480 and glycated haemoglobin in 234 of these patients. To assess the value of FCG, fructosamine and glycated haemoglobin in predicting post-load glycaemia and detecting glucose tolerance abnormalities, multiple linear regression analysis and Receiver Operating Characteristics analysis were done. Fructosamine correlated stronger with 2h-postload glucose concentrations than with fasting glucose. HbA(1c) correlated stronger with FCG than with 2h-postload glucose. Combined use of fructosamine and FCG predicted 2h-postload glucose better than combined use of FCG and HbA(1c). Receiver Operating Characteristics curve analysis 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. The

  5. 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

  6. Oral glucose tolerance test for preoperative assessment of liver function in liver resection

    PubMed Central

    Rachapoodivenkata, Raghavendra Rao

    2017-01-01

    Backgrounds/Aims We intended to determine the role of the Oral glucose tolerance test (OGTT), in addition to volumetry, in preoperative assessment of patients undergoing liver resection. Methods This was a prospective study conducted at a tertiary care hospital, between February 2009 and February 2011. OGTT curve (parabolic/linear), linearity index (LI) and Parenchymal Hepatic Resection Rate (PHRR) were correlated with postoperative outcomes in terms of postoperative liver failure (PLF), by 50-50 criteria, morbidity, mortality and hospital stay. Results Of the 33 patients included in the study, 23 (69.7%) patients underwent major liver resections. Hepatocellular carcinoma (30.3%) was the leading indication. The overall postoperative morbidity rate was 72.7%, but major complications occurred in 3 (9.1%) patients only. There was no 90-day mortality. The 50-50 criteria were met by 3 patients undergoing major resection. Significant correlation was noted between the linear OGTT curve and the overall hospital stay (12.1 days vs. 9.6 days in parabolic; p=0.04). Patients with linear OGTT met the 50-50 criteria more often (18%) than those having a parabolic curve (4.5%; p=0.25). Although the OGTT was more often linear with occurrence of morbidity (41.7% vs 11.1%), major morbidity (66.7% vs 30%) and PLF by 50-50 criteria (66.7% vs 30%), it was not statistically significant. The linearity index was marginally lower (0.9 vs 1.2) in the presence of major morbidity and PLF by 50-50 criteria. Conclusions Linear OGTT affects the PLF and major morbidity, therein impacting the hospital stay. OGTT LI and PHRR can help predict postoperative outcome for a given extent of liver resection. PMID:28317039

  7. Addition of a Gastrointestinal Microbiome Modulator to Metformin Improves Metformin Tolerance and Fasting Glucose Levels

    PubMed Central

    Burton, Jeffrey H.; Johnson, Matthew; Johnson, Jolene; Hsia, Daniel S.; Greenway, Frank L.; Heiman, Mark L.

    2015-01-01

    Background: Adverse effects of metformin are primarily related to gastrointestinal (GI) intolerance that could limit titration to an efficacious dose or cause discontinuation of the medication. Because some metformin side effects may be attributable to shifts in the GI microbiome, we tested whether a GI microbiome modulator (GIMM) used in combination with metformin would ameliorate the GI symptoms. Methods: A 2-period crossover study design was used with 2 treatment sequences, either placebo in period 1 followed by GIMM in period 2 or vice versa. Study periods lasted for 2 weeks, with a 2-week washout period between. During the first week, type 2 diabetes patients (T2D) who experienced metformin GI intolerance took 500 mg metformin along with their assigned NM504 (GIMM) or placebo treatment with breakfast and with dinner. In the second week, the 10 subjects took 500 mg metformin (t.i.d.), with GIMM or placebo consumed with the first and third daily metformin doses. Subjects were permitted to discontinue metformin dosing if it became intolerable. Results: The combination of metformin and GIMM treatment produced a significantly better tolerance score to metformin than the placebo combination (6.78 ± 0.65 [mean ± SEM] versus 4.45 ± 0.69, P = .0006). Mean fasting glucose levels were significantly (P < .02) lower with the metformin–GIMM combination (121.3 ± 7.8 mg/dl) than with metformin-placebo (151.9 ± 7.8 mg/dl). Conclusion: Combining a GI microbiome modulator with metformin might allow the greater use of metformin in T2D patients and improve treatment of the disease. PMID:25802471

  8. Sleep Duration, Lifestyle Intervention, and Incidence of Type 2 Diabetes in Impaired Glucose Tolerance

    PubMed Central

    Tuomilehto, Henri; Peltonen, Markku; Partinen, Markku; Lavigne, Gilles; Eriksson, Johan G.; Herder, Christian; Aunola, Sirkka; Keinänen-Kiukaanniemi, Sirkka; Ilanne-Parikka, Pirjo; Uusitupa, Matti; Tuomilehto, Jaakko; Lindström, Jaana

    2009-01-01

    OBJECTIVE Both short and long sleep duration have frequently been found to be associated with an increased risk for diabetes. The aim of the present exploratory analysis was to examine the association between sleep duration and type 2 diabetes after lifestyle intervention in overweight individuals with impaired glucose tolerance in a 7-year prospective follow-up. RESEARCH DESIGN AND METHODS A total of 522 individuals (aged 40–64 years) were randomly allocated either to an intensive diet-exercise counseling group or to a control group. Diabetes incidence during follow-up was calculated according to sleep duration at baseline. Sleep duration was obtained for a 24-h period. Physical activity, dietary intakes, body weight, and immune mediators (C-reactive protein and interleukin-6) were measured. RESULTS Interaction between sleep duration and treatment group was statistically significant (P = 0.003). In the control group, the adjusted hazard ratios (HRs) (95% CI) for diabetes were 2.29 (1.38–3.80) and 2.74 (1.67–4.50) in the sleep duration groups 9–9.5 h and ≥10 h, respectively, compared with for that of the 7–8.5 h group. In contrast, sleep duration did not influence the incidence of diabetes in the intervention group; for sleep duration groups 9–9.5 h and ≥10 h, the adjusted HRs (95% CI) were 1.10 (0.60–2.01) and 0.73 (0.34–1.56), respectively, compared with that in the reference group (7–8.5 h sleep). Lifestyle intervention resulted in similar improvement in body weight, insulin sensitivity, and immune mediator levels regardless of sleep duration. CONCLUSIONS Long sleep duration is associated with increased type 2 diabetes risk. Lifestyle intervention with the aim of weight reduction, healthy diet, and increased physical activity may ameliorate some of this excess risk. PMID:19651919

  9. 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.

  10. A double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension.

    PubMed

    Stears, Anna J; Woods, Sarah H; Watts, Michaela M; Burton, Timothy J; Graggaber, Johann; Mir, Fraz A; Brown, Morris J

    2012-05-01

    Hypertension guidelines advise limiting the dose of thiazide diuretics and avoiding combination with β-blockade, because of increased risk of diabetes mellitus. We tested whether changes in the 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with a thiazide and could be avoided by switching to amiloride. Two double-blind, placebo-controlled, crossover studies were performed. In study 1 (41 patients), we found that changes in glucose during a 2-hour oral glucose tolerance test could be detected after 4 weeks of treatment with bendroflumethiazide. In study 2, 37 patients with essential hypertension received, in random order, 4 weeks of once-daily treatment with hydrochlorothiazide (HCTZ) 25 to 50 mg, nebivolol 5 to 10 mg, combination (HCTZ 25-50 mg+nebivolol 5-10 mg), amiloride (10-20 mg), and placebo. Each drug was force titrated at 2 weeks and separated by a 4-week placebo washout. At each visit, we recorded blood pressure and performed a 75-g oral glucose tolerance test. Primary outcome was the difference in glucose (over the 2 hours of the oral glucose tolerance test) between 0 and 4 weeks, when HCTZ and amiloride were compared by repeated-measures analysis. For similar blood pressure reductions, there were opposite changes in glucose between the 2 diuretics (P<0.0001). Nebivolol did not impair glucose tolerance, either alone or in combination. There was a negative correlation between Δpotassium and Δ2-hour glucose (r=-0.28; P<0.0001). In 2 crossover studies, 4 weeks of treatment with a thiazide diuretic impaired glucose tolerance. No impairment was seen with K(+)-sparing diuretic or β(1)-selective blockade. Substitution or addition of amiloride may be the solution to preventing thiazide-induced diabetes mellitus.

  11. The Acute and Residual Effect of a Single Exercise Session on Meal Glucose Tolerance in Sedentary Young Adults

    PubMed Central

    Short, Kevin R.; Pratt, Lauren V.; Teague, April M.

    2012-01-01

    The study goals were to (1) establish the variability in postprandial glucose control in healthy young people consuming a mixed meal and, then (2) determine the acute and residual impact of a single exercise bout on postprandial glucose control. In study 1, 18 people completed two similar mixed meal trials and an intravenous glucose tolerance test (IVGTT). There were strong test-retest correlations for the post-meal area under the curve (AUC) for glucose, insulin, and Cpeptide (r = 0.73–0.83) and the Matsuda insulin sensitivity index (ISI, r = 0.76), and between meal and IVGTT-derived ISI (r = 0.83). In study 2, 11 untrained young adults completed 3 trials. One trial (No Ex) was completed after refraining from vigorous activity for ≥3 days. On the other 2 trials, a 45-min aerobic exercise bout was performed either 17-hours (Prior Day Ex) or 1-hour (Same Day Ex) before consuming the test meal. Compared to No Ex and Prior Day Ex, which did not differ from one another, there were lower AUCs on the Same Day Ex trial for glucose (6%), insulin (20%) and C-peptide (14%). Thus, a single moderate intensity exercise session can acutely improve glycemic control but the effect is modest and short-lived. PMID:22666560

  12. 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.

  13. 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

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

    PubMed Central

    CIUBOTARU, IRINA; GREEN, STEFAN J.; KUKREJA, SUBHASH; BARENGOLTS, ELENA

    2016-01-01

    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

  15. 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.

  16. Wholegrain barley β-glucan fermentation does not improve glucose tolerance in rats fed a high-fat diet.

    PubMed

    Belobrajdic, Damien P; Jobling, Stephen A; Morell, Matthew K; Taketa, Shin; Bird, Anthony R

    2015-02-01

    Fermentation of oat and barley β-glucans is believed to mediate in part their metabolic health benefits, but the exact mechanisms remain unclear. In this study, we sought to test the hypothesis that barley β-glucan fermentation raises circulating incretin hormone levels and improves glucose control, independent of other grain components. Male Sprague-Dawley rats (n = 30) were fed a high-fat diet for 6 weeks and then randomly allocated to 1 of 3 dietary treatments for 2 weeks. The low- (LBG, 0% β-glucan) and high- (HBG, 3% β-glucan) β-glucan diets contained 25% wholegrain barley and similar levels of insoluble dietary fiber, available carbohydrate, and energy. A low-fiber diet (basal) was included for comparison. Immediately prior to the dietary intervention, gastric emptying rate (using the (13)C-octanoic breath test) and postprandial glycemic response of each diet were determined. At the end of the study, circulating gut hormone levels were determined; and a glucose tolerance test was performed. The rats were then killed, and indices of cecal fermentation were assessed. Diet did not affect live weight; however, the HBG diet, compared to basal and LBG, reduced food intake, tended to slow gastric emptying, increased cecal digesta mass and individual and total short-chain fatty acid pools, and lowered digesta pH. In contrast, circulating levels of glucose, insulin, gastric-inhibitory peptide, and glucagon-like peptide-1, and glucose tolerance were unaffected by diet. In conclusion, wholegrain barley β-glucan suppressed feed intake and increased cecal fermentation but did not improve postprandial glucose control or insulin sensitivity.

  17. Serum metabolic variables associated with impaired glucose tolerance induced by high-fat-high-cholesterol diet in Macaca mulatta.

    PubMed

    Li, Xinli; Chen, Younan; Liu, Jingping; Yang, Guang; Zhao, Jiuming; Liao, Guangneng; Shi, Meimei; Yuan, Yujia; He, Sirong; Lu, Yanrong; Cheng, Jingqiu

    2012-11-01

    Dyslipidemia caused by 'Western-diet pattern' is a strong risk factor for the onset of diabetes. This study aimed to disclose the relationship between the serum metabolite changes induced by habitual intake of high-fat and high-cholesterol (HFHC) diet and the development of impaired glucose tolerance (IGT) and insulin resistance through animal models of Macaca mulatta. Sixteen M. mulatta (six months old) were fed a control diet or a HFHC diet for 18 months. The diet effect on serum metabolic profiles was investigated by longitudinal research. Islet function was assessed by intravenous glucose tolerance and hyperinsulinemic-euglycemic clamp test. Metabonomics were determined by (1)H proton nuclear magnetic resonance spectroscopy. Prolonged diet-dependent hyperlipidemia facilitated visceral fat accumulation in liver and skeletal muscle and disorder of glucose homeostasis in juvenile monkeys. Glucose disappearance rate (K(Glu)) and insulin response to the glucose challenge effects in HFHC monkeys were significantly lower than in control monkeys. Otherwise, serum trimethylamine-N-oxide (TMAO), lactate and leucine/isoleucine were significantly higher in HFHC monkeys. Sphingomyelin and choline were the most positively correlated with K(Glu) (R(2) = 0.778), as well as negative correlation (R(2) = 0.64) with total cholesterol. The HFHC diet induced visceral fat, abnormal lipid metabolism and IGT prior to weight gain and body fat content increase in juvenile monkeys. We suggest that increased serum metabolites, such as TMAO, lactate, branched-chain amino acids and decreased sphingomyelin and choline, may serve as possible predictors for the evaluation of IGT and insulin resistance risks in the prediabetic state.

  18. Brain GLUT4 Knockout Mice Have Impaired Glucose Tolerance, Decreased Insulin Sensitivity, and Impaired Hypoglycemic Counterregulation.

    PubMed

    Reno, Candace M; Puente, Erwin C; Sheng, Zhenyu; Daphna-Iken, Dorit; Bree, Adam J; Routh, Vanessa H; Kahn, Barbara B; Fisher, Simon J

    2017-03-01

    GLUT4 in muscle and adipose tissue is important in maintaining glucose homeostasis. However, the role of insulin-responsive GLUT4 in the central nervous system has not been well characterized. To assess its importance, a selective knockout of brain GLUT4 (BG4KO) was generated by crossing Nestin-Cre mice with GLUT4-floxed mice. BG4KO mice had a 99% reduction in GLUT4 protein expression throughout the brain. Despite normal feeding and fasting glycemia, BG4KO mice were glucose intolerant, demonstrated hepatic insulin resistance, and had reduced glucose uptake in the brain. In response to hypoglycemia, BG4KO mice had impaired glucose sensing, noted by impaired epinephrine and glucagon responses and impaired c-fos activation in the hypothalamic paraventricular nucleus. Moreover, in vitro glucose sensing of glucose-inhibitory neurons from the ventromedial hypothalamus was impaired in BG4KO mice. In summary, BG4KO mice are glucose intolerant, insulin resistant, and have impaired glucose sensing, indicating a critical role for brain GLUT4 in sensing and responding to changes in blood glucose.

  19. Insulin Dynamics in Young Women with Polycystic Ovary Syndrome and Normal Glucose Tolerance across Categories of Body Mass Index

    PubMed Central

    Manco, Melania; Castagneto-Gissey, Lidia; Arrighi, Eugenio; Carnicelli, Annamaria; Brufani, Claudia; Luciano, Rosa; Mingrone, Geltrude

    2014-01-01

    Background Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls. Research Design and Methods Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16–49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method). Results Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons). Conclusion Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls. PMID:24705280

  20. 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

  1. 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

  2. Gastrin treatment stimulates β-cell regeneration and improves glucose tolerance in 95% pancreatectomized rats.

    PubMed

    Téllez, Noèlia; Joanny, Géraldine; Escoriza, Jéssica; Vilaseca, Marina; Montanya, Eduard

    2011-07-01

    β-Cell mass reduction is a central aspect in the development of type 1 and type 2 diabetes, and substitution or regeneration of the lost β-cells is a potentially curative treatment of diabetes. To study the effects of gastrin on β-cell mass in rats with 95% pancreatectomy (95%-Px), a model of pancreatic regeneration, rats underwent 95% Px or sham Px and were treated with [15 leu] gastrin-17 (Px+G and S+G) or vehicle (Px+V and S+V) for 15 d. In 95% Px rats, gastrin treatment reduced hyperglycemia (280 ± 52 mg vs. 436 ± 51 mg/dl, P < 0.05), and increased β-cell mass (1.15 ± 0.15 mg)) compared with vehicle-treated rats (0.67 ± 0.15 mg, P < 0.05). Gastrin treatment induced β-cell regeneration by enhancing β-cell neogenesis (increased number of extraislet β-cells in Px+G: 0.42 ± 0.05 cells/mm(2) vs. Px+V: 0.27 ± 0.07 cells/mm(2), P < 0.05, and pancreatic and duodenal homeobox 1 expression in ductal cells of Px+G: 1.21 ± 0.38% vs. Px+V: 0.23 ± 0.10%, P < 0.05) and replication (Px+G: 1.65 ± 0.26% vs. S+V: 0.64 ± 0.14%; P < 0.05). In addition, reduced β-cell apoptosis contributed to the increased β-cell mass in gastrin-treated rats (Px+G: 0.07 ± 0.02%, Px+V: 0.23 ± 0.05%; P < 0.05). Gastrin action on β-cell regeneration and survival increased β-cell mass and improved glucose tolerance in 95% Px rats, supporting a potential role of gastrin in the treatment of diabetes.

  3. Pioglitazone is equally effective for diabetes prevention in older versus younger adults with impaired glucose tolerance.

    PubMed

    Espinoza, Sara E; Wang, Chen-Pin; Tripathy, Devjit; Clement, Stephen C; Schwenke, Dawn C; Banerji, Mary Ann; Bray, George A; Buchanan, Thomas A; Henry, Robert R; Kitabchi, Abbas E; Mudaliar, Sunder; Stentz, Frankie B; Reaven, Peter D; DeFronzo, Ralph A; Musi, Nicolas

    2016-12-01

    To determine the efficacy of pioglitazone to prevent type 2 diabetes in older compared to younger adults with pre-diabetes. Six hundred two participants with impaired glucose tolerance (IGT) were randomized in double blind fashion to placebo or pioglitazone for diabetes prevention in the ACT NOW study (NEJM 364:1104-1115, 2011). Cox proportional hazard regression was used to compare time to development of diabetes over a mean of 2 years between older (≥61 years) and younger participants. We compared effects of pioglitazone versus placebo on metabolic profiles, inflammatory markers, adipokines, β cell function (disposition index), insulin sensitivity (Matsuda index), and body composition by ANOVA. Diabetes incidence was reduced by 85 % in older and 69 % in younger subjects (p = 0.41). β cell function (disposition index) increased by 35.0 % in the older and 26.7 % in younger subjects (p = 0.83). Insulin sensitivity (Matsuda index) increased by 3.07 (5.2-fold) in older and by 2.54 (3.8-fold) in younger participants (p = 0.58). Pioglitazone more effectively increased adiponectin in older versus younger subjects (22.9 ± 3.2 μg/mL [2.7-fold] vs. 12.7 ± 1.4 μg/mL [2.2-fold], respectively; p = 0.04). Younger subjects tended to have a greater increase in whole body fat mass compared to older subjects (3.6 vs. 3.1 kg; p = 0.061). Younger and older subjects had similar decreases in bone mineral density (0.018 ± 0.0071 vs. 0.0138 ± 0.021 g/cm(2)). Younger and older pre-diabetic adults taking pioglitazone had similar reductions in conversion to diabetes and older adults had similar or greater improvements in metabolic risk factors, demonstrating that pioglitazone is useful in preventing diabetes in older adults.

  4. Effect of Rosiglitazone and Ramipril on {beta}-cell function in people with impaired glucose tolerance or impaired fasting glucose: the DREAM trial.

    PubMed

    Hanley, Anthony J; Zinman, Bernard; Sheridan, Patrick; Yusuf, Salim; Gerstein, Hertzel C

    2010-03-01

    OBJECTIVE The objective of this study was to determine the degree to which ramipril and/or rosiglitazone changed beta-cell function over time among individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) who participated in the Diabetes Reduction Assessment With Ramipril and Rosiglitazone Medication (DREAM) Trial, which evaluated whether ramipril and/or rosiglitazone could prevent or delay type 2 diabetes in high-risk individuals. RESEARCH DESIGN AND METHODS The present analysis included subjects (n = 982) from DREAM trial centers in Canada who had oral glucose tolerance tests at baseline, after 2 years, and at the end of the study. beta-Cell function was assessed using the fasting proinsulin-to-C-peptide ratio (PI/C) and the insulinogenic index (defined as 30-0 min insulin/30-0 min glucose) divided by homeostasis model assessment of insulin resistance (insulinogenic index [IGI]/insulin resistance [IR]). RESULTS Subjects receiving rosiglitazone had a significant increase in IGI/IR between baseline and end of study compared with the placebo group (25.59 vs. 1.94, P < 0.0001) and a significant decrease in PI/C (-0.010 vs. -0.006, P < 0.0001). In contrast, there were no significant changes in IGI/IR or PI/C in subjects receiving ramipril compared with placebo (11.71 vs. 18.15, P = 0.89, and -0.007 vs. -0.008, P = 0.64, respectively). The impact of rosiglitazone on IGI/IR and PI/C was similar within subgroups of isolated IGT and IFG + IGT (all P < 0.001). Effects were more modest in those with isolated IFG (IGI/IR: 8.95 vs. 2.13, P = 0.03; PI/C: -0.003 vs. -0.001, P = 0.07). CONCLUSIONS Treatment with rosiglitazone, but not ramipril, resulted in significant improvements in measures of beta-cell function over time in pre-diabetic subjects. Although the long-term sustainability of these improvements cannot be determined from the present study, these findings demonstrate that the diabetes preventive effect of rosiglitazone was in part a

  5. Effect of Pseudocereal-Based Breakfast Meals on the First and Second Meal Glucose Tolerance in Healthy and Diabetic Subjects

    PubMed Central

    Gabrial, Shreef G. N.; Shakib, Marie-Christine R.; Gabrial, Gamal N.

    2016-01-01

    min. At the end of the second meal period, values were below or near-fasting baseline levels in the breakfast period. The blood glucose concentration after consuming quinoa meal showed a high peak at 30 min similar to that of WWB reference meal. This peak resulted in a high glycemic index (GI) for quinoa (89.4). The GI of buckwheat recorded a low value (26.8). CONCLUSION: The two studied pseudocereals; quinoa and buckwheat have high potential to improve glucose tolerance at the first and second meal (lunch) and are recommended to be introduced in our daily diet for healthy and diabetic subjects. PMID:28028392

  6. A trial of simple versus intensified dietary modification for prevention of progression to diabetes mellitus in women with impaired glucose tolerance.

    PubMed

    Wein, P; Beischer, N; Harris, C; Permezel, M

    1999-05-01

    Women with impaired glucose tolerance are at high risk of developing noninsulin dependent diabetes mellitus (NIDDM). The Mercy Hospital for Women has a long-term follow-up programme for women with gestational diabetes, which identifies many women with impaired glucose tolerance. Two hundred of these women were entered into a randomized controlled trial of intensive versus routine dietary advice. Seven women were lost to follow-up. The annual incidence rates of diabetes mellitus for the 2 groups were 6.1% (intervention) and 7.3% (control), an incident rate ratio of 0.83, 95% confidence interval 0.47-1.48, p = 0.50. Overall, there was a return to normal glucose tolerance in 44% of patients. Multivariate analysis showed that body mass index, fasting and 2-hour plasma glucose levels at trial entry were significantly associated with an increased risk of diabetes mellitus. Impaired glucose tolerance is an important condition that should be treated with advice about lifestyle modification (diet and/or exercise). We consider that future trials in the management of women with previous gestational diabetes who have impaired glucose tolerance should investigate the effect of pharmacological intervention in addition to diet and/or exercise, the latter providing a therapy that it would be unethical to exclude on the evidence presently available.

  7. 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

  8. Influence of the interleukin-6 -174 G/C gene polymorphism on exercise training-induced changes in glucose tolerance indexes.

    PubMed

    McKenzie, Jennifer A; Weiss, Edward P; Ghiu, Ioana A; Kulaputana, Onanong; Phares, Dana A; Ferrell, Robert E; Hagberg, James M

    2004-10-01

    A polymorphism in the IL-6 gene, a G-to-C substitution 176 bp upstream of the ATG translation initiation site, has been associated with diabetes prevalence and insulin resistance. Interventions including exercise training are frequently used to modify cardiovascular disease risk factors. Consequently, this project examined associations between the IL-6 -174 genotype and oral glucose tolerance test outcomes in 50- to 75-yr-old sedentary men and postmenopausal women before and after aerobic exercise training. Among the 87 individuals who started the study, 56 were retested after 6 mo of aerobic exercise training. Subject characteristics at baseline did not differ between the IL-6 genotype groups with the exception of fasting glucose, which was higher (P = 0.02, covariates age, gender, and ethnicity) in the CC genotype group. The training-induced change in glucose area under the curve during the oral glucose tolerance test varied between the IL-6 -174 genotype groups (P = 0.05, covariates age, gender, ethnicity, baseline glucose area under the curve, and percent body fat change) with a significant decrease occurring only in the GG genotype group. Insulin outcomes did not differ among the groups at baseline or after training. Training-induced changes in weight, percent body fat, maximal oxygen consumption, fasting glucose, and an insulin sensitivity index also changed similarly among the genotype groups. In conclusion, fasting glucose and the extent to which glucose tolerance changes with exercise training may be influenced by the IL-6 -174 gene polymorphism.

  9. Decrease of serum S100B during an oral glucose tolerance test correlates inversely with the insulin response.

    PubMed

    Steiner, Johann; Bernstein, Hans-Gert; Schiltz, Kolja; Haase, Thekla; Meyer-Lotz, Gabriela; Dobrowolny, Henrik; Müller, Ulf J; Martins-de-Souza, Daniel; Borucki, Katrin; Schroeter, Matthias L; Isermann, Berend; Bogerts, Bernhard; Westphal, Sabine

    2014-01-01

    Increased S100B serum levels have been considered as a marker of glial pathology, brain damage, and blood-brain-barrier impairment. However, S100B expression has also been detected outside the nervous system, suggesting that altered S100B serum levels may not exclusively reflect brain-specific pathologies. Notably, S100B secretion in adipocytes seems to be down-regulated by insulin, and up-regulated by stress and fasting. Therefore, we assumed that dynamic changes of S100B could be observed by challenging healthy subjects with an oral glucose tolerance test (OGTT). OGTT was performed in 17 healthy adult test persons (9 male and 8 female). Apart from S100B, glucose, free fatty acids, insulin, C-peptide, and cortisol were determined in all samples after an overnight fast (0 h), as well as 1h and 2h after ingestion of 75 g glucose. Mean S100B concentrations decreased about 20% during the first hour after glucose ingestion (P<0.001). This decrease of S100B levels was not related to the declining morning peak of cortisol. However, the decrease of serum-S100B 1h after glucose ingestion correlated inversely with the respective changes of serum-insulin (r = -0.484, P=0.049) and serum-C-peptide (r = -0.570, P = 0.017). Our study suggests an inverse correlation between insulin secretion and S100B release after a standardized OGTT. Additional experiments, including the administration of insulin and the measurement of other food intake-related factors are important to ascertain an insulin-regulated S100B release in vivo. To improve comparability between clinical studies assessing conditions with rather mild changes of serum S100B, blood should be taken in a more standardized way (e.g., after fasting overnight).

  10. The effect of a low-calorie diet with and without fenfluramine on the glucose tolerance and insulin secretion of obese maturity-onset diabetics

    PubMed Central

    Dykes, J. Ranald W.

    1973-01-01

    Glucose tolerance and insulin secretion have been measured in twenty-three obese maturity-onset diabetics (twelve high-insulin secretors and eleven lowor normal-insulin secretors) on first presentation and after 10 weeks on a low-calorie diet. There was a significant improvement in glucose tolerance alone, when the results were compared with those from diabetics not on any form of treatment. Thereafter nine of these subjects (five high-insulin secretors and four low- or normal-insulin secretors) continued on the dietary therapy alone, and eleven of the remaining fourteen subjects (six high-insulin secretors and five low- or normal-insulin secretors) continued on the low-calorie diet with the addition of fenfluramine, and their glucose tolerance and insulin secretion were measured again after a further 10 weeks. The remaining three subjects were no longer studied. The nine subjects continuing on the diet alone showed maintenance of the improvement in glucose tolerance achieved during the first 10-week period with no significant change in insulin secretion. The eleven subjects placed on fenfluramine in addition to the diet also showed maintenance of the improvement in glucose tolerance achieved during the first 10-week period with a significant decrease in insulin secretion in the six high-insulin secreting subjects and no significant change in insulin secretion in the five lowor normal-secretors. PMID:4804456

  11. Excessive Gestational Weight Gain in the First Trimester among Women with Normal Glucose Tolerance and Resulting Neonatal Adiposity

    PubMed Central

    Josefson, Jami L.; Simons, Hannah; Zeiss, Dinah M.; Metzger, Boyd E.

    2016-01-01

    Objective To assess whether weight gain above or below Institute of Medicine (IOM) recommended amounts in an ethnically diverse obstetric population with normal glucose tolerance is associated with differences in neonatal adiposity. Study Design In this prospective cohort study, healthy women with normal glucose tolerance based on the International Association of Diabetes and Pregnancy Study Groups guidelines were enrolled. Gestational weight at multiple time points were collected. Neonatal adiposity was measured by air displacement plethysmography at 24-72 hours of life. Analyses included Fisher's exact test, ANOVA, and a trajectory analysis using a group-based weight gain trajectory model with a censored normal distribution. Result Overweight and obese women were more likely to exceed IOM weight gain guidelines. Regardless, there was no significant difference in %body fat of neonates born to mothers who either met or exceeded gestational weight gain guidelines. Gestational weight gain timing influenced neonatal anthropometrics: women who gained excessively by the first prenatal visit had neonates with significantly higher birth weight (3.91 kg vs. 3.45 kg, p<0.001), and %body fat (13.7% vs. 10.9%, p=0.0001) compared to women who had steady, moderate gestational weight gain. Conclusion Avoidance of excessive gestational weight gain in the first trimester may prevent high amounts of neonatal adiposity. PMID:27583397

  12. Omega-3 improves glucose tolerance but increases lipid peroxidation and DNA damage in hepatocytes of fructose-fed rats.

    PubMed

    de Castro, Gabriela Salim Ferreira; dos Santos, Raquel Alves; Portari, Guilherme Vannucchi; Jordão, Alceu Afonso; Vannucchi, Helio

    2012-04-01

    The high consumption of fructose is linked to the increase in various characteristics of the metabolic syndrome. Fish oil is beneficial for the treatment of these comorbidities, such as insulin resistance, dyslipidemia, and hepatic steatosis. The objective of this study was to evaluate the consequences of the administration of fish oil concomitant to fructose ingestion during the experiment (45 days) and during the final 15 days in high-fructose-fed rats. Male Wistar rats were divided into 5 groups: control; those receiving 10% fish oil (FO); those receiving 60% fructose (Fr); those receiving 60% fructose and 10% fish oil for 45 days (FrFO); and those receiving fructose plus soybean oil for 30 days and fish oil for the final 15 days of the study (FrFO15). There was an increase in triacylglycerol, serum total cholesterol, and hepatic volume in the Fr group. The FO and FrFO groups experienced an increase in lipid peroxidation and a decrease in serum reduced glutathione. The FrFO group suffered greater hepatic injury, with increased alanine aminotransferase levels and DNA damage. Marked n-3 incorporation occurred in the groups receiving fish oil, favoring a better response to the oral glucose tolerance test. Fructose induced comorbidities of the metabolic syndrome, and the use of fish oil promoted a better glucose tolerance, although it was accompanied by more hepatocyte damage.

  13. 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

  14. In vivo laboratory practicals in research-led teaching: an example using glucose tolerance tests in lean and obese mice.

    PubMed

    King, Aileen J F; Bowe, James E; Sprake, Juliet A; Kinchin, Ian M

    2011-01-01

    The use of animal models is an essential part of medical research and drug development. The essential skills required to be able to do such research includes experimental design, statistical analysis and the actual handling and treating of the animals (in vivo skills). The number of students in the U.K. receiving training in handling and experimenting on animals has declined rapidly in the last few decades which has led to initiatives to increase numbers of students with these skills to meet demand. Within the Department of Pharmacology and Therapeutics at King's College London, we run a course for 2nd year undergraduates entitled "Animal models of disease and injury". This course not only covers the theoretical and ethical aspects of using animals in research, but also contains practical laboratory classes in which students get hands-on experience using animals. One of the laboratory classes we run is a glucose tolerance test in obese and lean mice. This is an example of research-led teaching which aims to develop research skills through engaging students in research like activities. In this paper, we outline the methodology of the glucose tolerance practical and highlight some of the skills we and the students think they gain by research-led teaching such as this.

  15. Comparison of glucose tolerance tests to detect the insulin sensitizing effects of a bout of continuous exercise.

    PubMed

    Ortega, Juan Fernando; Hamouti, Nassim; Fernández-Elías, Valentín Emilio; Mora-Rodriguez, Ricardo

    2014-07-01

    The aim of the present study was to determine which of the available glucose tolerance tests (oral (OGTT) vs. intravenous (IVGTT)) could more readily detect the insulin sensitizing effects of a bout of continuous exercise. Ten healthy moderately fit young men (V̇O2peak of 45.4 ± 1.8 mL·kg(-1)·min(-1); age 27.5 ± 2.7 yr) underwent 4 OGTT and 4 IVGTT on different days following a standardized dinner and overnight fast. One test was performed immediately after 55 min of cycle-ergometer exercise at 60% V̇O2peak. Insulin sensitivity index was determined during a 50 min IVGTT according to Tura (CISI) and from a 120 min OGTT using the Matsuda composite index (MISI). After exercise, MISI improved 29 ± 10% without reaching statistical significance (p = 0.182) due to its low reproducibility (coefficient of variation 16 ± 3%; intra-class reliability 0.846). However, CISI significantly improved (50 ± 4%; p < 0.001) after exercise showing better reproducibility (coefficient of variation 13 ± 4%; intra-class reliability 0.955). Power calculation revealed that 6 participants were required for detecting the effects of exercise on insulin sensitivity when using IVGTT, whereas 54 were needed when using OGTT. The superior response of CISI compared with MISI suggests the preferential use of IVGTT to assess the effects of exercise on insulin sensitivity when using a glucose tolerance test.

  16. IVGTT-based simple assessment of glucose tolerance in the Zucker fatty rat: Validation against minimal models

    PubMed Central

    Morettini, Micaela; Faelli, Emanuela; Perasso, Luisa; Fioretti, Sandro; Burattini, Laura

    2017-01-01

    For the assessment of glucose tolerance from IVGTT data in Zucker rat, minimal model methodology is reliable but time- and money-consuming. This study aimed to validate for the first time in Zucker rat, simple surrogate indexes of insulin sensitivity and secretion against the glucose-minimal-model insulin sensitivity index (SI) and against first- (Φ1) and second-phase (Φ2) β-cell responsiveness indexes provided by C-peptide minimal model. Validation of the surrogate insulin sensitivity index (ISI) and of two sets of coupled insulin-based indexes for insulin secretion, differing from the cut-off point between phases (FPIR3-SPIR3, t = 3 min and FPIR5-SPIR5, t = 5 min), was carried out in a population of ten Zucker fatty rats (ZFR) and ten Zucker lean rats (ZLR). Considering the whole rat population (ZLR+ZFR), ISI showed a significant strong correlation with SI (Spearman’s correlation coefficient, r = 0.88; P<0.001). Both FPIR3 and FPIR5 showed a significant (P<0.001) strong correlation with Φ1 (r = 0.76 and r = 0.75, respectively). Both SPIR3 and SPIR5 showed a significant (P<0.001) strong correlation with Φ2 (r = 0.85 and r = 0.83, respectively). ISI is able to detect (P<0.001) the well-recognized reduction in insulin sensitivity in ZFRs, compared to ZLRs. The insulin-based indexes of insulin secretion are able to detect in ZFRs (P<0.001) the compensatory increase of first- and second-phase secretion, associated to the insulin-resistant state. The ability of the surrogate indexes in describing glucose tolerance in the ZFRs was confirmed by the Disposition Index analysis. The model-based validation performed in the present study supports the utilization of low-cost, insulin-based indexes for the assessment of glucose tolerance in Zucker rat, reliable animal model of human metabolic syndrome. PMID:28264067

  17. 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.

  18. 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.

  19. Age and body weight effects on glucose and insulin tolerance in colony cats maintained since weaning on high dietary carbohydrate.

    PubMed

    Backus, R C; Cave, N J; Ganjam, V K; Turner, J B M; Biourge, V C

    2010-12-01

    High dietary carbohydrate is suggested to promote development of diabetes mellitus in cats. Glucose tolerance, insulin sensitivity, and insulin secretion were assessed in young [0.8-2.3 (median = 1.1) years, n = 13] and mature [4.0-7.0 (median 5.8) years, n = 12] sexually intact females of a large (n ≅ 700) feline colony in which only dry-type diets (35% metabolizable energy as carbohydrate) were fed from weaning. Insulin sensitivity was assessed from the 'late-phase' (60-120 min) plasma insulin response of intravenous glucose tolerance tests (IVGTTs) and from fractional change in glycaemia from baseline 15 min after an insulin bolus (0.1 U/kg, i.v.). Insulin secretion was assessed from the 'early-phase' (0-15 min) plasma insulin response of IVGTTs. Compared to the young cats, the mature cats had greater body weights [2.3-3.8 (median = 2.9) vs. 3.0-6.3 (median = 4.0) kg, p < 0.01], greater late-phase insulin responses (p < 0.05), lower insulin-induced glycaemic changes (p = 0.06), lower early-phase insulin responses (p < 0.05), and non-significantly different rates of glucose disposal. The late-phase insulin response was correlated with body weight and age (p < 0.05). When group assignments were balanced for body weight, the age-group differences and correlations became non-significant. The findings indicate that body weight gain is more likely than dry-type diets to induce the pre-diabetic conditions of insulin resistance and secretion dysfunction.

  20. 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.

  1. Expression and characterization of a glucose-tolerant β-1,4-glucosidase with wide substrate specificity from Cytophaga hutchinsonii.

    PubMed

    Zhang, Cong; Wang, Xifeng; Zhang, Weican; Zhao, Yue; Lu, Xuemei

    2017-03-01

    Cytophaga hutchinsonii is a gram-negative bacterium that can efficiently degrade crystalline cellulose by a novel strategy without cell-free cellulases or cellulosomes. Genomic analysis implied that C. hutchinsonii had endoglucanases and β-glucosidases but no exoglucanases which could processively digest cellulose and produce cellobiose. In this study, BglA was functionally expressed in Escherichia coli and found to be a β-glucosidase with wide substrate specificity. It can hydrolyze pNPG, pNPC, cellobiose, and cellodextrins. Moreover, unlike most β-glucosidases whose activity greatly decreases with increasing length of the substrate chains, BglA has similar activity on cellobiose and larger cellodextrins. The K m values of BglA on cellobiose, cellotriose, and cellotetraose were calculated to be 4.8 × 10(-2), 5.6 × 10(-2), and 5.3 × 10(-2) mol/l, respectively. These properties give BglA a great advantage to cooperate with endoglucanases in C. hutchinsonii in cellulose degradation. We proposed that C. hutchinsonii could utilize a simple cellulase system which consists of endoglucanases and β-glucosidases to completely digest amorphous cellulose into glucose. Moreover, BglA was also found to be highly tolerant to glucose as it retained 40 % activity when the concentration of glucose was 100 times higher than that of the substrate, showing potential application in the bioenergy industry.

  2. 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

  3. 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, ...

  4. Nutrient infusion bypassing duodenum-jejunum improves insulin sensitivity in glucose-tolerant and diabetic obese subjects.

    PubMed

    Salinari, Serenella; Carr, Richard D; Guidone, Caterina; Bertuzzi, Alessandro; Cercone, Stefania; Riccioni, Maria E; Manto, Andrea; Ghirlanda, Giovanni; Mingrone, Geltrude

    2013-07-01

    The mechanisms of type 2 diabetes remission after bariatric surgery is still not fully elucidated. In the present study, we tried to simulate the Roux-en-Y gastric bypass with a canonical or longer biliary limb by infusing a liquid formula diet into different intestinal sections. Nutrients (Nutrison Energy) were infused into mid- or proximal jejunum and duodenum during three successive days in 10 diabetic and 10 normal glucose-tolerant subjects. Plasma glucose, insulin, C-peptide, glucagon, incretins, and nonesterified fatty acids (NEFA) were measured before and up to 360 min following. Glucose rate of appearance (Ra) and insulin sensitivity (SI), secretion rate (ISR), and clearance were assessed by mathematical models. SI increased when nutrients were delivered in mid-jejunum vs. duodenum (SI × 10⁴ min⁻¹·pM⁻¹: 1.11 ± 0.44 vs. 0.62 ± 0.22, P < 0.015, in controls and 0.79 ± 0.34 vs. 0.40 ± 0.20, P < 0.05, in diabetic subjects), whereas glucose Ra was not affected. In controls, Sensitivity of NEFA production was doubled in mid-jejunum vs. duodenum (2.80 ± 1.36 vs. 1.13 ± 0.78 × 10⁶, P < 0.005) and insulin clearance increased in mid-jejunum vs. duodenum (2.05 ± 1.05 vs. 1.09 ± 0.38 l/min, P < 0.03). Bypass of duodenum and proximal jejunum by nutrients enhances insulin sensitivity, inhibits lipolysis, and increases insulin clearance. These results may further our knowledge of the effects of bariatric surgery on both insulin resistance and diabetes.

  5. 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

  6. Efficient production of L-lactic acid by newly isolated thermophilic Bacillus coagulans WCP10-4 with high glucose tolerance.

    PubMed

    Zhou, Xingding; Ye, Lidan; Wu, Jin Chuan

    2013-05-01

    A thermophilic Bacillus coagulans WCP10-4 with tolerance to high concentration of glucose was isolated from soil and used to produce optically pure L-lactic acid from glucose and starch. In batch fermentation at pH 6.0, 240 g/L of glucose was completely consumed giving 210 g/L of L-lactic acid with a yield of 95 % and a productivity of 3.5 g/L/h. In simultaneous saccharification and fermentation at 50 °C without sterilizing the medium, 200 g/L of corn starch was completely consumed producing 202.0 g/L of L-lactic acid. To the best of our knowledge, this strain shows the highest osmotic tolerance to glucose among the strains ever reported for lactic acid production. This is the first report of simultaneous saccharification and fermentation of starch for lactic acid production under a non-sterilized condition.

  7. Insulin sensitivity and first-phase insulin secretion in obese Chinese with hyperglycemia in 30 and/or 60 min during glucose tolerance tests.

    PubMed

    Hong, Jie; Zhang, Yi-Fei; Gu, Wei-qiong; Zhang, Yu-wen; Su, Yu-xia; Chi, Zhen-ni; Wang, Wei-qing; Li, Xiao-ying; Ning, Guang

    2008-01-01

    The purpose of this study was to investigate insulin sensitivity and first-phase insulin secretion in obesity with hyperglycemia in 30 and/or 60 min during oral glucose tolerance (OGTT, glucose > or = 11.1 mmol/l, post-loading hyperglycemia, PLH) in Chinese population. A total of 196 nondiabetic subjects were included in the present study, among them 99 had normal glucose tolerance (NGT, subdivided into 32 lean NGT and 67 obese NGT), 74 had obesity with impaired glucose tolerance (IGT) and 23 had obesity with PLH. A standard 75-g oral glucose tolerance test was performed after fasting and at 30 min, 1, 2 and 3 h. Insulin sensitivity index (S(I)) was assessed by the Bergman's minimal model method with frequently sampled intravenous glucose tolerance test (FSIGTT), insulin secretion was determined by acute insulin response to glucose (AIRg). The disposition index (DI), the product of AIRg and S(I) was used to determine whether AIRg was adequate to compensate for insulin resistance. S(I) was significantly equally lower in three obese subgroups. AIRg was significantly increased in obese NGT as compared with lean NGT controls, and reduced to the same extent in IGT and PLH subjects. There was no significant difference among lean NGT, IGT and PLH subjects. DI value was reduced from obese NGT individuals, IGT and PLH subjects had a similar lower level of DI. In conclusion, our present results demonstrated that the pathophysiological basis of obese subjects with PLH were clearly insulin resistance and defective in first-phase insulin secretion as that in IGT subjects in Chinese population.

  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. Concurrent Beet Juice and Carbohydrate Ingestion: Influence on Glucose Tolerance in Obese and Nonobese Adults

    PubMed Central

    Beals, Joseph W.; Binns, Scott E.; Davis, Janelle L.; Giordano, Gregory R.; Klochak, Anna L.; Paris, Hunter L.; Schweder, Melani M.; Peltonen, Garrett L.; Scalzo, Rebecca L.

    2017-01-01

    Insulin resistance and obesity are characterized by low nitric oxide (NO) bioavailability. Insulin sensitivity is improved with stimulation of NO generating pathways. Consumption of dietary nitrate (NO3−) increases NO formation, via NO3− reduction to nitrite (NO2−) by oral bacteria. We hypothesized that acute dietary nitrate (beet juice) ingestion improves insulin sensitivity in obese but not in nonobese adults. 12 nonobese (body mass index: 26.3 ± 0.8 kg/m2 (mean ± SE)) and 10 obese adults (34.0 ± 0.8 kg/m2) ingested beet juice, supplemented with 25 g of glucose (carbohydrate load: 75 g), with and without prior use of antibacterial mouthwash to inhibit NO3− reduction to NO2−. Blood glucose concentrations after beet juice and glucose ingestion were greater in obese compared with nonobese adults at 60 and 90 minutes (P = 0.004). Insulin sensitivity, as represented by the Matsuda Index (where higher values reflect greater insulin sensitivity), was lower in obese compared with nonobese adults (P = 0.009). Antibacterial mouthwash rinsing decreased insulin sensitivity in obese (5.7 ± 0.7 versus 4.9 ± 0.6) but not in nonobese (8.1 ± 1.0 versus 8.9 ± 0.9) adults (P = 0.048). In conclusion, insulin sensitivity was improved in obese but not in nonobese adults following coingestion of beet juice and glucose when oral bacteria nitrate reduction was not inhibited. Obese adults may benefit from ingestion of healthy nitrate-rich foods during meals. PMID:28203456

  12. Evaluation of intragastric vs intraperitoneal glucose tolerance tests in the evaluation of insulin resistance in a rodent model of burn injury and glucagon-like polypeptide-1 treatment.

    PubMed

    Watada, Susumu; Yu, Yong-Ming; Fischman, Alan J; Kurihara, Tomohiro; Shen, Chuan-An; Tompkins, Ronald G; Fagan, Shawn

    2014-01-01

    Evaluation of glucose tolerance in rodent models is usually performed after intraperitroneal administration of glucose (intraperitoneal glucose tolerance test [IPGTT]), whereas in humans the test is performed with oral glucose. Hyperglycemia is a major clinical manifestation of burn injury. Our previous studies using IPGTT have demonstrated burn injury-induced insulin resistance and the beneficial effects of glucagon-like polypeptide-1 (GLP-1) in improving insulin resistance. The goal of the present study is to compare the results of these two procedures under 1) burn injury-induced insulin resistance and 2) GLP-1 treatment after burn. Male CD rats were divided into three groups: sham burn, burn, and burn with GLP-1. Blood glucose and plasma insulin levels were measured during intragastric glucose tolerance test (IGGTT) on day 6 after 40% of full-thickness burn injury. The results were compared with our previous IPGTT. Blood glucose curves for IGGTT and IPGTT showed a similar pattern. However, IGGTT demonstrated a significant lower level of maximal blood glucose when compared with IPGTT. This was accompanied by higher peak insulin levels in sham burn and burn groups. In contrast, peak insulin levels of each burn with GLP-1 group were similar. 1) Both IPGTT and IGGTT demonstrated burn injury-induced insulin resistance and the efficacy of GLP-1 for reducing hyperglycemia after burn injury. 2) The observed differences in the plasma glucose and insulin levels between IGGTT and IPGTT suggest that endogenously produced GLP-1 during the IGGTT may play a role in ameliorating insulin resistance after burn injury.

  13. 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.

  14. Effect of chicory seed extract on glucose tolerance test (GTT) and metabolic profile in early and late stage diabetic rats

    PubMed Central

    2012-01-01

    Background and purpose of the study The goal was to evaluate and compare the effects of aqueous extract of the seeds of chicory, Cichorium intybus L., on glucose tolerance test (GTT) and blood biochemical indices of experimentally-induced hyperglycemic rats. Methods Late stage and early stage of Type 2 diabetes mellitus (T2DM) were induced in rats by streptozotocin (STZ) and a combination of STZ and niacinamide (NIA/STZ), respectively. Within each group, one subgroup received daily i. p. injections of chicory extract (125 mg/kg body weight, for 28 days). Body weight and fasting blood sugar (FBS) were measured weekly. Blood was analyzed for glycosylated hemoglobin (HbA1c) and sera for alanine aminotransferase (ALT), aspartate aminotransferase (AST), nitric oxide (NO), triacylglycerol (TG), total cholesterol (TC), total protein, and insulin on days 10 and 28 after treatment. Intraperitoneal glucose tolerance test (IPGTT) along with insulin determination was performed on a different set of rats in which the chicory-treated groups received the extract for 10 days. Results During 4 weeks of treatment, chicory prevented body-weight loss and decreased FBS. ALT activities and levels of TG, TC and HbA1c decreased, and concentration of NO increased in the chicory treated groups (p < 0.05). Unlike late-stage diabetes, fasting serum insulin concentrations were higher and GTT pattern approximated to normal in chicory-treated early-stage diabetic rats. Conclusions Chicory appeared to have short-term (about 2 hours, as far as GTT is concerned) and long-term (28 days, in this study) effects on diabetes. Chicory may be useful as a natural dietary supplement for slowing down the pace of diabetes progress, and delaying the development of its complications. PMID:23352214

  15. A novel animal model of impaired glucose tolerance induced by the interaction of vitamin E deficiency and (60)Co radiation.

    PubMed

    Guan, Yue; Cheng, Yan; Yin, Ying; Duan, Jialin; Wei, Guo; Weng, Yan; Guo, Chao; Zhu, Yanrong; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2015-01-01

    Impaired glucose tolerance (IGT), known as the prediabetes stage, is usually induced by habits of life or environmental factors. Established IGT animal models are mostly conducted with chemical compounds such as streptozocin or genetic modification. However, the occasion of exposure to these factors in daily life is seldom. The objective of this study was to establish a new animal model of IGT induced by VE deficiency in diet and exposure to radiation. SD rats were treated individually or in combination of these two factors. In the combination group, the calculated insulin sensitivity index decreased; then HOMA-β value increased. Oxidative damage and IGT were observed. Insulin secretion level in perfusate from pancreas response to glucose was characterized by a rapid but reduced first phase and an obviously defective second phase upon pancreas perfusion. Histopathological images demonstrated the pathological changes. Western blotting analysis showed that the insulin signaling pathway was downregulated. The interaction of VE deficiency in diet and exposure to radiation could break the equilibrium of oxidation and antioxidation and result in IGT. More importantly, a new IGT model was successfully established which may be conducive to further research into development of drugs against human IGT.

  16. A Novel Animal Model of Impaired Glucose Tolerance Induced by the Interaction of Vitamin E Deficiency and 60Co Radiation

    PubMed Central

    Guan, Yue; Cheng, Yan; Yin, Ying; Duan, Jialin; Wei, Guo; Weng, Yan; Guo, Chao; Zhu, Yanrong; Wang, Yanhua; Xi, Miaomiao; Wen, Aidong

    2015-01-01

    Impaired glucose tolerance (IGT), known as the prediabetes stage, is usually induced by habits of life or environmental factors. Established IGT animal models are mostly conducted with chemical compounds such as streptozocin or genetic modification. However, the occasion of exposure to these factors in daily life is seldom. The objective of this study was to establish a new animal model of IGT induced by VE deficiency in diet and exposure to radiation. SD rats were treated individually or in combination of these two factors. In the combination group, the calculated insulin sensitivity index decreased; then HOMA-β value increased. Oxidative damage and IGT were observed. Insulin secretion level in perfusate from pancreas response to glucose was characterized by a rapid but reduced first phase and an obviously defective second phase upon pancreas perfusion. Histopathological images demonstrated the pathological changes. Western blotting analysis showed that the insulin signaling pathway was downregulated. The interaction of VE deficiency in diet and exposure to radiation could break the equilibrium of oxidation and antioxidation and result in IGT. More importantly, a new IGT model was successfully established which may be conducive to further research into development of drugs against human IGT. PMID:25954750

  17. Kinin B1 Receptor in Adipocytes Regulates Glucose Tolerance and Predisposition to Obesity

    PubMed Central

    Motta, Fabiana Louise; Fonseca, Raphael Gomes; Alenina, Natalia; Guadagnini, Dioze; Schadock, Ines; Silva, Elton Dias; Torres, Hugo A. M.; dos Santos, Edson Lucas; Castro, Charlles Heldan; D’Almeida, Vânia; Andreotti, Sandra; Campaña, Amanda Baron; Sertié, Rogério A. L.; Saad, Mario J. A.; Lima, Fabio Bessa; Bader, Michael; Pesquero, João Bosco

    2012-01-01

    Background Kinins participate in the pathophysiology of obesity and type 2 diabetes by mechanisms which are not fully understood. Kinin B1 receptor knockout mice (B1−/−) are leaner and exhibit improved insulin sensitivity. Methodology/Principal Findings Here we show that kinin B1 receptors in adipocytes play a role in controlling whole body insulin action and glucose homeostasis. Adipocytes isolated from mouse white adipose tissue (WAT) constitutively express kinin B1 receptors. In these cells, treatment with the B1 receptor agonist des-Arg9-bradykinin improved insulin signaling, GLUT4 translocation, and glucose uptake. Adipocytes from B1−/− mice showed reduced GLUT4 expression and impaired glucose uptake at both basal and insulin-stimulated states. To investigate the consequences of these phenomena to whole body metabolism, we generated mice where the expression of the kinin B1 receptor was limited to cells of the adipose tissue (aP2-B1/B1−/−). Similarly to B1−/− mice, aP2-B1/B1−/− mice were leaner than wild type controls. However, exclusive expression of the kinin B1 receptor in adipose tissue completely rescued the improved systemic insulin sensitivity phenotype of B1−/− mice. Adipose tissue gene expression analysis also revealed that genes involved in insulin signaling were significantly affected by the presence of the kinin B1 receptor in adipose tissue. In agreement, GLUT4 expression and glucose uptake were increased in fat tissue of aP2-B1/B1−/− when compared to B1−/− mice. When subjected to high fat diet, aP2-B1/B1−/− mice gained more weight than B1−/− littermates, becoming as obese as the wild types. Conclusions/Significance Thus, kinin B1 receptor participates in the modulation of insulin action in adipocytes, contributing to systemic insulin sensitivity and predisposition to obesity. PMID:23024762

  18. 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

  19. Meal feeding improves oral glucose tolerance in male rats and causes adaptations in postprandial islet hormone secretion that are independent of plasma incretins or glycemia

    PubMed Central

    P., Torsten; Aulinger, Benedikt A.; Smith, Eric P.; Drazen, Deborah L.; Ulrich-Lai, Yve; Seeley, Randy J.; Woods, Stephen C.

    2014-01-01

    Meal-fed (MF) rats with access to food for only 4 consecutive hours during the light cycle learn to eat large meals to maintain energy balance. MF animals develop behavioral and endocrine changes that permit glucose tolerance despite increased meal size. We hypothesized that enhanced activity of the enteroinsular axis mediates glucose homeostasis during MF. Cohorts of rats were allocated to MF or ad libitum (AL) regimens for 2–4 wk. Insulin secretion and glucose tolerance were determined after oral carbohydrate and intraperitoneal (ip) and intravenous (iv) glucose. MF rats ate less than AL in the first week but maintained a comparable weight trajectory thereafter. MF rats had decreased glucose excursions after a liquid mixed meal (AUC: MF 75 ± 7, AL 461 ± 28 mmol·l−1·min, P < 0.001), with left-shifted insulin secretion (AUC0–15: MF 31.0 ± 4.9, AL 9.6 ± 4.4 pM·min, P < 0.02), which peaked before a significant rise in blood glucose. Both groups had comparable fasting glucagon levels, but postprandial responses were lower with MF. However, neither intestinal expression of proGIP and proglucagon mRNA nor plasma incretin levels differed between MF and AL groups. There were no differences in the insulin response to ip or iv glucose between MF and AL rats. These findings demonstrate that MF improves oral glucose tolerance and is associated with significant changes in postprandial islet hormone secretion. Because MF enhanced β-cell function during oral but not parenteral carbohydrate administration, and was not accounted for by changes in circulating incretins, these results support a neural mechanism of adaptive insulin secretion. PMID:25159330

  20. Deficiency of FcϵR1 Increases Body Weight Gain but Improves Glucose Tolerance in Diet-Induced Obese Mice.

    PubMed

    Lee, Yun-Jung; Liu, Conglin; Liao, Mengyang; Sukhova, Galina K; Shirakawa, Jun; Abdennour, Meriem; Iamarene, Karine; Andre, Sebastien; Inouye, Karen; Clement, Karine; Kulkarni, Rohit N; Banks, Alexander S; Libby, Peter; Shi, Guo-Ping

    2015-11-01

    Prior studies demonstrated increased plasma IgE in diabetic patients, but the direct participation of IgE in diabetes or obesity remains unknown. This study found that plasma IgE levels correlated inversely with body weight, body mass index, and body fat mass among a population of randomly selected obese women. IgE receptor FcϵR1-deficient (Fcer1a(-/-)) mice and diet-induced obesity (DIO) mice demonstrated that FcϵR1 deficiency in DIO mice increased food intake, reduced energy expenditure, and increased body weight gain but improved glucose tolerance and glucose-induced insulin secretion. White adipose tissue from Fcer1a(-/-) mice showed an increased expression of phospho-AKT, CCAAT/enhancer binding protein-α, peroxisome proliferator-activated receptor-γ, glucose transporter-4 (Glut4), and B-cell lymphoma 2 (Bcl2) but reduced uncoupling protein 1 (UCP1) and phosphorylated c-Jun N-terminal kinase (JNK) expression, tissue macrophage accumulation, and apoptosis, suggesting that IgE reduces adipogenesis and glucose uptake but induces energy expenditure, adipocyte apoptosis, and white adipose tissue inflammation. In 3T3-L1 cells, IgE inhibited the expression of CCAAT/enhancer binding protein-α and peroxisome proliferator-activated receptor-γ, and preadipocyte adipogenesis and induced adipocyte apoptosis. IgE reduced the 3T3-L1 cell expression of Glut4, phospho-AKT, and glucose uptake, which concurred with improved glucose tolerance in Fcer1a(-/-) mice. This study established two novel pathways of IgE in reducing body weight gain in DIO mice by suppressing adipogenesis and inducing adipocyte apoptosis while worsening glucose tolerance by reducing Glut4 expression, glucose uptake, and insulin secretion.

  1. Tolerance to glucose polymers in malnourished infants with diarrhea and disaccharide intolerance.

    PubMed

    Fagundes-Neto, U; Viaro, T; Lifshitz, F

    1985-02-01

    The response of infants with diarrhea and lactose intolerance to feedings containing soy protein and sucrose (Sobee), and/or to a carbohydrate free formula (RCF), to which glucose polymers (GP) were added, was assessed in twenty patients. They all were less than ten months of age and had varying degrees of malnutrition. Eleven had acute diarrhea and nine had chronic diarrhea. None of them had classical enteropathogenic strains and parasites in the stools. All had lactose intolerance when feedings were begun with cow's milk formula and some also had sucrose intolerance when fed sucrose containing soy formulas. They had persistent loose stools and excreted feces with an acid pH and with carbohydrates, thus they were given dietary treatment with RCF with GP. There were 9 patients with acute diarrhea and lactose intolerance (1 of them also had sucrose intolerance), who improved on RCF with GP feedings; but 2 patients (lactose and sucrose intolerant) failed to respond to this diet. There were six patients with chronic diarrhea and lactose intolerance (four of them also had sucrose intolerance), who improved on RCF with GP formula, but there were three patients who failed on this treatment. These data show that some infants with diarrhea, malnutrition, and lactose-sucrose intolerance may also develop intolerance to GP and require further dietary management with glucose as the source of carbohydrate in the diet.

  2. Effects of olanzapine and ziprasidone on glucose tolerance in healthy volunteers.

    PubMed

    Sacher, Julia; Mossaheb, Nilufar; Spindelegger, Christoph; Klein, Nikolas; Geiss-Granadia, Thomas; Sauermann, Robert; Lackner, Edith; Joukhadar, Christian; Müller, Markus; Kasper, Siegfried

    2008-06-01

    Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n = 14) or ziprasidone 80 mg/day (n = 15) for 10 days. A significant decrease (p<0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( = mean, SM = 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( = mean, SM = 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2+/-0.3 ml/h/kg baseline vs 5.1+/-0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

  3. [Evaluation of oral glucose tolerance test in the assessment of reserved function of liver for patients with hepatocellular carcinoma].

    PubMed

    Wen, T; Zheng, G; Meng, X; Chen, L

    1997-06-01

    The aim of this study was to evaluate oral glucose tolerance test(OGTT)in the assessment of reserved function of liver for predicting the tolerability of patients to hepatectomy and hence provided a criteria for selecting the candidates for undergoing hepatectomy, since the majority of hepatocellular carcinoma (HCC) patients were associated with posthepatitis cirrhosis. The preoperative and postoperative OGTT and liver biopsy for pathological investigation were carried out in 62 cases of hepatecomized patients and 49 cases of unresected patients for comparison. The results revealed that the patients whose preoperative OGTT curve was of P type recovered uneventfully after hepatectomy, but those whose curve was of L type of tolerated poorly to hepatectomy and were liable to postoperative hepatic failure and complications. The severity of cirrbosis in those poor risk patients fell to C III or C IV histological degree. 29 patients with intermediate feature of OGTT curve between P type and L type, i.e. I type underwent regional vascular occlusion at hepatic hilus as hepatectomy, and infusion of Danshen extract solution before vascular occlusion to prevent hepatocytes from reperfusion injury. Of them, 20 recovered uneventfully, 8 suffered from complications such as ascites and/or juandice, and 1 died within 1 month after operation. The followup study showed that the survival time of patients with P type OGTT curve was longer than that of I type, and the latter was longer than that of L type. The pattern of OGTT curve could change from preoperative P type to postoperative L type, depending on the severity of vascular interruption of liver and the ischemic injury to hepatocytic mass in operation.

  4. Self-reported fast eating is a potent predictor of development of impaired glucose tolerance in Japanese men and women: Tsukuba Medical Center Study.

    PubMed

    Totsuka, Kumiko; Maeno, Takami; Saito, Kazumi; Kodama, Satoru; Asumi, Mihoko; Yachi, Yoko; Hiranuma, Yuri; Shimano, Hitoshi; Yamada, Nobuhiro; Ono, Yukio; Naito, Takashi; Sone, Hirohito

    2011-12-01

    We recorded self-reported eating patterns in 172 Japanese men and women who were subsequently followed for 3 years for the occurrence of impaired glucose tolerance (IGT). Incidence of IGT was significantly higher in those who reported eating fast. Self-reported eating fast is a potent risk factor for development of IGT.

  5. Abnormal Glucose Tolerance, White Blood Cell Count, and Telomere Length in Newly Diagnosed, Antidepressant-Naïve Patients with Depression

    PubMed Central

    Garcia-Rizo, Clemente; Fernandez-Egea, Emilio; Miller, Brian J.; Oliveira, Cristina; Justicia, Azucena; Griffith, Jeffrey K.; Heaphy, Christopher M.; Bernardo, Miguel; Kirkpatrick, Brian

    2012-01-01

    Chronic mood disorders have been associated with a shortened telomere, a marker of increased mortality rate and ageing, and impaired cellular immunity. However, treatment may confound these relationships. We examined the relationship of glucose tolerance, white blood cell count and telomere length to depression in newly diagnosed, antidepressant-naïve patients. Subjects with major depression (n=15), and matched healthy control subjects (n=70) underwent a two-hour oral glucose tolerance test and evaluation of blood cell count and telomere content. The depression group had significantly higher two-hour glucose concentrations and a lower lymphocyte count than control subjects (respective means [SD] for two-hour glucose were 125.0 mg/dL [67.9] vs 84.6 [25.6] (p<.001); for lymphocyte count 2.1 × 109/L [0.6] vs. 2.5 ×109/L [0.7] p=.028).Telomere content was significantly shortened in the depression group (87.9 [7.6]) compared to control subjects (101.0 [14.3]; p<0.01). Abnormal glucose tolerance, lymphopenia and a shortened telomere are present early in the course of depression independently of the confounding effect of antidepressant treatment, supporting the concept of major depression as an accelerated ageing disease. PMID:23207109

  6. Manipulation of the gut microbiota in C57BL/6 mice changes glucose tolerance without affecting weight development and gut mucosal immunity.

    PubMed

    Bech-Nielsen, Gunilla Veslemøy; Hansen, Camilla Hartmann Friis; Hufeldt, Majbritt Ravn; Nielsen, Dennis Sandris; Aasted, Bent; Vogensen, Finn Kvist; Midtvedt, Tore; Hansen, Axel Kornerup

    2012-06-01

    Inflammatory diseases such as type 2 diabetes (T2D) in humans and mice are under the influence of the composition of the gut microbiota (GM). It was previously demonstrated that treating Lep(ob) mice with antibiotics improved glucose tolerance. However, wild type C57BL/6J mice may also exhibit plasma glucose intolerance reminiscent of human T2D. We hypothesized that antibiotic treatment in C57BL/6 mice would have an impact on glucose tolerance without affecting weight and gut immunology. When compared to mice treated with erythromycin or the controls, treatment for five weeks with ampicillin improved glucose tolerance without significantly affecting the weight or the number of gut mucosal regulatory T cells, tolerogenic dendritic cells or T helper cells type 1. 16S rRNA gene based denaturing gradient gel electrophoresis profiles clearly clustered according to treatment and showed that antibiotic treatment reduced GM diversity. It is concluded that antibiotic treatment changes glucose metabolism as well as the composition of the GM in C57BL/6 mice, and that this does not seem to be correlated to weight development in the mice.

  7. 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.

  8. Glucose Tolerance, MTHFR C677T and NOS3 G894T Polymorphisms, and Global DNA Methylation in Mixed Ancestry African Individuals

    PubMed Central

    Mutize, Tinashe; Erasmus, Rajiv T.

    2016-01-01

    The aim of this study is to quantify global DNA methylation and investigate the relationship with diabetes status and polymorphisms in MTHFR C677T and NOS3 G894T genes in mixed ancestry subjects from South Africa. Global DNA methylation was measured, and MTHFR rs1801133 and NOS3 rs1799983 polymorphisms were genotyped using high throughput real-time polymerase chain reaction and direct DNA sequencing. Of the 564 participants, 158 (28%) individuals had T2DM of which 97 (17.2%) were screen-detected cases. Another 119 (21.1%) had prediabetes, that is, impaired fasting glucose, impaired glucose tolerance, or the combination of both, and the remainder 287 (50.9%) had normal glucose tolerance. Global DNA methylation was significantly higher in prediabetes and screen-detected diabetes than in normal glucose tolerance (both p ≤ 0.033) and in screen-detected diabetes compared to known diabetes on treatment (p = 0.019). There was no difference in global DNA methylation between known diabetes on treatment and normal glucose tolerance (p > 0.999). In multivariable linear regression analysis, only NOS3 was associated with increasing global DNA methylation (β = 0.943; 95% CI: 0.286 to 1.560). The association of global DNA methylation with screen-detected diabetes but not treated diabetes suggests that glucose control agents to some extent may be reversing DNA methylation. The association between NOS3 rs1799983 polymorphisms and DNA methylation suggests gene-epigenetic mechanisms through which vascular diabetes complications develop despite adequate metabolic control. PMID:27990443

  9. Lower maternal body condition during pregnancy affects skeletal muscle structure and glut-4 protein levels but not glucose tolerance in mature adult sheep.

    PubMed

    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; Green, Lucy R

    2013-10-01

    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/mm(2), P < .05) and fast myofiber density (HBCS, 226 ± 10; LBCS 194 ± 10 fibers/mm(2), 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.

  10. Delphinidin-Rich Maqui Berry Extract (Delphinol®) Lowers Fasting and Postprandial Glycemia and Insulinemia in Prediabetic Individuals during Oral Glucose Tolerance Tests

    PubMed Central

    Alvarado, Jorge L.; Salgado, Ana-María; Lyon, Carolina; Vigil, Pilar

    2016-01-01

    Delphinidin anthocyanins have previously been associated with the inhibition of glucose absorption. Blood glucose lowering effects have been ascribed to maqui berry (Aristotelia chilensis) extracts in humans after boiled rice consumption. In this study, we aimed to explore whether a standardized delphinidin-rich extract from maqui berry (Delphinol) affects glucose metabolism in prediabetic humans based on glycemia and insulinemia curves obtained from an oral glucose tolerance test (OGTT) after a challenge with pure glucose. Volunteers underwent four consecutive OGTTs with at least one week washout period, in which different doses of Delphinol were administered one hour before glucose intake. Delphinol significantly and dose-dependently lowered basal glycemia and insulinemia. Lower doses delayed postprandial glycemic and insulinemic peaks, while higher doses reversed this tendency. Glycemia peaks were dose-dependently lowered, while insulinemia peaks were higher for the lowest dose and lower for other doses. The total glucose available in blood was unaffected by treatments, while the total insulin availability was increased by low doses and decreased by the highest dose. Taken together, these open exploratory results suggest that Delphinol could be acting through three possible mechanisms: by inhibition of intestinal glucose transporters, by an incretin-mediated effect, or by improving insulin sensitivity. PMID:28025651

  11. Oleanolic acid, a natural triterpenoid improves blood glucose tolerance in normal mice and ameliorates visceral obesity in mice fed a high-fat diet.

    PubMed

    de Melo, Célio L; Queiroz, Maria Goretti R; Fonseca, Said G C; Bizerra, Ayla M C; Lemos, Telma L G; Melo, Tiago S; Santos, Flavia A; Rao, Vietla S

    2010-04-15

    Excess visceral adiposity may predispose to chronic diseases like hypertension and type 2 diabetes with a high risk for coronary artery disease. Adipose tissue secreted cytokines and oxidative stress play an important role in chronic disease progression. To combat adiposity, plant-derived triterpenes are currently receiving much attention as they possess antioxidant and anti-inflammatory properties and the ability to regulate glucose and lipid metabolism. In the search for potential antiobese compounds from natural sources, this study evaluated the effects of oleanolic acid (OA), a pentacyclic triterpene commonly present in fruits and vegetables, in glucose tolerance test and on high-fat diet (HFD)-induced obesity in mice. Adult male Swiss mice treated or not with OA (10 mg/kg) were fed a HFD during 15 weeks. Sibutramine (SIB) treated group (10 mg/kg) was included for comparison. Weekly body weights, food and water consumption were measured, and at the end of study period, the levels of blood glucose and lipids, plasma hormone levels of insulin, ghrelin and leptin, and the visceral abdominal fat content were analysed. Mice treated with OA and fed a HFD showed significantly (p<0.05) improved glucose tolerance, decreased body weights, visceral adiposity, blood glucose, plasma lipids relative to their respective controls fed no OA. Additionally, OA treatment, while significantly elevating the plasma hormone level of leptin, decreased the level of ghrelin. However, it caused a greater decrease in plasma amylase activity than lipase. Sibutramine-treated group also manifested similar effects like OA except for blood glucose level that was not different from HFD control. These findings suggest that OA ameliorates visceral adiposity and improves glucose tolerance in mice and thus has an antiobese potential through modulation of carbohydrate and fat metabolism.

  12. Identification of the mechanism of action of a glucokinase activator from oral glucose tolerance test data in type 2 diabetic patients based on an integrated glucose-insulin model.

    PubMed

    Jauslin, Petra M; Karlsson, Mats O; Frey, Nicolas

    2012-12-01

    A mechanistic drug-disease model was developed on the basis of a previously published integrated glucose-insulin model by Jauslin et al. A glucokinase activator was used as a test compound to evaluate the model's ability to identify a drug's mechanism of action and estimate its effects on glucose and insulin profiles following oral glucose tolerance tests. A kinetic-pharmacodynamic approach was chosen to describe the drug's pharmacodynamic effects in a dose-response-time model. Four possible mechanisms of action of antidiabetic drugs were evaluated, and the corresponding affected model parameters were identified: insulin secretion, glucose production, insulin effect on glucose elimination, and insulin-independent glucose elimination. Inclusion of drug effects in the model at these sites of action was first tested one-by-one and then in combination. The results demonstrate the ability of this model to identify the dual mechanism of action of a glucokinase activator and describe and predict its effects: Estimating a stimulating drug effect on insulin secretion and an inhibiting effect on glucose output resulted in a significantly better model fit than any other combination of effect sites. The model may be used for dose finding in early clinical drug development and for gaining more insight into a drug candidate's mechanism of action.

  13. Sustained sleep fragmentation affects brain temperature, food intake and glucose tolerance in mice.

    PubMed

    Baud, Maxime O; Magistretti, Pierre J; Petit, Jean-Marie

    2013-02-01

    Sleep fragmentation is present in numerous sleep pathologies and constitutes a major feature of patients with obstructive sleep apnea. A prevalence of metabolic syndrome, diabetes and obesity has been shown to be associated to obstructive sleep apnea. While sleep fragmentation has been shown to impact sleep homeostasis, its specific effects on metabolic variables are only beginning to emerge. In this context, it is important to develop realistic animal models that would account for chronic metabolic effects of sleep fragmentation. We developed a 14-day model of instrumental sleep fragmentation in mice, and show an impact on both brain-specific and general metabolism. We first report that sleep fragmentation increases food intake without affecting body weight. This imbalance was accompanied by the inability to adequately decrease brain temperature during fragmented sleep. In addition, we report that sleep-fragmented mice develop glucose intolerance. We also observe that sleep fragmentation slightly increases the circadian peak level of glucocorticoids, a factor that may be involved in the observed metabolic effects. Our results confirm that poor-quality sleep with sustained sleep fragmentation has similar effects on general metabolism as actual sleep loss. Altogether, these results strongly suggest that sleep fragmentation is an aggravating factor for the development of metabolic dysfunctions that may be relevant for sleep disorders such as obstructive sleep apnea.

  14. 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 ...

  15. Autoreactive human T-cell receptor initiates insulitis and impaired glucose tolerance in HLA DR4 transgenic mice.

    PubMed

    Gebe, John A; Unrath, Kellee A; Yue, Betty B; Miyake, Tom; Falk, Ben A; Nepom, Gerald T

    2008-06-01

    A human T-cell receptor (TcR) derived from an autoreactive T-cell specific for GAD65, from a subject at high risk for autoimmune diabetes, was introduced into HLA-DR4 transgenic mice. The source of TcR was a CD4(+) T(H)1(+) T-cell clone which responded to an immunodominant epitope of the human islet protein GAD65, an epitope shared with both GAD65 and GAD67 in the mouse. The resulting HLA-DR4/GAD-TcR transgenic mice on a Rag2(o/o)/I-Ab(o/o)/B6 background exhibited a CD4(+) infiltrate into pancreatic islets that correlated with a loss of insulin in infiltrated islets. These mice also exhibited a subclinical impaired tolerance to exogenously fed glucose as assayed by an intraperitoneal glucose tolerance test. T cells containing the GAD65/67 (555-567) responsive TcR undergo strong negative selection as evidenced by a 10-fold lower thymocyte cellularity compared to non-TcR transgenic mice, and clonotype peripheral T cells represented approximately 1% of CD4(+) T cells in Rag2 sufficient mice. Upon in vitro stimulation, GAD65/67 555-567 responsive T cells secrete interferon-gamma, minimal interleukin (IL)-2 and tumor necrosis factor-alpha, and no IL-4, IL-5, IL-10, or IL-17, consistent with a T(H)1 profile. These data demonstrate that CD4(+) T cells specific for a naturally processed epitope within GAD can specifically home to pancreatic islets and lead to impaired islet beta-cell function in diabetes-associated HLA-DR4 transgenic mice on the relatively non-autoimmune C57BL/6 background. The relatively slow progression and patchy insulitis are reminiscent of the chronic pre-clinical phase similar to a majority of human at-risk subjects, and models these indolent features of human T1D.

  16. 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.

  17. A cross-over study of the acute effects of espresso coffee on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus.

    PubMed

    Krebs, Jeremy D; Parry-Strong, Amber; Weatherall, Mark; Carroll, Richard W; Downie, Michelle

    2012-09-01

    The objective was to determine the effect of a single dose of espresso caffeinated coffee, decaffeinated coffee, or water on glucose tolerance and insulin sensitivity in people with type 2 diabetes mellitus. Eighteen participants who were habitual coffee drinkers, were studied using a random-order cross-over design. After a fasting blood sample participants consumed either a double-shot black espresso coffee, decaffeinated coffee, or hot water. The main outcomes were area under the curve (AUC) glucose and insulin, and insulin sensitivity (Matsuda index) during a 75 g oral glucose tolerance test (OGTT) performed one hour later. Other outcomes were change in glucose and insulin and also the insulinogenic index (IGI) and disposition index (DI). AUC glucose was marginally different between beverages (P=.06) being greater following caffeinated coffee than water, mean difference 104 mmol/L/180 min (95% CI 0.1 to 198.1, P=.031), or decaffeinated coffee, mean difference 92.1 mmol/L/180 min (95% CI -1.9 to 186.1, P=.055). There was no difference in AUC insulin (P=.87) or insulin sensitivity (P=.47), nor in change in glucose or insulin over the hour following beverage consumption. There was a marginal difference in IGI between beverages (P=.097) with coffee having a lower incremental increase in insulin/glucose than water (P=.037) though no difference between coffee and decaffeinated coffee (P=.54) and no difference in DI (P=.23). Black espresso coffee in people with type 2 diabetes mellitus results in a marginally greater excursion of glucose during a following OGTT compared with water or decaffeinated coffee. This effect does not appear to be mediated by changes in insulin sensitivity.

  18. Longitudinal hair chromium profiles of elderly subjects with normal glucose tolerance and type 2 diabetes mellitus.

    PubMed

    Stupar, Janez; Vrtovec, Matjaz; Dolinsek, Franci

    2007-01-01

    Longitudinal hair chromium (H-Cr) profiles in a group of patients with type 2 diabetes mellitus (n = 59; age, 62 +/- 9 years) and healthy elderly (control) subjects (n = 49; age, 59 +/- 10 years) matched by age and sex were measured by solid sampling electrothermal atomic absorption spectrometry, providing data on the magnitude of variation of Cr content along the hair length. H-Cr average (H-Cr(av)) and H-Cr proximal (H-Cr(pr))(.), relating to the average Cr content of the whole hair and the proximal 3-mm hair length, respectively, were also obtained. No significant difference between the healthy and diabetic group was found in mean H-Cr(av) or H-Cr(pr) contents (248 +/- 108 vs 247 +/- 143 and 233 +/- 98 vs 278 +/- 195 ng/g, respectively. However, women in the control group had significantly lower H-Cr values (P < .01) compared with men, but this difference was absent in the diabetic population. The distribution of log H-Cr(pr) values in the control population displayed a Gaussian shape, in contrast to the substantially wider distribution, skewed toward lower H-Cr(pr) values, observed in the diabetic group. The magnitude of variation in H-Cr content in the patient group over an interval of approximately 2 to 3 months (time of growth of the hair sampled) was found to be a factor of more than 2 larger than that in the control population (+/- 58% vs +/- 26%). A strong relationship (R = 0.656; P < .01) between log H-Cr(pr) and log fasting plasma Cr was observed in the diabetic group (n = 20). The mean fasting plasma Cr value of this group was 0.41 +/- 0.10 microg Cr per liter. No correlation between H-Cr(av.) and duration of diabetes was observed. A strong positive association was observed in the control population between H-Cr(pr) and fasting plasma insulin (n = 22; R = 0.6157; P < .01), and H-Cr(pr) and fasting plasma glucose (n = 24; R = 0.4118; P < .05), which is indicative of the interrelation of these parameters. In the control population, H-Cr(av) showed a

  19. 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.

  20. Skeletal muscle insulin resistance in zebrafish induces alterations in β-cell number and glucose tolerance in an age- and diet-dependent manner.

    PubMed

    Maddison, Lisette A; Joest, Kaitlin E; Kammeyer, Ryan M; Chen, Wenbiao

    2015-04-15

    Insulin resistance creates an environment that promotes β-cell failure and development of diabetes. Understanding the events that lead from insulin resistance to diabetes is necessary for development of effective preventional and interventional strategies, and model systems that reflect the pathophysiology of disease progression are an important component toward this end. We have confirmed that insulin enhances glucose uptake in zebrafish skeletal muscle and have developed a zebrafish model of skeletal muscle insulin resistance using a dominant-negative IGF-IR. These zebrafish exhibit blunted insulin signaling and glucose uptake in the skeletal muscle, confirming insulin resistance. In young animals, we observed an increase in the number of β-cells and normal glucose tolerance that was indicative of compensation for insulin resistance. In older animals, the β-cell mass was reduced to that of control with the appearance of impaired glucose clearance but no elevation in fasting blood glucose. Combined with overnutrition, the insulin-resistant animals have an increased fasting blood glucose compared with the control animals, demonstrating that the β-cells in the insulin-resistant fish are in a vulnerable state. The relatively slow progression from insulin resistance to glucose intolerance in this model system has the potential in the future to test cooperating genes or metabolic conditions that may accelerate the development of diabetes and provide new therapeutic targets.

  1. 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.

  2. Angiotensin-converting enzyme inhibition reduces food intake and weight gain and improves glucose tolerance in melanocortin-4 receptor deficient female rats.

    PubMed

    Mul, Joram D; Seeley, Randy J; Woods, Stephen C; Begg, Denovan P

    2013-09-10

    Functional loss of melanocortin-4 receptor (MC4R) activity leads to hyperphagia and an obese, glucose intolerant phenotype. We have previously established that inhibition of angiotensin-converting enzyme (ACE) reduces food intake, body weight and glucose homeostasis in diet-induced obesity. The current study assessed the effect of ACE inhibitor treatment in MC4R-deficient female rats on body weight, adiposity and glucose tolerance. Rats homozygous (HOM) for a loss of function Mc4r mutation had an obese phenotype relative to their wildtype (WT) littermates. Inhibition of ACE for 8weeks produced reductions in body weight gain in both HOM and WT rats; however, food intake was only reduced in HOM rats. Weight loss following ACE inhibitor treatment was specific to fat mass while lean mass was unaffected. HOM rats were severely glucose intolerant and insensitive to exogenous insulin injection, and treatment with an ACE inhibitor improved both glucose tolerance and insulin sensitivity in HOM rats although not fully to that of the level of WT rats. The current study indicates that HOM rats are sensitive to the anorectic effects of ACE inhibition, unlike their WT littermates. This resulted in a more rapid reduction in body weight gain and a more substantial loss of adipose mass in HOM animals, relative to WT animals, treated with an ACE inhibitor. Overall, these data demonstrate that MC4R signaling is not required for weight loss following treatment with an ACE inhibitor.

  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. 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

  5. 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.

  6. Framingham risk score in impaired glucose tolerant population: A sub analysis of Diabetes Prevention and Awareness Program of Pakistan

    PubMed Central

    Fawwad, Asher; Moin, Hassan; Siddiqui, Iftikhar Ahmed; Hydrie, Muhammad Zafar Iqbal; Basit, Abdul

    2016-01-01

    Objective: To assess the 10-year risk of coronary artery disease (CAD) in subjects with impaired glucose tolerance (IGT) using Framingham risk score. Methods: Data for this study was collected from Diabetes Prevention and Awareness Program. Primary prevention team visited different primary health care centers, factories, service organizations and offices within Karachi, Pakistan. IGT was diagnosed according to World Health Organization criteria after taking informed consent. Information regarding social-demography, dietary habits and physical activities were obtained by a designed questionnaire on one-to-one based interview. Framingham risk score (FRS) was used to assess risk of developing CAD. Results: A total of 315 subjects with IGT were recruited for the study. Mean age of subjects was 44.1 ± 9.8 years and mean BMI was 27.3 ± 5.0 kg/m2. Overall, 31.4% of the participants were at risk of having CAD. Males were 6.4 times and hypertensive subjects were 2.44 times more likely to have CAD in next 10 years. Conclusion: According to the findings of the study, male and hypertensive IGT subjects were more likely to develop CAD in next 10 years. Community based awareness programs are needed to educate people regarding healthy lifestyle in order to reduce the risk of IGT and CAD. PMID:27882006

  7. 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.

  8. The interleukin-1 receptor antagonist anakinra improves first-phase insulin secretion and insulinogenic index in subjects with impaired glucose tolerance.

    PubMed

    van Poppel, P C M; van Asseldonk, E J P; Holst, J J; Vilsbøll, T; Netea, M G; Tack, C J

    2014-12-01

    Inflammation at the level of the β cell appears to be involved in progressive β-cell dysfunction in type 2 diabetes. We assessed the effect of blocking interleukin-1 (IL-1) by anakinra [recombinant human interleukin-1 receptor antagonist (IL-1Ra)] on β-cell function. Sixteen participants with impaired glucose tolerance were treated with 150 mg anakinra daily for 4 weeks in a double blind, randomized, placebo-controlled cross-over study with a wash-out period of 4 weeks. At the end of each treatment period, oral glucose tolerance tests (OGTTs) and hyperglycaemic clamps were performed. First-phase insulin secretion improved after anakinra treatment compared with placebo, 148 ± 20 versus 123 ± 14 mU/l, respectively (p = 0.03), and the insulinogenic index was higher after anakinra treatment. These results support the concept of involvement of IL-1β in the (progressive) decrease of insulin secretion capacity associated with type 2 diabetes.

  9. 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

    2011-02-04

    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.

  10. All-cause cancer mortality over 15 years in multi-ethnic Mauritius: the impact of diabetes and intermediate forms of glucose tolerance.

    PubMed

    Harding, Jessica L; Soderberg, Stefan; Shaw, Jonathan E; Zimmet, Paul Z; Pauvaday, Vassen; Kowlessur, Sudhir; Tuomilehto, Jaakko; Alberti, K George M M; J Magliano, Dianna

    2012-11-15

    There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi-ethnic cohort from the developing nation of Mauritius. Population-based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h-PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00-7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98-2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

  11. Effect of Progression From Impaired Glucose Tolerance to Diabetes on Cardiovascular Risk Factors and Its Amelioration by Lifestyle and Metformin Intervention

    PubMed Central

    Goldberg, Ronald B.; Temprosa, Marinella; Haffner, Steven; Orchard, Trevor J.; Ratner, Robert E.; Fowler, Sarah E.; Mather, Kieren; Marcovina, Santica; Saudek, Chris; Matulik, Margaret J.; Price, David

    2009-01-01

    OBJECTIVE Although subjects with diabetes have increased risk for cardiovascular disease (CVD), the evolution of this increased risk as pre-diabetic individuals progress to diabetes is not understood. This study examines the longitudinal relationship between selected CVD risk factors (blood pressure, triglycerides, HDL and LDL cholesterol, and LDL peak particle density [PPD]) and glycemia in the three treatment groups of the Diabetes Prevention Program. RESEARCH DESIGN AND METHODS A total of 3,234 participants with impaired glucose tolerance (IGT) were followed for a mean of 3.2 years after randomization to intensive lifestyle intervention (ILS), metformin, or placebo. Using repeated-measures models, adjusted mean levels of risk factors were estimated for an annual change in glycemic status. Tests were also conducted to assess the risk factor trends with improvement or worsening of glycemic status. RESULTS CVD risk factor values and changes from baseline became more unfavorable as glucose tolerance status deteriorated but improved with reversion to normal glucose tolerance (NGT), especially in the ILS intervention group (trend test P < 0.001 for all risk factors except for LDL PPD [P = 0.02] in ILS and HDL cholesterol [P = 0.02] in placebo). Although there were few significant differences in the transition from IGT to diabetes, there were strong relationships between risk factors and continuous measures of glycemia. CONCLUSIONS Progression from IGT to diabetes is associated with mild deterioration, whereas reversion to NGT is associated with improvement in risk factors. Early intervention with ILS, but less so with metformin, in participants at high risk for diabetes improves the cardiovascular risk and glucose tolerance profile simultaneously. PMID:19171717

  12. Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with β-thalassemia major: Pilot study

    PubMed Central

    Soliman, Ashraf T.; Yasin, Mohamed; El-Awwa, Ahmed; De Sanctis, Vincenzo

    2013-01-01

    Background: Both insulin deficiency and resistance are reported in patients with β-thalassemia major (BTM). The use of continuous blood glucose monitoring (CGM), among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. Materials and Methods: To assess the oralglucose tolerance (OGT) and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. Results: Sixteen adolescents with BTM (age: 19.75 ± 3 years) were investigated. Using OGTT, (25%) had impaired fasting blood (plasma) glucose concentration (BG) (>5.6 mmol/L). 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic) and two had impaired glucose tolerance (IGT) (BG > 7.8 and <11.1 mmol/L). Monitoring the maximum (postprandial) BG using CGMS,4 adolescents were diagnosed with diabetes (25%) (BG >11.1 mmol/L) and 9 with IGT (56%). HOMA and QUICKI revealed levels <2.6 (1.6 ± 0.8) and >0.33 (0.36 ± 0.03), respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B%) on one hand and the fasting and the 2-h BG (r=−0.6, and − 0.48, P < 0.01, respectively) on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01) and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001). Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r

  13. Effects of rosglitazone on plasma adiponectin, insulin sensitivity, and insulin secretion in high-risk African Americans with impaired glucose tolerance test and type 2 diabetes.

    PubMed

    Osei, Kwame; Gaillard, Trudy; Kaplow, June; Bullock, Matthew; Schuster, Dara

    2004-12-01

    We examined the metabolic effects of rosiglitazone therapy on glucose control, insulin sensitivity, insulin secretion, and adiponectin in first-degree relatives of African Americans with type 2 diabetes (DM) with impaired glucose tolerance (IGT) and DM for 3 months. The study was comprised of 12 first-degree relatives with IGT, 17 newly diagnosed DM, and 19 healthy relatives with normal glucose tolerance (NGT). Oral glucose tolerance test (OGTT) was performed before and after 3 months of rosiglitazone therapy (4 to 8 mg/d) in patients with IGT and DM. Serum glucose, insulin, C-peptide, and adiponectin levels were measured before and 2 hours during OGTT in the NGT and patients with IGT and DM. Insulin resistance index (HOMA-IR) and beta-cell function (HOMA-%B) were calculated in each subject using homeostasis model assessment (HOMA). Rosglitazone improved the overall glycemic control in the IGT and DM groups. Following rosiglitazone, the beta-cell secretion remained unchanged, while HOMR-IR was reduced in DM by 30% (4.12 +/- 1.95 v 6.33 +/- 3.54, P < .05) and the IGT group (3.78 +/- 2.45 v 4.81 +/- 3.49, P = not significant [NS]). Mean plasma adiponectin levels were significantly (P < .05) lower in the DM (6.74 +/- 1.95 microg/mL) when compared with the NGT group(9.61 +/- 5.09). Rosiglitazone significantly (P < .001) increased adiponectin levels by 2-fold in patients with IGT (22.2 +/- 10.97 microg/mL) and 2.5-fold greater in DM (15.68 +/- 8.23 microg/mL) at 3 months when compared with the 0 month. We conclude that adiponectin could play a significant role (1) in the pathogenesis of IGT and DM and (2) the beneficial metabolic effects of thiazolidinediones (TZDs) in high-risk African American patients.

  14. Bile Acid Determination after Standardized Glucose Load in Pregnant Women

    PubMed Central

    Adams, April; Jacobs, Katherine; Vogel, Rachel Isaksson; Lupo, Virginia

    2015-01-01

    Objective Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disorder, usually manifesting in the third trimester and associated with increased perinatal morbidity and mortality. The hallmark laboratory abnormality in ICP is elevated fasting serum bile acids; however, there are limited data on whether a nonfasting state affects a pregnant woman's total bile acids. This study assesses fasting and nonfasting bile acid levels in 10 healthy pregnant women after a standardized glucose load to provide insight into the effects of a glucose load on bile acid profiles. Study Design Pilot prospective cohort analysis of serum bile acids in pregnant women. A total of 10 healthy pregnant women from 28 to 32 weeks' gestation were recruited for the study before undergoing a glucose tolerance test. Total serum bile acids were collected for each subject in the overnight fasting state, and 1 and 3 hours after the 100-g glucose load. Results There was a statistically significant difference between fasting versus 3-hour values. There was no statistically significant difference between fasting versus 1-hour and 1-hour versus 3-hour values. Conclusion There is a difference between fasting and nonfasting total serum bile acids after a 100-g glucose load in healthy pregnant women. PMID:26495178

  15. Genetic Association Analysis of Fasting and 1- and 2-Hour Glucose Tolerance Test Data Using a Generalized Index of Dissimilarity Measure for the Korean Population

    PubMed Central

    Yee, Jaeyong; Kim, Yongkang; Park, Taesung

    2016-01-01

    Glucose tolerance tests have been devised to determine the speed of blood glucose clearance. Diabetes is often tested with the standard oral glucose tolerance test (OGTT), along with fasting glucose level. However, no single test may be sufficient for the diagnosis, and the World Health Organization (WHO)/International Diabetes Federation (IDF) has suggested composite criteria. Accordingly, a single multi-class trait was constructed with three of the fasting phenotypes and 1- and 2-hour OGTT phenotypes from the Korean Association Resource (KARE) project, and the genetic association was investigated. All of the 18 possible combinations made out of the 3 sets of classification for the individual phenotypes were taken into our analysis. These were possible due to a method that was recently developed by us for estimating genomic associations using a generalized index of dissimilarity. Eight single-nucleotide polymorphisms (SNPs) that were found to have the strongest main effect are reported with the corresponding genes. Four of them conform to previous reports, located in the CDKAL1 gene, while the other 4 SNPs are new findings. Two-order interacting SNP pairs of are also presented. One pair (rs2328549 and rs6486740) has a prominent association, where the two single-nucleotide polymorphism locations are CDKAL1 and GLT1D1. The latter has not been found to have a strong main effect. New findings may result from the proper construction and analysis of a composite trait. PMID:28154509

  16. Long-term effects of high dietary fiber intake on glucose tolerance and lipid metabolism in GK rats: comparison among barley, rice, and cornstarch.

    PubMed

    Li, Jue; Kaneko, Takashi; Qin, Li-Qiang; Wang, Jing; Wang, Yuan; Sato, Akio

    2003-09-01

    Whether the intake of high dietary fiber may improve glycemic control in individuals with type 2 diabetes has been controversial. This study was conducted to observe the long-term effects of dietary fiber intake on glucose tolerance and lipid metabolism in rats. Thirty male type 2 diabetic model GK rats were divided randomly into 3 groups. Each group was fed either a barley (high-dietary fiber) diet, rice (low-dietary fiber) diet, or cornstarch (very-low-dietary fiber) diet. The rats were pair-fed for 9 months. The intake of the barley diet significantly improved the area under the plasma glucose concentration time curves, lowered the fasting plasma glucose and glycosylated hemoglobin levels, and decreased plasma total cholesterol (T Chol), triglycerides (TG), and free fatty acid (FFA) levels. This study demonstrated that long-term intake of barley has beneficial effects on glucose tolerance and lipid metabolism and suggests the intake of unrefined cereal foods should increase as a diet therapy for type 2 diabetes.

  17. A low-carbohydrate high-fat diet increases weight gain and does not improve glucose tolerance, insulin secretion or β-cell mass in NZO mice

    PubMed Central

    Lamont, B J; Waters, M F; Andrikopoulos, S

    2016-01-01

    Background/Objectives: Dietary guidelines for the past 20 years have recommended that dietary fat should be minimized. In contrast, recent studies have suggested that there could be some potential benefits for reducing carbohydrate intake in favor of increased fat. It has also been suggested that low-carbohydrate diets be recommended for people with type 2 diabetes. However, whether such diets can improve glycemic control will likely depend on their ability to improve β-cell function, which has not been studied. The objective of the study was to assess whether a low-carbohydrate and therefore high-fat diet (LCHFD) is beneficial for improving the endogenous insulin secretory response to glucose in prediabetic New Zealand Obese (NZO) mice. Methods: NZO mice were maintained on either standard rodent chow or an LCHFD from 6 to 15 weeks of age. Body weight, food intake and blood glucose were assessed weekly. Blood glucose and insulin levels were also assessed after fasting and re-feeding and during an oral glucose tolerance test. The capacity of pancreatic β-cells to secrete insulin was assessed in vivo with an intravenous glucose tolerance test. β-Cell mass was assessed in histological sections of pancreata collected at the end of the study. Results: In NZO mice, an LCHFD reduced plasma triglycerides (P=0.001) but increased weight gain (P<0.0001), adipose tissue mass (P=0.0015), high-density lipoprotein cholesterol (P=0.044) and exacerbated glucose intolerance (P=0.013). Although fasting insulin levels tended to be higher (P=0.08), insulin secretory function in LCHFD-fed mice was not improved (P=0.93) nor was β-cell mass (P=0.75). Conclusions: An LCHFD is unlikely to be of benefit for preventing the decline in β-cell function associated with the progression of hyperglycemia in type 2 diabetes. PMID:26878317

  18. 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.

  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. Seven-Day Caloric and Saturated Fat Restriction Increases Myocardial Dietary Fatty Acid Partitioning in Impaired Glucose-Tolerant Subjects.

    PubMed

    Noll, Christophe; Kunach, Margaret; Frisch, Frédérique; Bouffard, Lucie; Dubreuil, Stéphanie; Jean-Denis, Farrah; Phoenix, Serge; Cunnane, Stephen C; Guérin, Brigitte; Turcotte, Eric E; Carpentier, André C

    2015-11-01

    Subjects with impaired glucose tolerance (IGT) have increased myocardial partitioning of dietary fatty acids (DFAs) with left ventricular dysfunction, both of which are improved by modest weight loss over 1 year induced by lifestyle changes. Here, we determined the effects of a 7-day hypocaloric diet (-500 kcal/day) low in saturated fat (<7% of energy) (LOWCAL study) versus isocaloric with the usual amount saturated fat (∼10% of energy) diet (ISOCAL) on DFA metabolism in subjects with IGT. Organ-specific DFA partitioning and cardiac and hepatic DFA fractional uptake rates were measured in 15 IGT subjects (7 males/8 females) using the oral 14(R,S)-[18F]-fluoro-6-thia-heptadecanoic acid positron emission tomography method after 7 days of an ISOCAL diet versus a LOWCAL diet using a randomized crossover design. The LOWCAL diet led to reductions in weight and postprandial insulin area under the curve. Myocardial DFA partitioning over 6 h was increased after the LOWCAL diet (2.3 ± 0.1 vs. 1.9 ± 0.2 mean standard uptake value, P < 0.04). However, the early (90-120 min) myocardial DFA fractional uptake was unchanged after the LOWCAL diet (0.055 ± 0.025 vs. 0.046 ± 0.009 min(-1), P = 0.7). Liver DFA partitioning was unchanged, but liver fractional uptake of DFA tended to be increased. Very short-term caloric and saturated fat dietary restrictions do not lead to the same changes in organ-specific DFA metabolism as those associated with weight loss in subjects with IGT.

  1. Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes

    PubMed Central

    Burgos, Sergio A; Chandurkar, Vikram; Tsoukas, Michael A; Chevalier, Stéphanie; Morais, José A; Lamarche, Marie; Marliss, Errol B

    2016-01-01

    Objective To test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D). Research design and methods Seven lean, normoglycemic T2D offspring (T2D-O) and eight matched participants without family history (controls; C) underwent a 3-hour hyperinsulinemic (40 mU/m2/min), euglycemic (5.5 mmol/L) and isoaminoacidemic clamp. Whole-body glucose and protein kinetics were measured with d-[3–3H]glucose and l-[l-13C]leucine, respectively. Plasma amino acids were measured by liquid chromatography-tandem mass spectrometry. Results Fasting glycemia and glucose kinetic variables did not differ between groups. Clamp decreases in glucose rate of appearance were not different, but rate of disappearance increased 29% less in T2D-O, to a significantly lower rate. Fasting leucine was higher in T2D-O, but kinetics did not differ. Clamp increases in leucine oxidation and decreases in endogenous rate of appearance (protein breakdown) were equal, but in T2D-O, non-oxidative rate of disappearance (protein synthesis) did not increase and net balance (synthesis—breakdown) did not become positive as in C. Conclusions Resistance of whole-body protein anabolism (synthesis and net balance) accompanies resistance of glucose uptake in T2D-O. Mechanisms responsible, possible roles in the increased risk of developing diabetes, and its potential impact on long-term protein balance require definition. PMID:27933189

  2. Thiazolidinediones increase hepatic insulin extraction in African Americans with impaired glucose tolerance and type 2 diabetes mellitus. A pilot study of rosiglitazone.

    PubMed

    Osei, Kwame; Gaillard, Trudy; Schuster, Dara

    2007-01-01

    Peripheral insulin levels are determined by beta-cell secretion, insulin sensitivity, and hepatic insulin extraction (HIE). We have previously shown that whereas sulfonylureas reduce insulin extraction, metformin enhances HIE. However, the effects of thiazolidinediones (TZDs) on HIE remain uncertain. Thus, we investigated the potential contribution of hepatic insulin clearance to peripheral insulin levels during rosiglitazone therapy in African Americans with impaired glucose tolerance (IGT) and type 2 diabetes mellitus (DM). The study was composed of 12 first-degree relatives with IGT and 17 patients with newly diagnosed type 2 DM. Nineteen healthy relatives with normal glucose tolerance served as controls. Serum glucose, insulin, and C-peptide, and HIE (C-peptide-insulin molar ratios) were measured at t = 0 and 120 minutes during oral glucose tolerance test (OGTT) in all the subjects. The OGTT was performed before and after 3 months of rosiglitazone therapy (4 mg/d x 4 weeks and >8 mg/d x 8 weeks) in patients with IGT and type 2 DM. Insulin resistance index and beta-cell function were calculated in each subject using homeostasis model assessment (HOMA). Rosiglitazone therapy improved but did not normalize the overall glycemic control in the IGT and type 2 DM groups. After rosiglitazone therapy, the mean serum insulin and C-peptide levels at fasting remained unchanged. However, the 2-hour serum glucose and insulin were lower, whereas serum C-peptide was unchanged during 3 months of rosiglitazone treatment. Mean insulin resistance index of HOMA was reduced by 30% (4.12 +/- 1.95 vs 6.33 +/- 3.54, P < .05) in the type 2 DM group and by 21% (3.78 +/- 2.45 vs 4.81 +/- 3.49, P = NS) in the IGT group. Mean HIE values were significantly lower (70%) in the type 2 DM and IGT groups when compared with the normal glucose tolerance group. At 3 months, basal HIE was not significantly changed by rosiglitazone therapy in IGT and type 2 DM groups when compared with the baseline (0

  3. 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

  4. The effects of long- or medium-chain fat diets on glucose tolerance and myocellular content of lipid intermediates in rats.

    PubMed

    De Vogel-van den Bosch, Johan; Hoeks, Joris; Timmers, Silvie; Houten, Sander M; van Dijk, Paul J; Boon, Wendy; Van Beurden, Denis; Schaart, Gert; Kersten, Sander; Voshol, Peter J; Wanders, Ronald J A; Hesselink, Matthijs K; Schrauwen, Patrick

    2011-04-01

    Accumulation of triacylglycerols (TAGs) and acylcarnitines in skeletal muscle upon high-fat (HF) feeding is the resultant of fatty acid uptake and oxidation and is associated with insulin resistance. As medium-chain fatty acids (MCFAs) are preferentially β-oxidized over long-chain fatty acids, we examined the effects of medium-chain TAGs (MCTs) and long-chain TAGs (LCTs) on muscle lipid storage and whole-body glucose tolerance. Rats fed a low-fat (LF), HFLCT, or an isocaloric HFMCT diet displayed a similar body weight gain over 8 weeks of treatment. Only HFLCT increased myocellular TAG (42.3 ± 4.9, 71.9 ± 6.7, and 48.5 ± 6.5 µmol/g for LF, HFLCT, and HFMCT, respectively, P < 0.05) and long-chain acylcarnitine content (P < 0.05). Neither HF diet increased myocellular diacylglycerol (DAG) content. Intraperitoneal (IP) glucose tolerance tests (1.5 g/kg) revealed a significantly decreased glucose tolerance in the HFMCT compared to the HFLCT-fed rats (802 ± 40, 772 ± 18, and 886 ± 18 area under the curve for LF, HFLCT, and HFMCT, respectively, P < 0.05). Finally, no differences in myocellular insulin signaling after bolus insulin injection (10 U/kg) were observed between LF, HFLCT, or HFMCT-fed rats. These results show that accumulation of TAGs and acylcarnitines in skeletal muscle in the absence of body weight gain do not impede myocellular insulin signaling or whole-body glucose intolerance.

  5. 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.

  6. Beneficial effects of vildagliptin combined with miglitol on glucose tolerance and islet morphology in diet-controlled db/db mice.

    PubMed

    Ishibashi, Keita; Hara, Akemi; Fujitani, Yoshio; Uchida, Toyoyoshi; Komiya, Koji; Tamaki, Motoyuki; Abe, Hiroko; Ogihara, Takeshi; Kanazawa, Akio; Kawamori, Ryuzo; Watada, Hirotaka

    2013-11-01

    Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes primarily by increasing plasma active glucagon-like peptide-1 (GLP-1) levels. While various combination therapies based on DPP-4 inhibitors have been proposed for treatment of type 2 diabetes, the effects of combination therapy of DPP-4 inhibitors and alpha-glucosidase inhibitors on β-cell function are less characterized. We evaluated the effects of long-term treatment with vildagliptin, a DPP-4 inhibitor, on metabolic parameters and β-cell function, in combination with miglitol, an alpha-glucosidase inhibitor, in diet-controlled db/db mice. In this study, 6-week-old male db/db mice were provided with standard chow twice a day for 6 weeks. Meal tolerance tests and glucose tolerance tests showed that the combination therapy of vildagliptin with miglitol, but not each alone, suppressed postprandial glycemic excursion, enhanced postprandial active GLP-1 levels and prevented deterioration of glucose tolerance in the db/db mice. The combination treatment did not alter β-cell mass, but resulted in preserved expression of glucose transporter 2, Zinc transporter 8 and MafA and reduced the number of α cells. These results suggest that the combination of vildagliptin and miglitol prevents the development of overt diabetes in diet-controlled pre-diabetic db/db mice by normalizing postprandial glucose and incretin response, and by preserving β-cell structure and the expression of factors essential for β-cell function.

  7. Exaggerated glucagon-like peptide 1 response is important for improved β-cell function and glucose tolerance after Roux-en-Y gastric bypass in patients with type 2 diabetes.

    PubMed

    Jørgensen, Nils B; Dirksen, Carsten; Bojsen-Møller, Kirstine N; Jacobsen, Siv H; Worm, Dorte; Hansen, Dorte L; Kristiansen, Viggo B; Naver, Lars; Madsbad, Sten; Holst, Jens J

    2013-09-01

    β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)-specific antagonist. Nine patients with type 2 diabetes were examined before and 1 week and 3 months after surgery. Each visit consisted of two experimental days, allowing a meal test with randomized infusion of saline or Ex-9. After RYGB, glucose tolerance improved, β-cell glucose sensitivity (β-GS) doubled, the GLP-1 response greatly increased, and glucagon secretion was augmented. GLP-1R blockade did not affect β-cell function or meal-induced glucagon release before the operation but did impair glucose tolerance. After RYGB, β-GS decreased to preoperative levels, glucagon secretion increased, and glucose tolerance was impaired by Ex-9 infusion. Thus, the exaggerated effect of GLP-1 after RYGB is of major importance for the improvement in β-cell function, control of glucagon release, and glucose tolerance in patients with type 2 diabetes.

  8. Is non-insulin dependent glucose uptake a therapeutic alternative? Part 2: Do such mechanisms fulfil the required combination of power and tolerability?

    PubMed

    Wiernsperger, N F

    2005-12-01

    The worldwide burden of diabetes, the unavoidable worsening which is observed in long-term clinical trials despite treatment and the close link between glycaemia and microangiopathy appeal for much stronger treatment strategies. This, in turn, either requires polypharmacy (with new risks) or new, more powerful drugs to be invented. The first part of this review dealt with a thorough analysis of pros and cons for some selected pathways which could potentially increase glucose uptake without necessitating insulin. The choice of such targets for developing completely new drugs, however, requires a favourable background from existing tentatives with either drugs or cell biology approaches. Moreover, because vascular complications are what must ultimately be avoided when treating diabetic patients, we must be sure that increasing glucose uptake in a fashion which is no more controlled by normal physiology is compatible with the physiology of vascular cells (long-term tolerance). The aspect of drug side-effects must therefore be considered systematically. For reasons which are individually developed, it appears that each of the potential pathways analyzed either lacks sufficient power and/or is likely to induce side effects which are not acceptable for long-term application. The fact that GLUT-1 transporters are ubiquitously distributed even extends this cardinal question to the general principle of increasing glucose uptake. In conclusion a precise evaluation suggests that, although non-insulin dependent glucose uptake represents (3/4) of whole body glucose transport, it is difficult to consider such mechanisms able to generate a new treatment fulfilling the unavoidable request of combined efficacy and tolerability.

  9. Effect of glucose ingestion in plasma markers of inflammation and oxidative stress: analysis of 16 plasma markers from oral glucose tolerance test samples of normal and diabetic patients.

    PubMed

    Choi, Hyung Jin; Jeon, Soon Young; Hong, Won Kyung; Jung, Seung Eun; Kang, Hyun Ju; Kim, Jun-Woo; Jeon, Jae-Pil; Han, Bok-Ghee

    2013-02-01

    Sixteen plasma markers of inflammation and oxidative stress were measured during OGTT in 54 subjects. Leptin, RBP4, CRP, OPN, ANG, MDC, and MCSF concentrations significantly decreased during OGTT (P<0.05). IL6, IL8, and MCP3 concentrations significantly increased during OGTT (P<0.05). These results provide evidence that glucose ingestion affects systemic inflammation and oxidative stress.

  10. [Voglibose for the prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese subjects with impaired glucose tolerance].

    PubMed

    Kawamori, Ryuzo

    2010-05-01

    The study to assess whether voglibose could prevent type 2 diabetes developing in high-risk Japanese subjects with impaired glucose tolerance (IGT) were performed. This was a multicenter, randomised, double-blind, parallel group trial comparing voglibose 0.2 mg three times a day and corresponding placebo. 1,780 eligible subjects received standard diet and exercise therapy, and 897 were randomised to receive voglibose and 883 placebo. The study was planned for treatment to be continued until participants developed type 2 diabetes[primary endpoint; determined by bi-annual oral glucose tolerance tests (OGTTs) as well as fasting blood glucose measured every 3 months] or normalisation of the OGTT or for a minimum of 3 years, subject to the findings of an interim analysis. The interim analysis significantly favoured voglibose and this end-of-study report involves individuals treated for an average of 48.1 weeks. Subjects treated with voglibose had a significantly lower risk for the progression to type 2 diabetes than placebo (50/897 vs 106/881: hazard ratio 0.595). Also, significantly more subjects in the voglibose group achieved a normal OGTT compared with those in the placebo group (599/897 vs 454/881: hazard ratio 1.539). Voglibose, in addition to standard care with diet and exercise, was effective in preventing the progression of IGT to type 2 diabetes and in facilitating the normalisation of the OGTT in high-risk Japanese subjects with IGT.

  11. Favourable effects of the Dietary Approaches to Stop Hypertension diet on glucose tolerance and lipid profiles in gestational diabetes: a randomised clinical trial.

    PubMed

    Asemi, Zatollah; Tabassi, Zohreh; Samimi, Mansooreh; Fahiminejad, Taherh; Esmaillzadeh, Ahmad

    2013-06-01

    Although gestational diabetes mellitus (GDM) is associated with an increased risk of maternal and neonatal morbidity, there is no consensus as to the optimal approach of nutritional management in these patients. The present study was designed to assess the effect of the Dietary Approaches to Stop Hypertension (DASH) eating plan on glucose tolerance and lipid profiles of pregnant women with GDM. The present randomised controlled clinical trial was performed among thirty-four women diagnosed with GDM at 24-28 weeks of gestation. Subjects were randomly assigned to consume either the control diet (n 17) or the DASH eating pattern (n 17) for 4 weeks. The control diet was designed to contain 45-55% carbohydrates, 15-20% protein and 25-30% total fat. The macronutrient composition of the DASH diet was similar to the control diet; however, the DASH diet was rich in fruits, vegetables, whole grains and low-fat dairy products, and contained lower amounts of saturated fats, cholesterol and refined grains with a total of 2400 mg Na/d. Fasting blood samples were taken at baseline and after 4 weeks of intervention to measure fasting plasma glucose, glycated Hb (HbA1c) and lipid profiles. Participants underwent a 3 h oral glucose tolerance tests and blood samples were collected at 60, 120 and 180 min to measure plasma glucose levels. Adherence to the DASH eating pattern, compared with the control diet, resulted in improved glucose tolerance such that plasma glucose levels reduced at 60 (21·86 v. 20·45 mmol/l, Pgroup = 0·02), 120 (22·3 v. 0·2 mmol/l, Pgroup = 0·001) and 180 min (21·7 v. 0·22 mmol/l, Pgroup = 0·002) after the glucose load. Decreased HbA1c levels (20·2 v. 0·05 %, Pgroup = 0·001) was also seen in the DASH group compared with the control group. Mean changes for serum total (20·42 v. 0·31 mmol/l, Pgroup = 0·01) and LDL-cholesterol (20·47 v. 0·22 mmol/l, Pgroup = 0·005), TAG (20·17 v. 0·34 mmol/l, Pgroup = 0·01) and total:HDL-cholesterol ratio (20·6

  12. 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

  13. 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

  14. Effect of α-lipoic acid and exercise training on cardiovascular disease risk in obesity with impaired glucose tolerance.

    PubMed

    McNeilly, Andrea M; Davison, Gareth W; Murphy, Marie H; Nadeem, Nida; Trinick, Tom; Duly, Ellie; Novials, Anna; McEneny, Jane

    2011-11-22

    Obese subjects with impaired glucose tolerance (IGT) are more susceptible than healthy individuals to oxidative stress and cardiovascular disease. This randomised controlled investigation was designed to test the hypothesis that α-lipoic acid supplementation and exercise training may elicit favourable clinical changes in obese subjects with IGT. All data were collected from 24 obese (BMI ≥ 30 kg/m2) IGT patients. Following participant randomisation into two groups, fasting venous blood samples were obtained at baseline, and before and following intervention. The first group consisted of 12 participants who completed a 12 week control phase followed by 12 weeks of chronic exercise at 65% HRmax for 30 minutes a day, 5 days per week, while ingesting 1 gram per day of α-lipoic acid for 12 weeks. The second group consisted of 12 participants who completed the same 12 week control phase, but this was followed by 12 weeks of 1 gram per day of α-lipoic acid supplementation only (no exercise). The main findings show a comparatively greater rate of low density lipoprotein (LDL) oxidation in the group consisting of α-lipoic acid only (p < 0.05 vs. pre intervention), although total oxidant status was lower post intervention (p < 0.05 vs. baseline) in this group. However, exercise and α-lipoic acid in combination attenuates LDL oxidation. Furthermore, in the α-lipoic acid supplement plus exercise training group, total antioxidant capacity was significantly increased (p < 0.05 vs. baseline and pre intervention). Body fat percentage and waist and hip circumference decreased following exercise training (p < 0.05 vs. post intervention). There were no selective treatment differences for a range of other clinical outcomes including glycaemic regulation (p > 0.05). These findings report that α-lipoic acid ingestion may increase the atherogenicity of LDL when ingested in isolation of exercise, suggesting that in IGT the use of this antioxidant treatment does not ameliorate

  15. Identification of hexose kinase genes in Kluyveromyces marxianus and thermo-tolerant one step producing glucose-free fructose strain construction

    PubMed Central

    Zhang, Guorong; Lu, Min; Wang, Jichao; Wang, Dongmei; Gao, Xiaolian; Hong, Jiong

    2017-01-01

    In yeast, the hexose assimilation is started at hexose phosphorylation. However, in Kluyveromyces marxianus, the hexokinase (HXK) and glucokinase (GLK) genes were not identified by experiments. Meanwhile, the glucose-free fructose product requires more cost-efficient method. In this study, the KmHXK1 and KmGLK1 genes were functionally identified through gene disruption, over-expression and recombinant enzymes characterization. Both glucose and fructose assimilation ability decreased significantly in KmHXK1 disrupted strain YLM001, however, this ability was not changed obviously in KmGLK1 disrupted strain YLM002. When over-expressing KmGLK1 in YLM001, only the glucose assimilation ability was recovered in obtained strain (YLM005). The kinetic constant analysis of recombinant enzymes also proved that KmHXK1 could phosphorylate glucose (Vmax 553.01 U/mg, Km 0.83 mM) and fructose (Vmax 609.82 U/mg, Km 0.52 mM), and KmGLK1 only phosphorylate glucose with a Vmax of 0.73 U/mg and a Km 4.09 mM. A thermo-tolerant strain YGR003 which produced glucose-free fructose from Jerusalem artichoke tuber in one step was constructed based on the obtained information. The highest production and fastest productivity were 234.44 g/L and 10.26 g/L/h, respectively, which were several folds of the results in previous reports. PMID:28338054

  16. Effect of fructose or sucrose feeding with different levels on oral glucose tolerance test in normal and type 2 diabetic rats

    PubMed Central

    Kwon, Sanghee; Kim, You Jin

    2008-01-01

    This study was designed to determine whether acute fructose or sucrose administration at different levels (0.05 g/kg, 0.1 g/kg or 0.4 g/kg body weight) might affect oral glucose tolerance test (OGTT) in normal and type 2 diabetic rats. In OGTT, there were no significant differences in glucose responses between acute fructose- and sucrose-administered groups. However, in normal rats, the AUCs of the blood glucose response for the fructose-administered groups tended to be lower than those of the control and sucrose-administered groups. The AUCs of the lower levels fructoseor sucrose-administered groups tended to be smaller than those of higher levels fructose- or sucrose-administered groups. In type 2 diabetic rats, only the AUC of the lowest level of fructose-administered (0.05 g/kg body weight) group was slightly smaller than that of the control group. The AUCs of fructose-administered groups tended to be smaller than those of the sucrose-administered groups, and the AUCs of lower levels fructose-administered groups tended to be smaller than those fed higher levels of fructose. We concluded from this experiment that fructose has tendency to be more effective in blood glucose regulation than sucrose, and moreover, that smaller amount of fructose is preferred to larger amount. Specifically, our experiments indicated that the fructose level of 0.05 g/kg body weight as dietary supplement was the most effective amount for blood glucose regulation from the pool of 0.05 g/kg, 0.1 g/kg and 0.4 g/kg body weights. Therefore, our results suggest the use of fructose as the substitute sweetener for sucrose, which may be beneficial for blood glucose regulation. PMID:20016727

  17. Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests.

    PubMed

    Otsuka, Hiroki; Sasai, Hideo; Abdelkreem, Elsayed; Kawamoto, Norio; Kawamoto, Minako; Kamiya, Toshiya; Tanimoto, Yasuo; Kikuchi, Atsuo; Kure, Shigeo; Numakura, Chikahiko; Hayasaka, Kiyoshi; Fukao, Toshiyuki

    2016-01-01

    Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD(+) ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.

  18. [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.

  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. Chronic benzylamine administration in the drinking water improves glucose tolerance, reduces body weight gain and circulating cholesterol in high-fat diet-fed mice.

    PubMed

    Iffiú-Soltész, Zsuzsa; Wanecq, Estelle; Lomba, Almudena; Portillo, Maria P; Pellati, Federica; Szöko, Eva; Bour, Sandy; Woodley, John; Milagro, Fermin I; Alfredo Martinez, J; Valet, Philippe; Carpéné, Christian

    2010-04-01

    Benzylamine is found in Moringa oleifera, a plant used to treat diabetes in traditional medicine. In mammals, benzylamine is metabolized by semicarbazide-sensitive amine oxidase (SSAO) to benzaldehyde and hydrogen peroxide. This latter product has insulin-mimicking action, and is involved in the effects of benzylamine on human adipocytes: stimulation of glucose transport and inhibition of lipolysis. This study examined whether chronic, oral administration of benzylamine could improve glucose tolerance and the circulating lipid profile without increasing oxidative stress in overweight and pre-diabetic mice. The benzylamine diffusion across the intestine was verified using everted gut sacs. Then, glucose handling and metabolic markers were measured in mice rendered insulin-resistant when fed a high-fat diet (HFD) and receiving or not benzylamine in their drinking water (3600micromol/(kgday)) for 17 weeks. HFD-benzylamine mice showed lower body weight gain, fasting blood glucose, total plasma cholesterol and hyperglycaemic response to glucose load when compared to HFD control. In adipocytes, insulin-induced activation of glucose transport and inhibition of lipolysis remained unchanged. In aorta, benzylamine treatment partially restored the nitrite levels that were reduced by HFD. In liver, lipid peroxidation markers were reduced. Resistin and uric acid, surrogate plasma markers of metabolic syndrome, were decreased. In spite of the putative deleterious nature of the hydrogen peroxide generated during amine oxidation, and in agreement with its in vitro insulin-like actions found on adipocytes, the SSAO-substrate benzylamine could be considered as a potential oral agent to treat metabolic syndrome.

  1. Long-term administration of PACAP receptor antagonist, PACAP(6-27), impairs glucose tolerance and insulin sensitivity in obese diabetic ob/ob mice.

    PubMed

    Green, Brian D; Irwin, Nigel; Cassidy, Roslyn S; Gault, Victor A; Flatt, Peter R

    2006-09-01

    Pituitary adenylate cyclase-activating peptide (PACAP) is a ubiquitous peptide of the glucagon superfamily that is involved in glucose homeostasis and regulation of insulin secretion. This study employed the PACAP receptor antagonist, PACAP(6-27) to evaluate the role of endogenous PACAP in genetic obesity-related diabetes and related metabolic abnormalities using ob/ob mice. Acute in vivo antagonistic potency of PACAP(6-27) was confirmed in ob/ob mice by blockade of the insulin-releasing action but not hyperglycaemia. In longer-term studies, ob/ob mice were given once daily injections of PACAP(6-27) or vehicle for 14 days. Feeding activity, body weight, basal plasma glucose and plasma insulin concentrations were not significantly affected by chronic PACAP(6-27) treatment. However, PACAP(6-27) treatment impaired glucose tolerance, insulin sensitivity and the glycaemic response to feeding. Plasma glucagon and lipids were unchanged. These observations indicate a role of endogenous PACAP for normal glucose homeostasis, but indicate a minor involvement in the regulation of insulin secretion in ob/ob mice.

  2. Quantitative analysis of methylglyoxal, glyoxal and free advanced glycation end-products in the plasma of Wistar rats during the oral glucose tolerance test.

    PubMed

    Chen, Si Jing; Aikawa, Chiwa; Matsui, Toshiro

    2015-01-01

    The purpose of this study was to gain insight into the production behavior of free adducts of advanced glycation end-products (AGEs) in Wistar rats under acute hyperglycemic conditions. Five AGE-free adducts as well as their precursors (i.e., highly reactive carbonyl intermediates of methylglyoxal and glyoxal) in rat plasma were quantitatively determined at greater than nanomolar levels using the liquid chromatography/tandem mass spectrometry method coupled with 2,4,6-trinitrobenzene sulfonate and 2,3-diaminonaphthalene derivatization techniques. An oral glucose (2 g/kg dose) tolerance test to 10-week-old Wistar rats provided evidence that the plasma levels of diabetes-related metabolites did not change acutely within 120 min, irrespective of increasing blood glucose levels.

  3. Association of the ACTN3 R557X polymorphism with glucose tolerance and gene expression of sarcomeric proteins in human skeletal muscle

    PubMed Central

    Riedl, Isabelle; Osler, Megan E; Benziane, Boubacar; Chibalin, Alexander V; Zierath, Juleen R

    2015-01-01

    A common polymorphism (R577X) in the α-actinin (ACTN) 3 gene, which leads to complete deficiency of a functional protein in skeletal muscle, could directly influence metabolism in the context of health and disease. Therefore, we tested the hypothesis that states of glucose tolerance are associated with the ACTN3 R577X genotype. We analyzed the prevalence of the ACTN3 R577X polymorphism in people with normal glucose tolerance (NGT) and type 2 diabetes (T2D) and measured muscle-specific α-actinin 2 and 3 mRNA and protein abundance in skeletal muscle biopsies. Furthermore, we investigated the protein abundance of the myosin heavy chain isoforms and the components of the mitochondrial electron transport chain in skeletal muscle from people with NGT or T2D. mRNA of selected sarcomeric z-disk proteins was also assessed. Although the prevalence of the ACTN3 577XX genotype was higher in T2D patients, genotype distribution was unrelated to metabolic control or obesity. ACTN2 and ACTN3 mRNA expression and protein abundance was unchanged between NGT and T2D participants. Protein abundance of mitochondrial complexes II and IV was related to genotype and glucose tolerance status. Gene expression of sarcomeric z-disk proteins was increased in skeletal muscle from NGT participants with the ACTN3 577XX genotype. While genetic variation in ACTN3 does not influence metabolic control, genotype does appear to influence gene expression of other sarcomeric proteins, which could contribute to the functional properties of skeletal muscle and the fatigue-resistant phenotype associated with the R577X polymorphism. PMID:25780092

  4. Differences by sex in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa: a systematic review and meta-analysis

    PubMed Central

    Yatsuya, Hiroshi; Kawaguchi, Leo; Aoyama, Atsuko

    2013-01-01

    Abstract Objective To assess differences between men and women in the prevalence of diabetes mellitus, impaired fasting glycaemia and impaired glucose tolerance in sub-Saharan Africa. Methods In September 2011, the PubMed and Web of Science databases were searched for community-based, cross-sectional studies providing sex-specific prevalences of any of the three study conditions among adults living in parts of sub-Saharan Africa (i.e. in Eastern, Middle and Southern Africa according to the United Nations subregional classification for African countries). A random-effects model was then used to calculate and compare the odds of men and women having each condition. Findings In a meta-analysis of the 36 relevant, cross-sectional data sets that were identified, impaired fasting glycaemia was found to be more common in men than in women (OR: 1.56; 95% confidence interval, CI: 1.20–2.03), whereas impaired glucose tolerance was found to be less common in men than in women (OR: 0.84; 95% CI: 0.72–0.98). The prevalence of diabetes mellitus – which was generally similar in both sexes (OR: 1.01; 95% CI: 0.91–1.11) – was higher among the women in Southern Africa than among the men from the same subregion and lower among the women from Eastern and Middle Africa and from low-income countries of sub-Saharan Africa than among the corresponding men. Conclusion Compared with women in the same subregions, men in Eastern, Middle and Southern Africa were found to have a similar overall prevalence of diabetes mellitus but were more likely to have impaired fasting glycaemia and less likely to have impaired glucose tolerance. PMID:24101783

  5. Type II diabetes and impaired glucose tolerance due to severe hyperinsulinism in patients with 1p36 deletion syndrome and a Prader-Willi-like phenotype

    PubMed Central

    2014-01-01

    Background Deletion of the subtelomeric region of 1p36 is one of the most common subtelomeric deletion syndromes. In monosomy 1p36, the presence of obesity is poorly defined, and glucose metabolism deficiency is rarely reported. However, the presence of a typical Prader-Willi-like phenotype in patients with monosomy 1p36 is controversial. Case presentation In this report, we describe two female patients, one who is 6 years 2 months of age and another who is 10 years 1 month of age, both referred to our hospital for obesity and a Prader-Willi-like phenotype. These patients presented with severe obesity (body mass index [BMI] was 26.4 and 27.7, respectively), hyperphagia and developmental delay. Analysis of basal hormone levels showed normal thyroid function and adrenal function but considerable basal hyperinsulinism (the insulin levels were 54.5 and 49.2 μU/ml, respectively). In patient 1, glycaemia was 75 mg/dl (HOMA-R 10.09), and the HbA1c level was 6.1%; in patient 2, glycaemia was 122 mg/dl, and the HbA1c level was 6.6% (HOMA-R 14.82). An oral glucose tolerance test demonstrated impaired glucose tolerance and diabetes mellitus with marked insulin resistance (the peak insulin level for each patient was 197 and 279 μU/mL, respectively, while the 120’ insulin level of each patient was 167 and 234 μU/mL, respectively). Conclusion some patients with monosomy 1p36 may show Prader-Willi-like physical and physiologic characteristics such as obesity and hyperinsulinism with impaired glucose metabolism, which can cause type II diabetes mellitus. Further studies are necessary to evaluate these findings. PMID:24479866

  6. Conjugated linoleic acid versus high-oleic acid sunflower oil: effects on energy metabolism, glucose tolerance, blood lipids, appetite and body composition in regularly exercising individuals.

    PubMed

    Lambert, Estelle V; Goedecke, Julia H; Bluett, Kerry; Heggie, Kerry; Claassen, Amanda; Rae, Dale E; West, Sacha; Dugas, Jonathan; Dugas, Lara; Meltzeri, Shelly; Charlton, Karen; Mohede, Inge

    2007-05-01

    The aim of this study was to measure the effects of 12 weeks of conjugated linoleic acid (CLA) supplementation on body composition, RER, RMR, blood lipid profiles, insulin sensitivity and appetite in exercising, normal-weight persons. In this double-blind, randomised, controlled trial, sixty-two non-obese subjects (twenty-five men, thirty-seven women) received either 3.9 g/d CLA or 3.9 g high-oleic acid sunflower oil for 12 weeks. Prior to and after 12 weeks of supplementation, oral glucose tolerance, blood lipid concentrations, body composition (dual-energy X-ray absorptiometry and computerised tomography scans), RMR, resting and exercising RER and appetite were measured. There were no significant effects of CLA on body composition or distribution, RMR, RER or appetite. During the oral glucose tolerance tests, mean plasma insulin concentrations (0, 30, 120 min) were significantly lower (P= 0.04) in women who supplemented with CLA (24.3 (SD 9.7) to 20.4 (SD 8.5) microU/ml) compared to high-oleic acid sunflower oil control (23.7 (SD 9.8) to 26.0 (SD 8.8) microU/ml). Serum NEFA levels in response to oral glucose were attenuated in both men and women in the CLA (P=0.001) compared to control group. However, serum total cholesterol and LDL-cholesterol concentrations decreased in both groups and HDL-cholesterol concentrations decreased in women over 12 weeks (P=0.001, P=0.02, P=0.02, respectively). In conclusion, mixed-isomer CLA supplementation had a favourable effect on serum insulin and NEFA response to oral glucose in non-obese, regularly exercising women, but there were no CLA-specific effects on body composition, energy expenditure or appetite.

  7. Consumption of caffeinated coffee and a high carbohydrate meal affects postprandial metabolism of a subsequent oral glucose tolerance test in young, healthy males.

    PubMed

    Moisey, Lesley L; Robinson, Lindsay E; Graham, Terry E

    2010-03-01

    Caffeine and caffeinated coffee (CC) elicit acute insulin insensitivity when ingested before a carbohydrate load. The effects of CC on glucose tolerance and insulin sensitivity when co-ingested with a high carbohydrate meal and on postprandial metabolism of a subsequent (second) carbohydrate load have not been studied. In a randomised, crossover design, ten healthy males ingested either CC (5 mg caffeine/kg body weight), decaffeinated coffee (DC) or water (W; equal volume) co-ingested with a high glycaemic index cereal followed 3 h later by a 75 g oral glucose tolerance test. After the initial meal, insulin area under the curve (AUC) and insulin sensitivity index did not differ between treatments, although glucose AUC for CC (107 (sem 18) mmol/l x 3 h) and DC (74 (sem 15) mmol/l x 3 h) was greater than W ( - 0.2 (sem 29) mmol/l x 3 h, P < 0.05). After the second carbohydrate load, insulin AUC for CC was 49 % and 57 % greater (P < 0.01) than for DC and W, respectively. Despite the greater insulin response, glucose AUC for CC (217 (sem 24) mmol/l x 2 h) was greater than both DC (126 (sem 11) mmol/l x 2 h, P = 0.01) and W (55 (sem 34) mmol/l x 2 h, P < 0.001). Insulin sensitivity index after the second meal was lower after CC (8.2 (sem 0.9)) compared with both DC (12.4 (sem 1.2), P < 0.01) and W (13.4 (sem 1.4), P < 0.001). Co-ingestion of CC with one meal resulted in insulin insensitivity during the postprandial phase of a second meal in the absence of further CC ingestion. Thus, CC may play a role in daily glycaemic management.

  8. Acquired tolerance and in situ detoxification of furfural and HMF through glucose metabolic pathways by Saccharomyces cerevisiae

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Lignocellulosic biomass conversion inhibitors furfural and HMF inhibit microbial growth and interfere with subsequent fermentation of ethanol. Numerous yeast genes were found to be associated with the inhibitor tolerance. However, little is known about system mechanisms of the tolerance and detoxi...

  9. 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.

  10. Winter-feeding systems for gestating sheep II. Effects on feedlot performance, glucose tolerance, and carcass composition of lamb progeny.

    PubMed

    Radunz, A E; Fluharty, F L; Susin, I; Felix, T L; Zerby, H N; Loerch, S C

    2011-02-01

    Mature pregnant crossbred ewes (n = 90) were used in a randomized complete block design experiment and were assigned to 1 of 3 winter-feeding systems differing in primary feed source: haylage (HL), limit-fed corn (CN), or limit-fed dried distillers grains (DDGS). Effects of these winter-feeding strategies on postweaning progeny performance were determined. Lamb progeny (n = 96) were weaned at 61 ± 4 d of age and fed a common high-concentrate diet. Lambs were assigned to feedlot pen (n = 18) based on dam mid-gestation pen. Growth rate, DMI, and ADG were determined for the first 40 d of the finishing period. At 96 ± 4 d of age, 1 wether lamb was randomly selected from each pen (n = 18) for a glucose tolerance test. The experiment was terminated, and lambs were slaughtered individually when they were determined to have achieved 0.6-cm 12th-rib fat thickness. After a 24-h chill, carcass data were collected and a 2.54-cm chop was removed from each lamb from the LM posterior to the 12th rib for ether extract analysis. Additional carcass measurements of bone, muscle, and fat from the shoulder, rack, loin, and leg were collected on 35 carcasses. At weaning, lamb BW was not different among treatments, whereas final BW tended to be greater (P = 0.09) for lambs from ewes fed DDGS and CN during gestation than from those fed HL. Overall lamb growth rate from birth to slaughter was not different among treatments. Lambs from ewes fed DDGS vs. CN or HL tended to have a greater initial insulin response (P = 0.09). Dressing percent was less (P = 0.04) in lambs from ewes fed DDGS, but no difference (P = 0.16) was detected in HCW among treatments. As expected, 12th rib fat thickness was similar among treatments, whereas LM area was largest to smallest (P = 0.05) in lambs from ewes fed CN, HL, and DDGS, respectively. Proportion of internal fat tended to be greatest to smallest (P = 0.06) in lambs from ewes fed DDGS, CN, and HL, respectively. Calculated boneless trimmed retail cuts

  11. Deletion of the G protein-coupled receptor 30 impairs glucose tolerance, reduces bone growth, increases blood pressure, and eliminates estradiol-stimulated insulin release in female mice.

    PubMed

    Mårtensson, Ulrika E A; Salehi, S Albert; Windahl, Sara; Gomez, Maria F; Swärd, Karl; Daszkiewicz-Nilsson, Joanna; Wendt, Anna; Andersson, Niklas; Hellstrand, Per; Grände, Per-Olof; Owman, Christer; Rosen, Clifford J; Adamo, Martin L; Lundquist, Ingmar; Rorsman, Patrik; Nilsson, Bengt-Olof; Ohlsson, Claes; Olde, Björn; Leeb-Lundberg, L M Fredrik

    2009-02-01

    In vitro studies suggest that the G protein-coupled receptor (GPR) 30 is a functional estrogen receptor. However, the physiological role of GPR30 in vivo is unknown, and it remains to be determined whether GPR30 is an estrogen receptor also in vivo. To this end, we studied the effects of disrupting the GPR30 gene in female and male mice. Female GPR30((-/-)) mice had hyperglycemia and impaired glucose tolerance, reduced body growth, increased blood pressure, and reduced serum IGF-I levels. The reduced growth correlated with a proportional decrease in skeletal development. The elevated blood pressure was associated with an increased vascular resistance manifested as an increased media to lumen ratio of the resistance arteries. The hyperglycemia and impaired glucose tolerance in vivo were associated with decreased insulin expression and release in vivo and in vitro in isolated pancreatic islets. GPR30 is expressed in islets, and GPR30 deletion abolished estradiol-stimulated insulin release both in vivo in ovariectomized adult mice and in vitro in isolated islets. Our findings show that GPR30 is important for several metabolic functions in female mice, including estradiol-stimulated insulin release.

  12. 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.

  13. Bg10: A Novel Metagenomics Alcohol-Tolerant and Glucose-Stimulated GH1 ß-Glucosidase Suitable for Lactose-Free Milk Preparation

    PubMed Central

    Gomes-Pepe, Elisângela Soares; Machado Sierra, Elwi Guillermo; Pereira, Mariana Rangel; Castellane, Tereza Cristina Luque

    2016-01-01

    New ß-glucosidases with product (glucose) or ethanol tolerances are greatly desired to make industrial processes more marketable and efficient. Therefore, this report describes the in silico/vitro characterization of Bg10, a metagenomically derived homodimeric ß-glucosidase that exhibited a Vmax of 10.81 ± 0.43 μM min-1, Kcat of 175.1± 6.91 min-1, and Km of 0.49 ± 0.12 mM at a neutral pH and 37°C when pNP-ß-D-glucopyranoside was used as the substrate, and the enzyme retained greater than 80% activity within the respective pH and temperature ranges of 6.5 to 8.0 and 35 to 40°C. The enzyme was stimulated by its product, glucose; consequently, the Bg10 activity against 50 and 100 mM of glucose were increased by 36.8% and 22%, respectively, while half of the activity was retained at 350 mM. Moreover, the Bg10 was able to hydrolyse 55% (milk sample) and 100% (purified sugar) of the lactose at low (6°C) and optimum (37°C) temperatures, respectively, suggesting the possibility of further optimization of the reaction for lactose-free dairy production. In addition, the enzyme was able to fully hydrolyse 40 mM of cellobiose at one hour and was tolerant to ethanol up to concentrations of 500 mM (86% of activity), while a 1 M concentration still resulted in 41% residual activity, which could be interesting for biofuel production. PMID:28002476

  14. High-protein diet selectively reduces fat mass and improves glucose tolerance in Western-type diet-induced obese rats.

    PubMed

    Stengel, Andreas; Goebel-Stengel, Miriam; Wang, Lixin; Hu, Eugenia; Karasawa, Hiroshi; Pisegna, Joseph R; Taché, Yvette

    2013-09-15

    Obesity is an increasing health problem. Because drug treatments are limited, diets remain popular. High-protein diets (HPD) reduce body weight (BW), although the mechanisms are unclear. We investigated physiological mechanisms altered by switching diet induced obesity (DIO) rats from Western-type diet (WTD) to HPD. Male rats were fed standard (SD) or WTD (45% calories from fat). After developing DIO (50% of rats), they were switched to SD (15% calories from protein) or HPD (52% calories from protein) for up to 4 weeks. Food intake (FI), BW, body composition, glucose tolerance, insulin sensitivity, and intestinal hormone plasma levels were monitored. Rats fed WTD showed an increased FI and had a 25% greater BW gain after 9 wk compared with SD (P < 0.05). Diet-induced obese rats switched from WTD to HPD reduced daily FI by 30% on day 1, which lasted to day 9 (-9%) and decreased BW during the 2-wk period compared with SD/SD (P < 0.05). During these 2 wk, WTD/HPD rats lost 72% more fat mass than WTD/SD (P < 0.05), whereas lean mass was unaltered. WTD/HPD rats had lower blood glucose than WTD/SD at 30 min postglucose gavage (P < 0.05). The increase of pancreatic polypeptide and peptide YY during the 2-h dark-phase feeding was higher in WTD/HPD compared with WTD/SD (P < 0.05). These data indicate that HPD reduces BW in WTD rats, which may be related to decreased FI and the selective reduction of fat mass accompanied by improved glucose tolerance, suggesting relevant benefits of HPD in the treatment of obesity.

  15. [Alpha-glucosidase inhibitor for the prevention of type 2 diabetes mellitus: a randomised, double-blind trial in Japanese subjects with impaired glucose tolerance].

    PubMed

    Kawamori, Ryuzo; Tajima, Naoko; Iwamoto, Yasuhiko; Kashiwagi, Atsunori; Shimamoto, Kazuaki; Kaku, Kohei

    2009-09-01

    The detrimental effects of a sedentary lifestyle and poor dietary habits are having a significant negative impact on health statistics, with obesity and its attendant risks becoming a major problem in most developed nations, including Japan. Interventions which prevent or delay the development of type 2 diabetes have the potential to reduce the morbidity and mortality associated with the disease and, as a consequence, related healthcare costs. The study conducted to assess whether alpha-glucosidase inhibitor, voglibose could prevent type 2 diabetes developing in high-risk Japanese subjects with impaired glucose tolerance (IGT). 1,780 eligible subjects received standard diet and exercise therapy, and 897 were randomised to receive voglibose and 883 placebo. The study was planned for treatment to be continued until participants developed type 2 diabetes [primary endpoint; determined by bi-annual oral glucose tolerance tests (OG'Ts) as well as fasting blood glucose measured every 3 months] or normoglycaemia or for a minimum of 3 years, subject to the findings of an interim analysis. The interim analysis significantly favoured voglibose and end-of-study report involves individuals treated for an average of 48.1 weeks. Subjects treated with voglibose had a significantly lower risk for the progression to type 2 diabetes than placebo (50/897 vs 106/881: hazard ratio 0.595). Also, significantly more subjects in the voglibose group achieved normoglycaemia compared with those in the placebo group (599/897 vs 454/881: hazard ratio 1.539). Voglibose, in addition to standard care with diet and exercise, was effective in preventing the progression of IGT to type 2 diabetes and in increasing the proportion of individuals with normoglycaemia in high-risk Japanese subjects with IGT.

  16. Colonic delivery of docosahexaenoic acid improves impaired glucose tolerance via GLP-1 secretion and suppresses pancreatic islet hyperplasia in diabetic KK-A(y) mice.

    PubMed

    Shida, Takayuki; Kamei, Noriyasu; Takeda-Morishita, Mariko; Isowa, Koichi; Takayama, Kozo

    2013-06-25

    Glucagon-like peptide-1 (GLP-1) is an incretin hormone that regulates the insulin secretion depending on blood glucose level. Recent studies show that the unsaturated fatty acids can promote GLP-1 secretion from intestinal L-cells. We have shown previously that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) administered into a mouse closed intestinal loop, especially into the colonic segment, stimulate GLP-1 and insulin secretion and have a hypoglycemic effect, suggesting that DHA and EPA have potential as antidiabetic agents. The present study examined the antidiabetic effect of DHA following long-term in vivo delivery to the colon using normal ddY and diabetic KK-A(y) mice. The plasma GLP-1 concentration of KK-A(y) mice increased after long-term DHA administration, and this had a significant hypoglycemic effect. In contrast, although GLP-1 secretion in ddY mice tended to increase after DHA administration, blood glucose concentration did not differ between vehicle- and DHA-treated ddY mice. Immunostaining of the pancreas after long-term DHA administration showed that continuous DHA treatment stimulated β-cell apoptosis and accordingly suppressed islet cell growth in KK-A(y) mice. Colon targeting of DHA may provide a new strategy for improving impaired glucose tolerance in type 2 diabetes mellitus by stimulating GLP-1 secretion, which may subsequently suppress the compensatory hyperplasia of pancreatic islets.

  17. Hepatic and Extrahepatic Insulin Clearance Are Differentially Regulated: Results From a Novel Model-Based Analysis of Intravenous Glucose Tolerance Data.

    PubMed

    Polidori, David C; Bergman, Richard N; Chung, Stephanie T; Sumner, Anne E

    2016-06-01

    Insulin clearance is a highly variable and important factor that affects circulating insulin concentrations. We developed a novel model-based method to estimate both hepatic and extrahepatic insulin clearance using plasma insulin and C-peptide profiles obtained from the insulin-modified frequently sampled intravenous glucose tolerance test. Data from 100 African immigrants without diabetes (mean age 38 years, body weight 81.7 kg, fasting plasma glucose concentration 83 mg/dL, and fasting insulin concentration 37 pmol/L) were used. Endogenous insulin secretion (calculated by C-peptide deconvolution) and insulin infusion rates were used as inputs to a new two-compartment model of insulin kinetics and hepatic and extrahepatic clearance parameters were estimated. Good agreement between modeled and measured plasma insulin profiles was observed (mean normalized root mean square error 6.8%), and considerable intersubject variability in parameters of insulin clearance among individuals was identified (the mean [interquartile range] for hepatic extraction was 25.8% [32.7%], and for extrahepatic insulin clearance was 20.7 mL/kg/min [11.7 mL/kg/min]). Parameters of insulin clearance were correlated with measures of insulin sensitivity and acute insulin response to glucose. The method described appears promising for future research aimed at characterizing variability in insulin clearance and the mechanisms involved in the regulation of insulin clearance.

  18. 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

  19. Phosphorylated S6K1 (Thr389) is a molecular adipose tissue marker of altered glucose tolerance.

    PubMed

    Moreno-Navarrete, José María; Ortega, Francisco; Sánchez-Garrido, Miguel Ángel; Sabater, Mònica; Ricart, Wifredo; Zorzano, Antonio; Tena-Sempere, Manuel; Fernández-Real, José Manuel

    2013-01-01

    Molecular tissue markers of altered glucose metabolism will be useful as potential targets for antidiabetic drugs. S6K1 is a downstream signal of insulin action. We aimed to evaluate (pThr389)S6K1 and total S6K1 levels in human and rat fat depots as candidate markers of altered glucose metabolism. (pThr389)S6K1 and total S6K1 levels were measured using enzyme linked immune sorbent assay (ELISA) in 49 adipose tissue samples from subjects with morbid obesity and in 18 peri-renal white adipose tissue samples from rats. The effects of high glucose and rosiglitazone have been explored in human preadipocytes. (pThr389)S6K1/(total)S6K1 in subcutaneous adipose tissue was significantly increased subjects with Type 2 diabetes (0.78 ± 0.26 vs. 0.55 ± 0.14, P=.02) and associated with fasting glucose (r=0.46, P=.04) and glycated hemoglobin (r=0.63, P=.02) in SAT. Similar associations with fasting glucose (r=0.43, P=.03) and IRS1 (r=-0.41, P=.04) gene expression were found in visceral adipose tissue. In addition, rat experiments confirmed the higher (pThr389)S6K1/totalS6K1 levels in adipose tissue in association with obesity-associated metabolic disturbances. (pThr389)S6K1/totalS6K1 was validated using western blot in rat adipose tissue. Both ELISA and western blot data significantly correlated (r=0.85, P=.005). In human preadipocytes, high glucose medium led to increased (pThr389)S6K1/total S6K1 levels in comparison with normal glucose medium, which was significantly decreased under rosiglitazone administration. In conclusion, in human and rat adipose tissue, phosphorylated S6K1 is a marker for increased glucose levels.

  20. Mitochondrial DNA copy number augments performance of A1C and oral glucose tolerance testing in the prediction of type 2 diabetes

    PubMed Central

    Cho, Seong Beom; Koh, InSong; Nam, Hye-Young; Jeon, Jae-Pil; Lee, Hong Kyu; Han, Bok-Ghee

    2017-01-01

    Here, we tested the performance of the mitochondrial DNA copy number (mtDNA-CN) in predicting future type 2 diabetes (n = 1108). We used the baseline clinical data (age, sex, body mass index, waist-to-hip ratio, systolic and diastolic blood pressure) and the mtDNA-CN, hemoglobin A1c (A1C) levels and results of oral glucose tolerance test (OGTT) including fasting plasma glucose, 1-hour glucose, and 2-hour glucose levels, to predict future diabetes. We built a prediction model using the baseline data and the diabetes status at biannual follow-up of 8 years. The mean area under curve (AUC) for all follow-ups of the full model including all variables was 0.92 ± 0.04 (mean ± standard deviation), while that of the model excluding the mtDNA-CN was 0.90 ± 0.03. The sensitivity of the f4ull model was much greater than that of the model not including mtDNA-CN: the mean sensitivities of the model with and without mtDNA-CN were 0.60 ± 0.06 and 0.53 ± 0.04, respectively. We found that the mtDNA-CN of peripheral leukocytes is a biomarker that augments the predictive power for future diabetes of A1C and OGTT. We believe that these results could provide invaluable information for developing strategies for the management of diabetes. PMID:28251996

  1. A mixture of cod and scallop protein reduces adiposity and improves glucose tolerance in high-fat fed male C57BL/6J mice.

    PubMed

    Tastesen, Hanne Sørup; Rønnevik, Alexander Krokedal; Borkowski, Kamil; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

    2014-01-01

    Low-protein and high-protein diets regulate energy metabolism in animals and humans. To evaluate whether different dietary protein sources modulate energy balance when ingested at average levels obesity-prone male C57BL/6J mice were pair-fed high-fat diets (67 energy percent fat, 18 energy percent sucrose and 15 energy percent protein) with either casein, chicken filet or a mixture of cod and scallop (1:1 on amino acid content) as protein sources. At equal energy intake, casein and cod/scallop fed mice had lower feed efficiency than chicken fed mice, which translated into reduced adipose tissue masses after seven weeks of feeding. Chicken fed mice had elevated hepatic triglyceride relative to casein and cod/scallop fed mice and elevated 4 h fasted plasma cholesterol concentrations compared to low-fat and casein fed mice. In casein fed mice the reduced adiposity was likely related to the observed three percent lower apparent fat digestibility compared to low-fat, chicken and cod/scallop fed mice. After six weeks of feeding an oral glucose tolerance test revealed that despite their lean phenotype, casein fed mice had reduced glucose tolerance compared to low-fat, chicken and cod/scallop fed mice. In a separate set of mice, effects on metabolism were evaluated by indirect calorimetry before onset of diet-induced obesity. Spontaneous locomotor activity decreased in casein and chicken fed mice when shifting from low-fat to high-fat diets, but cod/scallop feeding tended (P = 0.06) to attenuate this decrease. Moreover, at this shift, energy expenditure decreased in all groups, but was decreased to a greater extent in casein fed than in cod/scallop fed mice, indicating that protein sources regulated energy expenditure differently. In conclusion, protein from different sources modulates energy balance in C57BL/6J mice when given at normal levels. Ingestion of a cod/scallop-mixture prevented diet-induced obesity compared to intake of chicken filet and preserved glucose

  2. A Mixture of Cod and Scallop Protein Reduces Adiposity and Improves Glucose Tolerance in High-Fat Fed Male C57BL/6J Mice

    PubMed Central

    Tastesen, Hanne Sørup; Rønnevik, Alexander Krokedal; Borkowski, Kamil; Madsen, Lise; Kristiansen, Karsten; Liaset, Bjørn

    2014-01-01

    Low-protein and high-protein diets regulate energy metabolism in animals and humans. To evaluate whether different dietary protein sources modulate energy balance when ingested at average levels obesity-prone male C57BL/6J mice were pair-fed high-fat diets (67 energy percent fat, 18 energy percent sucrose and 15 energy percent protein) with either casein, chicken filet or a mixture of cod and scallop (1∶1 on amino acid content) as protein sources. At equal energy intake, casein and cod/scallop fed mice had lower feed efficiency than chicken fed mice, which translated into reduced adipose tissue masses after seven weeks of feeding. Chicken fed mice had elevated hepatic triglyceride relative to casein and cod/scallop fed mice and elevated 4 h fasted plasma cholesterol concentrations compared to low-fat and casein fed mice. In casein fed mice the reduced adiposity was likely related to the observed three percent lower apparent fat digestibility compared to low-fat, chicken and cod/scallop fed mice. After six weeks of feeding an oral glucose tolerance test revealed that despite their lean phenotype, casein fed mice had reduced glucose tolerance compared to low-fat, chicken and cod/scallop fed mice. In a separate set of mice, effects on metabolism were evaluated by indirect calorimetry before onset of diet-induced obesity. Spontaneous locomotor activity decreased in casein and chicken fed mice when shifting from low-fat to high-fat diets, but cod/scallop feeding tended (P = 0.06) to attenuate this decrease. Moreover, at this shift, energy expenditure decreased in all groups, but was decreased to a greater extent in casein fed than in cod/scallop fed mice, indicating that protein sources regulated energy expenditure differently. In conclusion, protein from different sources modulates energy balance in C57BL/6J mice when given at normal levels. Ingestion of a cod/scallop-mixture prevented diet-induced obesity compared to intake of chicken filet and preserved glucose

  3. Remission of pre-diabetes to normal glucose tolerance in obese adults with high protein versus high carbohydrate diet: randomized control trial

    PubMed Central

    Stentz, Frankie B; Brewer, Amy; Wan, Jim; Garber, Channing; Daniels, Blake; Sands, Chris; Kitabchi, Abbas E

    2016-01-01

    Objective Remission of pre-diabetes to normal is an important health concern which has had little success in the past. This study objective was to determine the effect on remission of pre-diabetes with a high protein (HP) versus high carbohydrate (HC) diet and effects on metabolic parameters, lean and fat body mass in prediabetic, obese subjects after 6 months of dietary intervention. Research design and methods We recruited and randomized 24 pre-diabetes women and men to either a HP (30% protein, 30% fat, 40% carbohydrate; n=12) or HC (15% protein, 30% fat, 55% carbohydrate; n=12) diet feeding study for 6 months in this randomized controlled trial. All meals were provided to subjects for 6 months with daily food menus for HP or HC compliance with weekly food pick-up and weight measurements. At baseline and after 6 months on the respective diets oral glucose tolerance and meal tolerance tests were performed with glucose and insulin measurements and dual energy X-ray absorptiometry scans. Results After 6 months on the HP diet, 100% of the subjects had remission of their pre-diabetes to normal glucose tolerance, whereas only 33.3% of subjects on the HC diet had remission of their pre-diabetes. The HP diet group exhibited significant improvement in (1) insulin sensitivity (p=0.001), (2) cardiovascular risk factors (p=0.04), (3) inflammatory cytokines (p=0.001), (4) oxidative stress (p=0.001), (5) increased percent lean body mass (p=0.001) compared with the HC diet at 6 months. Conclusions This is the first dietary intervention feeding study, to the best of our knowledge, to report 100% remission of pre-diabetes with a HP diet and significant improvement in metabolic parameters and anti-inflammatory effects compared with a HC diet at 6 months. Trial registration number NCT0164284. PMID:27843552

  4. The pathway by which the yeast protein kinase Snf1p controls acquisition of sodium tolerance is different from that mediating glucose regulation.

    PubMed

    Ye, Tian; Elbing, Karin; Hohmann, Stefan

    2008-09-01

    It recently became apparent that the highly conserved Snf1p protein kinase plays roles in controlling different cellular processes in the yeast Saccharomyces cerevisiae, in addition to its well-known function in glucose repression/derepression. We have previously reported that Snf1p together with Gis4p controls ion homeostasis by regulating expression of ENA1, which encodes the Ena1p Na(+) extrusion system. In this study we found that Snf1p is rapidly phosphorylated when cells are exposed to NaCl and this phosphorylation is required for the role of Snf1p in Na(+) tolerance. In contrast to activation by low glucose levels, the salt-induced phosphorylation of Snf1p promoted neither phosphorylation nor nuclear export of the Mig1p repressor. The mechanism that prevents Mig1p phosphorylation by active Snf1p under salt stress does not involve either hexokinase PII or the Gis4p regulator. Instead, Snf1p may mediate upregulation of ENA1 expression via the repressor Nrg1p. Activation of Snf1p in response to glucose depletion requires any of the three upstream protein kinases Sak1p, Tos3p and Elm1p, with Sak1p playing the most prominent role. The same upstream kinases were required for salt-induced Snf1p phosphorylation, and also under these conditions Sak1p played the most prominent role. Unexpectedly, however, it appears that Elm1p plays a dual role in acquisition of salt tolerance by activating Snf1p and in a presently unknown parallel pathway. Together, these results indicate that under salt stress Snf1p takes part in a different pathway from that during glucose depletion and this role is performed together as well as in parallel with its upstream kinase Elm1p. Snf1p appears to be part of a wider functional network than previously anticipated and the full complexity of this network remains to be elucidated.

  5. 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

  6. Stress Tolerance and Glucose Insensitive Phenotypes in Arabidopsis Overexpressing the CpMYB10 Transcription Factor Gene1

    PubMed Central

    Villalobos, Miguel Angel; Bartels, Dorothea; Iturriaga, Gabriel

    2004-01-01

    The resurrection plant Craterostigma plantagineum has the ability to survive complete dehydration. In an attempt to further understand desiccation tolerance in this plant, the CpMYB10 transcription factor gene was functionally characterized. CpMYB10 is rapidly induced by dehydration and abscisic acid (ABA) treatments in leaves and roots, but no expression was detected in fully hydrated tissues. Electrophoretic mobility shift assay experiments showed binding of rCpMYB10 to specific mybRE elements within the LEA Cp11-24 and CpMYB10 promoters. Localization of CpMYB10 transcript by in situ reverse transcription-PCR reactions showed expression in vascular tissues, parenchyma, and epidermis both in leaves and roots in response to ABA. Transgenic Arabidopsis plants transformed with CpMYB10 promoter fused to GUS gene showed reporter expression under ABA and stress conditions in several organs. Overexpression of CpMYB10 cDNA in Arabidopsis led to desiccation and salt tolerance of transgenics lines. Interestingly, it was found that plants overexpressing CpMYB10 exhibited Glc-insensitive and ABA hypersensitive phenotypes. Therefore, our results indicate that CpMYB10 in Arabidopsis is mediating stress tolerance and altering ABA and Glc signaling responses. PMID:15122027

  7. 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

  8. Mulberry-extract improves glucose tolerance and decreases insulin concentrations in normoglycaemic adults: Results of a randomised double-blind placebo-controlled study

    PubMed Central

    2017-01-01

    Background High sugar and refined carbohydrate intake is associated with weight gain, increased incidence of diabetes and is linked with increased cardiovascular mortality. Reducing the health impact of poor quality carbohydrate intake is a public health priority. Reducose, a proprietary mulberry leaf extract (ME), may reduce blood glucose responses following dietary carbohydrate intake by reducing absorption of glucose from the gut. Methods A double-blind, randomised, repeat measure, phase 2 crossover design was used to study the glycaemic and insulinaemic response to one reference product and three test products at the Functional Food Centre, Oxford Brooks University, UK. Participants; 37 adults aged 19–59 years with a BMI ≥ 20kg/m2 and ≤ 30kg/m2. The objective was to determine the effect of three doses of mulberry-extract (Reducose) versus placebo on blood glucose and insulin responses when co-administered with 50g maltodextrin in normoglycaemic healthy adults. We also report the gastrointestinal tolerability of the mulberry extract. Results Thirty-seven participants completed the study: The difference in the positive Incremental Area Under the Curve (pIAUC) (glucose (mmol / L x h)) for half, normal and double dose ME compared with placebo was -6.1% (-18.2%, 5.9%; p = 0.316), -14.0% (-26.0%, -2.0%; p = 0.022) and -22.0% (-33.9%, -10.0%; p<0.001) respectively. The difference in the pIAUC (insulin (mIU / L x h)) for half, normal and double dose ME compared with placebo was -9.7% (-25.8%, 6.3%; p = 0.234), -23.8% (-39.9%, -7.8%; p = 0.004) and -24.7% (-40.8%, -8.6%; p = 0.003) respectively. There were no statistically significant differences between any of the 4 groups in the odds of experiencing one or more gastrointestinal symptoms (nausea, abdominal cramping, distension or flatulence). Conclusions Mulberry leaf extract significantly reduces total blood glucose rise after ingestion of maltodextrin over 120 minutes. The pattern of effect demonstrates a

  9. De-phosphorylation of translation initiation factor 2α (eIF2α) enhances glucose tolerance and attenuates hepato-steatosis in mice

    PubMed Central

    Oyadomari, Seiichi; Harding, Heather P.; Zhang, Yuhong; Oyadomari, Miho; Ron, David

    2008-01-01

    Summary The molecular mechanisms linking the stress of unfolded proteins in the endoplasmic reticulum (ER stress) to glucose intolerance in obese animals are poorly understood. In this study enforced expression of a translation initiation 2α(eIF2α)-specific phosphatase, GADD34, was used to selectively compromise signaling in the eIF2(αP)-dependent arm of the ER unfolded protein response in liver of transgenic mice. The transgene resulted in lower liver glycogen levels and susceptibility to fasting hypoglycemia in lean mice and glucose tolerance and diminished hepato-steatosis in animals fed a high fat diet. Attenuated eIF2(αP) correlated with lower expression of the adipogenic nuclear receptor PPARγ and its upstream regulators, the transcription factors C/EBPα and C/EBPβ, in transgenic mouse liver, whereas eIF2α phosphorylation promoted C/EBP translation in cultured cells and primary hepatocytes. These observations suggest that eIF2(αP)-mediated translation of key hepatic transcriptional regulators of intermediary metabolism contributes to the detrimental consequences of nutrient excess. PMID:18522833

  10. [Prevalence of diabetes mellitus and glucose tolerance abnormality in Melanesians and subjects of Polynesian descent in the rural areas of New Caledonia and at Ouvea (Loyalty Islands)].

    PubMed

    Zimmet, P; Canteloube, D; Le Gonidec, G; Couzigou, P; Genelle, B; Peghini, M; Charpin, M; Bennett, P; Kuberski, T; Kleiber, N; Taylor, R

    1982-01-01

    The screening of different ethnic groups who live in the same natural system have enabled the authors to study interaction between genetic and environmental factors as a part of etiology of diabetes mellitus. In New Caledonian country areas, the prevalences of glucose tolerance abnormality (GTA) and diabetes mellitus (DM) have been higher with people of polynesian descent than with Melanesians. GTA 7.6 p. ct. versus 5.1 p. ct. DM 6.5 p. ct. versus 2.2 p. ct. The prevalence of these combined diseases have been 14 p. ct. with the Polynesians and 7.2 p. ct. with Melanesians. These two ethnic groups have shown mean ages and obesity rates similar enough to lead the authors to deny these two factors a major part in the difference between the ethnic prevalences of DM. Besides, the mean plasmatic glycemia two hours after a dose of glucose and the relative risk of DM and GTA according to age and obesity rate have shown that the slight differences between these groups are not involved in the different prevalences of DM. This inter-ethnic difference may be due to genetic factors. However, some environment linked factors besides obesity (such as diet and daily life activity) may share a major part in this difference.

  11. A very low carbohydrate ketogenic diet improves glucose tolerance in ob/ob mice independently of weight loss.

    PubMed

    Badman, Michael K; Kennedy, Adam R; Adams, Andrew C; Pissios, Pavlos; Maratos-Flier, Eleftheria

    2009-11-01

    In mice of normal weight and with diet-induced obesity, a high-fat, low-carbohydrate ketogenic diet (KD) causes weight loss, reduced circulating glucose and lipids, and dramatic changes in hepatic gene expression. Many of the effects of KD are mediated by fibroblast growth factor 21 (FGF21). We tested the effects of KD feeding on ob/ob mice to determine if metabolic effects would occur in obesity secondarily to leptin deficiency. We evaluated the effect of prolonged KD feeding on weight, energy homeostasis, circulating metabolites, glucose homeostasis, and gene expression. Subsequently, we evaluated the effects of leptin and fasting on FGF21 expression in ob/ob mice. KD feeding of ob/ob mice normalized fasting glycemia and substantially reduced insulin and lipid levels in the absence of weight loss. KD feeding was associated with significant increases in lipid oxidative genes and reduced expression of lipid synthetic genes, including stearoyl-coenzyme A desaturase 1, but no change in expression of inflammatory markers. In chow-fed ob/ob mice, FGF21 mRNA was elevated 10-fold compared with wild-type animals, and no increase from this elevated baseline was seen with KD feeding. Administration of leptin to chow-fed ob/ob mice led to a 24-fold induction of FGF21. Fasting also induced hepatic FGF21 in ob/ob mice. Thus, KD feeding improved ob/ob mouse glucose homeostasis without weight loss or altered caloric intake. These data demonstrate that manipulation of dietary macronutrient composition can lead to marked improvements in metabolic profile of leptin-deficient obese mice in the absence of weight loss.

  12. Effect of dry tomato peel supplementation on glucose tolerance, insulin resistance, and hepatic markers in mice fed high-saturated-fat/high-cholesterol diets.

    PubMed

    Zidani, Sofiane; Benakmoum, Amar; Ammouche, Ali; Benali, Yasmine; Bouhadef, Anissa; Abbeddou, Souheila

    2017-02-01

    Many studies have investigated the effect of crude tomato peel in vivo, but no studies have determined the dose-effect of dry tomato peel (DTP) on glucose intolerance, insulin resistance, and atherogenic dyslipidemia induced by a high-saturated-fat (HSF) diet in vivo. The aim of this study was to investigate the effects of different doses of DTP on the levels of oxidative stress in mice fed an HSF and cholesterol-rich diet for 12 weeks. The main outcomes are glucose and insulin tolerance, plasma lipids, and hepatic steatosis and inflammation. BALB/c male mice (n=40) (8 weeks old, weighing 22.2±1.0 g) were divided into four treatment groups (10 mice/group): (a) high-fat control diet (HF Ctrl), which contains sunflower oil as a sole source of fat; (b) HSF/high-cholesterol (HC) diet; (c) HSF/HC diet supplemented with 9% DTP and (d) HSF/HC diet supplemented with 17% DTP. The HSF/HC diet significantly increased body weight gain, adipose tissue weight, fasting plasma glucose, fasting plasma insulin and lipid peroxidation and caused the development of liver steatosis and inflammation. Supplementation with DTP increased plasma lycopene concentration and reduced the development of indicators of metabolic syndrome, with no consistent effect of the DTP dose. Hepatic steatosis and inflammation were not reversed with DTP supplementation. Among mice fed the HSF/HC diet, DTP supplementation appears to have a beneficial effect on insulin resistance, which confirms the antiatherogenic effect of DTP.

  13. 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.

  14. The unfolded protein response in human skeletal muscle is not involved in the onset of glucose tolerance impairment induced by a fat-rich diet.

    PubMed

    Deldicque, Louise; Van Proeyen, Karen; Francaux, Marc; Hespel, Peter

    2011-07-01

    Endoplasmic reticulum (ER) stress in pancreas, liver, and adipose tissue is a key event in the pathogenesis of obesity-related metabolic disease. Lipid-induced ER stress in liver and adipose tissue leads to inhibition of insulin signaling. Whether this mechanism exists in skeletal muscle is currently unknown. The present study aimed at assessing the ER stress response in skeletal muscle of subjects receiving a hyper-caloric fat-rich diet (HFD). Seven healthy males (20.6 ± 0.5 years; 70.9 ± 3.4 kg) volunteered to participate in the study. They received a hyper-caloric (+30% kcal) fat-rich (50% kcal) diet for 6 weeks. An oral glucose tolerance test (OGTT) was performed, and muscle biopsies were taken before and after HFD. HFD increased body mass by ~3 kg (P = 0.007) and the sum of skinfolds by 15% (P = 0.003). After HFD, blood glucose concentrations were higher during OGTT (two-way ANOVA, P = 0.023; +45% at 20 min, P = 0.002), and fasting plasma insulin level tended to be higher (+20%). HFD increased intramyocellular lipids content by ~50 and 75% in type I (P = 0.0009) and IIa fibers (P = 0.002), respectively. The protein expression of inositol-requiring enzyme 1α, protein kinase R-like ER protein kinase, BiP and calnexin and the mRNA level of spliced X box binding protein-1, CCAAT/enhancer binding protein homologous protein and activating transcription factor 4 were not changed after HFD. Despite the increase in body mass, subcutaneous fat deposits, and intramyocellular lipids content, ER stress markers were unchanged in skeletal muscle of subjects receiving a HFD for 6 weeks. This suggests that the onset of glucose intolerance is not related to ER stress in skeletal muscle.

  15. Group-based activities with on-site childcare and online support improve glucose tolerance in women within 5 years of gestational diabetes pregnancy

    PubMed Central

    2014-01-01

    Background Women with gestational diabetes history are at increased risk for type 2 diabetes. They face specific challenges for behavioural changes, including childcare responsibilities. The aim of this study is to test a tailored type 2 diabetes prevention intervention in women within 5 years of a pregnancy with gestational diabetes, in terms of effects on weight and cardiometabolic risk factors. Methods The 13-week intervention, designed based on focus group discussions, included four group sessions, two with spousal participation and all with on-site childcare. Web/telephone-based support was provided between sessions. We computed mean percentage change from baseline (95% confidence intervals, CI) for anthropometric measures, glucose tolerance (75 g Oral glucose tolerance test), insulin resistance/sensitivity, blood pressure, physical activity, dietary intake, and other cardiometabolic risk factors. Results Among the 36 enrolled, 27 completed final evaluations. Most attended ≥ 3 sessions (74%), used on-site childcare (88%), and logged onto the website (85%). Steps/day (733 steps, 95% CI 85, 1391) and fruit/vegetable intake (1.5 servings/day, 95% CI 0.3, 2.8) increased. Proportions decreased for convenience meal consumption (−30%, 95% CI −50, −9) and eating out (−22%, 95% CI −44, −0) ≥ 3 times/month. Body mass index and body composition were unchanged. Fasting (−4.9%, 95% CI −9.5, −0.3) and 2-hour postchallenge (−8.0%, 95% CI −15.6, −0.5) glucose declined. Insulin sensitivity increased (ISI 0,120 23.7%, 95% CI 9.1, 38.4; Matsuda index 37.5%, 95% CI 3.5, 72.4). Insulin resistance (HOMA-IR −9.4%, 95% CI −18.6, −0.1) and systolic blood pressure (−3.3%, 95% CI −5.8, −0.8) decreased. Conclusions A tailored group intervention appears to lead to improvements in health behaviours and cardiometabolic risk factors despite unchanged body mass index and body composition. This approach merits further study. Clinical trial

  16. Baseline characteristics of the Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial population: comparison with other diabetes prevention trials.

    PubMed

    Krum, Henry; McMurray, John J V; Horton, Edward; Gerlock, Teresa; Holzhauer, Bjoern; Zuurman, Lineke; Haffner, Steven M; Bethel, M Angelyn; Holman, Rury R; Califf, Robert M

    2010-04-01

    The Nateglinide and Valsartan Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) trial is exploring two pharmacological strategies (nateglinide and valsartan, both alone and in combination) in the prevention of overt diabetes mellitus (DM) and the reduction of cardiovascular disease (CVD) in subjects at high risk for these events. In this analysis, we provide baseline characteristics of the randomized NAVIGATOR study population and contrast them with those from other trials of DM prevention. Key eligibility criteria include impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), a history of CVD (in patients aged > or =50 years), and > or =1 cardiovascular risk factor (in patients aged > or =55 years). Baseline demographic characteristics, laboratory findings, cardiovascular risk factors, CVD history, and medication use are described and compared with other trials of DM prevention. The full analysis set of subjects (N = 9306) showed a clustering of risk factors consistent with the metabolic syndrome: high rates of hypertension (77.5%), dyslipidemia (44.7%), increased waist circumference (101.0 cm), and high body mass index (BMI) (47.5% with BMI > or =30 kg/m(2)). A minority of patients had a history of CVD (24.3%); of these, 11.7% had a history of myocardial infarction and most of the remainder had evidence of coronary artery disease. Subjects also had elevated blood pressure (BP) (predominantly systolic) (139.7/82.6 mm Hg), increased serum low-density lipoproteins cholesterol levels (3.27 mmol/L), and borderline elevation of triglyceride levels (1.97 mmol/L). Demographic data, BP, and lipid profiles in NAVIGATOR were similar to those of previous DM prevention trials, which were also based largely on meeting criteria for IGT. Medication use at baseline among NAVIGATOR subjects, which frequently included aspirin, beta-blockers, calcium channel blockers, diuretics, and lipid-lowering agents, reflects enhanced CVD risk. However, little prescribing

  17. Mosapride, a selective serotonin 5-HT4 receptor agonist, and alogliptin, a selective dipeptidyl peptidase-4 inhibitor, exert synergic effects on plasma active GLP-1 levels and glucose tolerance in mice.

    PubMed

    Nonogaki, Katsunori; Kaji, Takao

    2015-12-01

    Pharmacologic stimulation of serotonin 5-HT4 receptors increased plasma active glucagon-like-peptide-1 (GLP-1) levels independent of feeding, and that pharmacologic stimulation of 5-HT4 receptors and pharmacologic inhibition of dipeptidyl peptidase-4 exerted synergic effects on plasma active GLP-1 levels and glucose tolerance in mice.

  18. The solvent-tolerant Pseudomonas putida S12 as host for the production of cinnamic acid from glucose.

    PubMed

    Nijkamp, Karin; van Luijk, Nicole; de Bont, Jan A M; Wery, Jan

    2005-11-01

    A Pseudomonas putida S12 strain was constructed that efficiently produced the fine chemical cinnamic acid from glucose or glycerol via the central metabolite phenylalanine. The gene encoding phenylalanine ammonia lyase from the yeast Rhodosporidium toruloides was introduced. Phenylalanine availability was the main bottleneck in cinnamic acid production, which could not be overcome by the overexpressing enzymes of the phenylalanine biosynthesis pathway. A successful approach in abolishing this limitation was the generation of a bank of random mutants and selection on the toxic phenylalanine anti-metabolite m-fluoro-phenylalanine. Following high-throughput screening, a mutant strain was obtained that, under optimised culture conditions, accumulated over 5 mM of cinnamic acid with a yield (Cmol%) of 6.7%.

  19. 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

  20. 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

  1. 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

  2. Up-regulation of heme oxygenase-1 by isoflurane preconditioning during tolerance against neuronal injury induced by oxygen glucose deprivation.

    PubMed

    Li, Qifang; Zhu, Yesen; Jiang, Hong; Xu, Hui; Liu, Heping

    2008-09-01

    Heme oxygenase (HO) is the rate-limiting enzyme in the degradation of heme to produce bile pigments and carbon monoxide. The HO-1 isozyme is induced by a variety of factors such as heat, heme, ischemia, and hydrogen peroxide. In recent years, mounting findings have suggested that HO-1 has a neuroprotective activity against ischemic injury. The neuroprotective role of isoflurane, a commonly used anesthetic, has been well documented, but little is known about the underlying mechanisms involved. Recently, isoflurane has been shown to up-regulate HO-1 in the liver. In this study, we show that isoflurane preconditioning promotes the survival of cultured ischemic hippocampal neurons by increasing the number of surviving neurons and their viability. Further study by reverse transcription-polymerase chain reaction and Western blot analysis showed that isoflurane preconditioning significantly increases HO-1 expression in oxygen glucose deprivation (OGD)-induced neuronal injury. Furthermore, inhibition of HO activity by tin protoporphyrin partially abolishes isoflurane preconditioning's protective effect as measured by lactate dehydrogenase release in OGD neurons. These findings indicated that the neuroprotective role of isoflurane preconditioning against OGD-induced injury might be associated with its role in up-regulating HO-1 in ischemic neurons.

  3. Reduced glycaemic and insulinaemic responses following trehalose and isomaltulose ingestion: implications for postprandial substrate use in impaired glucose-tolerant subjects.

    PubMed

    van Can, Judith G P; van Loon, Luc J C; Brouns, Fred; Blaak, Ellen E

    2012-10-01

    The impact of slowly digestible sugars in reducing the risk of developing obesity and related metabolic disorders remains unclear. We hypothesised that such carbohydrates (CHO), resulting in a lower glycaemic and insulinaemic response, may lead to greater postprandial fat oxidation rates in subjects with impaired glucose tolerance (IGT). The present study intends to compare the postprandial metabolic responses to the ingestion of glucose (GLUC) v. trehalose (TRE) and sucrose (SUC) v. isomaltulose (IMU). In a randomised, single-blind, cross-over design, ten overweight IGT subjects were studied four times, following ingestion of different CHO drinks either at breakfast or in combination with a mixed meal at lunch. Before and 3 h after CHO ingestion, energy expenditure, substrate utilisation and circulating metabolite concentrations were determined. Ingestion of CHO drinks with a meal resulted in an attenuated rise in GLUC (-33 %) and insulin (-14 %) concentrations following TRE when compared with GLUC and following IMU, an attenuation of 43 and 34 % when compared with SUC ingestion, respectively. Additionally, there was less inhibition of the rise in NEFA concentrations and less decline in postprandial fat oxidation (22 %) after IMU when compared with SUC, whereas TRE did not differ from GLUC. The attenuated rise in GLUC and insulin concentrations following IMU ingestion attenuated the postprandial inhibition of fat oxidation compared with SUC when co-ingested with a meal. This suggests that exchange of SUC in the diet for IMU may result in a more favourable metabolic response and may help to reduce the risks associated with obesity and type 2 diabetes.

  4. Brevinin-2-related peptide and its [D4K] analogue stimulate insulin release in vitro and improve glucose tolerance in mice fed a high fat diet.

    PubMed

    Abdel-Wahab, Y H A; Patterson, S; Flatt, P R; Conlon, J M

    2010-08-01

    The cationic, alpha-helical frog skin antimicrobial peptide B2RP (brevinin-2-related peptide) shows sequence similarity to antimicrobial peptides belonging to the brevinin-2 family, but lacks the C-terminal cyclic heptapeptide domain (Cys-Lys-Xaa (4)-Cys). Synthetic B2RP produced a significant (p<0.05) stimulation of insulin release (148% of basal rate at a concentration of 1 muM with a maximum response of 222% of basal rate at a concentration of 3 muM) from BRIN-BD11 clonal beta-cells without increasing the release of the cytosolic enzyme, lactate dehydrogenase. Increasing cationicity of B2RP while maintaining amphipathicity by the substitution Asp (4) --> Lys enhanced the insulin-releasing potency (137% of basal rate at a concentration of 0.3 muM; p<0.05) with no stimulation of lactate dehydrogenase release. In contrast, the L18K, and D4K, L18K analogues were toxic to the cells, and the K16A analogue, with increased amphipathicity and hydrophobicity, showed reduced potency. Administration of [D4K]B2RP (100 nmol/kg body weight) to mice fed a high fat diet to induce obesity and insulin-resistance significantly (p<0.05) enhanced insulin release and improved glucose tolerance during the 60-minute period following an intraperitoneal glucose load (18 mmol/kg body weight). B2RP shows potential for development into an agent for the treatment of type 2 diabetes.

  5. Inhibition of Small Maf Function in Pancreatic β-Cells Improves Glucose Tolerance Through the Enhancement of Insulin Gene Transcription and Insulin Secretion

    PubMed Central

    Nomoto, Hiroshi; Miyoshi, Hideaki; Nakamura, Akinobu; Hida, Yoko; Yamashita, Ken-ichiro; Sharma, Arun J.; Atsumi, Tatsuya

    2015-01-01

    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

  6. 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

  7. A novel cobiotic containing a prebiotic and an antioxidant augments the glucose control and gastrointestinal tolerability of metformin: a case report.

    PubMed

    Greenway, F; Wang, S; Heiman, M

    2014-03-01

    The gut microbiome plays an important role in regulation of metabolic processes, including digestion, absorption, and synthesis of bioactive molecules that signal physiological host mechanisms. Changes in the human gut microbiome are associated with type 2 diabetes and insulin resistance. Water-soluble dietary fibres like inulin and beta-glucan are fermented in the colon, and beta-glucan increases viscosity. Blueberries improve insulin sensitivity through an antioxidant effect. A cobiotic, consisting of purified inulin, sugar-free blueberry pomace extract, and an oat preparation of purified beta-glucan was developed for twice a day (bid) consumption as a smoothie drink to repair the gastrointestinal dysbiosis in type 2 diabetes. A 30-year-old man presented with new onset type 2 diabetes and a fasting glucose (FBS) of 375 mg/dl. Metformin 500 mg bid was initiated and increased to 1 g bid after 1 week. During the first 9 days of metformin treatment, he developed diarrhoea, but his FBS only dropped to 325 mg/dl. The cobiotic bid was added on the 9th day of metformin treatment, and after 2 days, his FBS dropped to 175 mg/dl. After 8 weeks on metformin and the cobiotic, his blood sugar was 100 mg/dl and he lost 5.5 kg. His stools became soft and formed on the cobiotic, reverted to diarrhoea when off of it for 2 days, and returned to normal on resuming the cobiotic formulation. Metformin is a safe, effective and inexpensive generic medication favouring weight loss, recommended as initial treatment of type 2 diabetes by the American Diabetes Association. However, a 20% incidence of diarrhoea limits its tolerability. A safe food supplement that can increase the efficacy of metformin and its tolerability, as occurred in this case report, would have significant positive public health consequences. A controlled clinical trial of the cobiotic with metformin is planned.

  8. 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.

  9. 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

  10. [The content of individual fatty acids and numbers of double bonds, insulin, C-peptide and unesterified fatty acids in blood plasma in testing tolerance to glucose].

    PubMed

    Titov, V N; Sazhina, N N; Aripovskiĭ, A V; Evteeva, N M; Tkhagalizhokova, É M; Parkhimovich, R M

    2014-10-01

    The glucose tolerance test demonstrates that content of unesterified fatty acids in blood plasma decreases up to three times and the content of oleic and linoleic acids is more decreased in the pool of fatty acids lipids. Out of resistance to insulin, hormone secretion increases up to three times. The decreasing of level of individual fatty acids occurs in a larger extent. Under resistance to insulin secretion of insulin is increasing up to eight times. The decreasing of level of each fatty acid is less expressed. The effect of insulin reflects decreasing of content of double bonds in blood plasma. The number of double bonds characterizes the degree of unsaturation of fatty acids in lipids of blood plasma. The higher number of double bonds is in the pool of unesterified fatty acids the more active is the effect of insulin. The hyper-secretion of insulin is directly proportional to content of palmitic fatty acid in lipids of blood plasma on fasting. According the phylogenetic theory of general pathology, the effect of insulin on metabolism of glucose is mediated by fatty acids. The insulin is blocking lipolysis in insulin-depended subcutaneous adipocytes and decreases content of unesterified fatty acids in blood plasma. The insulin is depriving all cells of possibility to absorb unesterified fatty acids and "forces" them to absorb glucose increasing hereby number of GLUT4 on cell membrane. The resistance to insulin is manifested in high concentration of unesterfied fatty acids, hyperinsulinemia, hyperalbuminemia and increasing of concentration of C-reactive protein-monomer. The resistance to insulin is groundlessly referred to as a symptom of diabetes mellitus type II. The resistance to insulin is only a functional disorder lasting for years. It can be successfully arrested. The diabetes mellitus is developed against the background of resistance to insulin only after long-term hyper-secretion of insulin and under emaciation and death of β-cells. The diabetes

  11. Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young south african adults: early programming of cortisol axis.

    PubMed

    Levitt, N S; Lambert, E V; Woods, D; Hales, C N; Andrew, R; Seckl, J R

    2000-12-01

    Low birth weight is associated with increased cardiovascular and metabolic disorders in adult life, although the mechanisms of this effect remain uncertain. There is one report of increased morning plasma cortisol levels in an elderly low birth weight cohort, but whether this is primary or secondary to other aspects of the phenotype is unclear. We investigated the association between low birth weight and glucose intolerance, blood pressure, and dyslipidemia in young, nonobese adults from a community undergoing the health transition with a high prevalence of both noncommunicable diseases and low birth weight. Additionally, we investigated whether altered basal and stimulated cortisol levels as a marker of hypothalamic-pituitary-adrenal responsiveness or cortisol metabolism were associated with low birth weight in these young adults. Twenty-year-old, historically disadvantaged, urbanized South Africans (n = 137) with birth weights either below the 10th percentile [underweight for age (UFA)] or between the 25th and 75th percentiles [appropriate for gestational age (AFA)] had anthropometry, blood pressure, lipid levels, and glucose tolerance measured. In a subset (n = 62), 0900 h plasma cortisol concentrations, cortisol responses to 1 microg ACTH, and urinary glucocorticoid metabolites were measured. The mothers of UFA infants were themselves lighter and had a lower body mass index (P: = 0. 0016). At age 20 yr, although the UFA group was still smaller and lighter, with a lower body mass index, they had higher fasting plasma glucose levels (P: = 0.047), and a greater proportion demonstrated glucose intolerance (11.9% vs. 0%; P: < 0.01). The UFA group also had higher systolic [UFA, 126.0 +/- 13.3 (+/-SD); AFA, 122.0 +/- 11.7 mm Hg; P: = 0.007] and diastolic (72.3 +/- 8.4 vs. 69. 5 +/- 8.7 mm Hg; P: = 0.02) blood pressures, after covarying for current weight and gender. Plasma cortisol levels determined at 0900 h were higher in the UFA group (484.9 +/- 166.3 vs. 418

  12. Evaluation of a Standardized Extract from Morus alba against α-Glucosidase Inhibitory Effect and Postprandial Antihyperglycemic in Patients with Impaired Glucose Tolerance: A Randomized Double-Blind Clinical Trial

    PubMed Central

    Hwang, Seung Hwan; Li, Hong Mei; Wang, Zhiqiang

    2016-01-01

    To evaluate the antihyperglycemic effect of a standardized extract of the leaves of Morus alba (SEMA), the present study was designed to investigate the α-glucosidase inhibitory effect and acute single oral toxicity as well as evaluate blood glucose reduction in animals and in patients with impaired glucose tolerance in a randomized double-blind clinical trial. SEMA was found to inhibit α-glucosidase at a fourfold higher level than the positive control (acarbose), in a concentration-dependent manner. Moreover, blood glucose concentration was suppressed by SEMA in vivo. Clinical signs and weight changes were observed when conducting an evaluation of the acute toxicity of SEMA through a single-time administration, with clinical observation conducted more than once each day. After administration of the SEMA, observation was for 14 days; all of the animals did not die and did not show any abnormal symptoms. In addition, the inhibitory effects of rice coated with SEMA were evaluated in a group of impaired glucose tolerance patients on postprandial glucose and a group of normal persons, and results showed that SEMA had a clear inhibitory effect on postprandial hyperglycemia in both groups. Overall, SEMA showed excellent potential in the present study as a material for improving postprandial hyperglycemia. PMID:27974904

  13. 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.

  14. Sodium–glucose cotransporter-2 inhibitor combination therapy to optimize glycemic control and tolerability in patients with type 2 diabetes: focus on dapagliflozin–metformin

    PubMed Central

    Schwartz, Stanley S; Katz, Arie

    2016-01-01

    In type 2 diabetes (T2D), early combination therapy using agents that target a number of the underlying pathophysiologic defects contributing to hyperglycemia may improve patient outcomes. For many patients, the combination of metformin with a sodium–glucose cotransporter-2 (SGLT-2) inhibitor may be a good option because these agents have complementary mechanisms of action, neutral-to-positive effects on body weight, and a low risk of hypoglycemia. This review focuses on the combination of metformin with dapagliflozin, a member of the SGLT-2 inhibitor class of antidiabetes agents. In clinical trials, the combination of dapagliflozin with metformin produced significant and sustained reductions in glycated hemoglobin and body weight in a broad range of adult patients with T2D, including those initiating pharmacotherapy and those with more advanced disease. These reductions were accompanied by modest decreases in blood pressure. Dapagliflozin as add-on therapy to metformin was well tolerated and associated with low rates of hypoglycemia. Genital infections and, in some studies, urinary tract infections were more frequent with dapagliflozin than with placebo. Early combination therapy with dapagliflozin and metformin may be a safe and appropriate treatment option that enables patients with T2D to achieve individualized glycemic goals as either initial combination therapy in treatment-naïve patients or as dapagliflozin add-on in patients inadequately controlled with metformin therapy. PMID:27042132

  15. Assessment of the Medial Dorsal Cutaneous, Dorsal Sural, and Medial Plantar Nerves in Impaired Glucose Tolerance and Diabetic Patients With Normal Sural and Superficial Peroneal Nerve Responses

    PubMed Central

    Im, Sun; Kim, Sung-Rae; Park, Joo Hyun; Kim, Yang Soo; Park, Geun-Young

    2012-01-01

    OBJECTIVE This study evaluated the nerve conduction study (NCS) parameters of the most distal sensory nerves of the lower extremities—namely, the medial dorsal cutaneous (MDC), dorsal sural (DS), and medial plantar (MP) nerves—in diabetic (DM) and impaired glucose tolerance (IGT) patients who displayed normal findings on their routine NCSs. RESEARCH DESIGN AND METHODS Standard NCSs were performed on healthy control (HC), DM, and IGT groups (N = 147). The bilateral NCS parameters of the MDC, DS, and MP nerves were investigated. The Toronto Clinical Scoring System (TCSS) was assessed for the DM and IGT groups. RESULTS The mean TCSS scores of the IGT and DM groups were 2.5 ± 2.3 and 2.8 ± 2.2, respectively. No significant differences between the two groups were observed. After adjustment of age and BMI, the DM group showed significant NCS differences in DS and MDC nerves compared with the HC group (P < 0.05). These differences were also exhibited in the left DS of the IGT group (P = 0.0003). More advanced NCS findings were observed in the DM group. Bilateral abnormal NCS responses in these distal sensory nerves were found in 40 and 16% of DM and IGT patients, respectively. CONCLUSIONS These results showed that the simultaneous assessment of the most distal sensory nerves allowed the detection of early NCS changes in the IGT and DM groups, even when the routine NCS showed normal findings. PMID:22100966

  16. Overexpression of peroxisome proliferator-activated receptor α in pancreatic β-cells improves glucose tolerance in diet-induced obese mice.

    PubMed

    Hogh, K-Lynn N; Uy, Christopher E; Asadi, Ali; Baker, Robert K; Riedel, Michael J; Gray, Sarah L

    2013-02-01

    Lipotoxicity is implicated in pancreatic β-cell dysfunction in obesity-induced type 2 diabetes. In vitro, activation of peroxisome proliferator-activated receptor α (PPARα) has been shown to protect pancreatic β-cells from the lipotoxic effects of palmitate, thereby preserving insulin secretion. Utilizing an adeno-associated virus (dsAAV8), overexpression of PPARα was induced specifically in pancreatic β-cells of adult, C57Bl/6 mice fed a high-fat diet for 20 weeks and carbohydrate metabolism and β-cell mass assessed. We show that overexpression of PPARα in pancreatic β-cells in vivo preserves β-cell function in obesity, and this improves glucose tolerance by preserving insulin secretion in comparison to control mice with diet-induced obesity. No changes in β-cell mass were observed in PPARα-overexpressing mice compared with diet-induced obese control animals. This model of β-cell-specific PPARα overexpression provides a useful in vivo model for elucidating the mechanisms underlying β-cell lipotoxicity in obesity-induced type 2 diabetes.

  17. Reducing activity, glucose metabolism and acid tolerance response of Bacillus cereus grown at various pH and oxydo-reduction potential levels.

    PubMed

    Le Lay, Julien; Bahloul, Halim; Sérino, Sylvie; Jobin, Michel; Schmitt, Philippe

    2015-04-01

    Bacillus cereus is a major foodborne bacterial pathogen able to survive a large number of physical-chemical stresses. B. cereus encounters different pH and redox potential (Eh7) levels during its passage through the gastrointestinal tract. Analysis of the combined influence of pH and redox stresses on B. cereus F4430/73 physiology found that B. cereus F4430/73 growth at pH 7.0 at 37 °C had strong reducing capacities, with a total change of 315 mV from an initial redox value of +214 ± 17 mV. The combination of low Eh7 and low pH led to a drastic reduction of growth parameters compared to oxidative Eh7 and neutral pH. Metabolic analysis showed that low pH significantly modifies glucose fermentative metabolism, with changes including decreased production of acid metabolite (acetate, lactate, formate) and increased production of 2,3-butanediol. Low Eh7 slightly enhanced the acid-tolerance response of B. cereus whereas low pH pre-adaptation led to thermal stress cross-protection. These results highlight new mechanisms that bring fresh insight into B. cereus pH and redox stress adaptations.

  18. Molecular cloning and characterization of a novel β-glucosidase with high hydrolyzing ability for soybean isoflavone glycosides and glucose-tolerance from soil metagenomic library.

    PubMed

    Li, Gang; Jiang, Yang; Fan, Xin-Jiong; Liu, Yu-Huan

    2012-11-01

    A novel β-glucosidase (Bgl1269) was identified from a metagenomic library of mangrove soil by activity-based functional screening. Sequence analysis revealed that Bgl1269 encodes a protein of 422 amino acids. After being overexpressed in Escherichia coli and purified, the enzymatic properties of Bgl1269 were investigated. The recombinant enzyme displayed a pH optimum of 6.0 and a temperature optimum of 40°C, and the addition of most common metal ions (1 or 10mM) increased the enzymatic activity evidently. In addition, the enzyme showed high hydrolyzing ability for soybean isoflavone glycosides, and 0.8unit of enzyme could completely converted daidzin and genistin (0.5mg/mL) to daidzein and genistein at 40°C for 0.5h. Interestingly, Bgl1269 also exhibited a very high glucose-tolerance, with the highest inhibition constant K(i) (4.28M) among β-glucosidases reported so far. These properties make it a good candidate in the production of soybean isoflavone aglycones after further study.

  19. A 0.18 μm CMOS transmit physical coding sublayer IC for 100G Ethernet

    NASA Astrophysics Data System (ADS)

    Weihua, Ruan; Qingsheng, Hu

    2016-03-01

    This paper presents a transmit physical coding sublayer (PCS) circuit for 100G Ethernet. Based on the 4 × 25 Gb/s architecture according to the IEEE P802.3ba and IEEE P802.3bmTM/D1.1 standards, this PCS circuit is designed using a semi-custom design method and consists of 4 modules including 64B/66B encoder, scrambler, multiple lanes distribution and 66 : 8 gearbox. By using the pipeline structure and several optimization techniques, the working speed of the circuit is increased significantly. The parallel scrambling combined with logic optimization also improve the performance. In addition, a kind of phase-independent structure is employed in the design of the gearbox to ensure it can work stably and reliably at high frequency. This PCS circuit has been fabricated based on 0.18 μm CMOS technology and the total area is 1.7 × 1.7 mm2. Measured results show that the circuit can work properly at 100 Gb/s and the power consumption is about 284 mW with a 1.8 V supply. Project supported by the National Natural Science Foundation of China (No. 6504000129) and the National Basic Research Program of China (No. 6504000052).

  20. Generation and characterisation of stable ethanol-tolerant mutants of Saccharomyces cerevisiae.

    PubMed

    Stanley, Dragana; Fraser, Sarah; Chambers, Paul J; Rogers, Peter; Stanley, Grant A

    2010-02-01

    Saccharomyces spp. are widely used for ethanologenic fermentations, however yeast metabolic rate and viability decrease as ethanol accumulates during fermentation, compromising ethanol yield. Improving ethanol tolerance in yeast should, therefore, reduce the impact of ethanol toxicity on fermentation performance. The purpose of the current work was to generate and characterise ethanol-tolerant yeast mutants by subjecting mutagenised and non-mutagenised populations of Saccharomyces cerevisiae W303-1A to adaptive evolution using ethanol stress as a selection pressure. Mutants CM1 (chemically mutagenised) and SM1 (spontaneous) had increased acclimation and growth rates when cultivated in sub-lethal ethanol concentrations, and their survivability in lethal ethanol concentrations was considerably improved compared with the parent strain. The mutants utilised glucose at a higher rate than the parent in the presence of ethanol and an initial glucose concentration of 20 g l(-1). At a glucose concentration of 100 g l(-1), SM1 had the highest glucose utilisation rate in the presence or absence of ethanol. The mutants produced substantially more glycerol than the parent and, although acetate was only detectable in ethanol-stressed cultures, both mutants produced more acetate than the parent. It is suggested that the increased ethanol tolerance of the mutants is due to their elevated glycerol production rates and the potential of this to increase the ratio of oxidised and reduced forms of nicotinamide adenine dinucleotide (NAD(+)/NADH) in an ethanol-compromised cell, stimulating glycolytic activity.

  1. 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

  2. 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

  3. Screening of gestational diabetes mellitus in early pregnancy by oral glucose tolerance test and glycosylated fibronectin: study protocol for an international, prospective, multicentre cohort trial

    PubMed Central

    Huhn, E A; Fischer, T; Göbl, C S; Todesco Bernasconi, M; Kreft, M; Kunze, M; Schoetzau, A; Dölzlmüller, E; Eppel, W; Husslein, P; Ochsenbein-Koelble, N; Zimmermann, R; Bäz, E; Prömpeler, H; Bruder, E; Hahn, S; Hoesli, I

    2016-01-01

    Introduction As the accurate diagnosis and treatment of gestational diabetes mellitus (GDM) is of increasing importance; new diagnostic approaches for the assessment of GDM in early pregnancy were recently suggested. We evaluate the diagnostic power of an ‘early’ oral glucose tolerance test (OGTT) 75 g and glycosylated fibronectin (glyFn) for GDM screening in a normal cohort. Methods and analysis In a prospective cohort study, 748 singleton pregnancies are recruited in 6 centres in Switzerland, Austria and Germany. Women are screened for pre-existing diabetes mellitus and GDM by an ‘early’ OGTT 75 g and/or the new biomarker, glyFn, at 12–15 weeks of gestation. Different screening strategies are compared to evaluate the impact on detection of GDM by an OGTT 75 g at 24–28 weeks of gestation as recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG). A new screening algorithm is created by using multivariable risk estimation based on ‘early’ OGTT 75 g and/or glyFn results, incorporating maternal risk factors. Recruitment began in May 2014. Ethics and dissemination This study received ethical approval from the ethics committees in Basel, Zurich, Vienna, Salzburg and Freiburg. It was registered under http://www.ClinicalTrials.gov (NCT02035059) on 12 January 2014. Data will be presented at international conferences and published in peer-reviewed journals. Trial registration number NCT02035059. PMID:27733413

  4. Effects of long-term feeding of chitosan on postprandial lipid responses and lipid metabolism in a high-sucrose-diet-impaired glucose-tolerant rat model.

    PubMed

    Liu, Shing-Hwa; He, Sih-Pin; Chiang, Meng-Tsan

    2012-05-02

    This study was designed to investigate the effects of long-term feeding of chitosan on postprandial lipid response and lipid metabolism in a high-sucrose (HS)-diet-impaired glucose-tolerant rat model. As the results, HS-diet-fed rats supplemented with 5 and 7% chitosan in diets for 9 weeks had lower postprandial plasma total cholesterol (TC) levels, but 7% chitosan in the diet had higher postprandial plasma triglyceride (TG) and TG-rich lipoprotein TG levels. Supplementation of chitosan significantly decreased the postprandial ratio of apolipoprotein B (apoB)48/apoB100 in TG-rich lipoprotein fractions of HS-diet-fed rats. Long-term supplementation of 5 and 7% chitosan in diets for 16 weeks had lower plasma TC, low-density lipoprotein cholesterol (LDL-C) + very low density lipoprotein cholesterol (VLDL-C), TC/high-density lipoprotein (HDL-C) ratio, leptin, and tumor necrosis factor-α (TNF-α) levels in HS-diet-fed rats. Moreover, it was noticed that the VLDL receptor (VLDLR) protein expression in skeletal muscles of HS-diet-fed rats was significantly decreased, which could be significantly reversed by supplementation of 5 and 7% chitosan. Rats supplemented with 7% chitosan in the diet significantly elevated the lipolysis rate and decreased the accumulation of TG in epididymal fat pads of HS-diet-fed rats. The plasma angiopoietin-like 4 (ANGPTL4) protein expression was not affected in HS-diet-fed rats, but it was significantly increased in 7% chitosan-supplemented HS-diet-fed rats. Taken together, these results indicate that supplementation of chitosan in the diet can improve the impairment of lipid metabolism in a HS-diet-fed rat model, but long-term high-dose chitosan feeding may enhance postprandial plasma TG and TG-rich lipoprotein TG levels in HS-diet-fed rats through an ANGPTL4-regulated pathway.

  5. 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

    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.

  6. 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

  7. Difference between 2 h and 3 h 75 g glucose tolerance test in the diagnosis of gestational diabetes mellitus (GDM): results from a national survey on prevalence of GDM.

    PubMed

    Gao, Xue-Lian; Wei, Yu-Mei; Yang, Hui-Xia; Xu, Xian-Ming; Fan, Ling; He, Jing; Liu, Ning; Zhao, San-Cun; Hu, Ya-Li; Yang, Zi; Zhang, Yun-Ping; Liu, Xing-Hui; Chen, Xu; Zhang, Jian-Ping; Gou, Wen-Li; Xiao, Mei; Wu, Hai-Rong; Zhang, Mei-Hua

    2010-09-01

    The possibility of the 2 h oral glucose tolerance test (OGTT) as an alternative to the 3 h OGTT was investigated based on data from a national survey on pregnancy-associated diabetes. Data were retrieved from 4179 pregnant women who had OGTT performed after an abnormal 50 g glucose challenge test (GCT). All of the 4 glucose levels during their OGTT were collected and analyzed. According to American Diabetes Association (ADA) gestational diabetes mellitus (GDM) diagnostic criteria, among the 4179 pregnant women who required OGTT, 3429 (82.1%) were normal and 750 (17.9%) were diagnosed as GDM. If the 3rd h glucose levels were omitted from OGTT, 79 cases of GDM (10.5%) would be overlooked. No trend was shown where women with more risk factors were more likely to be overlooked if the 3rd h test was omitted (χ2 for trend=0.038, P>0.05). No significant differences were found in the rate of cesarean section (CS), preterm births or macrosomia between the 79 cases and those with normal OGTT results and in the gestational weeks when OGTT was performed. It shows that in order to diagnose one woman with GDM, another 52 pregnant women would have an innocent 3rd h glucose test. Omission of the 3rd h glucose test in OGTT might be reasonable due to its convenience, better compliance and a small number of possibly miss-diagnosed cases, and their pregnancy outcomes have no significant difference from those of normal pregnant women.

  8. Nuclear Factor Erythroid 2-Related Factor 2 Deletion Impairs Glucose Tolerance and Exacerbates Hyperglycemia in Type 1 Diabetic MiceS⃞

    PubMed Central

    Aleksunes, Lauren M.; Reisman, Scott A.; Yeager, Ronnie L.; Goedken, Michael J.

    2010-01-01

    The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) induces a battery of cytoprotective genes after oxidative stress. Nrf2 aids in liver regeneration by altering insulin signaling; however, whether Nrf2 participates in hepatic glucose homeostasis is unknown. Compared with wild-type mice, mice lacking Nrf2 (Nrf2-null) have lower basal serum insulin and prolonged hyperglycemia in response to an intraperitoneal glucose challenge. In the present study, blood glucose, serum insulin, urine flow rate, and hepatic expression of glucose-related genes were quantified in male diabetic wild-type and Nrf2-null mice. Type 1 diabetes was induced with a single intraperitoneal dose (200 mg/kg) of streptozotocin (STZ). Histopathology and serum insulin levels confirmed depleted pancreatic β-cells in STZ-treated mice of both genotypes. Five days after STZ, Nrf2-null mice had higher blood glucose levels than wild-type mice. Nine days after STZ, polyuria occurred in both genotypes with more urine output from Nrf2-null mice (11-fold) than wild-type mice (7-fold). Moreover, STZ-treated Nrf2-null mice had higher levels of serum β-hydroxybutyrate, triglycerides, and fatty acids 10 days after STZ compared with wild-type mice. STZ reduced hepatic glycogen in both genotypes, with less observed in Nrf2-null mice. Increased urine output and blood glucose in STZ-treated Nrf2-null mice corresponded with enhanced gluconeogenesis (glucose-6-phosphatase and phosphoenolpyruvate carboxykinase)- and reduced glycolysis (pyruvate kinase)-related mRNA expression in their livers. Furthermore, the Nrf2 activator oltipraz lowered blood glucose in wild-type but not Nrf2-null mice administered STZ. Collectively, these data indicate that the absence of Nrf2 worsens hyperglycemia in type I diabetic mice and Nrf2 may represent a therapeutic target for reducing circulating glucose levels. PMID:20086057

  9. Three 15-min bouts of moderate postmeal walking significantly improves 24-h glycemic control in older people at risk for impaired glucose tolerance

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of this study was to compare the effectiveness of three 15-min bouts of postmeal walking with 45 min of sustained walking on 24-h glycemic control in older persons at risk for glucose intolerance. Inactive older (=60 years of age) participants (N = 10) were recruited from the community a...

  10. Development of a Streptozotocin-induced Diabetic Rat Model for Studies on the Effects of Cinnamon on Glucose Tolerance and Insulin Secretion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A streptozotocin (STZ) dose response protocol using graded doses of STZ was utilized to develop a diabetic rat model. In addition to the presence of severe basal hyperglycemia, insulin responses to oral glucose showed no change from basal in rats given more than 45 mg of STZ/kg body wt. Oral gluc...

  11. 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.

  12. Identification of genes required for maximal tolerance to high-glucose concentrations, as those present in industrial alcoholic fermentation media, through a chemogenomics approach.

    PubMed

    Teixeira, Miguel C; Raposo, Luís R; Palma, Margarida; Sá-Correia, Isabel

    2010-04-01

    Chemogenomics, the study of genomic responses to chemical compounds, has the potential to elucidate the basis of cellular resistance to those chemicals. This knowledge can be applied to improve the performance of strains of industrial interest. In this study, a collection of approximately 5,000 haploid single deletion mutants of Saccharomyces cerevisiae in which each nonessential yeast gene was individually deleted, was screened for strains with increased susceptibility toward stress induced by high-glucose concentration (30% w/v), one of the main stresses occurring during industrial alcoholic fermentation processes aiming the production of alcoholic beverages or bio-ethanol. Forty-four determinants of resistance to high-glucose stress were identified. The most significant Gene Ontology (GO) terms enriched in this dataset are vacuolar organization, late endosome to vacuole transport, and regulation of transcription. Clustering the identified resistance determinants by their known physical and genetic interactions further highlighted the importance of nutrient metabolism control in this context. A concentration of 30% (w/v) of glucose was found to perturb vacuolar function, by reducing cell ability to maintain the physiological acidification of the vacuolar lumen. This stress also affects the active rate of proton efflux through the plasma membrane. Based on results of published studies, the present work revealed shared determinants of yeast resistance to high-glucose and ethanol stresses, including genes involved in vacuolar function, cell wall biogenesis (ANP1), and in the transcriptional control of nutrient metabolism (GCN4 and GCR1), with possible impact on the design of more robust strains to be used in industrial alcoholic fermentation processes.

  13. Heterologous expression of yeast Hxt2 in Arabidopsis thaliana alters sugar uptake, carbon metabolism and gene expression leading to glucose tolerance of germinating seedlings.

    PubMed

    Padilla-Chacón, Daniel; Cordoba, Elizabeth; Olivera, Teresa; Sánchez, Sobeida; Coello, Patricia; León, Patricia; Tiessen, Axel; Martínez-Barajas, Eleazar

    2010-04-01

    The hexose transporter 2 gene (Hxt2) from Saccharomyces cerevisiae was expressed in Arabidopsis thaliana under control of the 35S promoter. Several independent transgenic lines were selected after confirming single gene insertion by southern blot analysis in the T4 generation. Northern blots revealed the presence of heterologous transcript. Radiolabeling experiments revealed an increased rate of incorporation of the non-metabolizable analog 3-O-methyl-[U-14C]-glucose. This confirmed that the yeast Hxt2 transporter was functional in Arabidopsis. No phenotypic changes at the vegetative and reproductive stages could be detected in the transgenic lines when compared to wild type plants. Shortly after germination some differences in development and glucose signaling were observed. Transgenic seedlings cultivated in liquid medium or on solid agar plates were able to grow with 3% glucose (producing bigger plants and longer roots), while development of wild type plants was delayed under those conditions. Metabolite analysis revealed that the Hxt2 transgenic lines had higher rates of sugar utilization. Transcriptional profiling showed that particular genes were significantly up- or down-regulated. Some transcription factors like At1g27000 were repressed, while others, such as At3g58780, were induced. The mRNA from classical sugar signaling genes such as STP1, Hxk1, and ApL3 behaved similarly in transgenic lines and wild type lines. Results suggest that the Hxt2 transgene altered some developmental processes related to the perception of high carbon availability after the germination stage. We conclude that the developmental arrest of wild type plants at 3% glucose not only depends on Hxk1 as the only sugar sensor but might also be influenced by the route of hexose transport across the plasma membrane.

  14. Consumption of sericin reduces serum lipids, ameliorates glucose tolerance and elevates serum adiponectin in rats fed a high-fat diet.

    PubMed

    Okazaki, Yukako; Kakehi, Shoko; Xu, Yonghui; Tsujimoto, Kazuhisa; Sasaki, Masahiro; Ogawa, Hiroshi; Kato, Norihisa

    2010-01-01

    The effect was examined of dietary sericin on the lipid and carbohydrate metabolism in rats fed with a high-fat diet. The rats were fed with a 20% beef tallow diet with or without sericin at the level of 4% for 5 weeks. The final body weight and white adipose tissue weight were unaffected by dietary manipulation. The consumption of sericin significantly reduced the serum levels of triglyceride, cholesterol, phospholipids and free fatty acids. Serum very-low-density lipoprotein (VLDL)-triglyceride, VLDL-cholesterol, low-density lipoprotein (LDL)-cholesterol and LDL-phospholipids were also significantly reduced by the sericin intake. Liver triglyceride and the activities of glucose 6-phosphate dehydrogenase and malic enzyme, the lipogenic enzymes, were also reduced by the sericin intake. Dietary sericin caused a marked elevation in serum adiponectin. The consumption of sericin suppressed the increases in plasma glucose and insulin levels after an intraperitoneal glucose injection. These results imply the usefulness of sericin for improving the lipid and carbohydrate metabolism in rats fed on a high-fat diet.

  15. Chronic exposure to low doses of lipopolysaccharide and high-fat feeding increases body mass without affecting glucose tolerance in female rats

    PubMed Central

    Dudele, Anete; Fischer, Christina W; Elfving, Betina; Wegener, Gregers; Wang, Tobias; Lund, Sten

    2015-01-01

    Obesity-related inflammation may have a causal role in the development of diabetes and insulin resistance, and studies using animal models of chronic experimental endotoxemia have shown the link. However, many studies use only males, and much less is known about the role of obesity-related inflammation in females. Therefore, we addressed how experimentally induced chronic inflammation affects body mass, energy intake, and glucose metabolism in female rats. Adult female Sprague Dawley rats were instrumented with slow release pellets that delivered a constant daily dose of 53 or 207 μg of lipopolysaccharide (LPS) per rat for 60 days. Control rats were instrumented with vehicle pellets. Due to inflammatory nature of high-fat diet (HFD) half of the rats received HFD (60% of calories from lard), while the other half remained on control diet to detect possible interactions between two modes of induced inflammation. Our results showed that chronic LPS administration increased female rat body mass and calorie intake in a dose-dependent manner, and that HFD further exacerbated these effects. Despite these effects, no effects of LPS and HFD were evident on female rat glucose metabolism. Only LPS elevated expression of inflammatory markers in the hypothalamus. To conclude, female rats respond to experimentally induced chronic inflammation by increasing body mass, but do not develop glucose intolerance in the given period of time. PMID:26537342

  16. The final report for CCM.M-K7: key comparison of 5 kg, 100 g, 10 g, 5 g and 500 mg stainless steel mass standards

    NASA Astrophysics Data System (ADS)

    Lee, Sungjun; Borys, Michael; Abbott, Patrick; Becerra, Luis Omar; Eltawil, Alaaeldin A.; Jian, Wang; Malengo, Andrea; Medina, Nieves; Snegov, Victor; Wüthrich, Christian; Scholz, Frank

    2017-01-01

    In order to show equivalence in mass standards calibration among National Metrology Institutes (NMIs) of member countries of the "Comité international des poids et mesures" (CIPM), key comparisons (KC) of mass standards have been carried out under the auspices of the "Comité Consultatif pour la Masse et les Grandeurs Apparentées" (CCM). This key comparison of 5 kg, 100 g, 10 g, 5 g and 500 mg stainless steel mass standards was based on the decision of the CCM during the 12th meeting held in 2010 at the Bureau International des Poids et Mesures (BIPM). KRISS (Republic of Korea) and PTB (Germany) acted as pilot laboratory and co-pilot laboratory, respectively. The results were evaluated with the Monte Carlo method using measurement values based on participants' reference standards calculated following the recent BIPM amendments in 2015. Regarding participant results, VNIIM (100 g and 5 g) were not consistent with the key comparison reference values within their expanded uncertainties with the coverage factor, k = 2. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  17. Rapid effect of single-dose rosiglitazone treatment on endothelial function in healthy men with normal glucose tolerance: data from a randomised, placebo-controlled, double-blind study.

    PubMed

    Walcher, Thomas; Walcher, Daniel; Hetzel, Jürgen; Mielke, Catrin; Rau, Matthias; Rittig, Kilian; Balletshofer, Bernd; Schwedhelm, Edzard; Hombach, Vinzenz; Böger, Rainer H; Koenig, Wolfgang; Marx, Nikolaus

    2010-07-01

    Antidiabetic thiazolidinediones (TZDs) improve endothelial function in patients with or without type 2 diabetes. The present randomised, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD), metabolic parameters, and its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomised to a single dose of rosiglitazone (8 mg) or placebo, and FMD was assessed at baseline as well as after 6 h and 24 h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24 h compared with placebo. Treatment with rosiglitazone significantly increased FMD after 6 h from 4.3% (3.3; 4.9) to 7.6% (5.6; 9.2) (p<0.0001 vs. baseline) resulting in a highly significant effect compared with placebo (p<0.0001 for difference between groups). After 24 h FMD was still significantly higher in the rosiglitazone group compared with baseline (p=0.001), but the effect was no longer statistically significant versus placebo (p=0.171). Our study shows a very rapid effect of single dose rosiglitazone treatment on endothelial function in non-diabetic healthy men, underscoring the hypothesis that TZDs may exhibit direct effect in the vasculature independent of their metabolic action.

  18. Seasonal variations in plasma glucose and insulin concentrations after glucose loading in the edible dormouse (Glis glis L.).

    PubMed

    Castex, C; Donnio, R; Sutter, B C

    1979-01-01

    Glucose tolerance tests made in the Edible dormouse showed annual variations in B cell secretory capacity, associated with glucose tolerance changes. 1. During autumn and winter, the B cell is sensitive to glucose, and insulin regulates the high peripheral consumption of this hexose. 2. At the beginning of spring, insulin secretion decreases and glucose tolerance is impaired. In June, the B cell response si low or absent and a poor tolerance to glucose still persists. 3. The variations in B cell activity can be related to changing energy requirements during the year.

  19. Ablation of TRPM5 in Mice Results in Reduced Body Weight Gain and Improved Glucose Tolerance and Protects from Excessive Consumption of Sweet Palatable Food when Fed High Caloric Diets.

    PubMed

    Larsson, Marie H; Håkansson, Pernilla; Jansen, Frank P; Magnell, Kerstin; Brodin, Peter

    2015-01-01

    The calcium activated cation channel transient receptor potential channel type M5 (TRPM5) is part of the downstream machinery of the taste receptors and have been shown to play a central role in taste signalling. In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells. The aim of this study was to investigate the effects of TRPM5 gene ablation on body weight, insulin sensitivity and other metabolic parameters in long-term high caloric diet induced obesity. Trpm5-/- mice gained significantly less body weight and fat mass on both palatable carbohydrate and fat rich cafeteria diet and 60% high fat diet (HFD) and developed less insulin resistance compared to wild type mice. A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight. In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball. Thus the palatable sugar containing diet induced overeating was prevented in Trpm5-/- mice. This indicates that sweet taste induced overeating may be a cause for the increased energy intake and glucose intolerance development seen for wild type mice on a sugar and high fat rich cafeteria diet compared to when on a high fat diet. This study point to an important role for the taste signalling system and TRPM5 in diet induced glucose intolerance.

  20. Ablation of TRPM5 in Mice Results in Reduced Body Weight Gain and Improved Glucose Tolerance and Protects from Excessive Consumption of Sweet Palatable Food when Fed High Caloric Diets

    PubMed Central

    Larsson, Marie H.; Håkansson, Pernilla; Jansen, Frank P.; Magnell, Kerstin; Brodin, Peter

    2015-01-01

    The calcium activated cation channel transient receptor potential channel type M5 (TRPM5) is part of the downstream machinery of the taste receptors and have been shown to play a central role in taste signalling. In addition it is also found in other types of chemosensory cells in various parts of the body as well as in pancreatic β-cells. The aim of this study was to investigate the effects of TRPM5 gene ablation on body weight, insulin sensitivity and other metabolic parameters in long-term high caloric diet induced obesity. Trpm5-/- mice gained significantly less body weight and fat mass on both palatable carbohydrate and fat rich cafeteria diet and 60% high fat diet (HFD) and developed less insulin resistance compared to wild type mice. A main finding was the clearly improved glucose tolerance in Trpm5-/- mice compared to wild type mice on cafeteria diet, which was independent of body weight. In addition, it was shown that Trpm5-/- mice consumed the same amount of calories when fed a HFD only or a HFD in combination with a palatable chocolate ball, which is in contrast to wild type mice that increased their caloric intake when fed the combination, mainly due to excessive consumption of the chocolate ball. Thus the palatable sugar containing diet induced overeating was prevented in Trpm5-/- mice. This indicates that sweet taste induced overeating may be a cause for the increased energy intake and glucose intolerance development seen for wild type mice on a sugar and high fat rich cafeteria diet compared to when on a high fat diet. This study point to an important role for the taste signalling system and TRPM5 in diet induced glucose intolerance. PMID:26397098

  1. Experimental study of cross-phase modulation reduction in hybrid systems with co-propagating 100G PM-QPSK and 10G OOK.

    PubMed

    Searcy, Steven; Tibuleac, Sorin

    2013-12-16

    We experimentally investigate various methods for reducing cross-phase modulation in hybrid networks with mixed 100G and 10G traffic. The experimental results over standard single-mode and non-zero dispersion-shifted fiber types demonstrate the effectiveness of several different XPM reduction techniques as well as the interplay between them. Nonlinear transmission performance is quantified using the Nonlinear Threshold metric as a function of key system features, including DCM type, dispersion map, spectral guard bands, and carrier phase estimation window size. Fiber Bragg grating-based DCMs are shown to offer a distinct advantage over fiber-based DCMs under certain conditions, particularly in dispersion-managed systems with very strong XPM. The average walk-off per span is introduced as a simple yet effective metric to compare different methods of XPM mitigation.

  2. Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans.

    PubMed Central

    Boyle, P J; Scott, J C; Krentz, A J; Nagy, R J; Comstock, E; Hoffman, C

    1994-01-01

    Systemic glucose utilization declines during sleep in man. We tested the hypothesis that this decline in utilization is largely accounted for by reduced brain glucose metabolism. 10 normal subjects underwent internal jugular and radial artery cannulation to determine cerebral blood flow by N2O equilibrium technique and to quantitate cross-brain glucose and oxygen differences before and every 3 h during sleep. Sleep stage was graded by continuous electroencephalogram, and systemic glucose turnover was estimated by isotope dilution. Brain glucose metabolism fell from 33.6 +/- 2.2 mumol/100 g per min (mean +/- SE) before sleep (2300 h) to a mean nadir of 24.3 +/- 1.1 mumol/100 g per min at 0300 h during sleep (P = 0.001). Corresponding rates of systemic glucose utilization fell from 13.2 +/- 0.8 to 11.0 +/- 0.5 mumol/kg per min (P = 0.003). Diminished brain glucose metabolism was the product of a reduced arteriovenous glucose difference, 0.643 +/- 0.024 to 0.546 +/- 0.020 mmol/liter (P = 0.002), and cerebral blood flow, 50.3 +/- 2.8 to 44.6 +/- 1.4 cc/100 g per min (P = 0.021). Brain oxygen metabolism fell commensurately from 153.4 +/- 11.8 to 128.0 +/- 8.4 mumol/100 g per min (P = 0.045). The observed reduction in brain metabolism occurred independent of stage of central nervous system electrical activity (electroencephalographic data), and was more closely linked to duration of sleep. We conclude that a decline in brain glucose metabolism is a significant determinant of falling rates of systemic glucose utilization during sleep. Images PMID:8113391

  3. A study of the interactive effects of oral contraceptive use and dietary fat intake on blood pressure, cardiovascular reactivity and glucose tolerance in normotensive women.

    PubMed

    Straznicky, N E; Barrington, V E; Branley, P; Louis, W J

    1998-03-01

    The interactive effects of combined oral contraceptive (OC) use and dietary fat intake on cardiovascular hemodynamics and metabolic parameters were investigated in a comparative study of 16 normotensive OC users from Australia and 16 age- and weight-matched nonuser controls. The 6-week study's crossover design allocated women to consume either a high- or low-fat diet for 2-week periods. Analyses were performed at the end of each diet during the luteal phase of the menstrual cycle. Plasma triglyceride levels were significantly higher in OC users than nonusers in both diet groups; however, responses of lipoprotein levels to the 2 diets did not differ between study groups. Total and low-density lipoprotein cholesterol levels decreased by 15% and 17%, respectively, in OC users, and by 14% each in non-OC users on the low-fat, compared to the high-fat, diet. Fasting plasma insulin levels, the insulin production response to administration of glucose, and resting clinic and night-time systolic blood pressures were all significantly reduced on the low-fat diet, but only in nonusers. In OC users, blood pressure responses to noradrenaline and maximal heart rate response to cold were significantly attenuated by the low-fat diet. During the low-fat diet, resting systolic, 24-hour systolic, and diastolic blood pressures and areas under the curve were significantly higher in the OC group. OC users also demonstrated a greater systolic sensitivity to administration of both noradrenaline and angiotensin II, and had a higher plasma renin activity, regardless of diet. Overall, these findings confirm that OCs can cause adverse effects on blood pressure, cardiovascular reactivity, and the insulin production response to glucose administration, and negate some of the beneficial effects of a low-fat diet.

  4. Sex-related differences in peripheral glucose metabolism in normal subjects.

    PubMed

    Paula, F J; Pimenta, W P; Saad, M J; Paccola, G M; Piccinato, C E; Foss, M C

    1990-01-01

    The metabolic response of muscle tissue to glucose ingestion was studied in 10 normal men (M) and women (F) by using the forearm balance technique and indirect calorimetry simultaneously. During the 3 hours after a 75 g--oral glucose load, glucose uptake per unit muscle mass was significantly higher in women than in men, F = 187.3 +/- 26.9 vs M = 116.7 +/- 9.5 mg/100 g forearm muscle (P less than 0.05). A significant difference in muscle glucose fate was also observed since the amount of glucose utilized through a nonoxidative pathway was significantly higher in women, F = 84.5 +/- 2.6% (161.8 +/- 27.3 mg/100 g forearm muscle) vs M = 75.3 +/- 2.2% (87.2 +/- 8.6 mg/100 g forearm muscle) (P less than 0.05), whereas the amount of glucose oxidized in relation to glucose uptake was significantly higher in men, M = 24.7 +/- 2.2% (28.2 +/- 3.2 mg/100 g forearm muscle) vs F = 15.5 +/- 2.6% (27.8 +/- 5.4 mg/100 g forearm muscle) (P less than 0.05). No significant differences in insulin response to glucose ingestion were detected between groups. The women showed greater suppression of serum free fatty acids (FFA) levels in relation to basal levels than men. We conclude that: 1) after ingesting 75 g glucose, normal women showed greater glucose uptake per unit muscle mass than normal men, 2) for 3 hours after the ingestion of 75 g glucose, the predominant tendency toward utilizing glucose by a nonoxidative pathway is more marked in normal women than in normal men, and 3) the higher glucose uptake per unit muscle mass in the female group in the presence of an insulin response not significantly different from that of the male group suggests that muscle insulin sensitivity is greater in normal women.

  5. 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

  6. Aspartame intake is associated with greater glucose intolerance in individuals with obesity.

    PubMed

    Kuk, Jennifer L; Brown, Ruth E

    2016-07-01

    This study examined whether sucrose, fructose, aspartame, and saccharin influences the association between obesity and glucose tolerance in 2856 adults from the NHANES III survey. Aspartame intake significantly influenced the association between body mass index (BMI) and glucose tolerance (interaction: P = 0.004), wherein only those reporting aspartame intake had a steeper positive association between BMI and glucose tolerance than those reporting no aspartame intake. Therefore, consumption of aspartame is associated with greater obesity-related impairments in glucose tolerance.

  7. Glucose Variability

    PubMed Central

    Le Floch, Jean-Pierre; Kessler, Laurence

    2016-01-01

    Background: Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices. Methods: Glucose variability was studied in 150 insulin-treated diabetic patients (46% men, 42% type 1 diabetes, age 52 ± 11 years) using a continuous glucose monitoring system (668 ± 564 glucose values; mean glucose value 173 ± 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA). Results: CV, MAGE/m (ns), GCF and GFI (P < .05), MAG and MAG/m (P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values. Conclusions: Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients. PMID:26880391

  8. Rationale, Design, and Baseline Characteristics of Beijing Prediabetes Reversion Program: A Randomized Controlled Clinical Trial to Evaluate the Efficacy of Lifestyle Intervention and/or Pioglitazone in Reversion to Normal Glucose Tolerance in Prediabetes

    PubMed Central

    Luo, Yingying; Paul, Sanjoy K.; Zhou, Xianghai; Chang, Cuiqing; Guo, Xiaohui; Yang, Jinkui

    2017-01-01

    Background. Patients with prediabetes are at high risk for diabetes and cardiovascular disease (CVD). No study has explored whether intervention could revert prediabetes to normal glycemic status as the primary outcome. Beijing Prediabetes Reversion Program (BPRP) would evaluate whether intensive lifestyle modification and/or pioglitazone could revert prediabetic state to normoglycemia and improve the risk factors of CVD as well. Methods. BPRP is a randomized, multicenter, 2 × 2 factorial design study. Participants diagnosed as prediabetes were randomized into four groups (conventional/intensive lifestyle intervention and 30 mg pioglitazone/placebo) with a three-year follow-up. The primary endpoint was conversion into normal glucose tolerance. The trial would recruit 2000 participants (500 in each arm). Results. Between March 2007 and March 2011, 1945 participants were randomized. At baseline, the individuals were 53 ± 10 years old, with median BMI 26.0 (23.9, 28.2) kg/m2 and HbA1c 5.8 (5.6, 6.1)%. 85% of the participants had IGT and 15% had IFG. Parameters relevant to glucose, lipids, blood pressure, lifestyle, and other metabolic markers were similar between conventional and intensive lifestyle intervention group at baseline. Conclusion. BPRP was the first study to determine if lifestyle modification and/or pioglitazone could revert prediabetic state to normoglycemia in Chinese population. Major baseline parameters were balanced between two lifestyle interve