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Sample records for insulin sensitivity isi-ffa

  1. Effects of short-term metformin treatment on insulin sensitivity of blood glucose and free fatty acids.

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    Iannello, S; Camuto, M; Cavaleri, A; Milazzo, P; Pisano, M G; Bellomia, D; Belfiore, F

    2004-01-01

    Based on the known effect of metformin (MET) in improving insulin sensitivity in type 2 diabetes, with the scope to focus the effects on glycaemic and free fatty acids (FFA) levels, we studied the effects of a short-term treatment with this drug in obese subjects and obese patients with diabetes or family history of diabetes (FHD). We used a method to allow us to evaluate the possible difference of insulin sensibility with regard to the insulin action on glycaemia and blood FFA, both in the basal state and during oral glucose tolerance test (OGTT). Insulin sensitivity was investigated before and after MET treatment (850 mg bid for 10 days) in seven obese subjects with normal glucose tolerance and without FHD and 13 obese patients with diabetes (n=7) or FHD (n=6). By using specifically designed formulae, we calculated four insulin-sensitivity indices (ISI) from basal level (b) and area values (a) (during OGTT) of insulinaemia, glycaemia (gly) or FFA (ffa), namely: ISI (gly)-b, ISI (gly)-a, ISI (ffa)-b and ISI (ffa)-a. In patients with diabetes or FHD, MET improved ISI (gly)-b (0.79 +/- 0.06 vs. 0.59 +/- 0.07, p<0.001) and ISI (gly)-a (0.69 +/- 0.09 vs. 0.51 +/- 0.07, p<0.05), whereas only minor changes occurred for ISI (ffa)-b and ISI (ffa)-a. In contrast, in simple obese subjects, MET induced further deterioration of both ISI (gly)-a (0.47 +/- 0.07 vs. 0.64 +/- 0.10, p<0.01) and ISI (ffa)-a (0.43 +/- 0.07 vs. 0.55 +/- 0.08, p<0.05). Fasting level and total area of lactate were high in the obese patients and were not affected by MET. A statistically significant increase (p<0.01), however, was observed for the 'decremental' area of lactate in obese subjects with diabetes or FHD, which might probably contribute to the reduction of insulin resistance induced by the drug in these patients. Although the low number of subjects studied precludes absolute conclusions, data would suggest that MET improved ISI towards glucose but not towards FFA, in the diabetic and

  2. Conjugated Linoleic Acids Mediate Insulin Release through Islet G Protein-coupled Receptor FFA1/GPR40

    DEFF Research Database (Denmark)

    Schmidt, Johannes; Liebscher, Kathrin; Merten, Nicole

    2011-01-01

    of insulin resistance and the risk of developing diabetes. However, the mechanisms accounting for the effects of CLAs on glucose homeostasis are incompletely understood. Herein we provide evidence that CLAs specifically activate the cell surface receptor FFA1, an emerging therapeutic target to treat type 2...... found to activate FFA1 in vitro at concentrations sufficient to also account for FFA1 activation in vivo. Each CLA isomer markedly increased glucose-stimulated insulin secretion in insulin-producing INS-1E cells that endogenously express FFA1 and in primary pancreatic β-cells of wild type but not FFA1......(-/-) knock-out mice. Our findings establish a clear mechanistic link between CLAs and insulin production and identify the cell surface receptor FFA1 as a molecular target for CLAs, explaining their acute stimulatory effects on insulin secretion in vivo. CLAs are also revealed as insulinotropic components...

  3. New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

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    Kavita Venkataraman

    Full Text Available CONTEXT: Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. OBJECTIVES: To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. DESIGN AND PARTICIPANTS: Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian, 21 to 40 years, body mass index 18-30 kg/m(2. Predicted ISI (ISI-cal was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ. In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD, using ROC curves. SETTING: The study was conducted in a university academic medical centre. OUTCOME MEASURES: ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. RESULTS: A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR provided the best estimate of clamp-derived ISI (adjusted R(2 0.58 versus 0.32 HOMA-IR. In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05 for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (p<0.001 for incident CVD. ISI-cal also had greater sensitivity than defined metabolic syndrome in predicting CVD, with a four-fold increase in the risk of CVD independent of metabolic syndrome. CONCLUSIONS: Triglycerides and WHR, combined with fasting insulin levels, provide a better estimate of current insulin resistance state and improved identification of individuals with future risk of CVD, compared to HOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and

  4. Insulin sensitivity deteriorates after short-term lifestyle intervention in the insulin sensitive phenotype of obesity.

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    Gilardini, Luisa; Vallone, Luciana; Cottafava, Raffaella; Redaelli, Gabriella; Croci, Marina; Conti, Antonio; Pasqualinotto, Lucia; Invitti, Cecilia

    2012-01-01

    To investigate the effects of a 3-month lifestyle intervention on insulin sensitivity and its related cardiometabolic factors in obese patients. Anthropometry, body composition, oral glucose tolerance test, lipids, alanine aminotransferase, insulin sensitivity (insulinogenic index (ISI), homeostasis model assessment, β-cell performance (disposition index)) were evaluated in 263 obese women and 93 obese men before and after 3 months of hypocaloric low fat/high protein diet associated with physical activity 30 min/day. Patients were divided into 3 groups according to the intervention-induced ISI changes: group 1 (decrease), group 2 (stability) and group 3 (increase). Insulin sensitivity and the disposition index were significantly higher before the intervention in group 1 than in group 3. BMI, waist circumference, and fat mass significantly decreased in groups 1 and 3 in both sexes. β-cell performance decreased in group 1 and increased in group 3. Metabolic variables improved in group 3, whereas glucose levels increased in women of group 1. The post-intervention insulin sensitivity was lower in group 1 than in group 3. Lifestyle intervention induces changes in insulin sensitivity and metabolic factors that depend on the pre-intervention degree of insulin sensitivity. Weight loss leads to metabolic benefits in insulin-resistant, obese patients, whereas it may paradoxically worsen the metabolic conditions in the insulin-sensitive phenotype of obesity. Copyright © 2012 S. Karger GmbH, Freiburg.

  5. New measure of insulin sensitivity predicts cardiovascular disease better than HOMA estimated insulin resistance.

    Science.gov (United States)

    Venkataraman, Kavita; Khoo, Chin Meng; Leow, Melvin K S; Khoo, Eric Y H; Isaac, Anburaj V; Zagorodnov, Vitali; Sadananthan, Suresh A; Velan, Sendhil S; Chong, Yap Seng; Gluckman, Peter; Lee, Jeannette; Salim, Agus; Tai, E Shyong; Lee, Yung Seng

    2013-01-01

    Accurate assessment of insulin sensitivity may better identify individuals at increased risk of cardio-metabolic diseases. To examine whether a combination of anthropometric, biochemical and imaging measures can better estimate insulin sensitivity index (ISI) and provide improved prediction of cardio-metabolic risk, in comparison to HOMA-IR. Healthy male volunteers (96 Chinese, 80 Malay, 77 Indian), 21 to 40 years, body mass index 18-30 kg/m(2). Predicted ISI (ISI-cal) was generated using 45 randomly selected Chinese through stepwise multiple linear regression, and validated in the rest using non-parametric correlation (Kendall's tau τ). In an independent longitudinal cohort, ISI-cal and HOMA-IR were compared for prediction of diabetes and cardiovascular disease (CVD), using ROC curves. The study was conducted in a university academic medical centre. ISI measured by hyperinsulinemic euglycemic glucose clamp, along with anthropometric measurements, biochemical assessment and imaging; incident diabetes and CVD. A combination of fasting insulin, serum triglycerides and waist-to-hip ratio (WHR) provided the best estimate of clamp-derived ISI (adjusted R(2) 0.58 versus 0.32 HOMA-IR). In an independent cohort, ROC areas under the curve were 0.77±0.02 ISI-cal versus 0.76±0.02 HOMA-IR (p>0.05) for incident diabetes, and 0.74±0.03 ISI-cal versus 0.61±0.03 HOMA-IR (pHOMA-IR. This may be useful for estimating insulin sensitivity and cardio-metabolic risk in clinical and epidemiological settings.

  6. Genome-wide association study of the modified Stumvoll Insulin Sensitivity Index identifies BCL2 and FAM19A2 as novel insulin sensitivity loci

    DEFF Research Database (Denmark)

    Walford, Geoffrey A; Gustafsson, Stefan; Rybin, Denis

    2016-01-01

    of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-related traits Consortium. Discovery was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested...

  7. Sympathoadrenal influence on glucose, FFA, and insulin levels in exercising rats

    NARCIS (Netherlands)

    Scheurink, A.J.W.; Steffens, A.B.; Bouritius, H.; Dreteler, G.H.; Bruntink, R.; Remie, R.; Zaagsma, J.

    1989-01-01

    The effects of sympathoadrenal manipulations on the exercise-induced alterations in blood glucose, plasma free fatty acids (FFA), and insulin were investigated in intact and adrenodemedullated rats. Exercise consisted of strenuous swimming against a countercurrent for 15 min. Before, during, and

  8. Heart Rate Variability, Insulin Resistance, and Insulin Sensitivity in Japanese Adults: The Toon Health Study

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    Isao Saito

    2015-09-01

    Full Text Available Background: Although impaired cardiac autonomic function is associated with an increased risk of type 2 diabetes in Caucasians, evidence in Asian populations with a lower body mass index is limited. Methods: Between 2009–2012, the Toon Health Study recruited 1899 individuals aged 30–79 years who were not taking medication for diabetes. A 75-g oral glucose tolerance test was used to diagnose type 2 diabetes, and fasting and 2-h-postload glucose and insulin concentrations were measured. We assessed the homeostasis model assessment index for insulin resistance (HOMA-IR and Gutt’s insulin sensitivity index (ISI. Pulse was recorded for 5 min, and time-domain heart rate variability (HRV indices were calculated: the standard deviation of normal-to-normal intervals (SDNN and the root mean square of successive difference (RMSSD. Power spectral analysis provided frequency domain measures of HRV: high frequency (HF power, low frequency (LF power, and the LF:HF ratio. Results: Multivariate-adjusted logistic regression models showed decreased SDNN, RMSSD, and HF, and increased LF:HF ratio were associated significantly with increased HOMA-IR and decreased ISI. When stratified by overweight status, the association of RMSSD, HF, and LF:HF ratio with decreased ISI was also apparent in non-overweight individuals. The interaction between LF:HF ratio and decreased ISI in overweight individuals was significant, with the odds ratio for decreased ISI in the highest quartile of LF:HF ratio in non-overweight individuals being 2.09 (95% confidence interval, 1.41–3.10. Conclusions: Reduced HRV was associated with insulin resistance and lower insulin sensitivity. Decreased ISI was linked with parasympathetic dysfunction, primarily in non-overweight individuals.

  9. Changes in Gastrointestinal Hormone Responses, Insulin Sensitivity, and Beta-Cell Function Within 2 Weeks After Gastric Bypass in Non-diabetic Subjects

    DEFF Research Database (Denmark)

    Jacobsen, Siv Hesse; Olesen, S C; Dirksen, C

    2012-01-01

    measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin......, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated...... postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after...

  10. A model to estimate insulin sensitivity in dairy cows

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    Holtenius Kjell

    2007-10-01

    Full Text Available Abstract Impairment of the insulin regulation of energy metabolism is considered to be an etiologic key component for metabolic disturbances. Methods for studies of insulin sensitivity thus are highly topical. There are clear indications that reduced insulin sensitivity contributes to the metabolic disturbances that occurs especially among obese lactating cows. Direct measurements of insulin sensitivity are laborious and not suitable for epidemiological studies. We have therefore adopted an indirect method originally developed for humans to estimate insulin sensitivity in dairy cows. The method, "Revised Quantitative Insulin Sensitivity Check Index" (RQUICKI is based on plasma concentrations of glucose, insulin and free fatty acids (FFA and it generates good and linear correlations with different estimates of insulin sensitivity in human populations. We hypothesized that the RQUICKI method could be used as an index of insulin function in lactating dairy cows. We calculated RQUICKI in 237 apparently healthy dairy cows from 20 commercial herds. All cows included were in their first 15 weeks of lactation. RQUICKI was not affected by the homeorhetic adaptations in energy metabolism that occurred during the first 15 weeks of lactation. In a cohort of 24 experimental cows fed in order to obtain different body condition at parturition RQUICKI was lower in early lactation in cows with a high body condition score suggesting disturbed insulin function in obese cows. The results indicate that RQUICKI might be used to identify lactating cows with disturbed insulin function.

  11. [Effects of total glucosides of paeony on enhancing insulin sensitivity and antagonizing nonalcoholic fatty liver in rats].

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    Zheng, Lin-Ying; Pan, Jing-Qiang; Lv, Jun-Hua

    2008-10-01

    To study the pathological changes of blood glucose, serum lipid, insulin resistance, liver function, liver cell denaturalization of total glucosides of paeony on nonalcoholic fatty liver rats caused by insulin resistance and discuss the acting mechanism. Adult SD rats were maintained on high-fat-sugar-salt diet for 56 days. In the 57th day, their fasting blood glucose (FBG) and 2-hours blood glucose after oral glucose tolerance test (OGTT-2 hBG) were mensurated, according to which and the weight the rats were divided randomly into nonalcoholic fatty liver model group, metformin group (0.2 g x kg(-1)) and total glucosides of paeony group (high dosage 0.15 g x kg(-1), low dosage 0.05 g x kg(-1)). All the rats were still administered the same diet and given different drugs by intragastric administration for 28 days. In the 29th day, all of them were killed and the blood was sampled to measure the levels of blood glucose [FBG, OGTT-2 hBG, fasting insulin (Fins)] and serum lipid [free fatty acids (FFA), triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C)], then the HOMA insulin resistance index (HOMA-IRI, fasting glucosexinsulin) and insulin sensitivity index (ISI) were counted. The activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), cholinesterase (ChE), superoxide dismutase (SOD) and the contents of malondialdehyde (MDA) were measured also. Livers were weighed and collected to be observed the pathological changes. Compared with normal group, in nonalcoholic fatty liver model group the levels of Fins and IRI were increased obviously (P insulin resistence were resisted (P insulin resistance, and its action mechanism may be concerned with enhancing insulin sensitivity and antioxidative ability, decreasing serum lipid.

  12. Detection of Independent Associations of Plasma Lipidomic Parameters with Insulin Sensitivity Indices Using Data Mining Methodology.

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    Steffi Kopprasch

    Full Text Available Glucolipotoxicity is a major pathophysiological mechanism in the development of insulin resistance and type 2 diabetes mellitus (T2D. We aimed to detect subtle changes in the circulating lipid profile by shotgun lipidomics analyses and to associate them with four different insulin sensitivity indices.The cross-sectional study comprised 90 men with a broad range of insulin sensitivity including normal glucose tolerance (NGT, n = 33, impaired glucose tolerance (IGT, n = 32 and newly detected T2D (n = 25. Prior to oral glucose challenge plasma was obtained and quantitatively analyzed for 198 lipid molecular species from 13 different lipid classes including triacylglycerls (TAGs, phosphatidylcholine plasmalogen/ether (PC O-s, sphingomyelins (SMs, and lysophosphatidylcholines (LPCs. To identify a lipidomic signature of individual insulin sensitivity we applied three data mining approaches, namely least absolute shrinkage and selection operator (LASSO, Support Vector Regression (SVR and Random Forests (RF for the following insulin sensitivity indices: homeostasis model of insulin resistance (HOMA-IR, glucose insulin sensitivity index (GSI, insulin sensitivity index (ISI, and disposition index (DI. The LASSO procedure offers a high prediction accuracy and and an easier interpretability than SVR and RF.After LASSO selection, the plasma lipidome explained 3% (DI to maximal 53% (HOMA-IR variability of the sensitivity indexes. Among the lipid species with the highest positive LASSO regression coefficient were TAG 54:2 (HOMA-IR, PC O- 32:0 (GSI, and SM 40:3:1 (ISI. The highest negative regression coefficient was obtained for LPC 22:5 (HOMA-IR, TAG 51:1 (GSI, and TAG 58:6 (ISI.Although a substantial part of lipid molecular species showed a significant correlation with insulin sensitivity indices we were able to identify a limited number of lipid metabolites of particular importance based on the LASSO approach. These few selected lipids with the closest

  13. Fatty Acids, Obesity and Insulin Resistance

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    Peter Arner

    2015-04-01

    Full Text Available Objective: Although elevated free fatty acid (FFA levels in obesity have been considered to be of importance for insulin resistance, a recent meta-analysis suggested normal FFA levels in obese subjects. We investigated fasting circulating FFA and glycerol levels in a large cohort of non-obese and obese subjects. Methods: Subjects recruited for a study on obesity genetics were investigated in the morning after an overnight fast (n = 3,888. Serum FFA (n = 3,306, plasma glycerol (n = 3,776, and insulin sensitivity index (HOMA-IR,n = 3,469 were determined. Obesity was defined as BMI ≥ 30 kg/m2 and insulin resistance as HOMA-IR ≥ 2.21. Results: In obese subjects, circulating FFA and glycerol levels were higher than in non-obese individuals (by 26% and 47%, respectively; both p Conclusion: Circulating FFA and glycerol levels are markedly elevated in obesity but only marginally influenced by insulin resistance and type 2 diabetes. Whether these differences persist during diurnal variations in circulating FFA/glycerol, remains to be established.

  14. Natural history of insulin sensitivity and insulin secretion in the progression from normal glucose tolerance to impaired fasting glycemia and impaired glucose tolerance: the Inter99 study

    DEFF Research Database (Denmark)

    Faerch, Kristine; Vaag, Allan; Holst, Jens J

    2008-01-01

    of insulin sensitivity (HOMA-IS), early-phase insulin release (EPIR), and insulin secretion relative to insulin action (disposition index) were estimated. RESULTS: Five years before the pre-diabetes diagnoses (i-IFG, i-IGT, and IFG/IGT), ISI, HOMA-IS, EPIR, and disposition index were lower than...

  15. Characterising pharmacological ligands to study the long chain fatty acid receptors GPR40/FFA1 and GPR120/FFA4

    DEFF Research Database (Denmark)

    Milligan, G; Alvarez-Curto, E; Watterson, K R

    2015-01-01

    The G protein-coupled receptors FFA1 (previously designated GPR40) and FFA4 (previously GPR120) are both activated by saturated and unsaturated longer-chain free fatty acids. With expression patterns and functions anticipated to directly or indirectly promote insulin secretion, provide homeostati...

  16. Trajectories of glycaemia, insulin sensitivity and insulin secretion in South Asian and white individuals before diagnosis of type 2 diabetes

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    Hulman, Adam; Simmons, Rebecca K; Brunner, Eric J

    2017-01-01

    AIMS/HYPOTHESIS: South Asian individuals have reduced insulin sensitivity and increased risk of type 2 diabetes compared with white individuals. Temporal changes in glycaemic traits during middle age suggest that impaired insulin secretion is a particular feature of diabetes development among South...... Asians. We therefore aimed to examine ethnic differences in early changes in glucose metabolism prior to incident type 2 diabetes. METHODS: In a prospective British occupational cohort, subject to 5 yearly clinical examinations, we examined ethnic differences in trajectories of fasting plasma glucose...... (FPG), 2 h post-load plasma glucose (2hPG), fasting serum insulin (FSI), 2 h post-load serum insulin (2hSI), HOMA of insulin sensitivity (HOMA2-S) and secretion (HOMA2-B), and the Gutt insulin sensitivity index (ISI0,120) among 120 South Asian and 867 white participants who developed diabetes during...

  17. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.

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    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Lippi, Cristina; Casale, Raffaele; Properzi, Giuliana; Blumberg, Jeffrey B; Ferri, Claudio

    2008-09-01

    Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC

  18. The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

    NARCIS (Netherlands)

    Snel, M.; Sleddering, M.A.; Pijl, H.; Nieuwenhuizen, W.F.; Frölich, M.; Havekes, L.M.; Romijn, J.A.; Jazet, I.M.

    2010-01-01

    Background: Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity.Objective:To study the effect of dietary

  19. A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease

    DEFF Research Database (Denmark)

    Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Jürs, Anders

    2015-01-01

    followed by 2-4 weeks' weight maintenance diet. Glucose tolerance, insulin action, β-cell function and suppression of lipolysis were assessed using a 3-h oral glucose tolerance test. ISI-composite and ISI-HOMA (=1/HOMA-IR) were calculated as surrogate measures of whole-body and hepatic insulin sensitivity......, respectively. Magnetic resonance imaging estimated abdominal adipose tissue. Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. LED increased ISI-composite by 55% and ISI-HOMA by 70% (p0.7) revealing a significant...... difference between the groups (pHOMA and ISI-composite were associated with reduced visceral abdominal fat, waist circumference and body weight. Intention-to-treat analyses (n=64...

  20. The effect of dietary phytosphingosine on cholesterol levels and insulin sensitivity in subjects with the metabolic syndrome

    NARCIS (Netherlands)

    Snel, M.; Sleddering, M. A.; Pijl, H.; Nieuwenhuizen, W. F.; Frölich, M.; Havekes, L. M.; Romijn, J. A.; Jazet, I. M.

    2010-01-01

    Sphingolipids, like phytosphingosine (PS) are part of cellular membranes of yeasts, vegetables and fruits. Addition of PS to the diet decreases serum cholesterol and free fatty acid (FFA) levels in rodents and improves insulin sensitivity. To study the effect of dietary supplementation with PS on

  1. suPAR associates to glucose metabolic aberration during glucose stimulation in HIV-infected patients on HAART

    DEFF Research Database (Denmark)

    Andersen, Ove; Eugen-Olsen, Jesper; Kofoed, Kristian

    2008-01-01

    extend these findings by investigating the association of suPAR to glucose metabolic insufficiency during an oral glucose challenge (OGTT). METHODS: In 16 HIV-infected patients with lipodystrophy and 15 HIV-infected patients without lipodystrophy, glucose tolerance, insulin sensitivity (ISI......PAR correlated inversely with ISI(composite) and positively with 2h plasma glucose, fasting insulin secretion, fasting intact proinsulin and FFA level during the OGTT (all P...-RNA, duration of HIV infection), and dyslipidemia (plasma total cholesterol, triglyceride and free fatty acid level during the OGTT) were included, suPAR remained a significant marker of glucose tolerance and insulin sensitivity. Plasma suPAR exhibited a small CV (11%) during the 3h OGTT. CONCLUSIONS: su...

  2. Effect of lipoprotein-associated phospholipase A2 inhibitor on insulin resistance in streptozotocin-induced diabetic pregnant rats.

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    Wang, Guo-Hua; Jin, Jun; Sun, Li-Zhou

    2018-06-21

    This paper aims to investigate the influence of lipoprotein-associated phospholipase A2 (Lp-PLA2) inhibitor, darapladib, on insulin resistance (IR) in streptozotocin (STZ)-induced diabetic pregnant rats. The rat models were divided into Control (normal pregnancy), STZ + saline (STZ-induced diabetic pregnant rats), STZ + Low-dose and STZ + High-dose darapladib (STZ-induced diabetic pregnant rats treated with low-/high-dose darapladib) groups. Pathological changes were observed by Hematoxylin-eosin (HE) and Immunohistochemistry staining. Lp-PLA2 levels were determined by enzyme-linked immunosorbent assay (ELISA). An automatic biochemical analyzer was used to measure the serum levels of biochemical indicators, and homeostatic model assessment for insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were calculated. Western blot was applied to determine levels of inflammatory cytokines. Compared with Control group, rats in the STZ + saline group were significantly decreased in body weight, the number of embryo implantation, the number of insulin positive cells and pancreatic islet size as well as the islet endocrine cells, and high-density lipoprotein (HDL-C) level, but substantially increased in Lp-PLA2, low-density lipoprotein (LDL-C), fatty acids (FFA), serum total cholesterol (TC), triglyceride (TG) levels. Moreover, the increased fasting plasma glucose (FPG) and HOMA-IR and inflammatory cytokines but decreased fasting insulin (FINS) and ISI were also found in diabetic pregnant rats. On the contrary, rats in the darapladib-treated groups were just opposite to the STZ + saline group, and STZ + High-dose group improved better than STZ + Low-dose group. Thus, darapladib can improve lipid metabolism, and enhance insulin sensitivity of diabetic pregnant rats by regulating inflammatory cytokines.

  3. Effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome patients.

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    Karadağ, Cihan; Yoldemir, Tevfik; Yavuz, Dilek Gogas

    2018-02-01

    The aim of this study was to identify the effects of vitamin D supplementation on insulin sensitivity and androgen levels in vitamin-D-deficient polycystic ovary syndrome (PCOS) patients. Sixty-seven vitamin-D-deficient (25-hydroxyvitamin D [25(OH)D] levels below 20 ng/mL) PCOS patients and 54 vitamin-D-deficient non-PCOS volunteer subjects matched for age and body mass index were enrolled to this prospective study. All participants were given 50 000 IU/week cholecalciferol orally for 8 weeks and 1500 IU/day for 4 weeks. Insulin sensitivity was calculated with the Matsuda insulin sensitivity index (ISI) based on an oral glucose tolerance test. Matsuda ISI, gonadal hormones (estrogen, testosterone, androstenedione), and 25(OH)D levels were studied before and at the end of the 12th week of vitamin D load. After vitamin D supplementation, serum androstenedione levels had decreased significantly (P = 0.007) and Matsuda ISI values had increased significantly (P = 0.001) in the PCOS group but no significant changes were seen in those parameters in controls. We observed positive correlations between 25(OH)D levels and Matsuda ISI (r = 0.307; P < 0.01), and negative correlations between 25(OH)D levels and total testosterone (r = -0.306; P < 0.01) and androstenedione (r = -0.275; P < 0.01) levels in the PCOS group. Vitamin D supplementation increased insulin sensitivity and decreased androgen levels in vitamin-D-deficient women with PCOS but did not have any effect in vitamin-D-deficient non-PCOS women. These results may indicate the possible role of vitamin D in the complex pathogenesis of PCOS. © 2017 Japan Society of Obstetrics and Gynecology.

  4. Insulin induces a shift in lipid and primary carbon metabolites in a model of fasting-induced insulin resistance

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    Olmstead, Keedrian I.; La Frano, Michael R.; Fahrmann, Johannes; Grapov, Dmitry; Viscarra, Jose A.; Newman, John W.; Fiehn, Oliver; Crocker, Daniel E.; Filipp, Fabian V.; Ortiz, Rudy M.

    2017-01-01

    Introduction Prolonged fasting in northern elephant seals (NES) is characterized by a reliance on lipid metabolism, conservation of protein, and reduced plasma insulin. During early fasting, glucose infusion previously reduced plasma free fatty acids (FFA); however, during late-fasting, it induced an atypical elevation in FFA despite comparable increases in insulin during both periods suggestive of a dynamic shift in tissue responsiveness to glucose-stimulated insulin secretion. Objective To better assess the contribution of insulin to this fasting-associated shift in substrate metabolism. Methods We compared the responses of plasma metabolites (amino acids (AA), FFA, endocannabinoids (EC), and primary carbon metabolites (PCM)) to an insulin infusion (65 mU/kg) in early- and late-fasted NES pups (n = 5/group). Plasma samples were collected prior to infusion (T0) and at 10, 30, 60, and 120 min post-infusion, and underwent untargeted and targeted metabolomics analyses utilizing a variety of GC-MS and LC-MS technologies. Results In early fasting, the majority (72%) of metabolite trajectories return to baseline levels within 2 h, but not in late fasting indicative of an increase in tissue sensitivity to insulin. In late-fasting, increases in FFA and ketone pools, coupled with decreases in AA and PCM, indicate a shift toward lipolysis, beta-oxidation, ketone metabolism, and decreased protein catabolism. Conversely, insulin increased PCM AUC in late fasting suggesting that gluconeogenic pathways are activated. Insulin also decreased FFA AUC between early and late fasting suggesting that insulin suppresses triglyceride hydrolysis. Conclusion Naturally adapted tolerance to prolonged fasting in these mammals is likely accomplished by suppressing insulin levels and activity, providing novel insight on the evolution of insulin during a condition of temporary, reversible insulin resistance. PMID:28757815

  5. [Effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice].

    Science.gov (United States)

    Jin, Xin; Zhang, Hui-xin; Zhang, Yan-fen; Cui, Wen-wen; Bi, Yao; He, Qi-long; Zhou, Sheng-shan

    2015-03-01

    To study the effect of Jinlida on changes in expression of skeletal muscle lipid transport enzymes in fat-induced insulin resistance ApoE -/- mice. Eight male C57BL/6J mice were selected in the normal group (NF), 40 male ApoE -/- mice were fed for 16 weeks, divided into the model group (HF), the rosiglitazone group ( LGLT), the Jinlida low-dose group (JLDL), the Jinlida medium-dose group (JLDM), the Jinlida high-dose group (JLDH) and then orally given drugs for 8 weeks. The organization free fatty acids, BCA protein concentration determination methods were used to determine the skeletal muscle FFA content. The Real-time fluorescent quantitative reverse transcription PCR ( RT-PCR) and Western blot method were adopted to determine mRNA and protein expressions of mice fatty acids transposition enzyme (FAT/CD36), carnitine palm acyltransferase 1 (CPT1), peroxide proliferators-activated receptor α( PPAR α). Jinlida could decrease fasting blood glucose (FBG), cholesterol (TC), triglyceride (TG), free fatty acid (FFA) and fasting insulin (FIns) and raise insulin sensitive index (ISI) in mice to varying degrees. It could also up-regulate mRNA and protein expressions of CPT1 and PPARα, and down-regulate mRNA and protein levels of FAT/CD36. Jinlida can improve fat-induced insulin resistance ApoE -/- in mice by adjusting the changes in expression of skeletal muscle lipid transport enzymes.

  6. [Study on correlation of glucagons, type 2 diabetes and impaired glucose regulation].

    Science.gov (United States)

    Xu, Tao; Shi, Me; Qiu, Yun-Xia; Wang, Yan-Gang

    2014-06-01

    To analyze the changes of patients with type 2 diabetes in different stages in glucagon (GC) and free fatty acid (FFA) in fasting, OGT and L-Arg experiments, and discusses the role of pancreatic alphabeta cells in diabetes pathogenesis by studying the relations among indexes such as glucagon (GC), free fatty acid (FFA) and blood glucose (BG), insulin, insulin homeostasis model (HOMA) and glucose metabolism hormone secretion curve, in order to provide theoretical basis for the treatment of diabetes. Study objects were divided into the T2DM group (45 cases), the IGT group (28 cases) and the NGT group (30 cases) for an OGTT experiment and then an L-Arg experiment on the next day. Under the fasting state, their blood glucose (FBG), insulin (F), glucagon (FGC), free fatty acid (FFA) were detected to calculate HOMA-beta, insulin sensitivity index (ISI) and HOMA-IR of different groups. Meanwhile, efforts were made to calculate different time quantum detected in OGTT and L-Arg experiments and area under the curve AUC(BG), AUC(INS) and AUC(GC). Obvious overall differences were observed in FFA and FGC of the three groups. FGC of each group was negatively correlated with HOMA-beta and ISI. Among all of the 103 study objects, FGC was positively correlated with FBG and HOMA-IR and negatively correlated with HOMA-beta and ISI, with no correlation with FINS; FFA was positively correlated with FBG, HOMA-IR and negatively correlated with FINS, HOMA-beta, ISI. FGC and FFA were positively correlated in the T2DM group and the IGT group, but with no statistical correlation in the NGT group. The sequence of the three study objects was T2DM > IGR > NGT in AUC(GC) in the OGTT experiment and T2DM > IGR > NGT in in AUC(GC) in the L-Arg experiment, with the significant positive correlation between AUC(GC) and AUC(BG) and significant negative correlation with AUC(INS). Glucagon and free fatty acid of T2DM and IGT patients increased, which was positively correlated with blood glucose and HOMA

  7. Association Between Free Fatty Acid (FFA and Insulin Resistance: The Role of Inflammation (Adiponectin and high sensivity C-reactive Protein/hs-CRP and Stress Oxidative (Superoxide Dismutase/SOD in Obese Non-Diabetic Individual

    Directory of Open Access Journals (Sweden)

    Indriyanti Rafi Sukmawati

    2009-12-01

    Full Text Available BACKGROUND: Obesity is highly related to insulin resistance, therefore, the increased number of obesity is followed by the increased prevalence of type 2 Diabetes Melitus. Obesity is associated with increased of reactive oxygen species (ROS in muscle, liver and endothelial cells. The increase of ROS would lead to insulin resistance (IR and increased pro-inflammatory protein. FFA plays an important role in IR by inhibiting muscle glucose transport and oxidation via effects on serine/threonine phosphorylation of IRS-1. The aim of this study was discover the existence of SOD, hs-CRP and and adiponectin levels towards the occurrence of insulin resistance which was caused by elevated level of FFA and to discover the interaction between SOD, hs-CRP and adiponectin in non diabetic obese adult male. METHODS: This was observational study with cross sectional design. There were 65 obese male non diabetic subjects and 45 non obese male non diabetic subjects who met the criteria. In this study, measurements were done on body mass index (BMI, fasting glucose, insulin, adiponectin, hs-CRP and SOD. Obese was defined as BMI >25 kg/m2, normal weight was defined as BMI 18.5-23 kh/m2 and Insulin Resistance was defined as HOMA-IR >1. RESULTS: This study showed that Hypoadiponectinemia condition, decreased SOD level and high level of hs-CRP is associated with insulin resistance in obese non diabetic subject. Adiponectin and SOD were correlated negatively with insulin resistance in obese non diabetic (Adiponectin, r=-0.455, p<0.001; SOD, r=-0.262, p=0.003, hs-CRP was positively correlated with insulin resistance in obese non diabetic (r=0.592, p<0.001. FFA levels was increased in obese insulin resistance compared with non obese non insulin resistance. The Odds Ratio of Adiponectin, hs-CRP and SOD in this study was analyzed by logistic binary. The OR for SOD 3.6 (p=0.001, hs-CRP 9.1 (p<0.001 and Adiponectin 7.2 (p<0.001. CONCLUSIONS: This study suggested that FFA

  8. The application and evaluation of insulin release test and quantitative parameter in diabetic type II

    International Nuclear Information System (INIS)

    Huang Chenggang; Chen Xiaoyan; Guan Xiaofeng

    2002-01-01

    Objective: To analyse the curve of Insulin Release Test (IRT) about the patients whit type II diabetes, to evaluate β-cell function and the sensitivity of body to Insulin using Insulin Release Index (IRI) and Insulin Sensitivity Index (ISI), and to probe the value for clinical therapy. Methods: 1) Have a IRT of 396 cases with type II diabetes and 17 normal bodies and acquire the IRT curve, 2) Design the count methods about IRI and ISI, IRI = Ins max/Ins FBI x Δ Ins max/T max (minute), ISI=(Ins max-Ins FBI)/(Ins 180'-Ins FBI), 3) Compare IRI Changes of before and after treatment for 12 cases with no insulin release and 9 cases with less insulin release. Results: IRT curve type (No release type 21.0%, less release type 33.3%, peak delay type 36.9%, high insulin type 6.0%, release delay type 2.8%); respective IRI, ISI compared to normal, P<0.01; IRI of before and after treatment with insulin P<0.01. Conclusions: IRT Curve combining IRI and ISI can reflect accurately β-cell function with type II diabetes and the sensitivity of body to insulin, Also it has some reference value for clinical therapy

  9. Chronic treatment with pioglitazone does not protect obese patients with diabetes mellitus type II from free fatty acid-induced insulin resistance

    NARCIS (Netherlands)

    Serlie, Mireille J.; Allick, Gideon; Groener, Johanna E.; Ackermans, Mariette T.; Heijligenberg, Rik; Voermans, Barbara C.; Aerts, Johannes M.; Meijer, Alfred J.; Sauerwein, Hans P.

    2007-01-01

    CONTEXT: Thiazolidinediones increase peripheral insulin sensitivity and decrease plasma free fatty acids (FFA). However, their exact mechanism of action has not been fully elucidated. OBJECTIVE: We studied the protective effect of pioglitazone on FFA-induced insulin resistance and the effects on

  10. Modification and Validation of the Triglyceride-to-HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus: The Single Point Insulin Sensitivity Estimator (SPISE).

    Science.gov (United States)

    Paulmichl, Katharina; Hatunic, Mensud; Højlund, Kurt; Jotic, Aleksandra; Krebs, Michael; Mitrakou, Asimina; Porcellati, Francesca; Tura, Andrea; Bergsten, Peter; Forslund, Anders; Manell, Hannes; Widhalm, Kurt; Weghuber, Daniel; Anderwald, Christian-Heinz

    2016-09-01

    The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI), fasting TG, and HDL cholesterol and compared to the clamp-derived M-value as an estimate of insulin sensitivity. Each modeling result was scored by identifying insulin resistance and correlation coefficient. The Single Point Insulin Sensitivity Estimator (SPISE) was compared to traditional insulin sensitivity indices using area under the ROC curve (aROC) analysis and χ(2) test. The novel formula for SPISE was computed as follows: SPISE = 600 × HDL-C(0.185)/(TG(0.2) × BMI(1.338)), with fasting HDL-C (mg/dL), fasting TG concentrations (mg/dL), and BMI (kg/m(2)). A cutoff value of 6.61 corresponds to an M-value smaller than 4.7 mg · kg(-1) · min(-1) (aROC, M:0.797). SPISE showed a significantly better aROC than the TG/HDL-C ratio. SPISE aROC was comparable to the Matsuda ISI (insulin sensitivity index) and equal to the QUICKI (quantitative insulin sensitivity check index) and HOMA-IR (homeostasis model assessment-insulin resistance) when calculated with M-values. The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI

  11. Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

    Science.gov (United States)

    Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

    2015-01-01

    Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

  12. Matsuda-DeFronzo insulin sensitivity index is a better predictor than HOMA-IR of hypertension in Japanese: the Tanno-Sobetsu study.

    Science.gov (United States)

    Furugen, M; Saitoh, S; Ohnishi, H; Akasaka, H; Mitsumata, K; Chiba, M; Furukawa, T; Miyazaki, Y; Shimamoto, K; Miura, T

    2012-05-01

    Here we examined whether the Matsuda-DeFronzo insulin sensitivity index (ISI-M) is more efficient than the homeostasis model assessment of insulin resistance (HOMA-IR) for assessing risk of hypertension. Cross-sectional and longitudinal analyses were conducted using normotensive subjects who were selected among 1399 subjects in the Tanno-Sobetsu cohort. In the cross-sectional analysis (n=740), blood pressure (BP) level was correlated with HOMA-IR and with ISI-M, but correlation coefficients indicate a tighter correlation with ISI-M. Multiple linear regression analysis adjusted by age, sex, body mass index (BMI) and serum triglyceride level (TG) showed contribution of ISI-M and fasting plasma glucose, but not of HOMA-IR. In the longitudinal analysis (n=607), 241 subjects (39.7%) developed hypertension during a 10-year follow-up period, and multiple logistic regression indicated that age, TG, systolic BP and ISI-M, but not HOMA-IR, were associated with development of hypertension. In subjects HOMA-IR. Non-hepatic IR may be a determinant, which is independent of TG, BP level and BMI, of the development of hypertension.

  13. [Effect of Jinlida on DGAT1 in Skeletal Muscle in Fat-Induced Insulin Resistance ApoE -/- Mice].

    Science.gov (United States)

    Jin, Xin; Zhang, Hui-xin; Cui, Wen-wen

    2015-06-01

    To investigate the effect of Jinlida on DGAT1 in skeletal muscle in fat-induced insulin resistance ApoE-/- mice. Eight male C57BL/6J mice were used as normal group. 40 male ApoE -/- mice were fed high-fat diet for 16 weeks and divided into five groups: control group, rosiglitazone group, and Jinlida low, middle and high dose groups. Then corresponding drugs were administrated intragastrically for eight weeks. TG content in skeletal muscle was measured by enzymic enzymatic, Glucose tolerance test (OGTT) was used to evaluate the degree of insulin resistance in mice. The mRNA and protein expression of insulin receptor substrate (IRS-1) and diacylglycerol acyltransferase 1 (DGAT1) in skeletal muscle were measured by real-time quantitative reverse transcription PCR (RT-PCR)and Western blot. Jinlida particles reduced fasting blood glucose (FBG) cholesterol (TC), triglyceride (TG), free fatty acid (FFA)and fasting insulin (FIns) levels, raised insulin sensitive index (ISI), improved glucose tolerance, and reduced skeletal muscle lipid deposition in ApoE -/- mice significantly. Jinlida particles increased the expression of IRS-1 mRNA and protein, and reduced DGAT1. Jinlida can alleviate the expression of DGAT in skeletal muscle in fat-induced insulin resistance ApoE-/- mice.

  14. Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

    Science.gov (United States)

    Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; Defronzo, Ralph A; Dubé, John J; Musi, Nicolas

    2013-06-01

    Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

  15. Fibroblast Growth Factor 21 (FGF21, Free Fatty Acid (FFA, High Sensitivity C-reactive Protein (hsCRP and Homeostasis Model Assessment of Insulin Resistance (HOMA-IR Among Indonesian Obese Non-Diabetic Males

    Directory of Open Access Journals (Sweden)

    Yani Lina

    2009-12-01

    Full Text Available BACKGROUND: Fibroblast growth factor-21 (FGF21 is known as an important endocrine and paracrine regulator of metabolic homeostasis. Recent studies have shown that FGF21 attenuates lipolysis in human adipocytes, which is suggested as a FGF21's mechanism as anti-hyperlipidemia, anti-hyperglycemia and anti-obesity. The aim of this study was to measure the correlation between FGF21, FFA, hsCRP and HOMA-IR among Indonesian obese non diabetic males. METHODS: The study was observational with cross sectional design. The analysis was done in 137 subjects aged 30-60 years with non diabetic abdominal obesity. We measured the biochemical markers FGF21, FFA, hsCRP, fasting insulin and fasting glucose. We also measured weight, height, waist circumrefence (WC, creatinine, serum glutamin oxaloacetic transaminase (SGOT, and serum glutamic pyruvic transaminase (SGPT, systolic blood pressure (SBP and diastolic blood pressure (DBP. Correlation between markers was measured using Pearson and Spearman's analysis. RESULTS: There were significant positive correlations between FGF21-HOMA-IR (r=0.314, p=0.000; FGF21-WC (r=0.173, p=0.043; FFA=hsCRP r=0.270, p=0.001; and WC-HOMA-IR (r=0.279, p=0.001. There was significant negative correlation between FGF21-FFA (r=-0.038, p=0.657 and FGF21-hsCRP (r=-0.061, p=0.482. CONCLUSIONS: In this study we found that although there was no significant correlation, FGF21 might act as an anti-lipolytic and anti-inflammation agent among Indonesian obese non-diabetic males. Our findings agree with results of previous studies that the positive correlation between FGF21-WC and FGF21-HOMA-IR might occur as a compensatory mechanism or resistance to FGF21 in obesity. KEYWORDS: obesity, FGF21, FFA, hsCRP, HOMA-IR.

  16. Stinging Nettle (Urtica dioica L.) Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

    Science.gov (United States)

    Obanda, Diana N; Zhao, Peng; Richard, Allison J; Ribnicky, David; Cefalu, William T; Stephens, Jacqueline M

    2016-01-01

    Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle) improves insulin action, yet the precise mechanism(s) are not known. Hence, we examined the effects of Urtica dioica L. (UT) on adipocytes. We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid) induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined. As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation. In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

  17. Age-dependent atypicalities in body- and face-sensitive activation of the EBA and FFA in individuals with ASD.

    Science.gov (United States)

    Okamoto, Yuko; Kosaka, Hirotaka; Kitada, Ryo; Seki, Ayumi; Tanabe, Hiroki C; Hayashi, Masamichi J; Kochiyama, Takanori; Saito, Daisuke N; Yanaka, Hisakazu T; Munesue, Toshio; Ishitobi, Makoto; Omori, Masao; Wada, Yuji; Okazawa, Hidehiko; Koeda, Tatsuya; Sadato, Norihiro

    2017-06-01

    Individuals with autism spectrum disorder (ASD) have difficuly in recognizing bodies and faces, which are more pronounced in children than adults. If such difficulties originate from dysfunction of the extrastriate body area (EBA) and the fusiform face area (FFA), activation in these regions might be more atypical in children than in adults. We preformed functional magnetic resonance imaging while children and adults with ASD and age-matched typically developed (TD) individuals observed face, body, car, and scene. To examine various aspects, we performed individual region of interest (ROI) analysis, as well as conventional random effect group analysis. At individual ROI analysis, we examined the ratio of participants showing a category-sensitive response, the size of regions, location and activation patterns among the four object categories. Adults with ASD showed no atypicalities in activation of the EBA and FFA, whereas children with ASD showed atypical activation in these regions. Specifically, a smaller percentage of children with ASD showed face-sensitive activation of the FFA than TD children. Moreover, the size of the EBA was smaller in children with ASD than in TD children. Our results revealed atypicalities in both the FFA and EBA in children with ASD but not in adults with ASD. Copyright © 2017 Elsevier Ireland Ltd and Japan Neuroscience Society. All rights reserved.

  18. Effect of trans-fatty acid intake on insulin sensitivity and intramuscular lipids - a randomized trial in overweight postmenopausal women

    DEFF Research Database (Denmark)

    Bendsen, Nathalie Tommerup; Haugaard, Steen; Larsen, Thomas Meinert

    2011-01-01

    lipid deposition in abdominally obese women. In a double-blind, parallel dietary intervention study, 52 healthy but overweight postmenopausal women were randomized to receive either partially hydrogenated soybean oil (15 g/d TFA) or a control oil (mainly oleic and palmitic acid) for 16 weeks. Three......-nine women completed the study. Insulin sensitivity (assessed by ISI(composite)), β-cell function (the disposition index), and the metabolic clearance rate of insulin were not significantly affected by the dietary intervention. Neither was the ability of insulin to suppress plasma nonesterified fatty acid...

  19. Stinging Nettle (Urtica dioica L. Attenuates FFA Induced Ceramide Accumulation in 3T3-L1 Adipocytes in an Adiponectin Dependent Manner.

    Directory of Open Access Journals (Sweden)

    Diana N Obanda

    Full Text Available Excess dietary lipids result in the accumulation of lipid metabolites including ceramides that can attenuate insulin signaling. There is evidence that a botanical extract of Urtica dioica L. (stinging nettle improves insulin action, yet the precise mechanism(s are not known. Hence, we examined the effects of Urtica dioica L. (UT on adipocytes.We investigated the effects of an ethanolic extract of UT on free fatty acid (palmitic acid induced inhibition of insulin-stimulated Akt serine phosphorylation and modulation of ceramidase expression in 3T3-L1 adipocytes. Adipocytes were exposed to excess FFAs in the presence or absence of UT. Effects on adiponectin expression, ceramidase expression, ceramidase activity, ceramide accumulation and insulin signaling were determined.As expected, FFAs reduced adiponectin expression and increased the expression of ceramidase enzymes but not their activity. FFA also induced the accumulation of ceramides and reduced insulin-stimulated phosphorylation of Akt in adipocytes. The effects of FFA were partially reversed by UT. UT enhanced adiponectin expression and ceramidase activity in the presence of excess FFAs. UT abated ceramide accumulation and increased insulin sensitivity via enhanced Akt phosphorylation. A siRNA knockdown of adiponectin expression prevented UT from exerting positive effects on ceramidase activity but not Akt phosphorylation.In adipocytes, the ability of UT to antagonize the negative effects of FFA by modulating ceramidase activity and ceramide accumulation is dependent on the presence of adiponectin. However, the ability of UT to enhance Akt phosphorylation is independent of adiponectin expression. These studies demonstrate direct effects of UT on adipocytes and suggest this botanical extract is metabolically beneficial.

  20. Insulin sensitivity and albuminuria

    DEFF Research Database (Denmark)

    Pilz, Stefan; Rutters, Femke; Nijpels, Giel

    2014-01-01

    OBJECTIVE: Accumulating evidence suggests an association between insulin sensitivity and albuminuria, which, even in the normal range, is a risk factor for cardiovascular diseases. We evaluated whether insulin sensitivity is associated with albuminuria in healthy subjects. RESEARCH DESIGN...... AND METHODS: We investigated 1,415 healthy, nondiabetic participants (mean age 43.9 ± 8.3 years; 54.3% women) from the RISC (Relationship between Insulin Sensitivity and Cardiovascular Disease) study, of whom 852 participated in a follow-up examination after 3 years. At baseline, insulin sensitivity...... was assessed by hyperinsulinemic-euglycemic clamps, expressed as the M/I value. Oral glucose tolerance test-based insulin sensitivity (OGIS), homeostasis model assessment of insulin resistance (HOMA-IR), and urinary albumin-to-creatinine ratio (UACR) were determined at baseline and follow-up. RESULTS...

  1. Postprandial changes in glucose oxidation and insulin sensitivity in metabolic syndrome: Influence of fibroblast growth factor 21 and vitamin D status.

    Science.gov (United States)

    Pathak, Kaveri; Soares, Mario J; Zhao, Yun; James, Anthony P; Sherriff, Jillian L; Newsholme, Philip

    2017-05-01

    Metabolic inflexibility due to insulin resistance has been reported in metabolic syndrome (MetS). Fibroblast growth factor 21 (FGF21) and vitamin D status may improve insulin sensitivity. The aim of this study was to investigate glucose-induced thermogenesis and oxidation in MetS, and to examine whether changes in FGF21 or prevailing vitamin D status modulated defined metabolic parameters. Forty-eight overweight and obese older adults (14 men, 34 women; ages 51 ± 15 y) were studied. Resting metabolic rate (RMR) and respiratory quotient (RQ) were measured before and intermittently for 2 h after an oral glucose tolerance test (OGTT). The total area under the curve (TAUC) was calculated. Insulin sensitivity index (ISI) was determined as 10 4 /(insulin × glucose) for fasting and 2 h venous blood. Fat mass (FM) and fat free mass (FFM) were measured by dual-energy x-ray absorptiometry. Participants were grouped by metabolic syndrome (MetS+ for disease presence; MetS- when no disease was present) and by median 25 hydroxyvitamin D (OHD) concentration as VD_low and VD_high. 25 OHD was also tested as a continuous variable. A parsimonious 2 × 2 analysis of variance included age, FM, FFM and MetS × sex interaction. Adjusted RMR was similar between groups but an interactive effect of MetS and sex was noted. Fasting RQ was significantly different between vitamin groups (VD_low: 0.835 ± 0.008 versus VD_high: 0.810 ± 0.008; P = 0.024) and fasting ISI was significantly greater in MetS- compared with MetS+ (P = 0.037). Postglucose increases in thermogenesis, RQ, and FGF21 were significant, but ISI decreased. Adjusted postprandial TAUC_RQ (VD_low: 1.71 ± 0.01; VD_high: 1.74 ± 0.001; P = 0.041) and ISI_2 h (VD_low: 35.41 ± 0.21; VD_high: 101.90 ± 0.21; P = 0.001) were significantly different. Adjusted FGF21 was similar across all comparisons before and after OGTT. Higher vitamin D status, but not FGF21, was associated with greater postprandial

  2. Fatty acid represses insulin receptor gene expression by impairing HMGA1 through protein kinase Cε

    International Nuclear Information System (INIS)

    Dey, Debleena; Bhattacharya, Anirban; Roy, SibSankar; Bhattacharya, Samir

    2007-01-01

    It is known that free fatty acid (FFA) contributes to the development of insulin resistance and type2 diabetes. However, the underlying mechanism in FFA-induced insulin resistance is still unclear. In the present investigation we have demonstrated that palmitate significantly (p < 0.001) inhibited insulin-stimulated phosphorylation of PDK1, the key insulin signaling molecule. Consequently, PDK1 phosphorylation of plasma membrane bound PKCε was also inhibited. Surprisingly, phosphorylation of cytosolic PKCε was greatly stimulated by palmitate; this was then translocated to the nuclear region and associated with the inhibition of insulin receptor (IR) gene transcription. A PKCε translocation inhibitor peptide, εV1, suppressed this inhibitory effect of palmitate, suggesting requirement of phospho-PKCε migration to implement palmitate effect. Experimental evidences indicate that phospho-PKCε adversely affected HMGA1. Since HMGA1 regulates IR promoter activity, expression of IR gene was impaired causing reduction of IR on cell surface and that compromises with insulin sensitivity

  3. Prediction of clamp-derived insulin sensitivity from the oral glucose insulin sensitivity index

    DEFF Research Database (Denmark)

    Tura, Andrea; Chemello, Gaetano; Szendroedi, Julia

    2018-01-01

    that underwent both a clamp and an OGTT or meal test, thereby allowing calculation of both the M value and OGIS. The population was divided into a training and a validation cohort (n = 359 and n = 154, respectively). After a stepwise selection approach, the best model for M value prediction was applied......AIMS/HYPOTHESIS: The euglycaemic-hyperinsulinaemic clamp is the gold-standard method for measuring insulin sensitivity, but is less suitable for large clinical trials. Thus, several indices have been developed for evaluating insulin sensitivity from the oral glucose tolerance test (OGTT). However......, most of them yield values different from those obtained by the clamp method. The aim of this study was to develop a new index to predict clamp-derived insulin sensitivity (M value) from the OGTT-derived oral glucose insulin sensitivity index (OGIS). METHODS: We analysed datasets of people...

  4. Improved insulin sensitivity and secretion in prediabetic patients with adrenal insufficiency on dual-release hydrocortisone treatment: a 36-month retrospective analysis.

    Science.gov (United States)

    Guarnotta, Valentina; Ciresi, Alessandro; Pillitteri, Giuseppe; Giordano, Carla

    2018-05-01

    Dual-release hydrocortisone (DR-HC) provides physiological cortisol exposure, leading to an improvement of anthropometric and metabolic parameters. The aim of the study was to evaluate the effects of DR-HC on insulin secretion and sensitivity and cardiometabolic risk, indirectly expressed by the visceral adiposity index (VAI). Retrospective analysis of 49 patients, 13 with primary and 36 with secondary adrenal insufficiency (AI), respectively, on conventional glucocorticoid treatment at baseline and switched to DR-HC for 36 months. Overall, 24 patients had AI-pre-diabetes (impaired fasting glucose, impaired glucose tolerance and the combination), and 25 had AI-normal glucose tolerance (NGT). Clinical and metabolic parameters, including VAI, insulin secretion and sensitivity indexes (fasting insulinaemia, AUC 2 h insulinaemia , oral disposition index [Dio] and ISI-Matsuda), were evaluated. In patients with AI-NGT and AI-prediabetes, a significant decrease in BMI (P = .017 and P 36 and P = .043) was, respectively, observed. In addition, in prediabetic patients, only we found a significant decrease in insulinaemia (P = .014), AUC 2 h insulinaemia (P = .038) and VAI (P = .001), in concomitance with a significant increase in DIo (P = .041) and ISI-Matsuda (P = .038). Long-term DR-HC therapy is associated with an improvement in insulin secretion and sensitivity in patients with prediabetes. However, all patients appear to benefit from the treatment in terms of improvement of metabolic and anthropometric parameters. Larger studies are required to confirm our preliminary data. © 2018 John Wiley & Sons Ltd.

  5. Association Between Free Fatty Acid (FFA) and Insulin Resistance: the Role of Inflammation (Adiponectin and High Sensivity C-reactive Protein/hs-CRP) and Stress Oxidative (Superoxide Dismutase/SOD) in Obese Non-Diabetic Individual

    OpenAIRE

    Sukmawati, Indriyanti Rafi; Donoseputro, Marsetio; Lukito, Widjaja

    2009-01-01

    BACKGROUND: Obesity is highly related to insulin resistance, therefore, the increased number of obesity is followed by the increased prevalence of type 2 Diabetes Melitus. Obesity is associated with increased of reactive oxygen species (ROS) in muscle, liver and endothelial cells. The increase of ROS would lead to insulin resistance (IR) and increased pro-inflammatory protein. FFA plays an important role in IR by inhibiting muscle glucose transport and oxidation via effects on serine/threonin...

  6. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    DEFF Research Database (Denmark)

    Bot, M; Pouwer, F; De Jonge, P

    2013-01-01

    Sensitivity and Cardiovascular Disease Risk (RISC) study. Presence of significant depressive symptoms was defined as a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16. Standard oral glucose tolerance tests were performed. Insulin sensitivity was assessed with the oral glucose insulin......AIM: This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. METHODS: The study population was derived from the 3-year follow-up of the Relationship between Insulin...... sensitivity (OGIS) index. Insulin secretion was estimated using three model-based parameters of insulin secretion (beta-cell glucose sensitivity, the potentiation factor ratio, and beta-cell rate sensitivity). RESULTS: A total of 162 out of 1027 participants (16%) had significant depressive symptoms. Having...

  7. Selective orthosteric free fatty acid receptor 2 (FFA2) agonists: identification of the structural and chemical requirements for selective activation of FFA2 versus FFA3

    DEFF Research Database (Denmark)

    Schmidt, Johannes; Smith, Nicola J; Christiansen, Elisabeth

    2011-01-01

    given its size. Propionate, however, does not discriminate between FFA2 and the closely related receptor FFA3 (GPR41). To identify FFA2 selective ligands and understand the molecular basis for FFA2 selectivity, a targeted library of small carboxylic acids (SCAs) was examined using holistic, label...

  8. Intralipid decreases apolipoprotein M levels and insulin sensitivity in rats.

    Directory of Open Access Journals (Sweden)

    Lu Zheng

    Full Text Available BACKGROUND: Apolipoprotein M (ApoM is a constituent of high-density lipoproteins (HDL. It plays a crucial role in HDL-mediated reverse cholesterol transport. Insulin resistance is associated with decreased ApoM levels. AIMS: To assess the effects of increased free fatty acids (FFAs levels after short-term Intralipid infusion on insulin sensitivity and hepatic ApoM gene expression. METHODS: Adult male Sprague-Dawley (SD rats infused with 20% Intralipid solution for 6 h. Glucose infusion rates (GIR were determined by hyperinsulinemic-euglycemic clamp during Intralipid infusion and plasma FFA levels were measured by colorimetry. Rats were sacrificed after Intralipid treatment and livers were sampled. Human embryonic kidney 293T cells were transfected with a lentivirus mediated human apoM overexpression system. Goto-Kakizaki (GK rats were injected with the lentiviral vector and insulin tolerance was assessed. Gene expression was assessed by real-time RT-PCR and PCR array. RESULTS: Intralipid increased FFAs by 17.6 folds and GIR was decreased by 27.1% compared to the control group. ApoM gene expression was decreased by 40.4% after Intralipid infusion. PPARβ/δ expression was not changed by Intralipid. Whereas the mRNA levels of Acaca, Acox1, Akt1, V-raf murine sarcoma 3611 viral oncogene homolog, G6pc, Irs2, Ldlr, Map2k1, pyruvate kinase and RBC were significantly increased in rat liver after Intralipid infusion. The Mitogen-activated protein kinase 8 (MAPK8 was significantly down-regulated in 293T cells overexpressing ApoM. Overexpression of human ApoM in GK rats could enhance the glucose-lowering effect of exogenous insulin. CONCLUSION: These results suggest that Intralipid could decrease hepatic ApoM levels. ApoM overexpression may have a potential role in improving insulin resistance in vivo and modulating apoM expression might be a future therapeutic strategy against insulin resistance in type 2 diabetes.

  9. Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

    Science.gov (United States)

    Sydow, Karsten; Mondon, Carl E.; Schrader, Joerg; Konishi, Hakuoh; Cooke, John P.

    2011-01-01

    Objective Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity. Methods and Results To test this hypothesis we employed a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22–70 weeks) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2μM) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle. Conclusions These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity. PMID:18239148

  10. Relationships between endothelin and insulin receptor of red blood cell and insulin resistance in patients with hypertension

    International Nuclear Information System (INIS)

    Tong Qian; Zheng Yang; Xu Hui

    2004-01-01

    Objective: To find the relationships between endothelin (ET) and insulin resistance (IR) and insulin receptor (INSR) in patients with essential hypertension. Methods: Forty patients including 20 cases of essential hypertension disease (EHD) and 20 health persons were divided into experimental group and control group. Blood glucose, serum insulin, ET and the number of erythrocyte INSR in all patients during fasting condition were detected by radioimmunoassay and radiometric analysis. Results: Both insulin sensitivity index (ISI) and the number of INSR in EHD group were much less than that of control group, on the contrary, ET level of EHD group was significantly higher than that of control group (P<0.05). Statistical analysis demonstrated a negative correlation between ET and ISI and INSR number existed in EHD group. Conclusion: IR is a common phenomenon in patient with EHD and possibly due to decrease of INSR number. The ET levels are higher in patients with EHD than that in health people and correlate with INSR, and the change of INSR number is the possible mediator for their relationship

  11. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

    DEFF Research Database (Denmark)

    Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

    2003-01-01

    of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

  12. Endocrine determinants of changes in insulin sensitivity and insulin secretion during a weight cycle in healthy men.

    Directory of Open Access Journals (Sweden)

    Judith Karschin

    Full Text Available Changes in insulin sensitivity (IS and insulin secretion occur with perturbations in energy balance and glycemic load (GL of the diet that may precede the development of insulin resistance and hyperinsulinemia. Determinants of changes in IS and insulin secretion with weight cycling in non-obese healthy subjects remain unclear.In a 6wk controlled 2-stage randomized dietary intervention 32 healthy men (26±4y, BMI: 24±2kg/m2 followed 1wk of overfeeding (OF, 3wks of caloric restriction (CR containing either 50% or 65% carbohydrate (CHO and 2wks of refeeding (RF with the same amount of CHO but either low or high glycaemic index at ±50% energy requirement. Measures of IS (basal: HOMA-index, postprandial: Matsuda-ISI, insulin secretion (early: Stumvoll-index, total: tAUC-insulin/tAUC-glucose and potential endocrine determinants (ghrelin, leptin, adiponectin, thyroid hormone levels, 24h-urinary catecholamine excretion were assessed.IS improved and insulin secretion decreased due to CR and normalized upon RF. Weight loss-induced improvements in basal and postprandial IS were associated with decreases in leptin and increases in ghrelin levels, respectively (r = 0.36 and r = 0.62, p<0.05. Weight regain-induced decrease in postprandial IS correlated with increases in adiponectin, fT3, TSH, GL of the diet and a decrease in ghrelin levels (r-values between -0.40 and 0.83, p<0.05 whereas increases in early and total insulin secretion were associated with a decrease in leptin/adiponectin-ratio (r = -0.52 and r = -0.46, p<0.05 and a decrease in fT4 (r = -0.38, p<0.05 for total insulin secretion only. After controlling for GL associations between RF-induced decrease in postprandial IS and increases in fT3 and TSH levels were no longer significant.Weight cycling induced changes in IS and insulin secretion were associated with changes in all measured hormones, except for catecholamine excretion. While leptin, adiponectin and ghrelin seem to be the major

  13. Urban FFA Members' Sense of the Organizational Culture of the FFA

    Science.gov (United States)

    Martin, Michael J.; Kitchel, Tracy

    2014-01-01

    Organizational culture shapes how members of a group act. The culture has the power to exclude potential new members who do not fit into the culture of the organization. Research on urban school-based agriculture programs has indicated that urban agriculture students face barriers to their participation in the National FFA Organization (FFA).…

  14. Preliminary study on the relationship between insulin resistance and stroke during acute stage

    International Nuclear Information System (INIS)

    Wang Xiaorong; Chen Xinghua

    2001-01-01

    Objective: To explore whether there are insulin resistance (IR) in the patients with stroke and the relationship between IR and the patients' condition and prognosis. Method: Fasting plasma glucose (FPG), fasting serum insulin and cortisol levels were determined in 30 patients with cerebral infarction, 31 patients with cerebral hemorrhage and 28 normal adults. The insulin sensitivity index (ISI) was calculated and the result was analyzed by linear correlation with the score of neurologic impairment and the size of lesions. Results: The study showed that the levels of FPG, FINS and cortisol of the patients with stroke were significantly higher than those of the control group (p < 0.001); ISI in patient was significantly lower than that in control group (p < 0.001). There were als significant deference in FPG, FINS levels and ISI between the mild group and moderate as well as severe groups of stroke (p < 0.001, p < 0.01, p < 0.05). ISI was negatively also correlated with area of infarction and volume of haemorrhage (r = -0.372, r -0.406, p < 0.05). It was also negatively correlated with the score of neurologic impairment (r = -0.321, p < 0.05). The mortality rate and the disability rate in moderate and severe groups were higher than those in mild group. Conclusion: There were presence of IR in the patients with stroke. The insulin level and IR during acute stage were correlated with patients condition and prognosis. It was suggested that insulin should be used to treat the patients with presence of IR (high plasma glucose level and low ISI)

  15. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    Increased skeletal muscle capillarization is associated with improved glucose tolerance and insulin sensitivity. However, a possible causal relationship has not previously been identified. We therefore investigated whether increased skeletal muscle capillarization increases insulin sensitivity....... Skeletal muscle specific angiogenesis was induced by adding the α1-adrenergic receptor antagonist Prazosin to the drinking water of Sprague Dawley rats (n=33) while 34 rats served as controls. Insulin sensitivity was measured ≥40 h after termination of the 3-week Prazosin treatment, which ensured...... that Prazosin was cleared from the blood stream. Whole-body insulin sensitivity was measured in conscious, unrestrained rats by hyperinsulinemic euglycemic clamp. Tissue specific insulin sensitivity was assessed by administration of 2-deoxy-[(3)H]-Glucose during the plateau phase of the clamp. Whole...

  16. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    NARCIS (Netherlands)

    Bot, M.; Pouwer, F.; de Jonge, P.; Nolan, J.J.; Mari, A.; Højlund, K.; Golay, A.; Balkau, B.; Dekker, J.M.

    2013-01-01

    Aim This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. Methods The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity

  17. Depressive symptoms, insulin sensitivity and insulin secretion in the RISC cohort study

    NARCIS (Netherlands)

    Bot, M.; Pouwer, F.; De Jonge, P.; Nolan, J. J.; Mari, A.; Hojlund, K.; Golay, A.; Balkau, B.; Dekker, J. M.

    Aim. This study explored the association of depressive symptoms with indices of insulin sensitivity and insulin secretion in a cohort of non-diabetic men and women aged 30 to 64 years. Methods. The study population was derived from the 3-year follow-up of the Relationship between Insulin Sensitivity

  18. Identification of a potent and selective free fatty acid receptor 1 (FFA1/GPR40) agonist with favorable physicochemical and in vitro ADME properties

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Urban, Christian; Grundmann, Manuel

    2011-01-01

    The free fatty acid receptor 1 (FFA1, also known as GPR40) enhances glucose-stimulated insulin secretion from pancreatic ß-cells and is recognized as an interesting new target for treatment of type 2 diabetes. Several series of selective FFA1 agonists are already known. Most of these are derived...... from free fatty acids (FFAs) or glitazones, and are relatively lipophilic. Aiming at the development of potent, selective and less lipophilic FFA1 agonists, the terminal phenyl of a known compound series was replaced by nitrogen containing heterocycles. This resulted in the identification of 37......, a selective FFA1 agonist with potent activity on recombinant human FFA1 receptors and on the rat insulinoma cell line INS-1E, optimal lipophilicity and excellent in vitro permeability and metabolic stability....

  19. Variability of HOMA and QUICKI insulin sensitivity indices.

    Science.gov (United States)

    Žarković, Miloš; Ćirić, Jasmina; Beleslin, Biljana; Stojković, Mirjana; Savić, Slavica; Stojanović, Miloš; Lalić, Tijana

    2017-07-01

    Assessment of insulin sensitivity based on a single measurement of insulin and glucose, is both easy to understand and simple to perform. The tests most often used are HOMA and QUICKI. The aim of this study was to assess the biological variability of estimates of insulin sensitivity using HOMA and QUICKI indices. After a 12-h fast, blood was sampled for insulin and glucose determination. Sampling lasted for 90 min with an intersample interval of 2 min. A total of 56 subjects were included in the study, and in nine subjects sampling was done before and after weight reduction, so total number of analyzed series was 65. To compute the reference value of the insulin sensitivity index, averages of all 46 insulin and glucose samples were used. We also computed point estimates (single value estimates) of the insulin sensitivity index based on the different number of insulin/glucose samples (1-45 consecutive samples). To compute the variability of point estimates a bootstrapping procedure was used using 1000 resamples for each series and for each number of samples used to average insulin and glucose. Using a single insulin/glucose sample HOMA variability was 26.18 ± 4.31%, and QUICKI variability was 3.30 ± 0.54%. For 10 samples variability was 11.99 ± 2.22% and 1.62 ± 0.31% respectively. Biological variability of insulin sensitivity indices is significant, and it can be reduced by increasing the number of samples. Oscillations of insulin concentration in plasma are the major cause of variability of insulin sensitivity indices.

  20. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

    Directory of Open Access Journals (Sweden)

    Nicole M. Templeman

    2017-07-01

    Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

  1. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

    Science.gov (United States)

    Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

    2017-07-11

    The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  2. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets.

    Science.gov (United States)

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD). Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and in regulation of appetite. More research is however required to clarify the potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets.

  3. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    Directory of Open Access Journals (Sweden)

    Trond eUlven

    2012-10-01

    Full Text Available The deorphanization of the free fatty acid (FFA receptors FFA1 (GPR40, FFA2 (GPR43, FFA3 (GPR41, GPR84 and GPR120 made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber produces high concentrations of the short-chain fatty acids (SCFAs acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane receptors free fatty acid receptor 2 (FFA2 and FFA3 are activated by these SCFAs, and several lines of evidence indicate that FFA2 and FFA3 mediate beneficial effects associated with a fiber-rich diet, and that they may be of interest as targets for treatment of inflammatory and metabolic diseases. FFA2 is highly expressed on immune cells, in particular neutrophils, and several studies suggest that the receptor plays a role in diseases involving a dysfunctional neutrophil response, such as inflammatory bowel disease (IBD. Both FFA2 and FFA3 have been implicated in metabolic diseases such as type 2 diabetes and regulation of appetite. More research is however required to clarify potential of the receptors as drug targets and establish if activation or inhibition would be the preferred mode of action. The availability of potent and selective receptor modulators is a prerequisite for these studies. The few modulators of FFA2 or FFA3 that have been published hitherto in the peer-reviewed literature in general have properties that make them less than ideal as such tools, but published patent applications indicate that the situation may soon improve, and that proper tool compounds will enable studies critical to validate the receptors as new drug targets.

  4. Involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells.

    Science.gov (United States)

    Takahashi, Kaede; Fukushima, Kaori; Onishi, Yuka; Minami, Kanako; Otagaki, Shiho; Ishimoto, Kaichi; Fukushima, Nobuyuki; Honoki, Kanya; Tsujiuchi, Toshifumi

    2018-08-01

    Free fatty acid receptor 1 (FFA1) and FFA4 mediate a variety of biological responses through binding of medium- and long-chain free fatty acids. The aim of this study was to investigate an involvement of FFA1 and FFA4 in the regulation of cellular functions during tumor progression in colon cancer cells. The long-term fluorouracil (5-FU) and cisplatin (CDDP) treated cells were generated from DLD1 cells (DLD-5FU and DLD-CDDP cells, respectively). FFAR1 expressions were lower in DLD-5FU and DLD-CDDP cells than in DLD1 cells. In contrast, DLD-5FU and DLD-CDDP cells showed the high FFAR4 expressions, compared with DLD1 cells. The cell motile activities of DLD-5FU and DLD-CDDP cells were reduced by GW9508 which is an agonist of FFA1 and FFA4. Moreover, GW1100, an antagonist of FFA1, inhibited the cell motile activities of DLD-5FU and DLD-CDDP cells. To evaluate whether FFA1 and FFA4 regulate the enhancement of cell motility, invasion and colony formation, highly migratory (hmDLD1) cells were established from DLD1 cells. FFAR1 expression was significantly higher in hmDLD1 cells than in DLD1 cells, but no change of FFAR4 expression was observed. The elevated cell motile and invasive activities and colony formation of hmDLD1 cells were suppressed by FFA1 inhibition. These results suggest that FFA1 and FFA4 are involved in the regulation of cellular functions during tumor progression in colon cancer DLD1 cells. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Defects in TLR3 expression and RNase L activation lead to decreased MnSOD expression and insulin resistance in muscle cells of obese people

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Breuker, C; Amouzou, C

    2014-01-01

    Obesity is associated with chronic low-grade inflammation and oxidative stress that blunt insulin response in its target tissues, leading to insulin resistance (IR). IR is a characteristic feature of type 2 diabetes. Skeletal muscle is responsible for 75% of total insulin-dependent glucose uptake...... with palmitate, a saturated free fatty acid (FFA) known to induce inflammation and oxidative stress via TLR4 activation. While RNase L and RLI levels remained unchanged, OAS level was decreased in primary myotubes from insulin-resistant obese subjects (OB-IR) compared with myotubes from insulin-sensitive obese......; consequently, skeletal muscle IR is considered to be the primary defect of systemic IR development. Interestingly, some obese people stay insulin-sensitive and metabolically healthy. With the aim of understanding this difference and identifying the mechanisms responsible for insulin sensitivity maintenance...

  6. Evidence for a relationship between VEGF and BMI independent of insulin sensitivity by glucose clamp procedure in a homogenous group healthy young men.

    Directory of Open Access Journals (Sweden)

    Michaela Loebig

    Full Text Available BACKGROUND: This is the first study to experimentally explore the direct relationship between circulating VEGF levels and body mass index (BMI as well as to unravel the role of insulin sensitivity in this context under standardized glucose clamp conditions as the methodical gold-standard. In order to control for known influencing factors such as gender, medication, and arterial hypertension, we examined a highly homogeneous group of young male subjects. Moreover, to encompass also subjects beyond the normal BMI range, low weight and obese participants were additionally included and stress hormones as a main regulator of VEGF were assessed. METHODOLOGY/PRINCIPAL FINDINGS: Under euglycemic clamp conditions, VEGF was measured in 15 normal weight (BMI 20-25 kg/m(2, 15 low weight (BMI30 kg/m(2 male subjects aged 18-30 years and the insulin sensitivity index (ISI was calculated. Since stress axis activation promotes VEGF secretion, concentrations of ACTH, cortisol, and catecholamines were monitored. Despite of comparable ACTH (P = 0.145, cortisol (P = 0.840, and norepinephrine (P = 0.065 levels, VEGF concentrations differed significantly between BMI-groups (P = 0.008 with higher concentrations in obese subjects as compared to normal weight (P = 0.061 and low weight subjects (P = 0.002. Pearson's correlation analysis revealed a positive relationship between BMI and VEGF levels (r = 0.407; P = 0.010 but no correlation of VEGF with ISI (r = 0.224; P = 0.175. CONCLUSIONS/SIGNIFICANCE: Our data demonstrate a positive correlation between concentrations of circulating VEGF levels and BMI in healthy male subjects under highly controlled conditions. This relationship which is apparently disconnected from insulin sensitivity may be part of some pathogenetic mechanisms underlying obesity and type 2 diabetes.

  7. Insulin sensitivity in post-obese women

    DEFF Research Database (Denmark)

    Toubro, S; Western, P; Bülow, J

    1994-01-01

    1. Both increased and decreased sensitivity to insulin has been proposed to precede the development of obesity. Therefore, insulin sensitivity was measured during a 2 h hyperinsulinaemia (100 m-units min-1 m-2) euglycaemic (4.5 mmol/l) glucose clamp combined with indirect calorimetry in nine weight......-1 kg-1, not significant). Basal plasma concentrations of free fatty acids were similar, but at the end of the clamp free fatty acids were lower in the post-obese women than in the control women (139 +/- 19 and 276 +/- 48 mumol/l, P = 0.02). 3. We conclude that the insulin sensitivity of glucose...... metabolism is unaltered in the post-obese state. The study, however, points to an increased antilipolytic insulin action in post-obese subjects, which may favour fat storage and lower lipid oxidation rate postprandially.(ABSTRACT TRUNCATED AT 250 WORDS)...

  8. Insulin resistance, insulin sensitization and inflammation in polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Dhindsa G

    2004-04-01

    Full Text Available It is estimated that 5-10% of women of reproductive age have polycystic ovarian syndrome (PCOS. While insulin resistance is not part of the diagnostic criteria for PCOS, its importance in the pathogenesis of PCOS cannot be denied. PCOS is associated with insulin resistance independent of total or fat-free body mass. Post-receptor defects in the action of insulin have been described in PCOS which are similar to those found in obesity and type 2 diabetes. Treatment with insulin sensitizers, metformin and thiazolidinediones, improve both metabolic and hormonal patterns and also improve ovulation in PCOS. Recent studies have shown that PCOS women have higher circulating levels of inflammatory mediators like C-reactive protein, tumour necrosis factor- , tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1 . It is possible that the beneficial effect of insulin sensitizers in PCOS may be partly due to a decrease in inflammation.

  9. Study on the phenomenon of insulin resistance (IR) in patients with acute cerebral infarction

    International Nuclear Information System (INIS)

    Chen Xinhua; Wang Genfa; Yu Lihua

    2007-01-01

    Objective: To investigate the presence of insulin resistance (IR) in patients with cerebral infarction and the indication for insulin therapy. Methods: Fasting blood glucose (FPG) (with biochemistry), fasting serum insulin (FINS) and cortisol (with RIA) levels were measured in 50 patients with cerebral infarction and 80 controls. Insulin sensitivity index (ISI) was calculated and correlation with the score of neurologic impairment as well as the size of lesion was studied. Results: FPG, FINS and cortisol levels in the patients were significantly higher than those in the controls (P<0.001 ) while the ISI was significantly lower (P <0.001 ) than that in the controls. Levels of there parameters were significantly higher in patients with moderate-severe lesions than those in patients with only mild lesion (P<0.001, P<0.01, P<0.05 respectively). ISI was negatively correlated to the size of infarction (r=-0.313, P<0.05) and also to the score of neurologic impairment (r=-0.317, P<0.05). The mortality and morbidity in the moderate severe group were naturally higher than those in the mild group. Conclusion: Insulin resistance does exist during the acute stage of cerebral infarction. Degree of hyperinsulinaemia and severity of the resistance are related to the course and prognosis of the disease process. Insulin therapy should be considered in those patients with hyperglycemia. (authors)

  10. Effect of Avocado Soybean Unsaponifiables on Insulin Secretion and Insulin Sensitivity in Patients with Obesity

    Directory of Open Access Journals (Sweden)

    Esperanza Martínez-Abundis

    2013-10-01

    Full Text Available Aim: To evaluate the effect of avocado soybean unsaponifiables (ASU on insulin secretion and insulin sensitivity in patients with obesity. Methods: A randomized, double-blind, placebo-controlled, clinical trial was carried out in 14 obese adult volunteers. After random allocation of the intervention, 7 patients received 300 mg of ASU or placebo during a fasting state for 3 months. A metabolic profile including IL-6 and high-sensitivity C-reactive protein (hs-CRP levels was carried out prior to the intervention. A hyperglycemic-hyperinsulinemic clamp technique was used to assess insulin secretion and insulin sensitivity phases. Mann-Whitney U test and Wilcoxon test were performed for statistical analyses. The study was approved by the local ethics committee of our institution. Results: At baseline, both groups were similar according to clinical and laboratory characteristics. There was no significant difference in insulin secretion and insulin sensitivity with ASU. Conclusions: ASU administration for 3 months did not modify insulin secretion and insulin sensitivity in patients with obesity.

  11. Insulin sensitivity : modulation by the brain

    NARCIS (Netherlands)

    Coomans, Claudia Pascalle

    2012-01-01

    The studies in this thesis contribute to the understanding of the role of the brain in insulin sensitivity. We demonstrate that disturbances in circadian rhythm resulting in alterations in SCN output, can contribute to the development of insulin resistance. We also shown that insulin-stimulated

  12. Mechanical stress regulates insulin sensitivity through integrin-dependent control of insulin receptor localization.

    Science.gov (United States)

    Kim, Jung; Bilder, David; Neufeld, Thomas P

    2018-01-15

    Insulin resistance, the failure to activate insulin signaling in the presence of ligand, leads to metabolic diseases, including type 2 diabetes. Physical activity and mechanical stress have been shown to protect against insulin resistance, but the molecular mechanisms remain unclear. Here, we address this relationship in the Drosophila larval fat body, an insulin-sensitive organ analogous to vertebrate adipose tissue and livers. We found that insulin signaling in Drosophila fat body cells is abolished in the absence of physical activity and mechanical stress even when excess insulin is present. Physical movement is required for insulin sensitivity in both intact larvae and fat bodies cultured ex vivo. Interestingly, the insulin receptor and other downstream components are recruited to the plasma membrane in response to mechanical stress, and this membrane localization is rapidly lost upon disruption of larval or tissue movement. Sensing of mechanical stimuli is mediated in part by integrins, whose activation is necessary and sufficient for mechanical stress-dependent insulin signaling. Insulin resistance develops naturally during the transition from the active larval stage to the immotile pupal stage, suggesting that regulation of insulin sensitivity by mechanical stress may help coordinate developmental programming with metabolism. © 2018 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

  13. Effects of Chronic Consumption of Sugar-Enriched Diets on Brain Metabolism and Insulin Sensitivity in Adult Yucatan Minipigs.

    Directory of Open Access Journals (Sweden)

    Melissa Ochoa

    Full Text Available Excessive sugar intake might increase the risk to develop eating disorders via an altered reward circuitry, but it remains unknown whether different sugar sources induce different neural effects and whether these effects are dependent from body weight. Therefore, we compared the effects of three high-fat and isocaloric diets varying only in their carbohydrate sources on brain activity of reward-related regions, and assessed whether brain activity is dependent on insulin sensitivity. Twenty-four minipigs underwent 18FDG PET brain imaging following 7-month intake of high-fat diets of which 20% in dry matter weight (36.3% of metabolisable energy was provided by starch, glucose or fructose (n = 8 per diet. Animals were then subjected to a euglycemic hyperinsulinemic clamp to determine peripheral insulin sensitivity. After a 7-month diet treatment, all groups had substantial increases in body weight (from 36.02±0.85 to 63.33±0.81 kg; P<0.0001, regardless of the diet. All groups presented similar insulin sensitivity index (ISI = 1.39±0.10 mL·min-1·μUI·kg. Compared to starch, chronic exposure to fructose and glucose induced bilateral brain activations, i.e. increased basal cerebral glucose metabolism, in several reward-related brain regions including the anterior and dorsolateral prefrontal cortex, the orbitofrontal cortex, the anterior cingulate cortex, the caudate and putamen. The lack of differences in insulin sensitivity index and body weight suggests that the observed differences in basal brain glucose metabolism are not related to differences in peripheral insulin sensitivity and weight gain. The differences in basal brain metabolism in reward-related brain areas suggest the onset of cerebral functional alterations induced by chronic consumption of dietary sugars. Further studies should explore the underlying mechanisms, such as the availability of intestinal and brain sugar transporter, or the appearance of addictive-like behavioral

  14. The importance of sensitive screening for abnormal glucose metabolism in patients with IgA nephropathy.

    Science.gov (United States)

    Jia, Xiaoyuan; Pan, Xiaoxia; Xie, Jingyuan; Shen, Pingyan; Wang, Zhaohui; Li, Ya; Wang, Weiming; Chen, Nan

    2016-01-01

    To investigate the prevalence of abnormal glucose metabolism, insulin resistance (IR) and the related risk factors in IgA nephropathy (IgAN) patients. We analyzed oral glucose tolerance test (OGTT) and clinical data of 107 IgAN patients and 106 healthy controls. Glucose metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) and the insulin sensitivity index (ISI) of both groups were evaluated. The prevalence of abnormal glucose metabolism was significantly higher in the IgAN group than in the control group (41.12% vs. 9.43%, p glucose, fasting insulin, OGTT 2-hour blood glucose, OGTT 2-hour insulin, HOMA-IR, and lower ISI than healthy controls. Triglyceride (OR = 2.55), 24-hour urine protein excretion (OR = 1.39), and age (OR = 1.06) were independent risk factors for abnormal glucose metabolism in IgAN patients. BMI, eGFR, 24-hour urine protein excretion, triglyceride, fasting blood glucose, fasting insulin, OGTT 2-hour blood glucose, and OGTT 2-hour insulin were significantly higher in IgAN patients with IR than in IgAN patients without IR, while HDL and ISI were significantly lower. BMI, serum albumin, and 24-hour urine protein excretion were correlated factors of IR in IgAN patients. Our study highlighted that abnormal glucose metabolism was common in IgAN patients. Triglyceride and 24-hour urine protein excretion were significant risk factors for abnormal glucose metabolism. Therefore, sensitive screening for glucose metabolism status and timely intervention should be carried out in clinical work.

  15. How can we measure insulin sensitivity?

    International Nuclear Information System (INIS)

    Hovorka, R.

    1999-01-01

    Insulin resistance is common in general population and prevalent in patients with obesity and Type 2 diabetes. Insulin sensitivity, reciprocal to insulin resistance, can be measured with a variety of experimental methods ranging from the 'gold' standard glucose clamp to the simple HOMA assessment. Each method has its merit and is applicable under different circumstances. Adoption of glucose tracers in the experimental protocols and more specifically in glucose clamp and minimal model allows hepatic vs. peripheral insulin sensitivity to be discriminated and estimated separately. The objective of this review is to give an account of the minimal modelling approach and provide summary information about other measurement methods together with information about reproducibility of the most popular methods, the minimal model and the glucose clamp techniques. (author)

  16. Study on the insulin resistance and β-cell function in individuals with normal and those with abnormal glucose metabolism

    International Nuclear Information System (INIS)

    Wei Zikun

    2006-01-01

    Objective: To study the insulin resistance and β-cell function in individuals with normal glucose tolerance (NGT) and those with glucose metabolism dysfunction. Methods: Insulin resistance and β-cell function were studied with oral glucose tolerance test and the following parameters: 2h insulin/2h plasma glucose (2hIns/2hPG), insulin resistance index (IRI), insulin sensitivity index (ISI) and 30 min net increment of insulin/30min net increment of glucose (AI 30 /AG 30 ) were examined in 44 individuals with NGT, 45 subjects with impaired glucose tolerance (IGT), 66 recently diagnosed diabetics and 175 well-established diabetics. Results: The insulin resistance index (IRI) increased progressively from that in NGT individuals to that in recently diabetics (20 ± 1. 5→3.1 ± 1.6→4.1 ± 1.8), while the 2hIns/2hPG, ΔI 30 /ΔG 30 and ISI decreased progressively with significant differences between those in successive groups (P 30 /ΔG 30 and ISI kept decreasing (values in patients with disease history less than 3 yrs vs those in patients with disease over 3yrs: 2.9 ± 3.2 vs 2.4 + 2.3, 30.2 + 1.1 vs 23.4 ± 2.3, P 30 /ΔG 30 were significantly correlated with ISI (F =96.3, 58.4 and 47.5 respectively). For principal component analysis display, the cumulative contribution rate of four parameters (2hIns/2hPG, ISI, ΔI 30 /ΔG 30 and 2h C-peptide) exceeded 85% (86.5%). Conclusion: As the dysfunction of glucose metabolism proceeded from IGT to well established diabetes, the IR increased first with decrease of β-cell secretion followed. The parameters 2hIns/2hPG, ISI, 2h C-peptide ΔI 30 /ΔG 30 were especially useful for the investigation . (authors)

  17. Short-chain free fatty acid receptors FFA2/GPR43 and FFA3/GPR41 as new potential therapeutic targets

    DEFF Research Database (Denmark)

    Ulven, Trond

    2012-01-01

    The deorphanization of the free fatty acid (FFA) receptors FFA1 (GPR40), FFA2 (GPR43), FFA3 (GPR41), GPR84, and GPR120 has made clear that the body is capable of recognizing and responding directly to nonesterified fatty acid of virtually any chain length. Colonic fermentation of dietary fiber...... produces high concentrations of the short-chain fatty acids (SCFAs) acetate, propionate and butyrate, a process which is important to health. The phylogenetically related 7-transmembrane (7TM) receptors free fatty acid receptor 2 (FFA2) and FFA3 are activated by these SCFAs, and several lines of evidence...... in general have properties that make them less than ideal as such tools, but published patent applications indicate that better tool compounds might soon become available which should enable studies critical to validate the receptors as new drug targets....

  18. A model to estimate insulin sensitivity in dairy cows

    OpenAIRE

    Holtenius, Paul; Holtenius, Kjell

    2007-01-01

    Abstract Impairment of the insulin regulation of energy metabolism is considered to be an etiologic key component for metabolic disturbances. Methods for studies of insulin sensitivity thus are highly topical. There are clear indications that reduced insulin sensitivity contributes to the metabolic disturbances that occurs especially among obese lactating cows. Direct measurements of insulin sensitivity are laborious and not suitable for epidemiological studies. We have therefore adopted an i...

  19. The performance of prototype position-sensitive neutron detectors on SXD at ISIS

    International Nuclear Information System (INIS)

    Wilson, C.C.

    1989-02-01

    The performance of two position-sensitive neutron detector designed for use on the single crystal diffractometer (SXD) at ISIS is assessed. The two detectors examined were the Anger camera 6 Li-glass scintillator PSD and a prototype fibre-optic encoded PSD based on 6 Li-doped ZnS plastic scintillator. The latter detector is found to be both simpler to fabricate and to produce better results on the evidence to date. A summary of some of the expected science from SXD and the performance of the detectors with respect to this is also given. (author)

  20. Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets

    Directory of Open Access Journals (Sweden)

    Paula I. Moreira

    2009-12-01

    Full Text Available Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-γ. Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer´s, Parkinson´s and Huntington´s diseases and amyotrophic lateral sclerosis will be also discussed.

  1. Effects of Acute Supramaximal Cycle Exercise on Plasma FFA Concentration in Obese Adolescent Boys.

    Directory of Open Access Journals (Sweden)

    Georges Jabbour

    Full Text Available The aims of the present study are 1 to evaluate the free fatty acid (FFA profile and 2 to determine the relative anaerobic and aerobic contributions to total energy consumption during repeated supramaximal cycling bouts (SCE in adolescent boys with different body weight statuses.Normal-weight (NW, overweight (OW, and obese (OB adolescent boys (n =15 per group completed a SCE sessions consisted of 6 x 6s maximal sprints with 2 min of passive rest between each repetition. Plasma FFA levels were determined at rest, immediately after a 10 min warm-up, and immediately at the end of SCE. The anaerobic and aerobic contributions (% were measured via repeated SCE bouts. Insulin resistance was calculated using the homoeostatic model assessment (HOMA-IR index.The FFA concentrations measured immediately after SCE were higher in the OB group than in the OW and NW (p<0.01 and p<0.01, respectively groups. Moreover, the anaerobic contributions to SCE were significantly lower in obese adolescents (p<0.01 and decreased significantly during the 2nd, 3rd and 4th repetitions. The FFA levels were significantly associated with the HOMA-IR index and aerobic contribution among adolescent boys (r=0.83 and r=0.91, respectively, p<0.01.In contrast to the NW and OW groups, there is an increase in lipid mobilization and sift to aerobic energy metabolism during SCE in the OB group.

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

    DEFF Research Database (Denmark)

    Solomon, Thomas; Haus, Jacob M; Marchetti, Christine M

    2009-01-01

    Elevated free fatty acids (FFA) are implicated with insulin resistance at the cellular level. However, the contribution of whole body lipid kinetics to FFA-induced insulin resistance is not well understood, and the effect of exercise and diet on this metabolic defect is not known. We investigated...... the effect of 12 wk of exercise training with and without caloric restriction on FFA turnover and oxidation (FFA(ox)) during acute FFA-induced insulin resistance. Sixteen obese subjects with impaired glucose tolerance were randomized to either a hypocaloric (n = 8; -598 +/- 125 kcal/day, 66 +/- 1 yr, 32.......8 +/- 1.8 kg/m(2)) or a eucaloric (n = 8; 67 +/- 2 yr, 35.3 +/- 2.1 kg/m(2)) diet and aerobic exercise (1 h/day at 65% of maximal oxygen uptake) regimen. Lipid kinetics ([1-(14)C]palmitate) were assessed throughout a 7-h, 40 mU x m(-2) x min(-1) hyperinsulinemic euglycemic clamp, during which insulin...

  3. The Effect of a Diet Moderately High in Protein and Fiber on Insulin Sensitivity Measured Using the Dynamic Insulin Sensitivity and Secretion Test (DISST

    Directory of Open Access Journals (Sweden)

    Lisa Te Morenga

    2017-11-01

    Full Text Available Evidence shows that weight loss improves insulin sensitivity but few studies have examined the effect of macronutrient composition independently of weight loss on direct measures of insulin sensitivity. We randomised 89 overweight or obese women to either a standard diet (StdD, that was intended to be low in fat and relatively high in carbohydrate (n = 42 or to a relatively high protein (up to 30% of energy, relatively high fibre (>30 g/day diet (HPHFib (n = 47 for 10 weeks. Advice regarding strict adherence to energy intake goals was not given. Insulin sensitivity and secretion was assessed by a novel method—the Dynamic Insulin Sensitivity and Secretion Test (DISST. Although there were significant improvements in body composition and most cardiometabolic risk factors on HPHFib, insulin sensitivity was reduced by 19.3% (95% CI: 31.8%, 4.5%; p = 0.013 in comparison with StdD. We conclude that the reduction in insulin sensitivity after a diet relatively high in both protein and fibre, despite cardiometabolic improvements, suggests insulin sensitivity may reflect metabolic adaptations to dietary composition for maintenance of glucose homeostasis, rather than impaired metabolism.

  4. Insulin sensitivity and insulin secretion at birth in intrauterine growth retarded infants.

    Science.gov (United States)

    Setia, Sajita; Sridhar, M G; Bhat, Vishnu; Chaturvedula, Lata; Vinayagamoorti, R; John, Mathew

    2006-06-01

    To study insulin sensitivity, secretion and relation of insulin levels with birth weight and ponderal index in intrauterine growth retarded (IUGR) infants at birth. We studied 30 IUGR and 30 healthy newborns born at term by vaginal delivery in Jipmer, Pondicherry, India. Cord blood was collected at the time of delivery for measurement of plasma glucose and insulin. When compared with healthy newborns, IUGR newborns had lower plasma glucose levels (mean 2.3+/-0.98 versus 4.1+/-0.51 mmol/L, p<0.001); lower plasma insulin levels (mean 4.5+/-2.64 versus 11.03+/-1.68 microU/L, p<0.001); higher insulin sensitivity calculated using G/I ratio (mean 11.6+/-5.1 versus 6.7+/-0.31, p<0.001), HOMA IS (mean 5.5+/-6.0 versus 0.53+/-0.15, p<0.001), and QUICKI (mean 0.47+/-0.12 versus 0.34+/-0.02, p<0.001); and decreased pancreatic beta-cell function test measured as I/G (mean 0.10+/-0.037 versus 0.15+/-0.006, p<0.001). A positive correlation was identified between insulin levels and birth weight in both the healthy control group (r2 = 0.17, p = 0.024) and IUGR group (r2 = 0.13, p = 0.048). However correlation of insulin levels with ponderal index was much more confident in both healthy control (r2 = 0.90, p<0.001) and IUGR groups (r2 = 0.28, p = 0.003). Insulin status correlated both with birth weight and ponderal index more confidently in control group than in IUGR group. At birth, IUGR infants are hypoglycaemic, hypoinsulinaemic and display increased insulin sensitivity and decreased pancreatic beta-cell function. Insulin levels correlate with ponderal index much more confidently than with birth weight.

  5. Nonoxidative free fatty acid disposal is greater in young women than men.

    Science.gov (United States)

    Koutsari, Christina; Basu, Rita; Rizza, Robert A; Nair, K Sreekumaran; Khosla, Sundeep; Jensen, Michael D

    2011-02-01

    Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal. The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia. We measured: systemic FFA turnover using a continuous iv infusion of [9-10, (3)H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model. the study was conducted at the Mayo Clinic General Clinical Research Center. Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men). There were no interventions. Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation. Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women. Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities.

  6. Role of AMPK in Regulating Muscle Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus

    The ability of insulin to stimulate skeletal muscle glucose uptake is instrumental for controlling whole-body glucose homeostasis. Decreased peripheral sensitivity to insulin increases the risk of developing type 2 diabetes. Insulin sensitivity can be defined as the concentration of insulin that ...... prevail in healthy lean subjects. In the present thesis, experimental results from the three studies as well as unpublished observations are placed in the context of existing literature in order to provide a general overview of the current understandings within this field of research....

  7. Nasal insulin changes peripheral insulin sensitivity simultaneously with altered activity in homeostatic and reward-related human brain regions.

    Science.gov (United States)

    Heni, M; Kullmann, S; Ketterer, C; Guthoff, M; Linder, K; Wagner, R; Stingl, K T; Veit, R; Staiger, H; Häring, H-U; Preissl, H; Fritsche, A

    2012-06-01

    Impaired insulin sensitivity is a major factor leading to type 2 diabetes. Animal studies suggest that the brain is involved in the regulation of insulin sensitivity. We investigated whether insulin action in the human brain regulates peripheral insulin sensitivity and examined which brain areas are involved. Insulin and placebo were given intranasally. Plasma glucose, insulin and C-peptide were measured in 103 participants at 0, 30 and 60 min. A subgroup (n = 12) was also studied with functional MRI, and blood sampling at 0, 30 and 120 min. For each time-point, the HOMA of insulin resistance (HOMA-IR) was calculated as an inverse estimate of peripheral insulin sensitivity. Plasma insulin increased and subsequently decreased. This excursion was accompanied by slightly decreased plasma glucose, resulting in an initially increased HOMA-IR. At 1 h after insulin spray, the HOMA-IR subsequently decreased and remained lower up to 120 min. An increase in hypothalamic activity was observed, which correlated with the increased HOMA-IR at 30 min post-spray. Activity in the putamen, right insula and orbitofrontal cortex correlated with the decreased HOMA-IR at 120 min post-spray. Central insulin action in specific brain areas, including the hypothalamus, may time-dependently regulate peripheral insulin sensitivity. This introduces a potential novel mechanism for the regulation of peripheral insulin sensitivity and underlines the importance of cerebral insulin action for the whole organism.

  8. The brain modulates insulin sensitivity in multiple tissues

    NARCIS (Netherlands)

    Parlevliet, Edwin T.; Coomans, Claudia P.; Rensen, Patrick C. N.; Romijn, Johannes A.

    2014-01-01

    Insulin sensitivity is determined by direct effects of circulating insulin on metabolically active tissues in combination with indirect effects of circulating insulin, i.e. via the central nervous system. The dose-response effects of insulin differ between the various physiological effects of

  9. Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance.

    Science.gov (United States)

    Haus, Jacob M; Solomon, Thomas P J; Marchetti, Christine M; Edmison, John M; González, Frank; Kirwan, John P

    2010-01-01

    The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans. Obese men and women (n = 23) with impaired glucose tolerance were randomly assigned to either exercise training with a eucaloric (EU; approximately 1800 kcal; n = 11) or hypocaloric (HYPO; approximately 1300 kcal; n = 12) diet for 12 wk. Hepatic glucose production (HGP; milligrams per kilogram fat-free mass(-1) per minute(-1)) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic (40 mU/m(2) . min(-1)) euglycemic (5.0 mm) clamp with [3-(3)H]glucose. Measures were obtained at basal, during insulin infusion (INS; 120 min), and insulin plus intralipid/heparin infusion (INS/FFA; 300 min). At baseline, basal HGP was similar between groups; hyperinsulinemia alone did not completely suppress HGP, whereas INS/FFA exhibited less suppression than INS (EU, 4.6 +/- 0.8, 2.0 +/- 0.5, and 2.6 +/- 0.4; HYPO, 3.8 +/- 0.5, 1.2 +/- 0.3, and 2.3 +/- 0.4, respectively). After the intervention the HYPO group lost more body weight (P HYPO: -50 +/- 20%, before vs. after, P = 0.02). In contrast, the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group (EU: -15 +/- 24% vs. HYPO: -58 +/- 19%, P = 0.02). Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions. However, the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention.

  10. The changes of serum leptin and insulin contents in elderly male patients with obesity-related hypertension

    International Nuclear Information System (INIS)

    Zhan Hao; Huang Daijuan; Yuan Bin; He Yong; Zhang Yongxue

    2004-01-01

    To study the contents of serum leptin and insulin in elderly male patients with obesity-related hypertension, the levels of serum leptin and insulin in 21 normotensive cases and 41 hypertensive cases of them were determined by RIA. The results showed that the levels of serum leptin and insulin between hypertensives and normotensives in the non-obese groups were not significantly different (P>0.05). Compared with normotensives, the levels of serum leptin and insulin of hypertensives in the obese groups remarkably increased 1.8μg/L and 2.7 mIU/L respectively (P<0.01). The levels of serum leptin and insulin in the patients with obesity - related hypertension were markedly higher than those in the patients with non-obesity-related hypertension and elevated 2.7μg/L and 4.7mIU/L (P<0.01) respectively. Insulin-sensitivity index (ISI) successively decreased in the groups of HBPOb, NBPOb, HBPNOb and NBPNOb (relative ISI 0.50, 0.68, 0.92, 1 respectively). It is concluded that leptin-resistance and insulin-resistance exist in male elderly patients with obesity-related hypertension

  11. Insulin resistance in young adults born small for gestational age (SGA).

    Science.gov (United States)

    Putzker, Stephanie; Bechtold-Dalla Pozza, Susanne; Kugler, Karl; Schwarz, Hans P; Bonfig, Walter

    2014-03-01

    This work aimed to assess glucose metabolism and insulin sensitivity in young adults born small for gestational age (SGA) as well as to measure the body composition and adipocytokines of these subjects. A total of 108 out of 342 SGA-born participants were invited for reexamination from the former Bavarian Longitudinal Study (BLS), in which 7505 risk-newborns of the years 1985 to 1986 were prospectively followed. Of these, 76 (34 female/42 male) participants at the age of 19.7±0.5 years were enrolled. Clinical examination and oral glucose tolerance testing (oGTT) was performed with assessment of insulin resistance indices, HbA1c, body mass index (BMI), adipocytokines, and body composition by bioimpedance analysis (BIA). A total of 25 out of 76 (32.9%) patients had abnormal fasting and/or glucose-stimulated insulin levels. Glucose values measured during oGTT showed no abnormalities, except one participant who had impaired glucose tolerance. Homeostasis model assessment insulin resistance index (HOMA-IR) was 1.92±4.2, and insulin sensitivity index by Matsuda (ISI(Matsuda)) showed mean values of 7.85±4.49. HOMA-IR>2.5 was found in 8 patients (10.5%), and 20 patients (26.3%) had an ISI(Matsuda)range for both genders and correlated significantly with BMI (r=0.465, p0.001), but not with adiponectin. Insulin resistance correlated with change in weight-for-height Z-score during the first 3 months of age, indicating that weight gain during that early phase might be a risk factor for the development of insulin resistance in children born SGA. A high percentage of insulin-resistant subjects were reconfirmed in a large German cohort of young adults born SGA. Therefore, regular screening for disturbances in glucose metabolism is recommended in these subjects.

  12. Dietary Sodium Restriction Decreases Insulin Secretion Without Affecting Insulin Sensitivity in Humans

    Science.gov (United States)

    Byrne, Loretta M.; Yu, Chang; Wang, Thomas J.; Brown, Nancy J.

    2014-01-01

    Context: Interruption of the renin-angiotensin-aldosterone system prevents incident diabetes in high-risk individuals, although the mechanism remains unclear. Objective: To test the hypothesis that activation of the endogenous renin-angiotensin-aldosterone system or exogenous aldosterone impairs insulin secretion in humans. Design: We conducted a randomized, blinded crossover study of aldosterone vs vehicle and compared the effects of a low-sodium versus a high-sodium diet. Setting: Academic clinical research center. Participants: Healthy, nondiabetic, normotensive volunteers. Interventions: Infusion of exogenous aldosterone (0.7 μg/kg/h for 12.5 h) or vehicle during low or high sodium intake. Low sodium (20 mmol/d; n = 12) vs high sodium (160 mmol/d; n = 17) intake for 5–7 days. Main Outcome Measures: Change in acute insulin secretory response assessed during hyperglycemic clamps while in sodium balance during a low-sodium vs high-sodium diet during aldosterone vs vehicle. Results: A low-sodium diet increased endogenous aldosterone and plasma renin activity, and acute glucose-stimulated insulin (−16.0 ± 5.6%; P = .007) and C-peptide responses (−21.8 ± 8.4%; P = .014) were decreased, whereas the insulin sensitivity index was unchanged (−1.0 ± 10.7%; P = .98). Aldosterone infusion did not affect the acute insulin response (+1.8 ± 4.8%; P = .72) or insulin sensitivity index (+2.0 ± 8.8%; P = .78). Systolic blood pressure and serum potassium were similar during low and high sodium intake and during aldosterone infusion. Conclusions: Low dietary sodium intake reduces insulin secretion in humans, independent of insulin sensitivity. PMID:25029426

  13. The Insulin-Sensitive Side of SHIP2

    Directory of Open Access Journals (Sweden)

    Stephane Schurmans

    2001-01-01

    Full Text Available A substantial and increasing proportion of death and disability in the EU (and elsewhere is attributable to diseases associated with insulin resistance (i.e., decreased insulin sensitivity. Beside type II diabetes, other diseases like obesity, hypertension, atherosclerosis, hyperlipidaemia, polycystic ovarian syndrome, and acromegaly are indeed associated with insulin resistance [1].

  14. Insulin resistance and hyperandrogenism drive steatosis and fibrosis risk in young females with PCOS.

    Science.gov (United States)

    Petta, Salvatore; Ciresi, Alessandro; Bianco, Jessica; Geraci, Vincenzo; Boemi, Roberta; Galvano, Luigi; Magliozzo, Franco; Merlino, Giovanni; Craxì, Antonio; Giordano, Carla

    2017-01-01

    Nonalcoholic fatty liver disease (NAFLD) and polycystic ovary syndrome (PCOS) recognize obesity and insulin resistance (IR) as common pathogenic background. We assessed 1) whether PCOS is a risk factor for steatosis, and 2) the impact, in PCOS patients, of IR and hyperandrogenism on steatosis and fibrosis. We considered 202 consecutive Italian PCOS nondiabetic patients and 101 age-matched controls. PCOS was diagnosed applying the Rotterdam diagnostic criteria. Steatosis was diagnosed if hepatic steatosis index (HSI) >36, while fibrosis by using the FIB-4 score. As surrogate estimate of insulin sensitivity we considered the insulin sensitivity index (ISI). Free androgen index (FAI) was calculated as estimate of biochemical hyperandrogenism. In the entire population, steatosis was observed in 68.8% of patients with PCOS, compared to 33.3 of controls (pPCOS patients, steatosis was independently linked to WC (OR 1.04, 95% CI 1.01-1.08; P = 0.006) and ISI Matsuda (OR 0.69, 95% CI 0.53-0.88; P = 0.004), not to free androgen index (OR 1.10, 95% CI 0.96-1.26; P = 0.14). Notably, ISI Matsuda was confirmed as independently associated with steatosis in both obese (OR 0.42, 95% CI 0.23-0.77, P = 0.005) and nonobese (OR 0.69, 95% CI 0.53-0.91, P = 0.009), patients, while FAI (OR 1.45, 95% CI 1.12-1.87; P = 0.004) emerged as an independent risk factor only in nonobese PCOS. Similarly, higher FIB-4 was independently associated with higher FAI (p = 0.02) in nonobese and with lower ISI Matsuda (p = 0.04) in obese patients. We found that PCOS is an independent risk factor for steatosis, and that, IR and hyperandrogenism, this last especially in nonobese patients, are the key players of liver damage in PCOS.

  15. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...

  16. FFA STUDY OF MACULAR LESIONS

    Directory of Open Access Journals (Sweden)

    K. Vinayagamurthy

    2017-08-01

    Full Text Available BACKGROUND Macula is an important portion of retina that occupies the posterior pole of retina. Any disease that affects macula results in significant loss of central vision, form vision and colour vision to an extent. Macular lesions can be hereditary as well as acquired. Macular lesions occur in both younger and older individuals. Anatomically, a macular lesions can vary from a simple lesion like an RPF defect to a vision-threatening lesions like choroidal neovascular membrane. Many screening tests that are sensitive and specific are available to assess the functioning of macula called as ‘macular function test’. But, the greater understanding of the retinal vascular led to the usage of fluorescein angiogram in the detection and screening of macular, retinovascular and optic disc lesions. Through fundus fluorescein angiogram is a thirty-year-old procedure; it is still in vogue in almost all parts of the world. It has its own merits. The aim of the study is to study the role of fluorescein angiography in the evaluation of macular lesions. MATERIALS AND METHODS A hospital-based prospective randomised study was done, which included 50 patients. Detailed patient history was taken and thorough ocular and systemic examination was done. All patients were examined by ophthalmoscopy (direct and indirect and slit-lamp examination with 90D followed by fluorescein angiography. Ophthalmoscopic and fluorescein angiography findings were analysed and categorised. Patients were advised proper ocular and systemic treatment and follow up. RESULTS 50 cases with macular lesions were analysed and categorised into conditions like ARMD, CSR, macular oedema, CME, degenerations and dystrophies and miscellaneous conditions. FFA altered the diagnosis in 8% cases and categorised the cases in all cases. 16% patients developed adverse reactions like allergy, vomiting and nausea. On statistical analysis, FFA proved to be cheap and superior diagnostic tool in confirming

  17. The adipose transcriptional response to insulin is determined by obesity, not insulin sensitivity

    DEFF Research Database (Denmark)

    Rydén, Mikael; Hrydziuszko, Olga; Mileti, Enrichetta

    2016-01-01

    Metabolically healthy obese subjects display preserved insulin sensitivity and a beneficial white adipose tissue gene expression pattern. However, this observation stems from fasting studies when insulin levels are low. We investigated adipose gene expression by 5'Cap-mRNA sequencing in 17 healthy...... non-obese (NO), 21 insulin-sensitive severely obese (ISO), and 30 insulin-resistant severely obese (IRO) subjects, before and 2 hr into a hyperinsulinemic euglycemic clamp. ISO and IRO subjects displayed a clear but globally similar transcriptional response to insulin, which differed from the small...... effects observed in NO subjects. In the obese, 231 genes were altered; 71 were enriched in ISO subjects (e.g., phosphorylation processes), and 52 were enriched in IRO subjects (e.g., cellular stimuli). Common cardio-metabolic risk factors and gender do not influence these findings. This study demonstrates...

  18. Calcineurin inhibitors acutely improve insulin sensitivity without affecting insulin secretion in healthy human volunteers

    DEFF Research Database (Denmark)

    Øzbay, Aygen; Møller, Niels; Juhl, Claus

    2012-01-01

    and tacrolimus has been attributed to both beta cell dysfunction and impaired insulin sensitivity. WHAT THIS STUDY ADDS: This is the first trial to investigate beta cell function and insulin sensitivity using gold standard methodology in healthy human volunteers treated with clinically relevant doses...... of ciclosporin and tacrolimus. We document that both drugs acutely increase insulin sensitivity, while first phase and pulsatile insulin secretion remain unaffected. This study demonstrates that ciclosporin and tacrolimus have similar acute effects on glucose metabolism in healthy humans. AIM The introduction...... of calcineurin inhibitors (CNIs) ciclosporin (CsA) and tacrolimus (Tac) has improved the outcome of organ transplants, but complications such as new onset diabetes mellitus after transplantation (NODAT) cause impairment of survival rates. The relative contribution of each CNI to the pathogenesis and development...

  19. Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity.

    Science.gov (United States)

    Baillargeon, Jean-Patrice; Carpentier, André

    2007-10-01

    To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity. Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH. Clinical research center of an academic hospital. Nine lean women (body mass index PCOS and normal insulin levels, as well as 17 lean healthy women. Lean PCOS women were reassessed after 8 days of diazoxide and after 1 month of leuprolide, which suppresses LH. Androgen levels and insulin-stimulated glucose disposal (metabolic insulin sensitivity), determined by euglycemic-hyperinsulinemic clamp (M-value). Mean M-value of lean PCOS women (48.5 micromol/kg.min) was similar to lean control subjects (52.9 micromol/kg.min). They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1. The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group. Androstenedione decreased significantly after diazoxide and even more after leuprolide. However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group. In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

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

    Science.gov (United States)

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

    2013-11-15

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance; however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilization in adults with IFG, IGT, or IFG + IGT is unknown. Twenty-four older (66.7 ± 0.8 yr) obese (34.2 ± 0.9 kg/m(2)) adults were categorized as IFG (n = 8), IGT (n = 8), or IFG + IGT (n = 8) according to a 75-g oral glucose tolerance test (OGTT). Subjects underwent 12-wk of exercise (60 min/day for 5 days/wk at ∼85% HRmax) and were instructed to maintain a eucaloric diet. A euglycemic hyperinsulinemic clamp (40 mU·m(2)·min(-1)) with [6,6-(2)H]glucose was used to determine peripheral and hepatic insulin sensitivity. Nonoxidative glucose disposal and metabolic flexibility [insulin-stimulated respiratory quotient (RQ) minus fasting RQ] were also assessed. Glucose incremental area under the curve (iAUCOGTT) was calculated from the OGTT. Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than with IFG + IGT (P work is required to assess the molecular mechanism(s) by which chronic hyperglycemia modifies insulin sensitivity following exercise training.

  1. Dissimilar association of conventional immune-reactive versus specific insulin with cardiovascular risk factors: a consequence of proinsulinaemia?

    NARCIS (Netherlands)

    Grootenhuis, P.A.; Mooy, J.M.; Kostense, P.J.; Popp-Snijders, C.; Bouter, L.M.; Heine, R.J.

    1998-01-01

    In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic

  2. Dissimilar association of conventional immuno-reactive versus specific insulin with cardiovascular risk factors : a consequence of proinsulinaemia?

    NARCIS (Netherlands)

    Grootenhuis, P A; Mooy, J M; Kostense, P J; Popp-Snijders, C; Bouter, L M; Heine, R J

    In this study involving 365 non-diabetic elderly Caucasians, we examined the relationship of immuno-specific insulin (ISI), total immuno-reactive insulin (IRI), proinsulin (PI) and proinsulin-insulin ratio (PI:ISI) to serum high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), systolic

  3. Current understanding of increased insulin sensitivity after exercise - emerging candidates

    DEFF Research Database (Denmark)

    Maarbjerg, Stine Just; Sylow, Lykke; Richter, Erik

    2011-01-01

    signaling component in the insulin signaling pathway such as aPKC, Rac1, TBC1D4 and TBC1D1 have been described. These are all affected by both insulin and exercise which means that they are likely converging points in promoting GLUT4 translocation and therefore possible candidates for regulating insulin...... sensitivity after exercise. Whereas TBC1D1 does not appear to regulate insulin sensitivity after exercise, correlative evidence in contrast suggests TBC1D4 to be a relevant candidate. Little is known about aPKC and Rac1 in relation to insulin sensitivity after exercise. Besides mechanisms involved...

  4. Lipid-anthropometric index optimization for insulin sensitivity estimation

    Science.gov (United States)

    Velásquez, J.; Wong, S.; Encalada, L.; Herrera, H.; Severeyn, E.

    2015-12-01

    Insulin sensitivity (IS) is the ability of cells to react due to insulińs presence; when this ability is diminished, low insulin sensitivity or insulin resistance (IR) is considered. IR had been related to other metabolic disorders as metabolic syndrome (MS), obesity, dyslipidemia and diabetes. IS can be determined using direct or indirect methods. The indirect methods are less accurate and invasive than direct and they use glucose and insulin values from oral glucose tolerance test (OGTT). The accuracy is established by comparison using spearman rank correlation coefficient between direct and indirect method. This paper aims to propose a lipid-anthropometric index which offers acceptable correlation to insulin sensitivity index for different populations (DB1=MS subjects, DB2=sedentary without MS subjects and DB3=marathoners subjects) without to use OGTT glucose and insulin values. The proposed method is parametrically optimized through a random cross-validation, using the spearman rank correlation as comparator with CAUMO method. CAUMO is an indirect method designed from a simplification of the minimal model intravenous glucose tolerance test direct method (MINMOD-IGTT) and with acceptable correlation (0.89). The results show that the proposed optimized method got a better correlation with CAUMO in all populations compared to non-optimized. On the other hand, it was observed that the optimized method has better correlation with CAUMO in DB2 and DB3 groups than HOMA-IR method, which is the most widely used for diagnosing insulin resistance. The optimized propose method could detect incipient insulin resistance, when classify as insulin resistant subjects that present impaired postprandial insulin and glucose values.

  5. The relationship between bone turnover and insulin sensitivity and secretion

    DEFF Research Database (Denmark)

    Frost, Morten; Balkau, Beverley; Hatunic, Mensud

    2018-01-01

    Bone metabolism appears to influence insulin secretion and sensitivity, and insulin promotes bone formation in animals, but similar evidence in humans is limited. The objectives of this study are to explore if bone turnover markers were associated with insulin secretion and sensitivity and to det...

  6. Bromocriptine and insulin sensitivity in lean and obese subjects

    Directory of Open Access Journals (Sweden)

    L Bahler

    2016-11-01

    Full Text Available Bromocriptine is a glucose-lowering drug, which was shown to be effective in obese subjects with insulin resistance. It is usually administered in the morning. The exact working mechanism of bromocriptine still has to be elucidated. Therefore, in this open-label randomized prospective cross-over mechanistic study, we assessed whether the timing of bromocriptine administration (morning vs evening results in different effects and whether these effects differ between lean and obese subjects. We studied the effect of bromocriptine on insulin sensitivity in 8 lean and 8 overweight subjects using an oral glucose tolerance test. The subjects used bromocriptine in randomized cross-over order for 2 weeks in the morning and 2 weeks in the evening. We found that in lean subjects, bromocriptine administration in the evening resulted in a significantly higher post-prandial insulin sensitivity as compared with the pre-exposure visit (glucose area under the curve (AUC 742 mmol/L * 120 min (695–818 vs 641 (504–750, P = 0.036, AUC for insulin did not change, P = 0.575. In obese subjects, both morning and evening administration of bromocriptine resulted in a significantly higher insulin sensitivity: morning administration in obese: insulin AUC (55,900 mmol/L * 120 min (43,236–96,831 vs 36,448 (25,213–57,711, P = 0.012 and glucose AUC P = 0.069; evening administration in obese: glucose AUC (735 mmol/L * 120 min (614–988 vs 644 (568–829, P = 0.017 and insulin AUC, P = 0.208. In conclusion, bromocriptine increases insulin sensitivity in both lean and obese subjects. In lean subjects, this effect only occurred when bromocriptine was administrated in the evening, whereas in the obese, insulin sensitivity increased independent of the timing of bromocriptine administration.

  7. Skeletal muscle phosphatidylcholine fatty acids and insulin sensitivity in normal humans.

    Science.gov (United States)

    Clore, J N; Li, J; Gill, R; Gupta, S; Spencer, R; Azzam, A; Zuelzer, W; Rizzo, W B; Blackard, W G

    1998-10-01

    The fatty acid composition of skeletal muscle membrane phospholipids (PL) is known to influence insulin responsiveness in humans. However, the contribution of the major PL of the outer (phosphatidylcholine, PC) and inner (phosphatidylethanolamine, PE) layers of the sarcolemma to insulin sensitivity is not known. Fatty acid composition of PC and PE from biopsies of vastus lateralis from 27 normal men and women were correlated with insulin sensitivity determined by the hyperinsulinemic euglycemic clamp technique at insulin infusion rates of 0.4, 1.0, and 10.0 mU . kg-1 . min-1. Significant variation in the half-maximal insulin concentration (ED50) was observed in the normal volunteers (range 24.0-146.0 microU/ml), which correlated directly with fasting plasma insulin (r = 0.75, P insulin sensitivity was observed in PE (NS). These studies suggest that the fatty acid composition of PC may be of particular importance in the relationship between fatty acids and insulin sensitivity in normal humans.

  8. Enhanced muscle insulin sensitivity after contraction/exercise is mediated by AMPK

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Munk-Hansen, Nanna; Birk, Jesper Bratz

    2017-01-01

    muscle and whole body insulin sensitivity in wild type (WT) mice, respectively. These effects were not found in AMPKα1α2 muscle-specific knockout mice. Prior in situ contraction did not increase insulin sensitivity in m. soleus from either genotype. Improvement in muscle insulin sensitivity....... Collectively, our data suggest that the AMPK-TBC1D4 signaling axis is likely mediating the improved muscle insulin sensitivity after contraction/exercise and illuminates an important and physiological relevant role of AMPK in skeletal muscle.......Earlier studies have demonstrated that muscle insulin sensitivity to stimulate glucose uptake is enhanced several hours after an acute bout of exercise. Using 5-aminoimidazole-4-carboxamide-ribonucleotide (AICAR), we recently demonstrated that prior activation of AMPK is sufficient to increase...

  9. Circulating docosahexaenoic acid levels are associated with fetal insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Jin-Ping Zhao

    Full Text Available Arachidonic acid (AA; C20∶4 n-6 and docosahexaenoic acid (DHA; C22∶6 n-3 are important long-chain polyunsaturated fatty acids (LC-PUFA in maintaining pancreatic beta-cell structure and function. Newborns of gestational diabetic mothers are more susceptible to the development of type 2 diabetes in adulthood. It is not known whether low circulating AA or DHA is involved in perinatally "programming" this susceptibility. This study aimed to assess whether circulating concentrations of AA, DHA and other fatty acids are associated with fetal insulin sensitivity or beta-cell function, and whether low circulating concentrations of AA or DHA are involved in compromised fetal insulin sensitivity in gestational diabetic pregnancies.In a prospective singleton pregnancy cohort, maternal (32-35 weeks gestation and cord plasma fatty acids were assessed in relation to surrogate indicators of fetal insulin sensitivity (cord plasma glucose-to-insulin ratio, proinsulin concentration and beta-cell function (proinsulin-to-insulin ratio in 108 mother-newborn pairs. Cord plasma DHA levels (in percentage of total fatty acids were lower comparing newborns of gestational diabetic (n = 24 vs. non-diabetic pregnancies (2.9% vs. 3.5%, P = 0.01. Adjusting for gestational age at blood sampling, lower cord plasma DHA levels were associated with lower fetal insulin sensitivity (lower glucose-to-insulin ratio, r = 0.20, P = 0.036; higher proinsulin concentration, r = -0.37, P <0.0001. The associations remained after adjustment for maternal and newborn characteristics. Cord plasma saturated fatty acids C18∶0 and C20∶0 were negatively correlated with fetal insulin sensitivity, but their levels were not different between gestational diabetic and non-diabetic pregnancies. Cord plasma AA levels were not correlated with fetal insulin sensitivity.Low circulating DHA levels are associated with compromised fetal insulin sensitivity, and may be involved in

  10. Intensive insulin therapy improves insulin sensitivity and mitochondrial function in severely burned children.

    Science.gov (United States)

    Fram, Ricki Y; Cree, Melanie G; Wolfe, Robert R; Mlcak, Ronald P; Qian, Ting; Chinkes, David L; Herndon, David N

    2010-06-01

    To institute intensive insulin therapy protocol in an acute pediatric burn unit and study the mechanisms underlying its benefits. Prospective, randomized study. An acute pediatric burn unit in a tertiary teaching hospital. Children, 4-18 yrs old, with total body surface area burned > or =40% and who arrived within 1 wk after injury were enrolled in the study. Patients were randomized to one of two groups. Intensive insulin therapy maintained blood glucose levels between 80 and 110 mg/dL. Conventional insulin therapy maintained blood glucose patients were included in the data analysis consisting of resting energy expenditure, whole body and liver insulin sensitivity, and skeletal muscle mitochondrial function. Studies were performed at 7 days postburn (pretreatment) and at 21 days postburn (posttreatment). Resting energy expenditure significantly increased posttreatment (1476 +/- 124 to 1925 +/- 291 kcal/m(2) x day; p = .02) in conventional insulin therapy as compared with a decline in intensive insulin therapy. Glucose infusion rate was identical between groups before treatment (6.0 +/- 0.8 conventional insulin therapy vs. 6.8 +/- 0.9 mg/kg x min intensive insulin therapy; p = .5). Intensive insulin therapy displayed a significantly higher glucose clamp infusion rate posttreatment (9.1 +/- 1.3 intensive insulin therapy versus 4.8 +/- 0.6 mg/kg x min conventional insulin therapy, p = .005). Suppression of hepatic glucose release was significantly greater in the intensive insulin therapy after treatment compared with conventional insulin therapy (5.0 +/- 0.9 vs. 2.5 +/- 0.6 mg/kg x min; intensive insulin therapy vs. conventional insulin therapy; p = .03). States 3 and 4 mitochondrial oxidation of palmitate significantly improved in intensive insulin therapy (0.9 +/- 0.1 to 1.7 +/- 0.1 microm O(2)/CS/mg protein/min for state 3, p = .004; and 0.7 +/- 0.1 to 1.3 +/- 0.1 microm O(2)/CS/mg protein/min for state 4, p protocol improves insulin sensitivity and mitochondrial

  11. Effects of exercise training on glucose control, lipid metabolism, and insulin sensitivity in hypertriglyceridemia and non-insulin dependent diabetes mellitus.

    Science.gov (United States)

    Lampman, R M; Schteingart, D E

    1991-06-01

    Exercise training has potential benefits for patients with hyperlipidemia and/or non-insulin dependent diabetes mellitus. In nondiabetic, nonobese subjects with hypertriglyceridemia, exercise training alone increased insulin sensitivity, improved glucose tolerance, and lowered serum triglyceride and cholesterol levels. These improvements did not occur when exercise training alone was given to similar patients with impaired glucose tolerance. In severely obese (X = 125 kg) subjects without diabetes melitus, a 600 calorie diet alone decreased glucose and insulin concentrations and improved glucose tolerance but did not increase insulin sensitivity. The addition of exercise training improved insulin sensitivity. Obese, non-insulin dependent diabetes mellitus subjects on sulfonylurea therapy alone increased insulin levels but failed to improve insulin sensitivity or glucose levels. In contrast, the addition of exercise training to this medication resulted in improved insulin sensitivity and lowered glucose levels. We conclude that exercise training has major effects on lowering triglyceride levels in hyperlipidemic subjects and can potentiate the effect of diet or drug therapy on glucose metabolism in patients with non-insulin dependent diabetes mellitus.

  12. Proximity to Delivery Alters Insulin Sensitivity and Glucose Metabolism in Pregnant Mice.

    Science.gov (United States)

    Musial, Barbara; Fernandez-Twinn, Denise S; Vaughan, Owen R; Ozanne, Susan E; Voshol, Peter; Sferruzzi-Perri, Amanda N; Fowden, Abigail L

    2016-04-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth, but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy at day 16 (D16) and near term at D19. Nonpregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by DEXA, tissue insulin signaling protein abundance by Western blotting, glucose tolerance and utilization, and insulin sensitivity using acute insulin administration and hyperinsulinemic-euglycemic clamps with [(3)H]glucose infusion. Whole-body insulin resistance occurred in D16 pregnant dams in association with basal hyperinsulinemia, insulin-resistant endogenous glucose production, and downregulation of several proteins in hepatic and skeletal muscle insulin signaling pathways relative to NP and D19 values. Insulin resistance was less pronounced at D19, with restoration of NP insulin concentrations, improved hepatic insulin sensitivity, and increased abundance of hepatic insulin signaling proteins. At D16, insulin resistance at whole-body, tissue, and molecular levels will favor fetal glucose acquisition, while improved D19 hepatic insulin sensitivity will conserve glucose for maternal use in anticipation of lactation. Tissue sensitivity to insulin, therefore, alters differentially with proximity to delivery in pregnant mice, with implications for human and other species. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Effects of body weight and alcohol consumption on insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Holcomb Valerie B

    2010-03-01

    Full Text Available Abstract Background Obesity is a risk factor for the development of insulin resistance, which can eventually lead to type-2 diabetes. Alcohol consumption is a protective factor against insulin resistance, and thus protects against the development of type-2 diabetes. The mechanism by which alcohol protects against the development of type-2 diabetes is not well known. To determine the mechanism by which alcohol improves insulin sensitivity, we fed water or alcohol to lean, control, and obese mice. The aim of this study was to determine whether alcohol consumption and body weights affect overlapping metabolic pathways and to identify specific target genes that are regulated in these pathways. Method Adipose tissue dysfunction has been associated with the development of type-2 diabetes. We assessed possible gene expression alterations in epididymal white adipose tissue (WAT. We obtained WAT from mice fed a calorie restricted (CR, low fat (LF Control or high fat (HF diets and either water or 20% ethanol in the drinking water. We screened the expression of genes related to the regulation of energy homeostasis and insulin regulation using a gene array composed of 384 genes. Results Obesity induced insulin resistance and calorie restriction and alcohol improved insulin sensitivity. The insulin resistance in obese mice was associated with the increased expression of inflammatory markers Cd68, Il-6 and Il-1α; in contrast, most of these genes were down-regulated in CR mice. Anti-inflammatory factors such as Il-10 and adrenergic beta receptor kinase 1 (Adrbk1 were decreased in obese mice and increased by CR and alcohol. Also, we report a direct correlation between body weight and the expression of the following genes: Kcnj11 (potassium inwardly-rectifying channel, subfamily J, member 11, Lpin2 (lipin2, and Dusp9 (dual-specificity MAP kinase phosphatase 9. Conclusion We show that alcohol consumption increased insulin sensitivity. Additionally, alterations

  14. A low dose lipid infusion is sufficient to induce insulin resistance and a pro-inflammatory response in human subjects.

    Science.gov (United States)

    Liang, Hanyu; Lum, Helen; Alvarez, Andrea; Garduno-Garcia, Jose de Jesus; Daniel, Benjamin J; Musi, Nicolas

    2018-01-01

    The root cause behind the low-grade inflammatory state seen in insulin resistant (obesity and type 2 diabetes) states is unclear. Insulin resistant subjects have elevations in plasma free fatty acids (FFA), which are ligands for the pro-inflammatory toll-like receptor (TLR)4 pathway. We tested the hypothesis that an experimental elevation in plasma FFA (within physiological levels) in lean individuals would upregulate TLR4 and activate downstream pathways (e.g., MAPK) in circulating monocytes. Twelve lean, normal glucose-tolerant subjects received a low dose (30 ml/h) 48 h lipid or saline infusion on two different occasions. Monocyte TLR4 protein level, MAPK phosphorylation, and expression of genes in the TLR pathway were determined before and after each infusion. The lipid infusion significantly increased monocyte TLR4 protein and phosphorylation of JNK and p38 MAPK. Lipid-mediated increases in TLR4 and p38 phosphorylation directly correlated with reduced peripheral insulin sensitivity (M value). Lipid increased levels of multiple genes linked to inflammation, including several TLRs, CD180, MAP3K7, and CXCL10. Monocytes exposed in vivo to lipid infusion exhibited enhanced in vitro basal and LPS-stimulated IL-1β secretion. In lean subjects, a small increase in plasma FFA (as seen in insulin resistant subjects) is sufficient to upregulate TLR4 and stimulate inflammatory pathways (MAPK) in monocytes. Moreover, lipids prime monocytes to endotoxin. We provide proof-of-concept data in humans indicating that the low-grade inflammatory state characteristic of obesity and type 2 diabetes could be caused (at least partially) by pro-inflammatory monocytes activated by excess lipids present in these individuals.

  15. Higher intramuscular triacylglycerol in women does not impair insulin sensitivity and proximal insulin signaling

    DEFF Research Database (Denmark)

    Høeg, Louise; Roepstorff, Carsten; Thiele, Maja

    2009-01-01

    that despite 47% higher IMTG levels in women in the follicular phase whole body as well as leg insulin sensitivity are higher than in matched men. This was not explained by sex differences in proximal insulin signalling in women. In women it seems that a high capillary density and type 1 muscle fiber...... expression may be important for insulin action. Key words: Muscle Triglycerides, gender, insulin action, sex paradox....

  16. Annual report ISIS

    International Nuclear Information System (INIS)

    Biggin, S.

    1988-07-01

    The paper presents the 1988 Annual Report for ISIS (United Kingdom). A description is given of the accelerator and target station. The capability of ISIS is described including the facilities available and the type of science carried out using the instruments. The development and support activities are outlined, along with the ISIS organisation and user interaction. The appendix contains experimental reports on research work conducted at ISIS. (U.K.)

  17. Insulin sensitizers prevent fine particulate matter-induced vascular insulin resistance and changes in endothelial progenitor cell homeostasis.

    Science.gov (United States)

    Haberzettl, Petra; McCracken, James P; Bhatnagar, Aruni; Conklin, Daniel J

    2016-06-01

    Exposure to fine particular matter (PM2.5) increases the risk of developing cardiovascular disease and Type 2 diabetes. Because blood vessels are sensitive targets of air pollutant exposure, we examined the effects of concentrated ambient PM2.5 (CAP) on vascular insulin sensitivity and circulating levels of endothelial progenitor cells (EPCs), which reflect cardiovascular health. We found that CAP exposure for 9 days decreased insulin-stimulated Akt phosphorylation in the aorta of mice maintained on control diet. This change was accompanied by the induction of IL-1β and increases in the abundance of cleaved IL-18 and p10 subunit of Casp-1, consistent with the activation of the inflammasome pathway. CAP exposure also suppressed circulating levels of EPCs (Flk-1(+)/Sca-1(+) cells), while enhancing the bone marrow abundance of these cells. Although similar changes in vascular insulin signaling and EPC levels were observed in mice fed high-fat diet, CAP exposure did not exacerbate diet-induced changes in vascular insulin resistance or EPC homeostasis. Treatment with an insulin sensitizer, metformin or rosiglitazone, prevented CAP-induced vascular insulin resistance and NF-κB and inflammasome activation and restored peripheral blood and bone marrow EPC levels. These findings suggest that PM2.5 exposure induces diet-independent vascular insulin resistance and inflammation and prevents EPC mobilization, and that this EPC mobilization defect could be mediated by vascular insulin resistance. Impaired vascular insulin sensitivity may be an important mechanism underlying PM2.5-induced vascular injury, and pharmacological sensitization to insulin action could potentially prevent deficits in vascular repair and mitigate vascular inflammation due to exposure to elevated levels of ambient air pollution. Copyright © 2016 the American Physiological Society.

  18. Relationship between insulin resistance and blood lipid and sport in patients with type II diabetes mellitus complicated with hypertension%2型糖尿病合并高血压患者胰岛素低抗

    Institute of Scientific and Technical Information of China (English)

    谭丽艳; 杨红玉; 柴国禄; 沈凌元

    2001-01-01

    Objective To study the relationship between insulin resistance and blood pressure and blood lipid in patients with type II diabetes mellitus complicated with hypertension.Methods The serum concentration of fasting glucose,insulin,lipids and the level of blood pressure were measured in 56 patients with type II diabetes mellitus complicated with hypertension.Results The insulin sensitivity index(ISI) decreased in patients with type II diabetes mellitus complicated with hypertension compared with the patients with type II diabetes mellitus with normal blood pressure(P< 0.05).A negative correlation with hypertension was found between ISI and SBP,DBP,TG,ApoB in patients with type II diabetes mellitus complicated with hypertension(P<0.05).There was a positive correlation between ISI and HDL in patients with type II diabetes mellitus complicated with hypertension(P<0.05).Conclusion Insulin resistance presents in patients of type II diabetes mellitus complicated with hypertension.Insulin resistance is the major cause of hypertension and lipid metabolic disturbance in patients with type II diabetes mellitus complicated with hypertension.

  19. Statin Intake Is Associated With Decreased Insulin Sensitivity During Cardiac Surgery

    Science.gov (United States)

    Sato, Hiroaki; Carvalho, George; Sato, Tamaki; Hatzakorzian, Roupen; Lattermann, Ralph; Codere-Maruyama, Takumi; Matsukawa, Takashi; Schricker, Thomas

    2012-01-01

    OBJECTIVE Surgical trauma impairs intraoperative insulin sensitivity and is associated with postoperative adverse events. Recently, preprocedural statin therapy is recommended for patients with coronary artery disease. However, statin therapy is reported to increase insulin resistance and the risk of new-onset diabetes. Thus, we investigated the association between preoperative statin therapy and intraoperative insulin sensitivity in nondiabetic, dyslipidemic patients undergoing coronary artery bypass grafting. RESEARCH DESIGN AND METHODS In this prospective, nonrandomized trial, patients taking lipophilic statins were assigned to the statin group and hypercholesterolemic patients not receiving any statins were allocated to the control group. Insulin sensitivity was assessed by the hyperinsulinemic-normoglycemic clamp technique during surgery. The mean, SD of blood glucose, and the coefficient of variation (CV) after surgery were calculated for each patient. The association between statin use and intraoperative insulin sensitivity was tested by multiple regression analysis. RESULTS We studied 120 patients. In both groups, insulin sensitivity gradually decreased during surgery with values being on average ∼20% lower in the statin than in the control group. In the statin group, the mean blood glucose in the intensive care unit was higher than in the control group (153 ± 20 vs. 140 ± 20 mg/dL; P statin group (SD, P statin use was independently associated with intraoperative insulin sensitivity (β = −0.16; P = 0.03). CONCLUSIONS Preoperative use of lipophilic statins is associated with increased insulin resistance during cardiac surgery in nondiabetic, dyslipidemic patients. PMID:22829524

  20. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne Kristine

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...... mellitus (GDM) and pre-eclampsia. Recent studies clearly indicate that physical activity before and during pregnancy can reduce the risk of GDM and pre-eclampsia....

  1. Insulin Sensitivity Determines Effects of Insulin and Meal Ingestion on Systemic Vascular Resistance in Healthy Subjects.

    Science.gov (United States)

    Woerdeman, Jorn; Meijer, Rick I; Eringa, Etto C; Hoekstra, Trynke; Smulders, Yvo M; Serné, Erik H

    2016-01-01

    In addition to insulin's metabolic actions, insulin can dilate arterioles which increase blood flow to metabolically active tissues. This effect is blunted in insulin-resistant subjects. Insulin's effect on SVR, determined by resistance arterioles, has, however, rarely been examined directly. We determined the effects of both hyperinsulinemia and a mixed meal on SVR and its relationship with insulin sensitivity. Thirty-seven lean and obese women underwent a hyperinsulinemic-euglycemic clamp, and 24 obese volunteers underwent a mixed-meal test. SVR was assessed using CPP before and during hyperinsulinemia as well as before and 60 and 120 minutes after a meal. SVR decreased significantly during hyperinsulinemia (-13%; p Insulin decreased SVR more strongly in insulin-sensitive individuals (standardized β: -0.44; p = 0.01). In addition, SVR at 60 minutes after meal ingestion was inversely related to the Matsuda index (β: -0.39; p = 0.04) and the change in postprandial SVR was directly related to postprandial glycemia (β: 0.53; p insulin resistance. This suggests that resistance to insulin-induced vasodilatation contributes to regulation of vascular resistance. © 2015 John Wiley & Sons Ltd.

  2. Role of PKCδ in Insulin Sensitivity and Skeletal Muscle Metabolism

    DEFF Research Database (Denmark)

    Li, Mengyao; Vienberg, Sara G; Bezy, Olivier

    2015-01-01

    Protein kinase C (PKC)δ has been shown to be increased in liver in obesity and plays an important role in the development of hepatic insulin resistance in both mice and humans. In the current study, we explored the role of PKCδ in skeletal muscle in the control of insulin sensitivity and glucose......-body insulin sensitivity and muscle insulin resistance and by 15 months of age improved the age-related decline in whole-body glucose tolerance. At 15 months of age, M-PKCδKO mice also exhibited decreased metabolic rate and lower levels of some proteins of the OXPHOS complex suggesting a role for PKCδ...... in the regulation of mitochondrial mass at older age. These data indicate an important role of PKCδ in the regulation of insulin sensitivity and mitochondrial homeostasis in skeletal muscle with aging....

  3. Skeletal Muscle Angiogenesis and Its Relation to Insulin Sensitivity

    DEFF Research Database (Denmark)

    Lindqvist, Anna Maria Charlotte K

    mediator of angiogenesis) are reduced in insulin resistant individuals. Exercise training can improve skeletal muscle capillarization and the angiogenic potential and physical activity has also been proven to enhance muscle insulin sensitivity. Increased skeletal muscle capillarization is associated......) or by overexpression of VEGF-A in the tibialis anterior muscle (transfection; study II) and the effect of the increased muscle capillarization on muscle insulin sensitivity was examined. In study I skeletal muscle specific angiogenesis was induced by administering an α1-adrenergic antagonist (prazosin) to healthy...

  4. Key Questions for Translation of FFA Receptors: From Pharmacology to Medicines.

    Science.gov (United States)

    Suckow, Arthur T; Briscoe, Celia P

    2017-01-01

    The identification of fatty acids as ligands for the G-protein coupled free fatty acid (FFA) receptor family over 10 years ago led to intensive chemistry efforts to find small-molecule ligands for this class of receptors. Identification of potent, selective modulators of the FFA receptors and their utility in medicine has proven challenging, in part due to their complex pharmacology. Nevertheless, ligands have been identified that are sufficient for exploring the therapeutic potential of this class of receptors in rodents and, in the case of FFA1, FFA2, FFA4, and GPR84, also in humans. Expression profiling, the phenotyping of FFA receptor knockout mice, and the results of studies exploring the effects of these ligands in rodents have uncovered a number of indications where engagement of one or a combination of FFA receptors might provide some clinical benefit in areas including diabetes, inflammatory bowel syndrome, Alzheimer's, pain, and cancer. In this chapter, we will review the clinical potential of modulating FFA receptors based on preclinical and in some cases clinical studies with synthetic ligands. In particular, key aspects and challenges associated with small-molecule ligand identification and FFA receptor pharmacology will be addressed with a view of the hurdles that need to be overcome to fully understand the potential of the receptors as therapeutic targets.

  5. Horticulture and the FFA

    Science.gov (United States)

    Nelson, Clifford L.

    1975-01-01

    The article offers teachers of vocational horticulture a number of specific suggestions for organizing FFA horticulture chapters that will appeal to urban and suburban students and that will improve the quality of their learning. (AJ)

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

    DEFF Research Database (Denmark)

    Malin, Steven K; Haus, Jacob M; Solomon, Thomas

    2013-01-01

    Impaired fasting glucose (IFG) blunts the reversal of impaired glucose tolerance (IGT) after exercise training. Metabolic inflexibility has been implicated in the etiology of insulin resistance, however, the efficacy of exercise on peripheral and hepatic insulin sensitivity or substrate utilizati...

  7. Extracellular ionic locks determine variation in constitutive activity and ligand potency between species orthologs of the free fatty acid receptors FFA2 and FFA3

    DEFF Research Database (Denmark)

    Hudson, Brian D; Tikhonova, Irina G; Pandey, Sunil K

    2012-01-01

    Free fatty acid receptors 2 and 3 (FFA2 and FFA3) are G protein-coupled receptors for short chain free fatty acids (SCFAs). They respond to the same set of endogenous ligands but with distinct rank-order of potency such that acetate (C2) has been described as FFA2-selective, whereas propionate (C...

  8. Insulin sensitizers in adolescents with polycystic ovary syndrome.

    Science.gov (United States)

    LE, Trang N; Wickham, Edmond P; Nestler, John E

    2017-10-01

    Polycystic ovary syndrome (PCOS) is the most common disorder of androgen excess in women of reproductive age. The diagnosis of PCOS can be more challenging in adolescents than in adult women given significant overlap between normal puberty and the signs of PCOS, including acne, menstrual irregularity, and polycystic ovarian morphology. Optimal treatments for adult women with PCOS vary depending on patient risk factors and reproductive goals, but mainly include hormonal contraception and insulin sensitizers. There is continued interest in targeting the intrinsic insulin resistance that contributes to metabolic and hormonal derangements associated with PCOS. The vast majority of published data on insulin sensitizing PCOS treatments are reported in adult women; these have included weight loss, metformin, thiazolidinediones, and the inositols. Furthermore, there is also a small but growing body of evidence in support of the use of insulin sensitizers in adolescents, with or without oral contraceptives. Discussion of the available treatments, including benefits, potential side effects, and incorporation of patient and family preferences is critical in developing a plan of care aimed at achieving patient-important improvements in PCOS signs and symptoms while addressing the longer-term cardiometabolic risks associated with the syndrome.

  9. A novel insulin resistance index to monitor changes in insulin sensitivity and glucose tolerance: the ACT NOW study.

    Science.gov (United States)

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

    2015-05-01

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

  10. Associations of infant nutrition with insulin resistance measures in early adulthood: evidence from the Barry-Caerphilly Growth (BCG study.

    Directory of Open Access Journals (Sweden)

    Dylan M Williams

    Full Text Available Previous studies suggest that over-nutrition in early infancy may programme long-term susceptibility to insulin resistance.To assess the association of breast milk and quantity of infant formula and cows' milk intake during infancy with insulin resistance measures in early adulthood.Long-term follow-up of the Barry Caerphilly Growth cohort, into which mothers and their offspring had originally been randomly assigned, between 1972-1974, to receive milk supplementation or not. Participants were the offspring, aged 23-27 years at follow-up (n = 679. Breastfeeding and formula/cows' milk intake was recorded prospectively by nurses. The main outcomes were insulin sensitivity (ISI(0 and insulin secretion (CIR(30.573 (84% individuals had valid glucose and insulin results and complete covariate information. There was little evidence of associations of breastfeeding versus any formula/cows' milk feeding or of increasing quartiles of formula/cows' milk consumption during infancy (<3 months with any outcome measure in young adulthood. In fully adjusted models, the differences in outcomes between breastfeeding versus formula/cows' milk feeding at 3 months were: fasting glucose (-0.07 mmol/l; 95% CI: -0.19, 0.05; fasting insulin (8.0%; -8.7, 27.6; ISI(0 (-6.1%; -11.3, 12.1 and CIR(30 (3.8%; -19.0, 32.8. There was also little evidence that increasing intakes of formula/cows' milk at 3 months were associated with fasting glucose (increase per quartile of formula/cows' milk intake = 0.00 mmol/l; -0.03, 0.03; fasting insulin (0.8%; -3.2, 5.1; ISI (0 (-0.9%; -5.1, 3.5 and CIR(30 (-2.6%; -8.4, 3.6.We found no evidence that increasing consumption of formula/cows' milk in early infancy was associated with insulin resistance in young adulthood.

  11. Partial sleep restriction decreases insulin sensitivity in type 1 diabetes

    NARCIS (Netherlands)

    Donga, Esther; van Dijk, Marieke [Leiden Univ., LUMC; van Dijk, J. Gert; Biermasz, Nienke R.; Lammers, Gert-Jan; van Kralingen, Klaas; Hoogma, Roel P. L. M.; Corssmit, Eleonora P. M.; Romijn, Johannes A.

    2010-01-01

    Sleep restriction results in decreased insulin sensitivity and glucose tolerance in healthy subjects. We hypothesized that sleep duration is also a determinant of insulin sensitivity in patients with type 1 diabetes. We studied seven patients (three men, four women) with type 1 diabetes: mean age 44

  12. APPL1 potentiates insulin sensitivity by facilitating the binding of IRS1/2 to the insulin receptor.

    Science.gov (United States)

    Ryu, Jiyoon; Galan, Amanda K; Xin, Xiaoban; Dong, Feng; Abdul-Ghani, Muhammad A; Zhou, Lijun; Wang, Changhua; Li, Cuiling; Holmes, Bekke M; Sloane, Lauren B; Austad, Steven N; Guo, Shaodong; Musi, Nicolas; DeFronzo, Ralph A; Deng, Chuxia; White, Morris F; Liu, Feng; Dong, Lily Q

    2014-05-22

    Binding of insulin receptor substrate proteins 1 and 2 (IRS1/2) to the insulin receptor (IR) is essential for the regulation of insulin sensitivity and energy homeostasis. However, the mechanism of IRS1/2 recruitment to the IR remains elusive. Here, we identify adaptor protein APPL1 as a critical molecule that promotes IRS1/2-IR interaction. APPL1 forms a complex with IRS1/2 under basal conditions, and this complex is then recruited to the IR in response to insulin or adiponectin stimulation. The interaction between APPL1 and IR depends on insulin- or adiponectin-stimulated APPL1 phosphorylation, which is greatly reduced in insulin target tissues in obese mice. appl1 deletion in mice consistently leads to systemic insulin resistance and a significant reduction in insulin-stimulated IRS1/2, but not IR, tyrosine phosphorylation, indicating that APPL1 sensitizes insulin signaling by acting at a site downstream of the IR. Our study uncovers a mechanism regulating insulin signaling and crosstalk between the insulin and adiponectin pathways. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Insulin-Sensitizers, Polycystic Ovary Syndrome and Gynaecological Cancer Risk

    Science.gov (United States)

    Lauretta, Rosa; Lanzolla, Giulia; Vici, Patrizia; Mariani, Luciano; Moretti, Costanzo

    2016-01-01

    Preclinical, early phase clinical trials and epidemiological evidence support the potential role of insulin-sensitizers in cancer prevention and treatment. Insulin-sensitizers improve the metabolic and hormonal profile in PCOS patients and may also act as anticancer agents, especially in cancers associated with hyperinsulinemia and oestrogen dependent cancers. Several lines of evidence support the protection against cancer exerted by dietary inositol, in particular inositol hexaphosphate. Metformin, thiazolidinediones, and myoinositol postreceptor signaling may exhibit direct inhibitory effects on cancer cell growth. AMPK, the main molecular target of metformin, is emerging as a target for cancer prevention and treatment. PCOS may be correlated to an increased risk for developing ovarian and endometrial cancer (up to threefold). Several studies have demonstrated an increase in mortality rate from ovarian cancer among overweight/obese PCOS women compared with normal weight women. Long-term use of metformin has been associated with lower rates of ovarian cancer. Considering the evidence supporting a higher risk of gynaecological cancer in PCOS women, we discuss the potential use of insulin-sensitizers as a potential tool for chemoprevention, hypothesizing a possible rationale through which insulin-sensitizers may inhibit tumourigenesis. PMID:27725832

  14. Enhanced insulin sensitivity in prepubertal children with constitutional delay of growth and development.

    Science.gov (United States)

    Wilson, Dyanne A; Hofman, Paul L; Miles, Harriet L; Sato, Tim A; Billett, Nathalie E; Robinson, Elizabeth M; Cutfield, Wayne S

    2010-02-01

    To test the hypothesis that prepubertal children with presumed constitutional delay of growth and development (CDGD) have enhanced insulin sensitivity and, therefore, insulin sensitivity is associated with later onset of puberty. Twenty-one prepubertal children with presumed CDGD and 23 prepubertal control children, underwent a frequently sampled intravenous glucose tolerance test to evaluate insulin sensitivity and other markers of insulin, glucose, and growth regulation. Children in the CDGD group were shorter and leaner than control subjects. Children with presumed CDGD were 40% more insulin sensitive (17.0 x 10(-4) min(-1)/[mU/L] versus 12.1 x 10(-4) min(-1)/[mU/L]; P = .0006) and had reduced acute insulin response, thus maintaining euglycemia (216 mU/L versus 330 mU/L; P = .02) compared with control subjects. In addition, the CDGD group had lower serum insulin-like growth factor binding protein 3 levels (3333 ng/mL versus 3775 ng/mL; P = .0004) and a trend toward lower serum insulin-like growth factor-II levels (794 ng/mL versus 911 ng/mL; P = .06). Prepubertal children with presumed CDGD have enhanced insulin sensitivity, supporting the hypothesis that insulin sensitivity is associated with timing of puberty. It may signify long-term biological advantages with lower risk of metabolic syndrome and malignancy. Copyright 2010 Mosby, Inc. All rights reserved.

  15. DHEA-induced modulation of renal gluconeogenesis, insulin sensitivity and plasma lipid profile in the control- and dexamethasone-treated rabbits. Metabolic studies.

    Science.gov (United States)

    Kiersztan, Anna; Nagalski, Andrzej; Nalepa, Paweł; Tempes, Aleksandra; Trojan, Nina; Usarek, Michał; Jagielski, Adam K

    2016-02-01

    In view of antidiabetic and antiglucocorticoid effects of dehydroepiandrosterone (DHEA) both in vitro and in vivo studies were undertaken: (i) to elucidate the mechanism of action of both dexamethasone phosphate (dexP) and DHEA on glucose synthesis in primary cultured rabbit kidney-cortex tubules and (ii) to investigate the influence of DHEA on glucose synthesis, insulin sensitivity and plasma lipid profile in the control- and dexP-treated rabbits. Data show, that in cultured kidney-cortex tubules dexP significantly stimulated gluconeogenesis by increasing flux through fructose-1,6-bisphosphatase (FBPase). DexP-induced effects were dependent only upon glucocorticoid receptor. DHEA decreased glucose synthesis via inhibition of glucose-6-phosphatase (G6Pase) and suppressed the dexP-induced stimulation of renal gluconeogenesis. Studies with the use of inhibitors of DHEA metabolism in cultured renal tubules showed for the first time that DHEA directly affects renal gluconeogenesis. However, in view of analysis of glucocorticoids and DHEA metabolites levels in urine, it seems likely, that testosterone may also contribute to DHEA-evoked effects. In dexP-treated rabbits, plasma glucose level was not altered despite increased renal and hepatic FBPase and G6Pase activities, while a significant elevation of both plasma insulin and HOMA-IR was accompanied by a decline of ISI index. It thus appears that increased insulin levels were required to maintain normoglycaemia and to compensate the insulin resistance. DHEA alone affected neither plasma glucose nor lipid levels, while it increased insulin sensitivity and diminished both renal and hepatic G6Pase activities. Surprisingly, DHEA co-administrated with dexP did not alter insulin sensitivity, while it partially suppressed the dexP-induced elevation of renal G6Pase activity and plasma cholesterol and triglyceride contents. As (i) gluconeogenic pathway in rabbit is similar to that in human, and (ii) DHEA counteracts several

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

    Science.gov (United States)

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

    1990-01-01

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

  17. [Insulin-sensitizing agents: metformin and thiazolidinedione derivatives].

    Science.gov (United States)

    Satoh, Jo

    2003-07-01

    Both metformin and thiazolidinedione derivatives(TZDs) improve insulin resistance, a major pathogenesis of type 2 diabetes, and decrease blood glucose levels without stimulating insulin secretion. Metformin inhibits glucose output from the liver, while TZDs increase glucose utilization in the peripheral tissues. In addition, there has been indicated that these agents ameliorate metabolic syndrome beyond glucose-level lowering. Molecular targets of these agents have recently been revealed; AMP-activated protein kinase (AMPK) for metformin and adiponectin, while PPAR gamma for TZDs which induce gene expression of adipocyte glycerol kinase and adiponectin. Insulin-sensitizing agents are clinically useful for obese diabetic patients with insulin resistance. However, periodical examinations are necessary to avoid serious adverse effects such as lactic acidosis, although rare, by metformin and liver injury by TZDs.

  18. Agrarianism: An Ideology of the National FFA Organization

    Science.gov (United States)

    Martin, Michael J.; Kitchel, Tracy

    2013-01-01

    The traditions of the National FFA Organization (FFA) are grounded in agrarianism. This ideology focuses on the ability of farming and nature to develop citizens and integrity within people. Agrarianism has been an important thread of American rhetoric since the founding of country. The ideology has morphed over the last two centuries as the…

  19. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats.

    Science.gov (United States)

    Yamazaki, Ricardo K; Brito, Gleisson A P; Coelho, Isabela; Pequitto, Danielle C T; Yamaguchi, Adriana A; Borghetti, Gina; Schiessel, Dalton Luiz; Kryczyk, Marcelo; Machado, Juliano; Rocha, Ricelli E R; Aikawa, Julia; Iagher, Fabiola; Naliwaiko, Katya; Tanhoffer, Ricardo A; Nunes, Everson A; Fernandes, Luiz Claudio

    2011-04-28

    Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish oil-treated normal weight group (FO), obese control group (Ob), coconut fat-treated obese group (ObCO) and fish oil-treated obese group (ObFO). Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day) for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Obese animals (Ob) presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt) showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO) similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30%) and triacylglycerol (TG; 33%) compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Low dose of fish oil supplementation (1 g/kg/day) was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

  20. Role of AMP-activated protein kinase for regulating post-exercise insulin sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Wojtaszewski, Jørgen; Treebak, Jonas Thue

    2016-01-01

    Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people that are diagno......Skeletal muscle insulin resistance precedes development of type 2 diabetes (T2D). As skeletal muscle is a major sink for glucose disposal, understanding the molecular mechanisms involved in maintaining insulin sensitivity of this tissue could potentially benefit millions of people...... that are diagnosed with insulin resistance. Regular physical activity in both healthy and insulin-resistant individuals is recognized as the single most effective intervention to increase whole-body insulin sensitivity and thereby positively affect glucose homeostasis. A single bout of exercise has long been known...... to increase glucose disposal in skeletal muscle in response to physiological insulin concentrations. While this effect is identified to be restricted to the previously exercised muscle, the molecular basis for an apparent convergence between exercise- and insulin-induced signaling pathways is incompletely...

  1. Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

    Science.gov (United States)

    Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

    2013-03-01

    Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

  2. The Relationship between 25-hydroxyvitamin D Levels, Insulin Sensitivity and Insulin Secretion in Women 3 Years after Delivery.

    Science.gov (United States)

    Tänczer, Tímea; Magenheim, Rita; Fürst, Ágnes; Domján, Beatrix; Janicsek, Zsófia; Szabó, Eszter; Ferencz, Viktória; Tabák, Ádám G

    2017-12-01

    There is a direct correlation between 25-hydroxyvitamin D (25[OH]D) levels and insulin sensitivity. Furthermore, women with gestational diabetes (GDM) may have lower levels of 25(OH)D compared to controls. The present study intended to investigate 25(OH)D levels and their association with insulin sensitivity and insulin secretion in women with prior GDM and in controls 3.2 years after delivery. A total of 87 patients with prior GDM and 45 randomly selected controls (age range, 22 to 44 years) with normal glucose tolerance during pregnancy nested within a cohort of all deliveries at Saint Margit Hospital, Budapest, between January 1 2005, and December 31 2006, were examined. Their 25(OH) D levels were measured by radioimmunoassay. Insulin sensitivity and fasting insulin secretion were estimated using the homeostasis model asssessment (HOMA) calculator and early insulin secretion by the insulinogenic index based on a 75 g oral glucose tolerance test. There was no significant difference in 25(OH)D levels between cases and controls (27.2±13.1 [±SD] vs. 26.9±9.8 ng/L). There was a positive association between HOMA insulin sensitivity and 25(OH)D levels (beta = 0.017; 95% CI 0.001 to 0.034/1 ng/mL) that was robust to adjustment for age and body mass index. There was a nonsignificant association between HOMA insulin secretion and 25(OH)D (p=0.099), while no association was found with the insulinogenic index. Prior GDM status was not associated with 25(OH)D levels; however, 25(OH) D levels were associated with HOMA insulin sensitivity. It is hypothesized that the association between HOMA insulin secretion and 25(OH)D levels is related to the autoregulation of fasting glucose levels because no association between 25(OH)D and insulinogenic index was found. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

  3. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

    2015-04-01

    Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

  4. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    Directory of Open Access Journals (Sweden)

    Iagher Fabiola

    2011-04-01

    Full Text Available Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG (4 mg/g body weight was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C, coconut fat-treated normal weight group (CO, fish oil-treated normal weight group (FO, obese control group (Ob, coconut fat-treated obese group (ObCO and fish oil-treated obese group (ObFO. Obese insulin-resistant rats were supplemented with fish oil or coconut fat (1 g/kg/day for 4 weeks. Insulin sensitivity, fasting blood biochemicals parameters, and skeletal muscle glucose metabolism were analyzed. Results Obese animals (Ob presented higher Index Lee and 2.5 fold epididymal and retroperitoneal adipose tissue than C. Insulin sensitivity test (Kitt showed that fish oil supplementation was able to maintain insulin sensitivity of obese rats (ObFO similar to C. There were no changes in glucose and HDL-cholesterol levels amongst groups. Yet, ObFO revealed lower levels of total cholesterol (TC; 30% and triacylglycerol (TG; 33% compared to Ob. Finally, since exposed to insulin, ObFO skeletal muscle revealed an increase of 10% in lactate production, 38% in glycogen synthesis and 39% in oxidation of glucose compared to Ob. Conclusions Low dose of fish oil supplementation (1 g/kg/day was able to reduce TC and TG levels, in addition to improved systemic and muscle insulin sensitivity. These results lend credence to the benefits of n-3 fatty acids upon the deleterious effects of insulin resistance mechanisms.

  5. Glutathione depletion prevents diet-induced obesity and enhances insulin sensitivity.

    Science.gov (United States)

    Findeisen, Hannes M; Gizard, Florence; Zhao, Yue; Qing, Hua; Jones, Karrie L; Cohn, Dianne; Heywood, Elizabeth B; Bruemmer, Dennis

    2011-12-01

    Excessive accumulation of reactive oxygen species (ROS) in adipose tissue has been implicated in the development of insulin resistance and type 2 diabetes. However, emerging evidence suggests a physiologic role of ROS in cellular signaling and insulin sensitivity. In this study, we demonstrate that pharmacologic depletion of the antioxidant glutathione in mice prevents diet-induced obesity, increases energy expenditure and locomotor activity, and enhances insulin sensitivity. These observations support a beneficial role of ROS in glucose homeostasis and warrant further research to define the regulation of metabolism and energy balance by ROS.

  6. Relationship between Inflammation markers, Coagulation Activation and Impaired Insulin Sensitivity in Obese Healthy Women

    International Nuclear Information System (INIS)

    Soliman, S.Et; Shousha, M.A.

    2011-01-01

    Obesity, insulin resistance syndrome, and atherosclerosis are closely linked phenomena, often connected with a chronic low grade inflammatory state and pro thrombotic hypo fibrinolytic condition. This study investigated the relationship between impaired insulin sensitivity and selected markers of inflammation and thrombin generation in obese healthy women. The study included 36 healthy obese women (body mass index ≥ 30), with normal insulin sensitivity (NIS, n = 18) or impaired insulin sensitivity (IIS, n 18), and 10 non obese women (body mass index < 25).Impaired insulin sensitivity patients had significantly higher levels of high sensitivity C-reactive protein (hs-CRP), transforming growth factor -β1(TGF-β1), plasminogen activator inhibitor-1 (PAI-1), activated factor VII (VIIa), and prothrombin fragments 1 + 2 (F1 + 2) compared with either control subjects or normal insulin sensitivity patients. On the other hand, NIS patients had higher hs-CRP, TGF-β1, PAI-1, and factor VIIa, but not F1 + 2, levels than controls. Significant inverse correlations were observed between the insulin sensitivity index and TGF-β1, hs-CRP, PAI-1; factor VIIa, and F1 + 2 levels. Moreover, significant direct correlations were noted between TGF-β1 and CRP, PAI-1, factor VIIa, and F1 + 2 concentrations. Finally, multiple regressions revealed that TGF-β1 and the insulin sensitivity index were independently related to F1 + 2. These results document an in vivo relationship between insulin sensitivity and coagulation activation in obesity. Here we report that obesity is associated with higher TGF-β, PAI-1, prothrombin fragments 1 and 2 (F1 + 2), and activated factor VII (VIIa) plasma levels, and that insulin resistance exacerbates these alterations. The elevated TGF-β1 levels detected in the obese population may provide a biochemical link between insulin resistance and an increased risk for cardiovascular disease

  7. Omentin, an adipokine with insulin-sensitizing properties, is negatively associated with insulin resistance in normal gestation.

    Science.gov (United States)

    Brandt, Benny; Mazaki-Tovi, Shali; Hemi, Rina; Yinon, Yoav; Schiff, Eyal; Mashiach, Roy; Kanety, Hannah; Sivan, Eyal

    2015-05-01

    Omentin, a newly identified adipokine, enhances insulin mediated glucose uptake in human adipocytes, thus, inducing systemic insulin-sensitizing effect. The aims of this study were to determine whether circulating maternal omentin levels are associated with insulin resistance indices and to assess which compartment, maternal, fetal, or placental, is the source of omentin in maternal circulation. Fasting serum glucose, insulin, and omentin were determined in 25 healthy pregnant women at the third trimester, before and 3 days after elective cesarean section. Cord blood omentin was measured in the 25 term neonates. Homeostasis model assessment (HOMA) was used to evaluate insulin sensitivity before and after delivery. Antepartum maternal omentin levels were negatively correlated with insulin levels (r=-0.41, P=0.04) and positively correlated with insulin sensitivity (HOMA%S; r=0.4, P=0.04). Postpartum omentin levels were negatively correlated with maternal body mass index (r=-0.44, P=0.02). Median maternal omentin levels was comparable before and after delivery (57.2, inter-quartile range: 38.2-76.2 ng/mL vs. 53.4, 39.8-69.4 ng/mL, respectively, P=0.25) and highly correlated (r=0.83, Pinsulin resistance indices, suggesting that this adipokine may play a role in metabolic adaptations of normal gestation. The strong correlation between anteparum and postpartum maternal omentin levels, as well as the lack of association between maternal and neonatal omentin levels, suggest that placental or fetal compartments are unlikely as the main source of circulating maternal omentin.

  8. Bcl10 links saturated fat overnutrition with hepatocellular NF-kB activation and insulin resistance

    NARCIS (Netherlands)

    Beek, M.H. van; Oravecz-Wilson, K.I.; Delekta, P.C.; Gu, S.; Li, X.; Jin, X.; Apel, I.J.; Konkle, K.S.; Feng, Y.; Teitelbaum, D.H.; Ruland, J.; McAllister-Lucas, L.M.; Lucas, P.C.

    2012-01-01

    Excess serum free fatty acids (FFAs) are fundamental to the pathogenesis of insulin resistance. With high-fat feeding, FFAs activate NF-kB in target tissues, initiating negative crosstalk with insulin signaling. However, the mechanisms underlying FFA-dependent NF-kB activation remain unclear. Here,

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

    Science.gov (United States)

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

    2018-04-25

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

  10. Nitric oxide is required for the insulin sensitizing effects of contraction in mouse skeletal muscle.

    Science.gov (United States)

    Zhang, Xinmei; Hiam, Danielle; Hong, Yet-Hoi; Zulli, Anthony; Hayes, Alan; Rattigan, Stephen; McConell, Glenn K

    2017-12-15

    People with insulin resistance or type 2 diabetes can substantially increase their skeletal muscle glucose uptake during exercise and insulin sensitivity after exercise. Skeletal muscle nitric oxide (NO) is important for glucose uptake during exercise, although how prior exercise increases insulin sensitivity is unclear. In the present study, we examined whether NO is necessary for normal increases in skeletal muscle insulin sensitivity after contraction ex vivo in mouse muscle. The present study uncovers, for the first time, a novel role for NO in the insulin sensitizing effects of ex vivo contraction, which is independent of blood flow. The factors regulating the increase in skeletal muscle insulin sensitivity after exercise are unclear. We examined whether nitric oxide (NO) is required for the increase in insulin sensitivity after ex vivo contractions. Isolated C57BL/6J mouse EDL muscles were contracted for 10 min or remained at rest (basal) with or without the NO synthase (NOS) inhibition (N G -monomethyl-l-arginine; l-NMMA; 100 μm). Then, 3.5 h post contraction/basal, muscles were exposed to saline or insulin (120 μU ml -1 ) with or without l-NMMA during the last 30 min. l-NMMA had no effect on basal skeletal muscle glucose uptake. The increase in muscle glucose uptake with insulin (57%) was significantly (P contraction (140% increase). NOS inhibition during the contractions had no effect on this insulin-sensitizing effect of contraction, whereas NOS inhibition during insulin prevented the increase in skeletal muscle insulin sensitivity post-contraction. Soluble guanylate cyclase inhibition, protein kinase G (PKG) inhibition or cyclic nucleotide phosphodiesterase inhibition each had no effect on the insulin-sensitizing effect of prior contraction. In conclusion, NO is required for increases in insulin sensitivity several hours after contraction of mouse skeletal muscle via a cGMP/PKG independent pathway. © 2017 The Authors. The Journal of Physiology

  11. Normocaloric Diet Restores Weight Gain and Insulin Sensitivity in Obese Mice

    Directory of Open Access Journals (Sweden)

    Giovanni Enrico Lombardo

    2016-05-01

    Full Text Available An increased incidence of obesity is registered worldwide, and its association with insulin resistance and type 2 diabetes is closely related with increased morbidity and mortality for cardiovascular diseases. A major clinical problem in the management of obesity is the non-adherence or low adherence of patients to a hypo-caloric dietetic restriction. In this study we evaluated in obese mice the effects on insulin sensitivity of shifting from high-calorie foods to normal diet. Male C57BL/6JolaHsd mice (n=20 were fed with high fat diet for a 24 weeks period. Afterwards, body weight, energy and food intake were measured in all animals, together with parameters of insulin sensitivity by homeostatic model assessment of insulin resistance and plasma glucose levels in response to insulin administration. Moreover, in half of these mice, Glut4 mRNA levels were measured in muscle at the end of the high fat treatment, whereas the rest of the animals (n=10 were shifted to normocaloric diet for 10 weeks, after which the same analyses were carried out. A significant reduction of body weight was found after the transition from high to normal fat diet, and this decrease correlated well with an improvement in insulin sensitivity. In fact, we found a reduction in serum insulin levels and the recovery of insulin responsiveness in terms of glucose disposal measured by insulin tolerance test and Glut4 mRNA and protein expression. These results indicate that obesity related insulin resistance may be rescued by shifting from high fat diet to normocaloric diet.

  12. Influence of Flavonoids on Mechanism of Modulation of Insulin Secretion.

    Science.gov (United States)

    Soares, Juliana Mikaelly Dias; Pereira Leal, Ana Ediléia Barbosa; Silva, Juliane Cabral; Almeida, Jackson R G S; de Oliveira, Helinando Pequeno

    2017-01-01

    The development of alternatives for insulin secretion control in vivo or in vitro represents an important aspect to be investigated. In this direction, natural products have been progressively explored with this aim. In particular, flavonoids are potential candidates to act as insulin secretagogue. To study the influence of flavonoid on overall modulation mechanisms of insulin secretion. The research was conducted in the following databases and platforms: PubMed, Scopus, ISI Web of Knowledge, SciELO, LILACS, and ScienceDirect, and the MeSH terms used for the search were flavonoids, flavones, islets of Langerhans, and insulin-secreting cells. Twelve articles were included and represent the basis of discussion on mechanisms of insulin secretion of flavonoids. Papers in ISI Web of Knowledge were in number of 1, Scopus 44, PubMed 264, ScienceDirect 511, and no papers from LILACS and SciELO databases. According to the literature, the majority of flavonoid subclasses can modulate insulin secretion through several pathways, in an indication that corresponding molecule is a potential candidate for active materials to be applied in the treatment of diabetes. The action of natural products on insulin secretion represents an important investigation topic due to their importance in the diabetes controlIn addition to their typical antioxidant properties, flavonoids contribute to the insulin secretionThe modulation of insulin secretion is induced by flavonoids according to different mechanisms. Abbreviations used: K ATP channels: ATP-sensitive K + channels, GLUT4: Glucose transporter 4, ERK1/2: Extracellular signal-regulated protein kinases 1 and 2, L-VDCCs: L-type voltage-dependent Ca +2 channels, GLUT1: Glucose transporter 1, AMPK: Adenosine monophosphate-activated protein kinase, PTP1B: Protein tyrosine phosphatase 1B, GLUT2: Glucose transporter 2, cAMP: Cyclic adenosine monophosphate, PKA: Protein kinase A, PTK: Protein tyrosine kinase, CaMK II: Ca 2+ /calmodulin

  13. Evaluación de la sensibilidad a la insulina en el síndrome de ovarios poliquísticos Evaluation of insulin-sensitivity in polycistic ovary syndrome

    Directory of Open Access Journals (Sweden)

    Yudit García García

    2009-12-01

    . OBJECTIVE: to determine the frequency and features of insulin sensitivity disorders in a group of women with polycistic ovary syndrome. METHODS: twenty three women with this diagnosis were studied according to the Androgen Excess Society (AES criteria,underwent basal glycemia and insulinemia determinations and during frequently sampled intravenous glucose tolerancetest. Several insulin sensitivity and insulin resistance mathematic indexes were calculated. RESULTS: sixty-five percent of women had insulin resistance (HOMA-IR ³ 3.22 rate. Analysis of area under the curve of insulin during the test revealed that women with insulin resistance had higher insulinemia rates in baseline state and post-stimulation;in both groups concentrations were similar to the initial ones at the end of test. Glycemia and insulinemia 0-10 areas and insulin area were higher in women with insulin resistance. All indexes including Io/Go, FIRI, ISI, Belfiore, BENNET and QUICKI had a good correlation with HOMA-IR. CONCLUSIONS: insulin resistance and hyperinsulinism frequency in women with policystic ovary syndrome was high and the fasting insulin resistance assessment may to predict the response during the glucose-intravenous stimulation.

  14. Dietary Fat – Insulin Sensitivity and Molecular Substrate Metabolism

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie

    metabolism in skeletal muscle. The high-fat diet was primarily comprised of unsaturated FA. We demonstrated in lean, healthy and moderately trained men that three days’ intake of 78 E% dietary fat coupled with 75% energy excess was sufficient to reduce whole-body insulin sensitivity by 17% and insulin...

  15. Increased insulin sensitivity in intrauterine growth retarded newborns--do thyroid hormones play a role?

    Science.gov (United States)

    Setia, Sajita; Sridhar, M G; Koner, B C; Bobby, Zachariah; Bhat, Vishnu; Chaturvedula, Lata

    2007-02-01

    Thyroid hormones are necessary for normal brain development. We studied thyroid hormone profile and insulin sensitivity in intrauterine growth retarded (IUGR) newborns to find correlation between insulin sensitivity and thyroid status in IUGR newborns. Fifty IUGR and fifty healthy control infants were studied at birth. Cord blood was collected for determination of T(3), T(4), TSH, glucose and insulin levels. IUGR newborns had significantly lower insulin, mean+/-S.D., 5.25+/-2.81 vs. 11.02+/-1.85microU/ml, but significantly higher insulin sensitivity measured as glucose to insulin ratio (G/I), 9.80+/-2.91 vs. 6.93+/-1.08 compared to healthy newborns. TSH was also significantly higher 6.0+/-2.70 vs. 2.99+/-1.05microU/ml with significantly lower T(4), 8.65+/-1.95 vs. 9.77+/-2.18microg/dl, but similar T(3) levels, 100.8+/-24.36 vs. 101.45+/-23.45ng/dl. On stepwise linear regression analysis in IUGR infants, insulin sensitivity was found to have a significant negative association with T(4) and significant positive association with TSH. Thyroid hormones may play a role in increased insulin sensitivity at birth in IUGR.

  16. Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

    Directory of Open Access Journals (Sweden)

    Morgan Kristen

    2011-01-01

    Full Text Available Abstract Background We and others have demonstrated previously that ghrelin receptor (GhrR knock out (KO mice fed a high fat diet (HFD have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG and hyperinsulinemic-euglycemic (HI-E clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd, and decreased hepatic glucose production (HGP. HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is

  17. Phospholipid environment alters hormone-sensitivity of the purified insulin receptor kinase.

    OpenAIRE

    Lewis, R E; Czech, M P

    1987-01-01

    Insulin receptor kinase, affinity-purified by adsorption and elution from immobilized insulin, is stimulated 2-3-fold by insulin in detergent solution. Reconstitution of the receptor kinase into leaky vesicles containing phosphatidylcholine and phosphatidylethanolamine (1:1, w/w) by detergent removal on Sephadex G-50 results in the complete loss of receptor kinase sensitivity to activation by insulin. Insulin receptors in these vesicles also exhibit an increase in their apparent affinity for ...

  18. The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system.

    Science.gov (United States)

    Coomans, C P; Geerling, J J; van den Berg, S A A; van Diepen, H C; Garcia-Tardón, N; Thomas, A; Schröder-van der Elst, J P; Ouwens, D M; Pijl, H; Rensen, P C N; Havekes, L M; Guigas, B; Romijn, J A

    2013-10-01

    Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro. Male C57Bl/6J mice were fed a run-in high-fat diet for 6 weeks, before receiving topiramate or vehicle mixed in high-fat diet for an additional 6 weeks. Insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp. The extent to which the insulin sensitizing effects of topiramate were mediated through the CNS were determined by concomitant i.c.v. infusion of vehicle or tolbutamide, an inhibitor of ATP-sensitive potassium channels in neurons. The direct effects of topiramate on insulin signalling and glucose uptake were assessed in vivo and in cultured muscle cells. In hyperinsulinaemic-euglycaemic clamp conditions, therapeutic plasma concentrations of topiramate (∼4 μg·mL(-1) ) improved insulin sensitivity (glucose infusion rate + 58%). Using 2-deoxy-D-[(3) H]glucose, we established that topiramate improved the insulin-mediated glucose uptake by heart (+92%), muscle (+116%) and adipose tissue (+586%). Upon i.c.v. tolbutamide, the insulin-sensitizing effect of topiramate was completely abrogated. Topiramate did not directly affect glucose uptake or insulin signalling neither in vivo nor in cultured muscle cells. In conclusion, topiramate stimulates insulin-mediated glucose uptake in vivo through the CNS. These observations illustrate the possibility of pharmacological modulation of peripheral insulin resistance through a target in the CNS. © 2013 The British Pharmacological Society.

  19. Sexual dimorphism in hepatic, adipose tissue and peripheral tissue insulin sensitivity in obese humans

    Directory of Open Access Journals (Sweden)

    Kasper W. ter Horst

    2015-11-01

    Full Text Available Glucose and lipid metabolism differ between men and women, and women tend to have better whole-body or muscle insulin sensitivity. This may be explained, in part, by differences in sex hormones and adipose tissue distribution. Few studies have investigated gender differences in hepatic, adipose tissue and whole-body insulin sensitivity between severely obese men and women. In this study, we aimed to determine the differences in glucose metabolism between severely obese men and women using tissue-specific measurements of insulin sensitivity. Insulin sensitivity was compared between age and body mass index (BMI-matched obese men and women by a two-step euglycemic hyperinsulinemic clamp with infusion of [6,6-2H2]glucose. Basal endogenous glucose production and insulin sensitivity of the liver, adipose tissue and peripheral tissues were assessed. Liver fat content was assessed by proton magnetic resonance spectroscopy in a subset of included subjects. We included 46 obese men and women (age, 48±2 vs 46±2 years, p=0.591; BMI, 41±1 vs 41±1 kg/m2, p=0.832. There was no difference in basal endogenous glucose production (14.4±1.0 vs 15.3±0.5 µmol•kg fat-free mass-1•min-1, p=0.410, adipose tissue insulin sensitivity (insulin-mediated suppression of free fatty acids, 71.6±3.6 vs 76.1±2.6%, p=0.314 or peripheral insulin sensitivity (insulin-stimulated rate of disappearance of glucose, 26.2±2.1 vs 22.7±1.7 µmol•kg-1•min-1, p=0.211. Obese men were characterized by lower hepatic insulin sensitivity (insulin-mediated suppression of endogenous glucose production, 61.7±4.1 vs 72.8±2.5% in men vs women, resp., p=0.028. Finally, these observations could not be explained by differences in liver fat content (men vs women, 16.5±3.1 vs 16.0±2.5%, p=0.913, n=27.We conclude that obese men have lower hepatic, but comparable adipose tissue and peripheral tissue, insulin sensitivity compared to similarly obese women. Hepatic insulin resistance may

  20. Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure

    DEFF Research Database (Denmark)

    Petrie, John R; Malik, Muhammad Omar; Balkau, Beverley

    2013-01-01

    and Cardiovascular disease (RISC) study, we measured insulin sensitivity (M/I) using the euglycemic clamp technique in 1073 healthy European adults (587 women, 486 men) aged 30 to 60 years followed up 3 years later. Systolic BP (SBP) at baseline was higher in insulin-resistant women (ie, those in the low sex...

  1. Dietary fat and carbohydrates differentially alter insulin sensitivity during caloric restriction.

    Science.gov (United States)

    Kirk, Erik; Reeds, Dominic N; Finck, Brian N; Mayurranjan, S Mitra; Mayurranjan, Mitra S; Patterson, Bruce W; Klein, Samuel

    2009-05-01

    We determined the effects of acute and chronic calorie restriction with either a low-fat, high-carbohydrate (HC) diet or a low-carbohydrate (LC) diet on hepatic and skeletal muscle insulin sensitivity. Twenty-two obese subjects (body mass index, 36.5 +/- 0.8 kg/m2) were randomized to an HC (>180 g/day) or LC (vs 8.9% +/- 1.4%; P vs 7.2% +/- 1.4%; P vs 7.9% +/- 1.2%; P < .05). Insulin-mediated glucose uptake did not change at 48 hours but increased similarly in both groups after 7% weight loss (48.4% +/- 14.3%; P < .05). In both groups, insulin-stimulated phosphorylation of c-Jun-N-terminal kinase decreased by 29% +/- 13% and phosphorylation of Akt and insulin receptor substrate 1 increased by 35% +/- 9% and 36% +/- 9%, respectively, after 7% weight loss (all P < .05). Moderate calorie restriction causes temporal changes in liver and skeletal muscle metabolism; 48 hours of calorie restriction affects the liver (IHTG content, hepatic insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

  2. Effects of turtle oil on insulin sensitivity and glucose metabolism in insulin resistant cell model

    International Nuclear Information System (INIS)

    Bai Jing; Tian Yaping; Guo Duo

    2007-01-01

    To evaluate the effects of turtle oil on insulin sensitivity and glucose metabolism in an insulin-resistant (IR) cell model which was established by the way of high concentration of insulin induction with HepG 2 cell in vitro culture. The IR cells were treated by turtle oil, the glucose consumption and 3 H-D-glucose incorporation rate in IR cells were detected by the way of glucose oxidase and 3 H-D-glucose incorporation assay respectively. The state of cell proliferation was tested by MTT method. The results showed that the incorporation rate of 3 H-D-glucose in IR cells was significantly lower than that in the control cells(P 3 H-D-glucose incorporation rate in either IR cells or control cells was increased with the increase of insulin concentration. Moreover, the 3 H-D-glucose incorporation rate of IR cells increased slower than that of control cells. The MTT assay showed that turtle oil can promote the proliferation of IR cell and control cell. The glucose uptake and glucose consumption in IR cell which treated with turtle oil was significantly increase than that in the control cells (P<0.05). Turtle oil can improve the insulin sensitivity and glucose metabolism in the IR cell model. (authors)

  3. A two-week reduction of ambulatory activity attenuates peripheral insulin sensitivity

    DEFF Research Database (Denmark)

    Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa

    2009-01-01

    after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the two-week period induced a 7% decline in VO2max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and truck, decreased concurrently. Taken together, one...... possible biological cause for the public health problem of type 2 diabetes has been identified. Reduced ambulatory activity for two weeks in healthy, non-exercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass. Key words: Inactivity, Insulin...... number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAkt(thr308)/total Akt decreased...

  4. Factors Influencing or Discouraging Secondary School Students' FFA Participation

    Science.gov (United States)

    Phelps, Kirstin; Henry, Anna L.; Bird, William A.

    2012-01-01

    Modern adolescents are faced with a variety of choices regarding how to spend their free time. As recruitment and increased student participation continues to be a major priority of the National FFA Organization, it is essential to explore the reasons why students make the choice to become or not to become a member of FFA. This study was a part of…

  5. Grizzly bears exhibit augmented insulin sensitivity while obese prior to a reversible insulin resistance during hibernation.

    Science.gov (United States)

    Nelson, O Lynne; Jansen, Heiko T; Galbreath, Elizabeth; Morgenstern, Kurt; Gehring, Jamie Lauren; Rigano, Kimberly Scott; Lee, Jae; Gong, Jianhua; Shaywitz, Adam J; Vella, Chantal A; Robbins, Charles T; Corbit, Kevin C

    2014-08-05

    The confluence of obesity and diabetes as a worldwide epidemic necessitates the discovery of new therapies. Success in this endeavor requires translatable preclinical studies, which traditionally employ rodent models. As an alternative approach, we explored hibernation where obesity is a natural adaptation to survive months of fasting. Here we report that grizzly bears exhibit seasonal tripartite insulin responsiveness such that obese animals augment insulin sensitivity but only weeks later enter hibernation-specific insulin resistance (IR) and subsequently reinitiate responsiveness upon awakening. Preparation for hibernation is characterized by adiposity coupled to increased insulin sensitivity via modified PTEN/AKT signaling specifically in adipose tissue, suggesting a state of "healthy" obesity analogous to humans with PTEN haploinsufficiency. Collectively, we show that bears reversibly cope with homeostatic perturbations considered detrimental to humans and describe a mechanism whereby IR functions not as a late-stage metabolic adaptation to obesity, but rather a gatekeeper of the fed-fasting transition. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. Insulin sensitivity and carotid intima-media thickness

    DEFF Research Database (Denmark)

    Kozakova, Michaela; Natali, Andrea; Dekker, Jacqueline

    2013-01-01

    Despite a wealth of experimental data in animal models, the independent association of insulin resistance with early carotid atherosclerosis in man has not been demonstrated. APPROACH AND RESULTS: We studied a European cohort of 525 men and 655 women (mean age, 44±8 years) free of conditions known...... to affect carotid wall (diabetes mellitus, hypertension, and dyslipidemia). All subjects received an oral glucose tolerance test, a euglycemic hyperinsulinemic clamp (M/I as a measure of insulin sensitivity), and B-mode carotid ultrasound. In 833 participants (380 men), the carotid ultrasound was repeated...

  7. [Metabolic profile in obese patients with obstructive sleep apnea. A comparison between patients with insulin resistance and with insulin sensitivity].

    Science.gov (United States)

    Dumitrache-Rujinski, Stefan; Dinu, Ioana; Călcăianu, George; Erhan, Ionela; Cocieru, Alexandru; Zaharia, Dragoş; Toma, Claudia Lucia; Bogdan, Miron Alexandru

    2014-01-01

    Obstructive sleep apnea syndrome (OSAS) may induce metabolic abnormalities through intermittent hypoxemia and simpathetic activation. It is difficult to demonstrate an independent role of OSAS in the occurrence of metabolic abnormalities, as obesity represents an important risk factor for both OSAS and metabolic abnormalities. to assess the relations between insulin resistance (IR), insulin sensitivity (IS), OSAS severity and nocturnal oxyhaemoglobin levels in obese, nondiabetic patients with daytime sleepiness. We evaluated 99 consecutive, obese, nondiabetic patients (fasting glycemia 5/hour and daytime sleepiness) by an ambulatory six channel cardio-respiratory polygraphy. Hight, weight serum triglycerides (TG), high density lipoprotein-cholesterol (HDL-C) levels were evaluated. Correlations between Apneea Hypopnea Index (AHI), Oxygen Desaturation Index (ODI), average and lowest oxyhaemoglobin saturation (SaO), body mass index (BMI) and insulin resistance or sensitivity were assesed. IR was defined as a TG/ HDL-Cratio > 3, and insulin sensitivity (IS) as a TG/HDL-C ratio obese nondiabetic patients. Preserving insulin sensitivity is more likely when oxyhaemoglobin levels are higher and ODI is lower. Mean lowest nocturnal SaO2 levels seems to be independently involved in the development of insulin resistance as no statistically significant differences were found for BMI between the two groups.

  8. Similar weight-adjusted insulin secretion and insulin sensitivity in short-duration late autoimmune diabetes of adulthood (LADA) and Type 2 diabetes

    DEFF Research Database (Denmark)

    Juhl, C B; Bradley, U; Holst, Jens Juul

    2014-01-01

    AIMS: To explore insulin sensitivity and insulin secretion in people with latent autoimmune diabetes in adulthood (LADA) compared with that in people with Type 2 diabetes. METHODS: A total of 12 people with LADA, defined as glutamic acid decarboxylase (GAD) antibody positivity and > 1 year...... of insulin independency (group A) were age-matched pairwise to people with Type 2 diabetes (group B) and to six people with Type 2 diabetes of similar age and BMI (group C). β-cell function (first-phase insulin secretion and assessment of insulin pulsatility), insulin sensitivity (hyperinsulinemic......-euglycemic clamp) and metabolic response during a mixed meal were studied. RESULTS: Both first-phase insulin secretion and insulin release during the meal were greater (P = 0.05 and P = 0.009, respectively) in Type 2 diabetes as compared with LADA; these differences were lost on adjustment for BMI (group C...

  9. Effect of Artemisia dracunculus Administration on Glycemic Control, Insulin Sensitivity, and Insulin Secretion in Patients with Impaired Glucose Tolerance.

    Science.gov (United States)

    Méndez-Del Villar, Miriam; Puebla-Pérez, Ana M; Sánchez-Peña, María J; González-Ortiz, Luis J; Martínez-Abundis, Esperanza; González-Ortiz, Manuel

    2016-05-01

    To evaluate the effect of Artemisia dracunculus on glycemic control, insulin sensitivity, and insulin secretion in patients with impaired glucose tolerance (IGT). A randomized, double blind, placebo-controlled clinical trial was performed in 24 patients with diagnosis of IGT. Before and after the intervention, glucose and insulin levels were measured every 30 min for 2 h after a 75-g dextrose load, along with glycated hemoglobin A1c (A1C) and lipid profile. Twelve patients received A. dracunculus (1000 mg) before breakfast and dinner for 90 days; the remaining 12 patients received placebo. Area under the curve (AUC) of glucose and insulin, total insulin secretion, first phase of insulin secretion, and insulin sensitivity were calculated. Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests were used for statistical analyses. The institutional ethics committee approved the protocol. After A. dracunculus administration, there were significant decreases in systolic blood pressure (SBP; 120.0 ± 11.3 vs. 113.0 ± 11.2 mmHg, P AUC of insulin (56,136.0 ± 27,426.0 vs. 44,472.0 ± 23,370.0 pmol/L, P AUC of insulin, and total insulin secretion with a significant increase in HDL-C levels.

  10. Correlations between insulin sensitivity and bone mineral density in non-diabetic men

    DEFF Research Database (Denmark)

    Abrahamsen, B.; Rohold, A.; Henriksen, Jan Erik

    2000-01-01

    AIMS: To investigate relationships between bone mineral density (BMD), insulin secretion and insulin sensitivity, controlling for body composition, in view of data suggesting that hyperglycaemia [corrected] leads to decreased osteoblast proliferation and a negative calcium balance and that insulin...

  11. Genetic Variants Associated With Glycine Metabolism and Their Role in Insulin Sensitivity and Type 2 Diabetes

    NARCIS (Netherlands)

    Xie, W.J.; Wood, A.R.; Lyssenko, V.; Weedon, M.N.; Knowles, J.W.; Alkayyali, S.; Assimes, T.L.; Quertermous, T.; Abbasi, F.; Paananen, J.; Haring, H.; Hansen, T.; Pedersen, O.; Smith, U.; Laakso, M.; Dekker, J.M.; Nolan, J.J.; Groop, L.; Ferrannini, E.; Adam, K.P.; Gall, W.E.; Frayling, T.M.; Walker, M.

    2013-01-01

    Circulating metabolites associated with insulin sensitivity may represent useful biomarkers, but their causal role in insulin sensitivity and diabetes is less certain. We previously identified novel metabolites correlated with insulin sensitivity measured by the hyperinsulinemic-euglycemic clamp.

  12. Free Fatty Acid Receptor 1 (FFA1/GPR40) Agonists

    DEFF Research Database (Denmark)

    Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian

    2012-01-01

    FFA1 (GPR40) is a new target for treatment of type 2 diabetes. We recently identified the potent FFA1 agonist TUG-469 (5). Inspired by the structurally related TAK-875, we explored the effects of a mesylpropoxy appendage on 5. The appendage significantly lowers lipophilicity and improves metaboli...

  13. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

    Science.gov (United States)

    Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

    2017-11-01

    Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  14. Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity.

    Directory of Open Access Journals (Sweden)

    Aprilianto E Wiria

    Full Text Available Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth (STH-infected subjects are more insulin sensitive than STH-uninfected subjects.We performed a cross-sectional study on Flores island, Indonesia, an area with high prevalence of STH infections.From 646 adults, stool samples were screened for Trichuris trichiura by microscopy and for Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale, and Strongyloides stercoralis by qPCR. No other helminth was found. We collected data on body mass index (BMI, kg/m2, waist-to-hip ratio (WHR, fasting blood glucose (FBG, mmol/L, insulin (pmol/L, high sensitive C-reactive protein (ng/ml and Immunoglobulin E (IU/ml. The homeostatic model assessment for insulin resistance (HOMAIR was calculated and regression models were used to assess the association between STH infection status and insulin resistance.424 (66% participants had at least one STH infection. STH infected participants had lower BMI (23.2 vs 22.5 kg/m2, p value = 0.03 and lower HOMAIR (0.97 vs 0.81, p value = 0.05. In an age-, sex- and BMI-adjusted model a significant association was seen between the number of infections and HOMAIR: for every additional infection with STH species, the HOMAIR decreased by 0.10 (p for linear trend 0.01. This effect was mainly accounted for by a decrease in insulin of 4.9 pmol/L for every infection (p for trend = 0.07.STH infections are associated with a modest improvement of insulin sensitivity, which is not accounted for by STH effects on BMI alone.

  15. Novel approach for streamflow forecasting using a hybrid ANFIS-FFA model

    Science.gov (United States)

    Yaseen, Zaher Mundher; Ebtehaj, Isa; Bonakdari, Hossein; Deo, Ravinesh C.; Danandeh Mehr, Ali; Mohtar, Wan Hanna Melini Wan; Diop, Lamine; El-shafie, Ahmed; Singh, Vijay P.

    2017-11-01

    The present study proposes a new hybrid evolutionary Adaptive Neuro-Fuzzy Inference Systems (ANFIS) approach for monthly streamflow forecasting. The proposed method is a novel combination of the ANFIS model with the firefly algorithm as an optimizer tool to construct a hybrid ANFIS-FFA model. The results of the ANFIS-FFA model is compared with the classical ANFIS model, which utilizes the fuzzy c-means (FCM) clustering method in the Fuzzy Inference Systems (FIS) generation. The historical monthly streamflow data for Pahang River, which is a major river system in Malaysia that characterized by highly stochastic hydrological patterns, is used in the study. Sixteen different input combinations with one to five time-lagged input variables are incorporated into the ANFIS-FFA and ANFIS models to consider the antecedent seasonal variations in historical streamflow data. The mean absolute error (MAE), root mean square error (RMSE) and correlation coefficient (r) are used to evaluate the forecasting performance of ANFIS-FFA model. In conjunction with these metrics, the refined Willmott's Index (Drefined), Nash-Sutcliffe coefficient (ENS) and Legates and McCabes Index (ELM) are also utilized as the normalized goodness-of-fit metrics. Comparison of the results reveals that the FFA is able to improve the forecasting accuracy of the hybrid ANFIS-FFA model (r = 1; RMSE = 0.984; MAE = 0.364; ENS = 1; ELM = 0.988; Drefined = 0.994) applied for the monthly streamflow forecasting in comparison with the traditional ANFIS model (r = 0.998; RMSE = 3.276; MAE = 1.553; ENS = 0.995; ELM = 0.950; Drefined = 0.975). The results also show that the ANFIS-FFA is not only superior to the ANFIS model but also exhibits a parsimonious modelling framework for streamflow forecasting by incorporating a smaller number of input variables required to yield the comparatively better performance. It is construed that the FFA optimizer can thus surpass the accuracy of the traditional ANFIS model in general

  16. Acupuncture treatment for insulin sensitivity of women with polycystic ovary syndrome and insulin resistance: a study protocol for a randomized controlled trial.

    Science.gov (United States)

    Li, Juan; Ng, Ernest Hung Yu; Stener-Victorin, Elisabet; Hu, Zhenxing; Shao, Xiaoguang; Wang, Haiyan; Li, Meifang; Lai, Maohua; Xie, Changcai; Su, Nianjun; Yu, Chuyi; Liu, Jia; Wu, Taixiang; Ma, Hongxia

    2017-03-09

    Our prospective pilot study of acupuncture affecting insulin sensitivity on polycystic ovary syndrome (PCOS) combined with insulin resistance (IR) showed that acupuncture had a significant effect on improving the insulin sensitivity of PCOS. But there is still no randomized controlled trial to determine the effect of acupuncture on the insulin sensitivity in women with PCOS and IR. In this article, we present the protocol of a randomized controlled trial to compare the effect of true acupuncture on the insulin sensitivity of these patients compared with metformin and sham acupuncture. Acupuncture may be an effective therapeutic alternative that is superior to metformin and sham acupuncture in improving the insulin sensitivity of PCOS combined with IR. This study is a multi-center, controlled, double-blind, and randomized clinical trial aiming to evaluate the effect of acupuncture on the insulin sensitivity in PCOS combined with IR. In total 342 patients diagnosed with PCOS and IR will be enrolled. Participants will be randomized to one of the three groups: (1) true acupuncture + metformin placebo; (2) sham acupuncture + metformin, and (3) sham acupuncture + metformin placebo. Participants and assessors will be blinded. The acupuncture intervention will be given 3 days per week for a total of 48 treatment sessions during 4 months. Metformin (0.5 g per pill) or placebo will be given, three times per day, and for 4 months. Primary outcome measures are changes in homeostasis model assessment of insulin resistance (HOMA-IR) and improvement rate of HOMA-IR by oral glucose tolerance test (OGTT) and insulin releasing test (Ins). Secondary outcome measures are homeostasis model assessment-β (HOMA-β), area under the curve for glucose and insulin, frequency of regular menstrual cycles and ovulation, body composition, metabolic profile, hormonal profile, questionnaires, side effect profile, and expectation and credibility of treatment. Outcome measures are

  17. Inside ISIS II

    CERN Multimedia

    1981-01-01

    ISIS stands for Identification of Secondaries by Ionization Sampling. It was a drift chamber with an active volume of about 40 m3 built by Oxford University as a particle identifier for the European Hybrid Spectrometer (EHS). The photo shows the electrostatic grading structure and the central anode-wire plane, with Roger Giles standing just under it (Annual Report 1981 p. 57, Fig. 4). ISIS-II differed from the prototype ISIS-I only in the depth of the track (4 m instead of 1 m) thus extending the momentum range for particle identification to 50 GeV/c. See Nucl. Instr. and Meth. 224 (1984) 396, and Nucl. Instr. and Meth. 258 (1987) 26.

  18. United States Counterterrorism on ISIS

    Directory of Open Access Journals (Sweden)

    ANTON MYNARDY

    2016-05-01

    Full Text Available The U.S. counter terrorism on ISIS had implemented with various strategies including degrading ISIS’s capability, shaping global coalition to defeat ISIS, and using trained military armed men for Iraq army forces, Kurdi army, Arabian army, and moderate opposition groups to fight against Bassar. In early 2015, U.S. government described the group as “losing this fight” and reported that anti- ISIS operations had killed more than 8,500 fighters, destroyed hundreds of vehicles and heavy weapons systems, and significantly degraded IS command and control capabilities. Unfortunately, ISIS still exists with their weapons. Moreover, the fear against ISIS and the worst conditions it brings are not exclusive in Syria, Iraq and Libya as the conflict has already spread to many countries in Europe. These countries are in dilemma because despite being affected by the conflict, still they intend to give asylum to the refugees, but their concern is that with refugees coming in, there might be exporting of ISIS’s ideologies which leads to bigger and more serious concerns than the possibility of economic instability. Inevitably, there have been questions regarding the existence of ISIS today: How can groups such as ISIS still exists despite being attacked for 3 years by the U.S? The reality is that the U.S. initiated the establishment of new and democratic governments in Afghanistan, Iraq, and Libya few years ago bothers some experts on the continuing existence of ISIS.

  19. Electroacupuncture and Rosiglitazone Combined Therapy as a Means of Treating Insulin Resistance and Type 2 Diabetes Mellitus: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Rong-Tsung Lin

    2013-01-01

    Full Text Available Aims. To evaluate the efficacy of rosiglitazone (TZD and electroacupuncture (EA combined therapy as a treatment for type 2 diabetes mellitus (T2DM patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N=15 and the experimental group (TZD + EA, N=16. Changes in their plasma free fatty acid (FFA, glucose, and insulin levels, together with their homeostasis model assessment (HOMA indices, were statistically compared before and after treatment. Hypoglycemic activity (% was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

  20. Dissociation of in vitro sensitivities of glucose transport and antilipolysis to insulin in NIDDM

    International Nuclear Information System (INIS)

    Yki-Jaervinen, H.; Kubo, K.; Zawadzki, J.; Lillioja, S.; Young, A.; Abbott, W.; Foley, J.E.

    1987-01-01

    It is unclear from previous studies whether qualitative or only quantitative differences exist in insulin action in adipocytes obtained from obese subjects with non-insulin-dependent diabetes mellitus (NIDDM) when compared with equally obese nondiabetic subjects. In addition, the role of changes in insulin binding as a cause of insulin resistance in NIDDM is still controversial. The authors compared the sensitivities of [ 14 C]-glucose transport and antilipolysis to insulin and measured [ 125 I]-insulin binding in abdominal adipocytes obtained from 45 obese nondiabetic, obese diabetic, and 15 nonobese female southwestern American Indians. Compared with the nonobese group, the sensitivities of glucose transport antilipolysis were reduced in both the obese nondiabetic and obese diabetic groups. Compared with the obese nondiabetic subjects, the ED 50 for stimulation of glucose transport was higher in the obese patients with NIDDM. In contrast, the ED 50 S for antilipolysis were similar in obese diabetic patients and obese nondiabetic subjects. No differences was found in insulin binding in patients with NIDDM when compared with the equally obese nondiabetic subjects. These data indicate 1) the mechanism of insulin resistance differs in NIDDM and obesity, and 2) the selective loss of insulin sensitivity in NIDDM precludes changes in insulin binding as a cause of insulin resistance in this disorder

  1. Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats.

    Science.gov (United States)

    Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

    2014-06-01

    We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment. Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress. We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats. Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2015-01-01

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

  3. The Proton-Activated Receptor GPR4 Modulates Glucose Homeostasis by Increasing Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Luca Giudici

    2013-11-01

    Full Text Available Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8 and is coupled to the production of cAMP. Methods: We examined mice lacking GPR4 and examined glucose tolerance and insulin sensitivity in young and aged mice as well as in mice fed with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines in white adipose tissue, liver and skeletal muscle was assessed. Results: Here we show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance test and increased insulin sensitivity. Insulin levels were comparable but leptin levels were increased in GPR4 KO mice. Gpr4-/- showed altered expression of PPARα, IL-6, IL-10, TNFα, and TGF-1β in skeletal muscle, white adipose tissue, and liver. High fat diet abolished the differences in glucose tolerance and insulin sensitivity between Gpr4+/+ and Gpr4-/- mice. In contrast, in aged mice (12 months old, the positive effect of GPR4 deficiency on glucose tolerance and insulin sensitivity was maintained. Liver and adipose tissue showed no major differences in the mRNA expression of pro- and anti-inflammatory factors between aged mice of both genotypes. Conclusion: Thus, GPR4 deficiency improves glucose tolerance and insulin sensitivity. The effect may involve an altered balance between pro- and anti-inflammatory factors in insulin target tissues.

  4. The Benefits of FFA Membership as Part of Agricultural Education

    Science.gov (United States)

    Rose, Chelsea; Stephens, Carrie A.; Stripling, Christopher; Cross, Tim; Sanok, Danielle E.; Brawner, Shelby

    2016-01-01

    The study sought to identify the benefits of FFA membership based on the fulfillment of three basic human needs: love and belonging, self-esteem, and self-actualization. The study focused on the fulfillment of FFA members' basic human needs as defined by Abraham Maslow. The three needs on which this study focused are: love and belonging,…

  5. Effects of Substituting Palm Olein with Carbohydrates on Insulin Sensitivity: A Review

    International Nuclear Information System (INIS)

    Kim-Tiu, T.; Faun, C.L.

    2016-01-01

    The role of palm olein on insulin resistance, which predisposes to disease progression of type 2 diabetes, is unclear. This article summarises the effects of substituting palm olein with carbohydrates on insulin sensitivity. Two intervention studies have reported conflicting findings. The RISCK (Reading, Imperial, Surreys, Cambridge and King's) study suggested that saturated fat-enriched diet consisting of mainly palm oil and milk fat did not differ from both high and low glycemic carbohydrates on insulin sensitivity in subjects at risk of developing metabolic syndrome. However, another study reported reduced insulin sensitivity after a diet enriched with palm olein and butter compared with high carbohydrate intake. No epidemiological data exists in this context. More clinical trials using solely palm olein in this area are needed. Further well-controlled large scale studies are needed to furnish the information on palm olein replacement with carbohydrates in diabetes prevention. (author)

  6. Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Xuemei Shi

    2017-11-01

    Conclusions: We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity.

  7. Vasoconstrictor effect of high FFA/albumin ratios in adipose tissue in vivo

    DEFF Research Database (Denmark)

    Bülow, J; Madsen, J; Astrup, A

    1985-01-01

    Subcutaneous or perirenal adipose tissue blood flow was measured with the 133Xe-washout technique before and after intravenous injection or infusion of Intralipid in six anesthetized, otherwise intact mongrel dogs. In four anesthetized mongrel puppies adipose tissue blood flow was measured...... as well as in young dogs after this treatment. The administration of Intralipid did not per se induce the vasoconstriction. The vasoconstriction took place simultaneously with increasing FFA/albumin molar ratios. The results support our previous findings in perfused fat pads that high molar FFA....../albumin ratios increase vascular resistance in adipose tissue and they give further support to our suggestion that this vasoconstriction may be a link in a negative-feedback mechanism regulating FFA-mobilization in relation to FFA utilization....

  8. The Role of lysophosphatidic acide (LPA) in the insulin resistence of the pancreatic β-cells

    OpenAIRE

    Mourad Agha, Zein

    2016-01-01

    The pathogenesis of the type-2-diabetes mellitus underlying is characterized by a combination of peripheral insulin resistance, β-cell dysfunction and reduction in the β cell mass. The increasing of FFA level or their metabolites lead to inhibition of insulin signaling. Consequent, the ability of insulin is reduced and therefore lead to insulin resistance. LPA is a lipid mediator that is associated with a progression of T2D. It has been suggested that LPA and the development of obesity are st...

  9. Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Suksomboon N

    2017-05-01

    Full Text Available Naeti Suksomboon,1 Nalinee Poolsup,2 Htoo Darli Ko Ko1 1Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon-Pathom, Thailand Objective: To perform a systematic review and meta-analysis of randomized, placebo-controlled trials to assess the effect of vitamin K supplementation on insulin sensitivity.Data sources: MEDLINE, the Cochrane Library, CINAHL, Web of Science, Scopus, clinicaltrials.gov, and clinicaltrialresults.org were searched up to January 2017. Reference lists of related papers were also scanned.Study selection: Randomized controlled trials were selected if they compared vitamin K supplementation with placebo or no treatment and reported homeostasis model assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein, adiponectin, leptin, or interleukin-6 levels.Data extraction: Data extraction and study quality assessment were performed independently by two investigators using a standardized data extraction form. Any inconsistencies were resolved by a third reviewer. Effect estimates were pooled using inverse-variance weighted method. Heterogeneity was assessed by the I2 and Q statistic.Results: A total of eight trials involving 1,077 participants met the inclusion criteria. A wide variety of participants were enrolled, including older men, postmenopausal women, prediabetic premenopausal women, and participants with a history of diabetes, hypertension, or vascular disease. Vitamin K1 and vitamin K2 (MK-4 and MK-7 subtypes were assessed. Supplementation period ranged from 4 weeks to 3 years. Vitamin K supplementation did not affect insulin sensitivity as measured by homeostasis model assessment of insulin resistance, fasting plasma glucose, fasting plasma insulin, C-reactive protein, adiponectin, leptin, and interleukin-6 levels.Conclusion: Our analysis suggests no effect of vitamin K

  10. A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity

    DEFF Research Database (Denmark)

    Krogh-Madsen, Rikke; Thyfault, John P; Broholm, Christa

    2010-01-01

    decreased after step reduction, with a post hoc analysis revealing the most pronounced effect after 4 h of insulin infusion. In addition, the 2-wk period induced a 7% decline in VO2 max (ml/min; cardiovascular fitness). Lean mass of legs, but not arms and trunk, decreased concurrently. Taken together, one...... possible biological cause for the public health problem of Type 2 diabetes has been identified. Reduced ambulatory activity for 2 wk in healthy, nonexercising young men significantly reduced peripheral insulin sensitivity, cardiovascular fitness, and lean leg mass........ A reduced number of daily steps induced a significant reduction of 17% in the glucose infusion rate (GIR) during the clamp. This reduction was due to a decline in peripheral insulin sensitivity with no effect on hepatic endogenous glucose production. The insulin-stimulated ratio of pAktthr308/total Akt...

  11. One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus.

    Science.gov (United States)

    van Asseldonk, Edwin J P; van Poppel, Pleun C M; Ballak, Dov B; Stienstra, Rinke; Netea, Mihai G; Tack, Cees J

    2015-10-01

    Inflammation associated with obesity is involved in the development of insulin resistance. We hypothesized that anti-inflammatory treatment with the Interleukin-1 receptor antagonist anakinra would improve insulin sensitivity. In an open label proof-of-concept study, we included overweight patients diagnosed with type 1 diabetes with an HbA1c level over 7.5%. Selecting insulin resistant patients with longstanding type 1 diabetes allowed us to study the effects of anakinra on insulin sensitivity. Patients were treated with 100mg anakinra daily for one week. Insulin sensitivity, insulin need and blood glucose profiles were measured before, after one week and after four weeks of follow-up. Fourteen patients completed the study. One week of anakinra treatment led to an improvement of insulin sensitivity, an effect that was sustained for four weeks. Similarly, glucose profiles, HbA1c levels and insulin needs improved. In conclusion, one week of treatment with anakinra improves insulin sensitivity in patients with type 1 diabetes. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Short-Term Exercise Training Improves Insulin Sensitivity but Does Not Inhibit Inflammatory Pathways in Immune Cells from Insulin-Resistant Subjects

    Directory of Open Access Journals (Sweden)

    Sara M. Reyna

    2013-01-01

    Full Text Available Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD. Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC were obtained for determination of Toll-like receptor (TLR 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

  13. Short-term exercise training improves insulin sensitivity but does not inhibit inflammatory pathways in immune cells from insulin-resistant subjects.

    Science.gov (United States)

    Reyna, Sara M; Tantiwong, Puntip; Cersosimo, Eugenio; Defronzo, Ralph A; Sriwijitkamol, Apiradee; Musi, Nicolas

    2013-01-01

    Background. Exercise has an anti-inflammatory effect against, and immune cells play critical roles in the development, of insulin resistance and atherosclerotic vascular disease (AVD). Thus, the goal of this study was to determine whether exercise improves insulin sensitivity in insulin-resistant subjects by downregulating proinflammatory signaling in immune cells. Methods. Seventeen lean, 8 obese nondiabetic, and 11 obese type 2 diabetic individuals underwent an aerobic exercise program for 15 days and an insulin clamp before and after exercise. Peripheral mononuclear cells (PMNC) were obtained for determination of Toll-like receptor (TLR) 2 and 4 protein content and mitogen-activated protein kinase phosphorylation. Results. Compared with that in lean individuals, TLR4 protein content was increased by 4.2-fold in diabetic subjects. This increase in TLR4 content was accompanied by a 3.0-fold increase in extracellular signal-regulated kinase (ERK) phosphorylation. Exercise improved insulin sensitivity in the lean, obese, and type 2 diabetes groups. However, exercise did not affect TLR content or ERK phosphorylation. Conclusions. TLR4 content and ERK phosphorylation are increased in PMNC of type 2 diabetic individuals. While exercise improves insulin sensitivity, this effect is not related to changes in TLR2/TLR4 content or ERK phosphorylation in PMNC of type 2 diabetic individuals.

  14. 4-H & FFA Livestock Projects: Life Skills Gained and Knowledge Learned

    Directory of Open Access Journals (Sweden)

    Lyle N. Holmgren

    2007-06-01

    Full Text Available Junior Livestock shows are one of the most popular 4-H and FFA projects in Utah. Thousands of youth participate in these shows from every county in Utah. County extension agents and FFA advisors spend much time with livestock committees, leaders, parents, and youth engaged in livestock shows. Can public funds spent on salaries be justified for county 4-H extension agents and FFA advisors who work with junior livestock shows? To help answer this question, 413 youth involved in livestock shows in Utah were surveyed in 2001. Youth were asked to share skills learned from their livestock projects. Value statements along with specific content skills were measured in the survey. The results indicate that from their 4-H and FFA projects, youth learned to accept responsibility, follow instructions, gain self-confidence, follow instructions, “do the right thing” as well as a variety of other values and content skills.

  15. AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

    Science.gov (United States)

    Steculorum, Sophie M; Ruud, Johan; Karakasilioti, Ismene; Backes, Heiko; Engström Ruud, Linda; Timper, Katharina; Hess, Martin E; Tsaousidou, Eva; Mauer, Jan; Vogt, Merly C; Paeger, Lars; Bremser, Stephan; Klein, Andreas C; Morgan, Donald A; Frommolt, Peter; Brinkkötter, Paul T; Hammerschmidt, Philipp; Benzing, Thomas; Rahmouni, Kamal; Wunderlich, F Thomas; Kloppenburg, Peter; Brüning, Jens C

    2016-03-24

    Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Differential regulation of PGC-1α expression in rat liver and skeletal muscle in response to voluntary running

    Directory of Open Access Journals (Sweden)

    Azhar Salman

    2010-04-01

    Full Text Available Abstract Background The beneficial actions of exercise training on lipid, glucose and energy metabolism and insulin sensitivity appear to be in part mediated by PGC-1α. Previous studies have shown that spontaneously exercised rats show at rest enhanced responsiveness to exogenous insulin, lower plasma insulin levels and increased skeletal muscle insulin sensitivity. This study was initiated to examine the functional interaction between exercise-induced modulation of skeletal muscle and liver PGC-1α protein expression, whole body insulin sensitivity, and circulating FFA levels as a measure of whole body fatty acid (lipid metabolism. Methods Two groups of male Wistar rats (2 Mo of age, 188.82 ± 2.77 g BW were used in this study. One group consisted of control rats placed in standard laboratory cages. Exercising rats were housed individually in cages equipped with running wheels and allowed to run at their own pace for 5 weeks. At the end of exercise training, insulin sensitivity was evaluated by comparing steady-state plasma glucose (SSPG concentrations at constant plasma insulin levels attained during the continuous infusion of glucose and insulin to each experimental group. Subsequently, soleus and plantaris muscle and liver samples were collected and quantified for PGC-1α protein expression by Western blotting. Collected blood samples were analyzed for glucose, insulin and FFA concentrations. Results Rats housed in the exercise wheel cages demonstrated almost linear increases in running activity with advancing time reaching to maximum value around 4 weeks. On an average, the rats ran a mean (Mean ± SE of 4.102 ± 0.747 km/day and consumed significantly more food as compared to sedentary controls (P P P P Conclusion These data suggest that PGC-1α most likely plays a restricted role in exercise-mediated improvements in insulin resistance (sensitivity and lowering of circulating FFA levels.

  17. Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation.

    Science.gov (United States)

    Zhang, Dongmei; Zhang, Li; Yue, Fangzhi; Zheng, Yingying; Russell, Ryan

    2015-01-01

    Evidence suggests that increased gut permeability may be associated with polycystic ovary syndrome (PCOS). Human zonulin is currently the only physiological mediator known to reversibly regulate gut permeability by disassembling intestinal tight junctions. So far, no data on serum zonulin levels in patients with PCOS are available. This study aimed to determine circulating serum zonulin levels in women with PCOS and discuss the relationship between zonulin, insulin resistance, and menstrual disorders in this group. A case-control study. The study includes 78 women recently diagnosed with PCOS and 63 age-matched healthy controls recruited. Serum zonulin levels were determined by ELISA. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda and DeFronzo's insulin sensitivity index (ISI). PCOS women had higher serum zonulin levels (P=0.022). After adjustment for age and BMI, zonulin levels significantly correlated with HOMA-IR and ISI. Furthermore, PCOS women with more severe menstrual disorders had significantly higher zonulin levels and displayed an inverse correlation between zonulin and the number of menstrual cycles per year (r=-0.398, Pzonulin, a biomarker for gut permeability, is increased in PCOS women and correlates with insulin resistance and severity of menstrual disorders. It suggests that alterations in gut permeability may play a role in the pathophysiology of PCOS, and serum zonulin might be used as a biomarker for both risk stratification and therapeutic outcomes in PCOS women. © 2015 European Society of Endocrinology.

  18. Student Self-Perceptions of Leadership in Two Missouri FFA Chapters: A Collective Case Study

    Science.gov (United States)

    Kagay, Rachel Bartholomew; Marx, Adam A.; Simonsen, Jon C.

    2015-01-01

    The focus of this study is the self-perceptions of leadership engagement of FFA members in two FFA chapters in Missouri. This multiple case study used documentation of student self-perceptions, researcher observations, and focus groups. The two cases included 24 high school students comprised of FFA officers and members, who provided their…

  19. Examining Year-Long Leadership Gains in FFA Members by Prior FFA Involvement, Class Year, and Gender

    Science.gov (United States)

    Rosch, David; Simonsen, Jon C.; Velez, Jonathan J.

    2015-01-01

    Students (N = 160) in three diverse FFA chapters were surveyed in early fall, midwinter, and late spring in regard to their leadership skills, confidence in leading, and motivation to engage in leadership-oriented behaviors. The results indicated small-to-moderate gains in transformational leadership skill and a marginally significant…

  20. Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

    Science.gov (United States)

    Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

    2014-06-01

    Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

  1. ISIS annual report

    International Nuclear Information System (INIS)

    Biggin, Sue

    1986-07-01

    The paper is the first 1985/6 report of the ISIS experimental facility for neutron scattering studies, which commenced operations June 1985, at the Rutherford Laboratory, United Kingdom. The report is divided into eight chapters, including: 1) accelerator, target station and moderators, 2) instruments and related science, 3) techniques, 4) future developments, 5) condensed matter theory research, 6) ISIS organisation and user interaction, 7) publications, and 8) experimental reports. (UK)

  2. Liraglutide increases FGF-21 activity and insulin sensitivity in high fat diet and adiponectin knockdown induced insulin resistance.

    Directory of Open Access Journals (Sweden)

    Mengliu Yang

    Full Text Available BACKGROUND: Liraglutide is a glucagon-like peptide-1 analogue that stimulates insulin secretion and improves β-cell function. However, it is not clear whether liraglutide achieves its glucose lowering effect only by its known effects or whether other as yet unknown mechanisms are involved. The aim of this study was to examine the effects of liraglutide on Fibroblast growth factor-21 (FGF-21 activity in High-fat diet (HFD fed ApoE(-/- mice with adiponectin (Acrp30 knockdown. METHOD: HFD-fed ApoE(-/- mice were treated with adenovirus vectors expressing shAcrp30 to produce insulin resistance. Hyperinsulinemic-euglycemic clamp studies were performed to evaluate insulin sensitivity of the mouse model. QRT-PCR and Western blot were used to measure the mRNA and protein expression of the target genes. RESULTS: The combination of HFD, ApoE deficiency, and hypoadiponectinemia resulted in an additive effect on insulin resistance. FGF-21 mRNA expressions in both liver and adipose tissues were significantly increased while FGF-21 receptor 1 (FGFR-1 and β-Klotho mRNA levels in adipose tissue, as well as FGFR-1-3 and β-Klotho mRNA levels in liver were significantly decreased in this model. Liraglutide treatment markedly improved insulin resistance and increased FGF-21 expression in liver and FGFR-3 in adipose tissue, restored β-Klotho mRNA expression in adipose tissue as well as FGFR-1-3, β-Klotho levels and phosphorylation of FGFR1 up to the levels observed in control mice in liver. Liraglutide treatment also further increased FGF-21 proteins in liver and plasma. In addition, as shown by hyperinsulinemic-euglycemic clamp, liraglutide treatment also markedly improved glucose metabolism and insulin sensitivity in these animals. CONCLUSION: These findings demonstrate an additive effect of HFD, ApoE deficiency, and adiponectin knockdown on insulin resistance and unveil that the regulation of glucose metabolism and insulin sensitivity by liraglutide may be

  3. Fitting Vo-Ag and FFA Together Best for Students and Teachers.

    Science.gov (United States)

    Snyder, H. Leon

    1979-01-01

    The Future Farmers of America (FFA) is more than a leadership development organization and when used as an intracurricular activity, it can serve as a teaching tool. The FFA adds advantages to the program in areas such as supervised experience, award motivation, providing real world experience, public relations, travel, and competition. (LRA)

  4. The PPARα/γ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat

    Directory of Open Access Journals (Sweden)

    Kristina Wallenius

    2013-01-01

    Full Text Available Metabolic flexibility was assessed in male Zucker rats: lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR agonist, tesaglitazar, 3 μmol/kg/day for 3 weeks. Whole body glucose disposal rate ( and hepatic glucose output (HGO were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,3H]glucose. Indices of tissue specific glucose utilization ( were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-3H]glucose. Finally, whole body and tissue specific FFA and glucose utilization and metabolic fate were evaluated under basal and hyperinsulinemic conditions using a combination of [U-13C]glucose, 2-deoxy-D-[U-14C]glucose, [U-14C]palmitate, and [9,10-3H]-(R-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of compared to obese controls. This involved increased insulin stimulation of in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (, and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or compared to obese controls. In conclusion, the results demonstrate that tesaglitazar has a remarkable ability to improve insulin mediated control of glucose and FFA fluxes in obese Zucker rats.

  5. Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice

    OpenAIRE

    Bradley, Richard L.; Jeon, Justin Y.; Liu, Fen-Fen; Maratos-Flier, Eleftheria

    2008-01-01

    Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high suc...

  6. PROXIMITY TO DELIVERY ALTERS INSULIN SENSITIVITY AND GLUCOSE METABOLISM IN PREGNANT MICE

    OpenAIRE

    Musial, Barbara; Fernandez-Twinn, Denise S.; Vaughan, Owen R.; Ozanne, Susan E.; Voshol, Peter; Sferruzzi-Perri, Amanda N.; Fowden, Abigail L.

    2016-01-01

    In late pregnancy, maternal insulin resistance occurs to support fetal growth but little is known about insulin-glucose dynamics close to delivery. This study measured insulin sensitivity in mice in late pregnancy, day (D) 16, and near term, D19, (term 20.5D). Non-pregnant (NP) and pregnant mice were assessed for metabolite and hormone concentrations, body composition by dual energy X-ray absorptiometry, tissue insulin signalling protein abundance by Western blotting, glucose tolerance and ut...

  7. mTORC2 Regulation of Muscle Metabolism and Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kleinert, Maximilian

    and skeletal muscle to take up blood glucose, ultimately lowering blood glucose levels. A hallmark of T2D is decreased organ sensitivity to the effects of the insulin. Therefore, an early event in the pathogenesis of T2D is an increase in insulin secretion in response to eating a meal, as more insulin....... In the absence of insulin, the majority of GLUT4 resides within the muscle. Conversely, insulin stimulation increases the muscle’s permeability to glucose, by triggering GLUT4 translocation to the plasma membrane. The effect of insulin on GLUT4 translocation is mediated by a chain of molecular signaling events...... that mTORC2 controls skeletal muscle glycolysis and lipid storage. In agreement, Ric mKO mice exhibited reduced muscle glycolytic flux, greater reliance on fat as an energy substrate, re-partitioning of lean to fat mass and higher intramyocellular triacylglycerol (IMTG) levels compared to Ric WT mice...

  8. Lack of effect of long-term amlodipine on insulin sensitivity and plasma insulin in obese patients with essential hypertension

    DEFF Research Database (Denmark)

    de Courten, Maximilian; Ferrari, P; Schneider, M

    1993-01-01

    Method of Bergman, fasting plasma insulin and glucose concentrations, serum total triglyceride and lipoprotein cholesterol fractions, and blood pressure in 20 obese, non-diabetic patients with essential hypertension before and after 6 weeks of placebo and again after 6 months of amlodipine. Ten patients......To evaluate the effects of long-term treatment antihypertensive with the dihydropyridine calcium antagonist amlodipine on insulin sensitivity, plasma insulin, and lipoprotein metabolism in obese hypertensive patients. We measured the insulin sensitivity index (SI), determined by the Minimal Model...... [mean body mass index (BMI) 30.2 kg.m-2] had been on prior treatment with a thiazide diuretic in low dosage and/or a beta-adrenoceptor blocker (group A), and 10 matched patients [BMI 31.8 kg.m-2] had been previously untreated (group B). Amlodipine was started in a dose of 5 mg and was increased to 10 mg...

  9. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1

    International Nuclear Information System (INIS)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-01-01

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. - Highlights: • A novel model of liver-specific Prep1 knockout is established. • Ablation of Prep1 in hepatocytes increases insulin sensitivity. • Prep1 controls hepatic insulin sensitivity by regulating localization of FOXO1. • Prep1 regulates

  10. Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

    DEFF Research Database (Denmark)

    Hribal, M L; Presta, I; Procopio, T

    2011-01-01

    The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry.......The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry....

  11. Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

    Science.gov (United States)

    Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

    2013-01-01

    Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

  12. Effect of Ursolic Acid on Metabolic Syndrome, Insulin Sensitivity, and Inflammation.

    Science.gov (United States)

    Ramírez-Rodríguez, Alejandra M; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Acuña Ortega, Natalhie

    2017-09-01

    To evaluate the effect of ursolic acid on metabolic syndrome, insulin sensitivity, and inflammation, a randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (30-60 years) with a diagnosis of metabolic syndrome without treatment. They were randomly assigned to two groups of 12 patients, each to receive orally 150 mg of ursolic acid or homologated placebo once a day for 12 weeks. Before and after the intervention, the components of metabolic syndrome, insulin sensitivity (Matsuda index), and inflammation profile (interleukin-6 and C-reactive protein) were evaluated. After ursolic acid administration, the remission of metabolic syndrome occurred in 50% of patients (P = .005) with significant differences in body weight (75.7 ± 11.5 vs. 71 ± 11 kg, P = .002), body mass index (BMI) (29.9 + 3.6 vs. 24.9 ± 1.2 kg/m 2 , P = .049), waist circumference (93 ± 8.9 vs. 83 + 8.6 cm, P = .008), fasting glucose (6.0 ± 0.5 vs. 4.7 ± 0.4 mmol/L, P = .002), and insulin sensitivity (3.1 ± 1.1 vs. 4.2 ± 1.2, P = .003). Ursolic acid administration leads to transient remission of metabolic syndrome, reducing body weight, BMI, waist circumference and fasting glucose, as well as increasing insulin sensitivity.

  13. Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

    DEFF Research Database (Denmark)

    Petersen, Kresten R.; Christiansen, Erik; Madsbad, Sten

    1999-01-01

    systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S(I)), glucose effectiveness (S(g)), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after...... randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also...... included. Both compounds increased fasting plasma insulin and reduced S(i) but did not affect S(g). The relationships between S(i) and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We...

  14. Bilirubin Increases Insulin Sensitivity by Regulating Cholesterol Metabolism, Adipokines and PPARγ Levels

    Science.gov (United States)

    Liu, Jinfeng; Dong, Huansheng; Zhang, Yong; Cao, Mingjun; Song, Lili; Pan, Qingjie; Bulmer, Andrew; Adams, David B.; Dong, Xiao; Wang, Hongjun

    2015-01-01

    Obesity can cause insulin resistance and type 2 diabetes. Moderate elevations in bilirubin levels have anti-diabetic effects. This study is aimed at determining the mechanisms by which bilirubin treatment reduces obesity and insulin resistance in a diet-induced obesity (DIO) mouse model. DIO mice were treated with bilirubin or vehicle for 14 days. Body weights, plasma glucose, and insulin tolerance tests were performed prior to, immediately, and 7 weeks post-treatment. Serum lipid, leptin, adiponectin, insulin, total and direct bilirubin levels were measured. Expression of factors involved in adipose metabolism including sterol regulatory element-binding protein (SREBP-1), insulin receptor (IR), and PPARγ in liver were measured by RT-PCR and Western blot. Compared to controls, bilirubin-treated mice exhibited reductions in body weight, blood glucose levels, total cholesterol (TC), leptin, total and direct bilirubin, and increases in adiponectin and expression of SREBP-1, IR, and PPARγ mRNA. The improved metabolic control achieved by bilirubin-treated mice was persistent: at two months after treatment termination, bilirubin-treated DIO mice remained insulin sensitive with lower leptin and higher adiponectin levels, together with increased PPARγ expression. These results indicate that bilirubin regulates cholesterol metabolism, adipokines and PPARγ levels, which likely contribute to increased insulin sensitivity and glucose tolerance in DIO mice. PMID:26017184

  15. Plasma Levels of Myonectin But Not Myostatin or Fibroblast-Derived Growth Factor 21 Are Associated with Insulin Resistance in Adult Humans without Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Freddy J. K. Toloza

    2018-01-01

    Full Text Available BackgroundMyokines are a group of protein mediators produced by skeletal muscle under stress or physical exertion. Even though their discovery and effects in cell culture and animal models of disease have elicited great enthusiasm, very little is known about their role in human metabolism. We assessed whether plasma concentrations of three known myokines [myonectin, myostatin, and fibroblast-derived growth factor 21 (FGF-21] would be associated with direct and indirect indicators of insulin resistance (IR in individuals who did not have a diagnosis of diabetes.MethodsWe studied 81 adults of both sexes comprising a wide range of body adiposity and insulin sensitivity. All participants underwent a thorough clinical assessment and a 5-point oral glucose tolerance test with calculation of multiple IR and insulin sensitivity indices. Twenty-one of them additionally underwent a hyperinsulinemic–euglycemic clamp with determination of steady-state whole-body insulin-stimulated glucose disposal (“M”. We compared plasma myokine concentrations across quartiles of IR indices and clinical IR surrogates, and explored the correlation of each myokine with the M-value.ResultsPlasma myonectin levels increased monotonically across quartiles of the incremental area under the insulin curve (higher values indicate more IR (p-trend = 0.021 and decreased monotonically across quartiles of the insulin sensitivity index (ISI – higher values indicate less IR (p-trend = 0.012. After multivariate adjustment for other relevant determinants of IR (body mass index, age, and sex, the negative association of myonectin with ISI persisted (standardized beta = −0.235, p = 0.023. Myostatin was not associated with any clinical IR indicator or direct IR index measure. In multivariate analyses, FGF-21 showed a trend toward a positive correlation with glucose disposal that did not reach statistical significance (standardized beta = 0.476, p = 0

  16. The effect on design of ISI

    International Nuclear Information System (INIS)

    Hart, J.D.

    The evolution of in-service inspection techniques from the Magnox reactors through the AGR constructions is described. The following aspects are mentioned: general principles; factors that have influenced the development of ISI; objectives of ISI; examples drawn from AGR experience; major design changes to accommodate ISI; PWR reactors; occupational safety. (U.K.)

  17. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Larsen, J J; Mikines, K J

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... (glucose only). Adipose tissue blood flow was measured by (133)Xe washout. In the basal state, adipose tissue blood flow tended to be higher in T compared with S subjects, and in both groups blood flow was constant during the clamp. The change from basal in arterial-interstitial glucose concentration......-time: T, 44 +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P training enhances insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis...

  18. Loss-of-function myostatin mutation increases insulin sensitivity and browning of white fat in Meishan pigs.

    Science.gov (United States)

    Cai, Chunbo; Qian, Lili; Jiang, Shengwang; Sun, Youde; Wang, Qingqing; Ma, Dezun; Xiao, Gaojun; Li, Biao; Xie, Shanshan; Gao, Ting; Chen, Yaoxing; Liu, Jie; An, Xiaorong; Cui, Wentao; Li, Kui

    2017-05-23

    Myostatin-deficient mice showed a remarkable hypertrophy of skeletal muscle, with a decreased fat mass and enhanced insulin sensitivity. Currently, it is unclear if the inhibition of myostatin could be used as an approach to treat human obesity and insulin resistance. In this study, we investigated if the inhibition of porcine myostatin has any effect on fat deposition and insulin sensitivity using genetically engineered Meishan pigs containing a myostatin loss-of-function mutation (Mstn -/- ). Our results indicated that, when compared with wild-type pigs, the amount of subcutaneous fat and leaf fat of Mstn -/- pigs were significantly decreased mainly due to the browning of subcutaneous adipose tissue. Additionally, the serum insulin level decreased and the insulin sensitivity increased significantly in Mstn -/- pigs. Moreover, we found a significant increase in levels of insulin receptor and insulin receptor substrate proteins in skeletal muscle of Mstn -/- pigs, which then activating the insulin signaling pathway. Irisin-mediated regulation is not the only pathway for the activation of insulin signal in Mstn -/- skeletal muscle. This study provides valuable insight for the treatment of human obesity and diabetes mellitus.

  19. Rebelling against the (Insulin Resistance: A Review of the Proposed Insulin-Sensitizing Actions of Soybeans, Chickpeas, and Their Bioactive Compounds

    Directory of Open Access Journals (Sweden)

    Jaime L. Clark

    2018-03-01

    Full Text Available Insulin resistance is a major risk factor for diseases such as type 2 diabetes and metabolic syndrome. Current methods for management of insulin resistance include pharmacological therapies and lifestyle modifications. Several clinical studies have shown that leguminous plants such as soybeans and pulses (dried beans, dried peas, chickpeas, lentils are able to reduce insulin resistance and related type 2 diabetes parameters. However, to date, no one has summarized the evidence supporting a mechanism of action for soybeans and pulses that explains their ability to lower insulin resistance. While it is commonly assumed that the biological activities of soybeans and pulses are due to their antioxidant activities, these bioactive compounds may operate independent of their antioxidant properties and, thus, their ability to potentially improve insulin sensitivity via alternative mechanisms needs to be acknowledged. Based on published studies using in vivo and in vitro models representing insulin resistant states, the proposed mechanisms of action for insulin-sensitizing actions of soybeans, chickpeas, and their bioactive compounds include increasing glucose transporter-4 levels, inhibiting adipogenesis by down-regulating peroxisome proliferator-activated receptor-γ, reducing adiposity, positively affecting adipokines, and increasing short-chain fatty acid-producing bacteria in the gut. Therefore, this review will discuss the current evidence surrounding the proposed mechanisms of action for soybeans and certain pulses, and their bioactive compounds, to effectively reduce insulin resistance.

  20. Synergistic effects of metformin, resveratrol, and hydroxymethylbutyrate on insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Bruckbauer A

    2013-02-01

    Full Text Available Antje Bruckbauer,1 Michael B Zemel1,21NuSirt Sciences Inc, 2Department of Nutrition, University of Tennessee, Knoxville, TN, USABackground: The purpose of this study was to determine whether a mixture of the polyphenol, resveratrol, and the leucine metabolite, hydroxymethylbutyrate (HMB, acts synergistically with low doses of metformin to impact insulin sensitivity and AMP-activated protein kinase-dependent outcomes in cell culture and in diabetic mice.Methods: C2C12 skeletal myotubes and 3T3-L1 adipocytes were treated with resveratrol 0.2 µM, HMB 5 µM, and metformin 0.1 mM alone or in combination. db/db mice were treated for 2 weeks with high (1.5 g/kg diet, low (0.75 g/kg diet, or very low (0.25 g/kg diet doses of metformin alone or in combination with a diet containing resveratrol 12.5 mg and CaHMB 2 g/kg.Results: The combination of metformin-resveratrol-HMB significantly increased fat oxidation, AMP-activated protein kinase, and Sirt1 activity in muscle cells compared with metformin or resveratrol-HMB alone. A similar trend was found in 3T3L1 adipocytes. In mice, the two lower doses of metformin exerted no independent effect but, when combined with resveratrol-HMB, both low-dose and very low-dose metformin improved insulin sensitivity (HOMAIR, plasma insulin levels, and insulin tolerance test response to a level comparable with that found for high-dose metformin. In addition, the metformin-resveratrol-HMB combination decreased visceral fat and liver weight in mice.Conclusion: Resveratrol-HMB combined with metformin may act synergistically on AMP-activated protein kinase-dependent pathways, leading to increased insulin sensitivity, which may reduce the therapeutic doses of metformin necessary in the treatment of diabetes.Keywords: diabetes, AMP-activated protein kinase, Sirt1, fat oxidation

  1. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

    Science.gov (United States)

    Grassi, Davide; Necozione, Stefano; Lippi, Cristina; Croce, Giuseppe; Valeri, Letizia; Pasqualetti, Paolo; Desideri, Giovambattista; Blumberg, Jeffrey B; Ferri, Claudio

    2005-08-01

    Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, Pbenefit if included as part of a healthy diet for patients with EH.

  2. Examining Camper Learning Outcomes and Knowledge Retention at Oklahoma FFA Leadership Camp

    Science.gov (United States)

    Brown, Nicholas R.; Terry, Robert, Jr.; Kelsey, Kathleen D.

    2014-01-01

    The National FFA Organization is committed to providing non-formal learning activities focusing on leadership education. Summer camps are a major component of FFA activities and concentrate on personal growth, leadership development, and recreational activities for youth. This repeated measures study determined the level of cognitive gain and the…

  3. Improved insulin sensitivity after exercise: focus on insulin signaling

    DEFF Research Database (Denmark)

    Frøsig, Christian; Richter, Erik

    2009-01-01

    After a single bout of exercise, the ability of insulin to stimulate glucose uptake is markedly improved locally in the previously active muscles. This makes exercise a potent stimulus counteracting insulin resistance characterizing type 2 diabetes (T2D). It is believed that at least part...... of the mechanism relates to an improved ability of insulin to stimulate translocation of glucose transporters (GLUT4) to the muscle membrane after exercise. How this is accomplished is still unclear; however, an obvious possibility is that exercise interacts with the insulin signaling pathway to GLUT4...... translocation allowing for a more potent insulin response. Parallel to unraveling of the insulin signaling cascade, this has been investigated within the past 25 years. Reviewing existing studies clearly indicates that improved insulin action can occur independent of interactions with proximal insulin signaling...

  4. Effect of weight reduction on insulin sensitivity, sex hormone-binding globulin, sex hormones and gonadotrophins in obese children

    DEFF Research Database (Denmark)

    Birkebaek, N H; Lange, Aksel; Holland-Fischer, P

    2010-01-01

    Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated. ....... The aim of the present study was to investigate the effect of weight reduction in obese Caucasian children on insulin sensitivity, sex hormone-binding globulin (SHBG), DHEAS and the hypothalamo-pituitary-gonadal axis.......Obesity in men is associated with reduced insulin sensitivity and hypoandrogenism, while obesity in women is associated with reduced insulin sensitivity and hyperandrogenism. In children, the effect of obesity and weight reduction on the hypothalamo-pituitary-gonadal axis is rarely investigated...

  5. Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

    Science.gov (United States)

    van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

    2011-01-01

    OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

  6. Polyunsaturated fatty acids acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increases postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, Anneke; Konings, Ellen; Goossens, Gijs H.; Bouwman, Freek G.; Moors, Chantalle C.; Boekschoten, Mark; Afman, Lydia; Muller, Michael; Mariman, Edwin C.; Blaak, Ellen E.

    2012-01-01

    Dietary fat quality may influence skeletal muscle lipid handling and fat accumulation, thereby modulating insulin sensitivity. Objective: To examine acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA handling and postprandial insulin sensitivity in obese insulin

  7. Monomeric tartrate resistant acid phosphatase induces insulin sensitive obesity.

    Directory of Open Access Journals (Sweden)

    Pernilla Lång

    2008-03-01

    Full Text Available Obesity is associated with macrophage infiltration of adipose tissue, which may link adipose inflammation to insulin resistance. However, the impact of inflammatory cells in the pathophysiology of obesity remains unclear. Tartrate resistant acid phosphatase (TRAP is an enzyme expressed by subsets of macrophages and osteoclasts that exists either as an enzymatically inactive monomer or as an active, proteolytically processed dimer.Using mice over expressing TRAP, we show that over-expression of monomeric, but not the dimeric form in adipose tissue leads to early onset spontaneous hyperplastic obesity i.e. many small fat cells. In vitro, recombinant monomeric, but not proteolytically processed TRAP induced proliferation and differentiation of mouse and human adipocyte precursor cells. In humans, monomeric TRAP was highly expressed in the adipose tissue of obese individuals. In both the mouse model and in the obese humans the source of TRAP in adipose tissue was macrophages. In addition, the obese TRAP over expressing mice exhibited signs of a low-grade inflammatory reaction in adipose tissue without evidence of abnormal adipocyte lipolysis, lipogenesis or insulin sensitivity.Monomeric TRAP, most likely secreted from adipose tissue macrophages, induces hyperplastic obesity with normal adipocyte lipid metabolism and insulin sensitivity.

  8. BEATING ISIS IN THE DIGITAL SPACE: FOCUS TESTING ISIS DEFECTOR COUNTER-NARRATIVE VIDEOS WITH AMERICAN COLLEGE STUDENTS

    Directory of Open Access Journals (Sweden)

    Allision McDowell-Smith

    2017-03-01

    Full Text Available ISIS recruits on a 24/7 basis in over 21 languages over the Internet using videos, memes, tweets and other social media postings and swarming in on anyone that retweets, likes or endorses their materials to try to seduce them into the group. Their unprecedented social media drive has resulted in over 30,000 foreign fighters from more than 100 countries migrating to Syria and Iraq. ISIS recruitment in the U.S. is for the most part Internet based and has resulted in the actual and attempted recruitment of over 100 individuals residing in the U.S. with over 200 Americans traveling to Syria to join terrorist groups. To date very little counter-narrative material exists and most of it is cognitive versus emotionally impactful. The International Center for the Study of Violent Extremism (ICSVE Breaking the ISIS Brand – the ISIS Defectors Interviews Project has managed to collect 43 ISIS defector interviews and thus far produce two video clips of ISIS defectors denouncing the group which were focus tested in this research in a small normative college student sample of 75 undergraduate students. The results demonstrate that American college students find the videos authentic, disturbing and turn them away from ISIS, fulfilling the goals that the project is aiming for in producing counter-narrative materials.

  9. FENOFIBRATE ADMINISTRATION DOES NOT AFFECT MUSCLE TRIGLYCERIDE CONCENTRATION OR INSULIN SENSITIVITY IN HUMANS

    Science.gov (United States)

    Perreault, Leigh; Bergman, Bryan C.; Hunerdosse, Devon M.; Howard, David J.; Eckel, Robert H.

    2010-01-01

    Objective Animal data suggest that males, in particular, rely on PPAR-α activity to maintain normal muscle triglyceride metabolism. We sought to examine whether this was also true in men vs. women and its relationship to insulin sensitivity. Materials/Methods Normolipidemic obese men (n=9) and women (n=9) underwent an assessment of insulin sensitivity (IVGTT) and intramuscular triglyceride metabolism (GC/MS and GC/C/IRMS from plasma and muscle biopsies taken after infusion of [U-13C]palmitate) before and after 12 weeks of fenofibrate treatment. Results Women were more insulin sensitive (Si; 5.2(0.7 vs. 2.4(0.4 ×10−4/uU/ml, W vs. M, ptriglyceride (IMTG) concentration (41.9(15.5 vs. 30.8(5.1 ug/mg dry weight, W vs. M, p=0.43), and IMTG fractional synthesis rate (FSR; 0.27(0.07 vs. 0.35(0.06/hr, W vs. M, p=0.41) as men. Fenofibrate enhanced FSR in men (0.35(0.06 to 0.54(0.06, p=0.05), with no such change seen in women (0.27(0.07 to 0.32(0.13, p=0.73), and no change in IMTG concentration in either group (23.0(3.9 in M, p=0.26 vs. baseline; 36.3(12.0 in W, p=0.79 vs. baseline). Insulin sensitivity was unaffected by fenofibrate (p>0.68). Lower percent saturation of IMTG in women vs. men before (29.1(2.3 vs. 35.2(1.7%, p=0.06) and after (27.3(2.8 vs. 35.1(1.9%, p=0.04) fenofibrate most closely related to their greater insulin sensitivity (R2=0.34, p=0.10), and was largely unchanged by the drug. Conclusions PPAR-α agonist therapy had little effect on IMTG metabolism in men or women. IMTG saturation, rather than IMTG concentration or FSR, most closely (but not significantly) related to insulin sensitivity and was unchanged by fenofibrate administration. PMID:21306746

  10. Stimulatory effect of insulin on glucose uptake by muscle involves the central nervous system in insulin-sensitive mice.

    Science.gov (United States)

    Coomans, Claudia P; Biermasz, Nienke R; Geerling, Janine J; Guigas, Bruno; Rensen, Patrick C N; Havekes, Louis M; Romijn, Johannes A

    2011-12-01

    Insulin inhibits endogenous glucose production (EGP) and stimulates glucose uptake in peripheral tissues. Hypothalamic insulin signaling is required for the inhibitory effects of insulin on EGP. We examined the contribution of central insulin signaling on circulating insulin-stimulated tissue-specific glucose uptake. Tolbutamide, an inhibitor of ATP-sensitive K(+) channels (K(ATP) channels), or vehicle was infused into the lateral ventricle in the basal state and during hyperinsulinemic-euglycemic conditions in postabsorptive, chow-fed C57Bl/6J mice and in postabsorptive C57Bl/6J mice with diet-induced obesity. Whole-body glucose uptake was measured by d-[(14)C]glucose kinetics and tissue-specific glucose uptake by 2-deoxy-d-[(3)H]glucose uptake. During clamp conditions, intracerebroventricular administration of tolbutamide impaired the ability of insulin to inhibit EGP by ∼20%. In addition, intracerebroventricular tolbutamide diminished insulin-stimulated glucose uptake in muscle (by ∼59%) but not in heart or adipose tissue. In contrast, in insulin-resistant mice with diet-induced obesity, intracerebroventricular tolbutamide did not alter the effects of insulin during clamp conditions on EGP or glucose uptake by muscle. Insulin stimulates glucose uptake in muscle in part through effects via K(ATP) channels in the central nervous system, in analogy with the inhibitory effects of insulin on EGP. High-fat diet-induced obesity abolished the central effects of insulin on liver and muscle. These observations stress the role of central insulin resistance in the pathophysiology of diet-induced insulin resistance.

  11. Impact of oral vancomycin on gut microbiota, bile acid metabolism, and insulin sensitivity

    DEFF Research Database (Denmark)

    Vrieze, Anne; Out, Carolien; Fuentes, Susana

    2014-01-01

    .i.d. At baseline and after 1 week of therapy, fecal microbiota composition (Human Intestinal Tract Chip phylogenetic microarray), fecal and plasma bile acid concentrations as well as insulin sensitivity (hyperinsulinemic euglycemic clamp using [6,6-(2)H2]-glucose tracer) were measured. RESULTS: Vancomycin reduced...... (pinsulin sensitivity (p... of vancomycin significantly impacts host physiology by decreasing intestinal microbiota diversity, bile acid dehydroxylation and peripheral insulin sensitivity in subjects with metabolic syndrome. These data show that intestinal microbiota, particularly of the Firmicutes phylum contributes to bile acid...

  12. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

    Science.gov (United States)

    Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

    2018-03-15

    Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

  13. The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system

    NARCIS (Netherlands)

    Coomans, C.P.; Geerling, J.J.; Berg, S.A.A. van den; Diepen, H.C. van; Garcia-Tardõn, N.; Thomas, A.; Schröder-Van Der Elst, J.P.; Ouwens, D.M.; Pijl, H.; Rensen, P.C.N.; Havekes, L.M.; Guigas, B.; Romijn, J.A.

    2013-01-01

    Background and Purpose Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro.

  14. Insulin secretion and sensitivity in space flight: diabetogenic effects

    Science.gov (United States)

    Tobin, Brian W.; Uchakin, Peter N.; Leeper-Woodford, Sandra K.

    2002-01-01

    Nearly three decades of space flight research have suggested that there are subclinical diabetogenic changes that occur in microgravity. Alterations in insulin secretion, insulin sensitivity, glucose tolerance, and metabolism of protein and amino acids support the hypothesis that insulin plays an essential role in the maintenance of muscle mass in extended-duration space flight. Experiments in flight and after flight and ground-based bedrest studies have associated microgravity and its experimental paradigms with manifestations similar to those of diabetes, physical inactivity, and aging. We propose that these manifestations are characterized best by an etiology that falls into the clinical category of "other" causes of diabetes, including, but not restricted to, genetic beta-cell defects, insulin action defects, diseases of the endocrine pancreas, endocrinopathies, drug or chemically induced diabetes, infections, immune-mediated metabolic alteration, and a host of genetic related diseases. We present data showing alterations in tumor necrosis factor-alpha production, insulin secretion, and amino acid metabolism in pancreatic islets of Langerhans cultured in a ground-based cell culture bioreactor that mimics some of the effects of microgravity. Taken together, space flight research, ground-based studies, and bioreactor studies of pancreatic islets of Langerhans support the hypothesis that the pancreas is unable to overcome peripheral insulin resistance and amino acid dysregulation during space flight. We propose that measures of insulin secretion and insulin action will be necessary to design effective countermeasures against muscle loss, and we advance the "disposition index" as an essential model to be used in the clinical management of space flight-induced muscle loss.

  15. Diabetes mellitus and insulin in an aspirin sensitive asthmatic.

    Science.gov (United States)

    Caplin, I

    1976-03-01

    The infrequency of diabetes mellitus and asthma in the same individual is re-examined. The antagonism between epinephrine and insulin, as suggested by Konig in 1935, is indeed accurate. The assays done by the Eli Lilly Research Department revealed no in vitro effect of insulin on the CAMP and GMP level of mast cells as occurs in liver cells. It is felt that this effect is probably an in vivo effect produced via the vagus nerve and alpha-adrenergic receptor system stimulation. This would explain the mechanism of aggravation of asthma by excess insulin. Dr. Petersen's studies, the negative intradermal skin tests to insulin and the absence of change on either beef or pork insulin usage by our patient all point to a nonatopic factor in the aggravation of the asthma of this patient. In the uncommon occurrence of asthma and diabetes in the same patient, insulin dosage should be considered as a factor in all such asthmatics who do not respond well to conventional therapy. Two additional asthmatics who also have diabetes did improve with cessation of nocturnal asthma by a reduction of their evening dose of insulin. A high fat, low carbohydrate diet, as suggested by Abrahamson to avoid dietary hyperinsulinism, is certainly worth considering in patients with nocturnal asthma. If patients cannot be made to follow a diet requiring frequent feedings high in protein and fats and low in carbohydrates, another approach suggests itself. Abrahamson was able to relieve the patients who developed nocturnal asthma with hypoglycemia by having them drink a glass of milk. Assuming other causes have been eliminated and a patient awakens each day at 3:00 a.m., an alarm clock could be set at 2:00 a.m. Milk or a milk substitute in milk sensitive patients could be taken at 2:00 a.m. to raise the blood sugar and hopefully prevent the asthma associated with hypoglycemia. Also to be noted is the ubiquitous use of tartrazine in so many drugs, including those used to relieve asthmatic symptoms

  16. Consumption of added sugars from liquid but not solid sources predicts impaired glucose homeostasis and insulin resistance among youth at risk of obesity.

    Science.gov (United States)

    Wang, Jiawei; Light, Kelly; Henderson, Mélanie; O'Loughlin, Jennifer; Mathieu, Marie-Eve; Paradis, Gilles; Gray-Donald, Katherine

    2014-01-01

    Little is known about longitudinal associations between added sugar consumption (solid and liquid sources) and glucose-insulin homeostasis among youth. Caucasian children (8-10 y) with at least one obese biological parent were recruited in the QUébec Adipose and Lifestyle InvesTigation in Youth (QUALITY) cohort (n = 630) and followed-up 2 y later (n = 564). Added sugars were assessed by 3 24-h dietary recalls at baseline. Two-year changes were examined in multivariate linear regression models, adjusting for baseline level, age, sex, Tanner stage, energy intake, fat mass (dual-energy X-ray absorptiometry), and physical activity (7 d accelerometer). Added sugar intake in either liquid or solid sources was not related to changes in adiposity measures (fat mass, body mass index, or waist circumference). However, a higher consumption (10 g/d) of added sugars from liquid sources was associated with 0.04 mmol/L higher fasting glucose, 2.3 pmol/L higher fasting insulin, 0.1 unit higher homeostasis model assessment of insulin resistance (HOMA-IR), and 0.4 unit lower Matsuda-insulin sensitivity index (Matsuda-ISI) in all participants (P added sugars from solid sources. Overweight/obese children at baseline had greater increases in adiposity indicators, fasting insulin, and HOMA-IR and decreases in Matsuda-ISI during those 2 y than normal-weight children. Consumption of added sugars from liquid or solid sources was not associated with changes in adiposity, but liquid added sugars were a risk factor for the development of impaired glucose homeostasis and insulin resistance over 2 y among youth at risk of obesity.

  17. Associations of objective physical activity with insulin sensitivity and circulating adipokine profile

    DEFF Research Database (Denmark)

    Spartano, N L; Stevenson, M D; Xanthakis, V

    2017-01-01

    The purpose of this study was to explore the relation of physical activity (PA) and sedentary time (SED) to insulin sensitivity and adipokines. We assessed PA and SED using Actical accelerometers and insulin resistance (HOMA-IR) in 2109 participants (free of type 1 and 2 diabetes mellitus) from...

  18. A comparison between the minimal model and the glucose clamp in the assessment of insulin sensitivity across the spectrum of glucose tolerance. Insulin Resistance Atherosclerosis Study.

    Science.gov (United States)

    Saad, M F; Anderson, R L; Laws, A; Watanabe, R M; Kades, W W; Chen, Y D; Sands, R E; Pei, D; Savage, P J; Bergman, R N

    1994-09-01

    An insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) with minimal model analysis was compared with the glucose clamp in 11 subjects with normal glucose tolerance (NGT), 20 with impaired glucose tolerance (IGT), and 24 with non-insulin-dependent diabetes mellitus (NIDDM). The insulin sensitivity index (SI) was calculated from FSIGTT using 22- and 12-sample protocols (SI(22) and SI(12), respectively). Insulin sensitivity from the clamp was expressed as SI(clamp) and SIP(clamp). Minimal model parameters were similar when calculated with SI(22) and SI(12). SI could not be distinguished from 0 in approximately 50% of diabetic patients with either protocol. SI(22) correlated significantly with SI(clamp) in the whole group (r = 0.62), and in the NGT (r = 0.53), IGT (r = 0.48), and NIDDM (r = 0.41) groups (P SIP(clamp) were expressed in the same units, SI(22) was 66 +/- 5% (mean +/- SE) and 50 +/- 8% lower than SI(clamp) and SIP(clamp), respectively. Thus, minimal model analysis of the insulin-modified FSIGTT provides estimates of insulin sensitivity that correlate significantly with those from the glucose clamp. The correlation was weaker, however, in NIDDM. The insulin-modified FSIGTT can be used as a simple test for assessment of insulin sensitivity in population studies involving nondiabetic subjects. Additional studies are needed before using this test routinely in patients with NIDDM.

  19. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

    Science.gov (United States)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-12-02

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. The Impact of Learning Styles on Learning Outcomes at FFA Camp: What Campers Retain over Time

    Science.gov (United States)

    Brown, Nicholas R.; Terry, Robert, Jr.; Kelsey, Kathleen D.

    2013-01-01

    Twenty-four states host FFA summer camps to support adolescent maturation along with indoctrination into the culture and values of the FFA. Camps typically include a variety of activities designed to engage members in social activities and non-formal academic content. More than 1500 campers attend the Oklahoma FFA Alumni Leadership Camp annually…

  1. Insulin sensitivity and secretion in Arab Americans with glucose intolerance.

    Science.gov (United States)

    Salinitri, Francine D; Pinelli, Nicole R; Martin, Emily T; Jaber, Linda A

    2013-12-01

    This study examined the pathophysiological abnormalities in Arab Americans with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT). Homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of insulin secretion (HOMA-%β), and the Matsuda Insulin Sensitivity Index composite (ISIcomposite) were calculated from the fasting and stimulated glucose and insulin concentrations measured during the oral glucose tolerance test in a population-based, representative, cross-sectional sample of randomly selected Arab Americans. In total, 497 individuals (42±14 years old; 40% males; body mass index [BMI], 29±6 kg/m(2)) were studied. Multivariate linear regression models were performed to compare HOMA-IR, HOMA-%β, and ISIcomposite among individuals with normal glucose tolerance (NGT) (n=191) versus isolated IFG (n=136), isolated IGT (n=22), combined IFG/IGT (n=43), and diabetes (n=105). Compared with individuals with NGT (2.9±1.6), HOMA-IR progressively increased in individuals with isolated IFG (4.8±2.7, Psex and BMI, these associations remained unchanged. Whole-body insulin sensitivity as measured by ISIcomposite was significantly lower in individuals with isolated IFG (3.9±2.3, Psex, and BMI, isolated IFG (146.6±80.2) was also significantly associated with a decline in HOMA-%β relative to NGT (P=0.005). This study suggests that differences in the underlying metabolic defects leading to diabetes in Arab Americans with IFG and/or IGT exist and may require different strategies for the prevention of diabetes.

  2. Insulin-sensitive phospholipid signaling systems and glucose transport. Update II.

    Science.gov (United States)

    Farese, R V

    2001-04-01

    Insulin provokes rapid changes in phospholipid metabolism and thereby generates biologically active lipids that serve as intracellular signaling factors that regulate glucose transport and glycogen synthesis. These changes include: (i) activation of phosphatidylinositol 3-kinase (PI3K) and production of PIP3; (ii) PIP3-dependent activation of atypical protein kinase Cs (PKCs); (iii) PIP3-dependent activation of PKB; (iv) PI3K-dependent activation of phospholipase D and hydrolysis of phosphatidylcholine with subsequent increases in phosphatidic acid (PA) and diacylglycerol (DAG); (v) PI3K-independent activation of glycerol-3-phosphate acylytansferase and increases in de novo synthesis of PA and DAG; and (vi) activation of DAG-sensitive PKCs. Recent findings suggest that atypical PKCs and PKB serve as important positive regulators of insulin-stimulated glucose metabolism, whereas mechanisms that result in the activation of DAG-sensitive PKCs serve mainly as negative regulators of insulin signaling through PI3K. Atypical PKCs and PKB are rapidly activated by insulin in adipocytes, liver, skeletal muscles, and other cell types by a mechanism requiring PI3K and its downstream effector, 3-phosphoinositide-dependent protein kinase-1 (PDK-1), which, in conjunction with PIP3, phosphorylates critical threonine residues in the activation loops of atypical PKCs and PKB. PIP3 also promotes increases in autophosphorylation and allosteric activation of atypical PKCs. Atypical PKCs and perhaps PKB appear to be required for insulin-induced translocation of the GLUT 4 glucose transporter to the plasma membrane and subsequent glucose transport. PKB also appears to be the major regulator of glycogen synthase. Together, atypical PKCs and PKB serve as a potent, integrated PI3K/PDK-1-directed signaling system that is used by insulin to regulate glucose metabolism.

  3. Insulin sensitivity is normalized in the third generation (F3 offspring of developmentally programmed insulin resistant (F2 rats fed an energy-restricted diet

    Directory of Open Access Journals (Sweden)

    Martin John F

    2008-10-01

    Full Text Available Abstract Background/Aims The offspring and grandoffspring of female rats fed low protein diets during pregnancy and lactation, but fed nutritionally adequate diets thereafter, have been shown to exhibit altered insulin sensitivity in adulthood. The current study investigates the insulin sensitivity of the offspring and grandoffspring of female rats fed low protein diets during pregnancy, and then maintained on energy-restricted diets post weaning over three generations. Methods Female Sprague Dawley rats (F0 were mated with control males and protein malnourished during pregnancy/lactation. F1 offspring were then weaned to adequate but energy-restricted diets into adulthood. F1 dams were fed energy-restricted diets throughout pregnancy/lactation. F2 offspring were also fed energy-restricted diets post weaning. F2 pregnant dams were maintained as described above. Their F3 offspring were split into two groups; one was maintained on the energy-restricted diet, the other was maintained on an adequate diet consumed ad libitum post weaning. Results F2 animals fed energy-restricted diets were insulin resistant (p ad libitum postweaning diets (p Conclusion Maternal energy-restriction did not consistently program reduced insulin sensitivity in offspring over three consecutive generations. The reasons for this remain unclear. It is possible that the intergenerational transmission of developmentally programmed insulin resistance is determined in part by the relative insulin sensitivity of the mother during pregnancy/lactation.

  4. Insulin sensitivity affects corticolimbic brain responses to visual food cues in polycystic ovary syndrome patients.

    Science.gov (United States)

    Alsaadi, Hanin M; Van Vugt, Dean A

    2015-11-01

    This study examined the effect of insulin sensitivity on the responsiveness of appetite regulatory brain regions to visual food cues. Nineteen participants diagnosed with polycystic ovary syndrome (PCOS) were divided into insulin-sensitive (n=8) and insulin-resistant (n=11) groups based on the homeostatic model assessment of insulin resistance (HOMA2-IR). Subjects underwent functional magnetic resonance imaging (fMRI) while viewing food pictures following water or dextrose consumption. The corticolimbic blood oxygen level dependent (BOLD) responses to high-calorie (HC) or low-calorie (LC) food pictures were compared within and between groups. BOLD responses to food pictures were reduced during a glucose challenge in numerous corticolimbic brain regions in insulin-sensitive but not insulin-resistant subjects. Furthermore, the degree of insulin resistance positively correlated with the corticolimbic BOLD response in the medial prefrontal cortex (mPFC), orbitofrontal cortex (OFC), anterior cingulate and ventral tegmental area (VTA) in response to HC pictures, and in the dorsolateral prefrontal cortex (DLPFC), mPFC, anterior cingulate, and insula in response to LC pictures following a glucose challenge. BOLD signal in the OFC, midbrain, hippocampus, and amygdala following a glucose challenge correlated with HOMA2-IR in response to HC-LC pictures. We conclude that the normal inhibition of corticolimbic brain responses to food pictures during a glucose challenge is compromised in insulin-resistant subjects. The increase in brain responsiveness to food pictures during postprandial hyperinsulinemia may lead to greater non-homeostatic eating and perpetuate obesity in insulin-resistant subjects.

  5. The insulin sensitizing effect of topiramate involves KATP channel activation in the central nervous system

    NARCIS (Netherlands)

    Coomans, C. P.; Geerling, J. J.; van den Berg, S. A. A.; van Diepen, H. C.; Garcia-Tardón, N.; Thomas, A.; Schröder-van der Elst, J. P.; Ouwens, D. M.; Pijl, H.; Rensen, P. C. N.; Havekes, L. M.; Guigas, B.; Romijn, J. A.

    2013-01-01

    Topiramate improves insulin sensitivity, in addition to its antiepileptic action. However, the underlying mechanism is unknown. Therefore, the present study was aimed at investigating the mechanism of the insulin-sensitizing effect of topiramate both in vivo and in vitro. Male C57Bl/6J mice were fed

  6. Adipocyte-specific blockade of gamma-secretase, but not inhibition of Notch activity, reduces adipose insulin sensitivity

    Directory of Open Access Journals (Sweden)

    David P. Sparling

    2016-02-01

    Full Text Available Objective: As the obesity pandemic continues to expand, novel molecular targets to reduce obesity-related insulin resistance and Type 2 Diabetes (T2D continue to be needed. We have recently shown that obesity is associated with reactivated liver Notch signaling, which, in turn, increases hepatic insulin resistance, opening up therapeutic avenues for Notch inhibitors to be repurposed for T2D. Herein, we tested the systemic effects of γ-secretase inhibitors (GSIs, which prevent endogenous Notch activation, and confirmed these effects through creation and characterization of two different adipocyte-specific Notch loss-of-function mouse models through genetic ablation of the Notch transcriptional effector Rbp-Jk (A-Rbpj and the obligate γ-secretase component Nicastrin (A-Nicastrin. Methods: Glucose homeostasis and both local adipose and systemic insulin sensitivity were examined in GSI-treated, A-Rbpj and A-Nicastrin mice, as well as vehicle-treated or control littermates, with complementary in vitro studies in primary hepatocytes and 3T3-L1 adipocytes. Results: GSI-treatment increases hepatic insulin sensitivity in obese mice but leads to reciprocal lowering of adipose glucose disposal. While A-Rbpj mice show normal body weight, adipose development and mass and unchanged adipose insulin sensitivity as control littermates, A-Nicastrin mice are relatively insulin-resistant, mirroring the GSI effect on adipose insulin action. Conclusions: Notch signaling is dispensable for normal adipocyte function, but adipocyte-specific γ-secretase blockade reduces adipose insulin sensitivity, suggesting that specific Notch inhibitors would be preferable to GSIs for application in T2D. Keywords: Notch, γ-secretase complex, Insulin resistance

  7. Insulin Sensitivity and Glucose Homeostasis Can Be Influenced by Metabolic Acid Load

    Directory of Open Access Journals (Sweden)

    Lucio Della Guardia

    2018-05-01

    Full Text Available Recent epidemiological findings suggest that high levels of dietary acid load can affect insulin sensitivity and glucose metabolism. Consumption of high protein diets results in the over-production of metabolic acids which has been associated with the development of chronic metabolic disturbances. Mild metabolic acidosis has been shown to impair peripheral insulin action and several epidemiological findings suggest that metabolic acid load markers are associated with insulin resistance and impaired glycemic control through an interference intracellular insulin signaling pathways and translocation. In addition, higher incidence of diabetes, insulin resistance, or impaired glucose control have been found in subjects with elevated metabolic acid load markers. Hence, lowering dietary acid load may be relevant for improving glucose homeostasis and prevention of type 2 diabetes development on a long-term basis. However, limitations related to patient acid load estimation, nutritional determinants, and metabolic status considerably flaws available findings, and the lack of solid data on the background physiopathology contributes to the questionability of results. Furthermore, evidence from interventional studies is very limited and the trials carried out report no beneficial results following alkali supplementation. Available literature suggests that poor acid load control may contribute to impaired insulin sensitivity and glucose homeostasis, but it is not sufficiently supportive to fully elucidate the issue and additional well-designed studies are clearly needed.

  8. Status report on ISIS

    International Nuclear Information System (INIS)

    Rees, G.H.

    1987-01-01

    The recent performance of the ISIS spallation neutron source is described and possible developments for the future are outlined. Aims for the near future are to raise the energy and intensity of the 50 Hz proton synchrotron to the design specification. Longer term aims are being evaluated by an International ISIS Project Group and an International Science Advisory Group. The hope is to develop the project in an international context to an improved specification

  9. RUTHERFORD APPLETON: ISIS nice

    Energy Technology Data Exchange (ETDEWEB)

    Anon.

    1986-07-15

    The ISIS pulsed spallation neutron source continues to make good progress. In March the machine reached its highest intensity when 5 x 10{sup 12} protons per pulse at 550 MeV and 50 pulses per second were delivered to the neutron production target. This 40 microamperes of mean proton current is 20% of the design performance and confirms once again the potential of ISIS as a powerful accelerator- based pulsed neutron source.

  10. High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes

    DEFF Research Database (Denmark)

    Vozarova, Barbora; Stefan, Norbert; Lindsay, Robert S

    2002-01-01

    -sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver...... with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat...... 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO...

  11. Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids

    DEFF Research Database (Denmark)

    Rasmussen, Jon Jarløv; Schou, Morten; Selmer, Christian

    2017-01-01

    Objective: Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current...

  12. Four days of simulated shift work reduces insulin sensitivity in humans.

    Science.gov (United States)

    Bescos, R; Boden, M J; Jackson, M L; Trewin, A J; Marin, E C; Levinger, I; Garnham, A; Hiam, D S; Falcao-Tebas, F; Conte, F; Owens, J A; Kennaway, D J; McConell, G K

    2018-06-01

    The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9; day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair samples respectively. Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L -1 ; P = .001) and insulin sensitivity decreased (25 ± 7%, P night shift, with no changes following the day shift. Night shift work had no effect on skeletal muscle protein expression (PGC1α, UCP3, TFAM and mitochondria Complex II-V) or insulin-stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642. Importantly, the metabolic changes after simulated night shifts occurred despite no changes in the timing of melatonin rhythmicity or hair follicle cell clock gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2). Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  13. Flaw distributions and use of ISI data in RPV integrity evaluations

    International Nuclear Information System (INIS)

    Dimitrijevic, V.; Ammirato, F.

    1993-01-01

    A probabilistic method for developing post-inspection flaw distributions has been developed that explicitly accounts for the capability of the inspection procedure to detect and size flaws. This methodology has been used to develop flaw distributions for calculating reactor vessel failure probability under postulated pressurized thermal shock (PTS) conditions. Realistic flaw distributions are important because plant-specific PTS safety assessments are very sensitive to assumptions made about major flaw parameters such as density, size, shape, and location. PTS analysis made in the past do not consider ISI. Two main reasons are (1) lack of a general and approved methodology which provides directions for involvement of ISI results in developing new flaw parameters and (2) lack of confidence in the capability of ISI procedures to detect critical flaws that may be present near the clad-to-base metal interface of the vessel, the location of most concern for PTS conditions. Recent developments in ISI practice, however, have led to substantial improvement in ISI capability and provide a basis for using ISI data to develop plant-specific post-inspection flaw distributions for vessel integrity evaluations. The key components of this evaluation are (1) the generic (preinspection) flaw distribution, (2) a probabilistic flaw detection model, and (3) Bayesian updating of the prior flaw distribution with the detection model to develop a post-inspection flaw distribution. Destructive analysis of RPV weld material was performed to develop data to support the pre-inspection flaw distributions. Since the probability of detection (POD) plays such an important role in the analysis and a high POD is needed to make significant reductions in probability of failure, a procedure was developed to achieve and demonstrate POD greater than 0.9 by using a combination of independent inspection techniques

  14. Impacto da perda de peso nas adipocitocinas, na proteína C-reativa e na sensibilidade à insulina em mulheres hipertensas com obesidade central Impact of weight loss on adipocytokines, C-reactive protein and insulin sensitivity in hypertensive women with central obesity

    Directory of Open Access Journals (Sweden)

    Rodolfo Leão Borges

    2007-12-01

    Full Text Available OBJETIVO: Avaliar o impacto do tratamento da obesidade nas adipocitocinas, na proteína C-reativa (PCR e na sensibilidade à insulina em pacientes hipertensas com obesidade central. MÉTODOS: O estudo foi realizado a partir do banco de dados e de amostras estocadas de soro de pacientes submetidas previamente a um estudo para tratamento de obesidade. Foram selecionadas 30 mulheres hipertensas, com idade entre 18 e 65 anos, índice de massa corpórea (IMC > 27 kg/m², com distribuição central de gordura. As pacientes foram aleatoriamente submetidas a dieta hipocalórica e orlistat 120 mg três vezes por dia ou apenas a dieta hipocalórica, durante 16 semanas. As pacientes que apresentaram perda de peso superior a 5% (n = 24 foram avaliadas em relação a níveis pressóricos, valores antropométricos, gordura visceral, índices de resistência (HOMA-R - homeostasis model assessment of insulin resistance e de sensibilidade à insulina (ISI - Insulin Sensitivity Index, perfil lipídico, e dosagens das adipocitocinas (adiponectina, leptina, IL-6 e TNF-a e de PCR. RESULTADOS: Após redução do IMC de cerca de 8% em ambos os grupos, foi verificada diminuição de gordura visceral, glicemia de jejum, triglicérides e TNF-a. Apenas o grupo orlistat, que inicialmente era mais resistente à insulina, apresentou redução significativa da glicemia pós-sobrecarga oral de glicose e aumento da sensibilidade à insulina. CONCLUSÃO: Os achados deste estudo indicam que a perda de peso superior a 5% se associa à melhora do perfil inflamatório e à redução da resistência à insulina, a qual ocorreu de maneira independente das variações de adiponectina e de TNF-a. Os maiores benefícios na sensibilidade à insulina obtidos no grupo orlistat não puderam ser atribuídos ao uso do medicamento em virtude da maior concentração de indivíduos resistentes à insulina nesse grupo.OBJECTIVE: To assess the impact of weight reduction on serum adipocytokines, C

  15. Brain GLP-1 and insulin sensitivity.

    Science.gov (United States)

    Sandoval, Darleen; Sisley, Stephanie R

    2015-12-15

    Type 2 diabetes is often treated with a class of drugs referred to as glucagon-like peptide-1 (GLP-1) analogs. GLP-1 is a peptide secreted by the gut that acts through only one known receptor, the GLP-1 receptor. The primary function of GLP-1 is thought to be lowering of postprandial glucose levels. Indeed, medications utilizing this system, including the long-acting GLP-1 analogs liraglutide and exenatide, are beneficial in reducing both blood sugars and body weight. GLP-1 analogs were long presumed to affect glucose control through their ability to increase insulin levels through peripheral action on beta cells. However, multiple lines of data point to the ability of GLP-1 to act within the brain to alter glucose regulation. In this review we will discuss the evidence for a central GLP-1 system and the effects of GLP-1 in the brain on regulating multiple facets of glucose homeostasis including glucose tolerance, insulin production, insulin sensitivity, hepatic glucose production, muscle glucose uptake, and connections of the central GLP-1 system to the gut. Although the evidence indicates that GLP-1 receptors in the brain are not necessary for physiologic control of glucose regulation, we discuss the research showing a strong effect of acute manipulation of the central GLP-1 system on glucose control and how it is relevant to type 2 diabetic patients. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. Barriers to Participation in the National FFA Organization According to Urban Agriculture Students

    Science.gov (United States)

    Martin, Michael J.; Kitchel, Tracy

    2014-01-01

    Urban youth engaged in after-school organizations have more positive attributes compared to their unengaged contemporaries. The FFA is one particular intra-curricular organization with after-school components; yet, urban students do not participate in FFA at the same levels as rural students. The purpose of this descriptive study was to explore…

  17. Influence of apolipoproteins on the association between lipids and insulin sensitivity

    DEFF Research Database (Denmark)

    Baldi, Simona; Bonnet, Fabrice; Laville, Martine

    2013-01-01

    We evaluated whether the association of insulin sensitivity with HDL cholesterol (HDL) and triglycerides is influenced by major plasma apolipoproteins, as suggested by recent experimental evidence....

  18. Examining ISIS Support and Opposition Networks on Twitter

    Science.gov (United States)

    2016-01-01

    Examining ISIS Support and Opposition Networks on Twitter Elizabeth Bodine-Baron, Todd C. Helmus, Madeline Magnuson, Zev Winkelman C O R P O R A T...Syria (ISIS), like no other terrorist organization before, has used Twitter and other social media channels to broadcast its message, inspire followers...and recruit new fighters. Though much less heralded, ISIS opponents have also taken to Twitter to cas- tigate the ISIS message. This report draws on

  19. Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons

    Science.gov (United States)

    Glucagon-like peptides (GLP-1/GLP-2) are coproduced and highlighted as key modulators to improve glucose homeostasis and insulin sensitivity after bariatric surgery. However, it is unknown if CNS GLP-2 plays any physiological role in the control of glucose homeostasis and insulin sensitivity. We sho...

  20. Determining pancreatic β-cell compensation for changing insulin sensitivity using an oral glucose tolerance test

    DEFF Research Database (Denmark)

    Solomon, Thomas; Malin, Steven K; Karstoft, Kristian

    2014-01-01

    Plasma glucose, insulin, and C-peptide responses during an OGTT are informative for both research and clinical practice in type 2 diabetes. The aim of this study was to use such information to determine insulin sensitivity and insulin secretion so as to calculate an oral glucose disposition index...

  1. [Effect of oral administration of ascorbic acid on insulin sensitivity and lipid profile in obese individuals].

    Science.gov (United States)

    Martínez-Abundis, E; Pascoe-González, S; González-Ortiz, M; Mora-Martínez, J M; Cabrera-Pivaral, C E

    2001-01-01

    The aim of this study was to identify the effect of an oral ascorbic acid (AA) supplement on lipid profile and insulin sensitivity in obese people. A randomized double-blind clinical trial placebo controlled was performed in 16 obese male volunteers [body mass index (BMI) 30-40 kg/m2]. Eight received orally 1 g of AA daily for four weeks and the other eight volunteers received placebo by the same scheme and period of time. Before and after the pharmacological intervention were measured total cholesterol, high-density-lipoprotein (HDL) cholesterol, triglycerides, glucose, creatinine and uric acid. Low-density-lipoprotein (LDL) cholesterol and very-low-density-lipoprotein (VLDL) triglycerides were calculated using formulas. In order to assess insulin sensitivity before and after the intervention, the steady-state glucose (SSG) was calculated from the insulin suppression test modified with octreotide. There were not significant differences in clinical characteristics between both groups. Basal metabolic profile and SSG were similar between both groups. There were not significant differences in both groups between before and after the intervention in metabolic profile and insulin sensitivity. AA did not modify the lipid profile nor insulin sensitivity in the group of obese people studied.

  2. MiR-155 Enhances Insulin Sensitivity by Coordinated Regulation of Multiple Genes in Mice

    Science.gov (United States)

    Lin, Taoyan; Lin, Xia; Chen, Li; Zeng, Hui; Han, Yanjiang; Wu, Lihong; Huang, Shun; Wang, Meng; Huang, Shenhao; Xie, Raoying; Liang, Liqi; Liu, Yu; Liu, Ruiyu; Zhang, Tingting; Li, Jing; Wang, Shengchun; Sun, Penghui; Huang, Wenhua; Yao, Kaitai; Xu, Kang; Du, Tao; Xiao, Dong

    2016-01-01

    miR-155 plays critical roles in numerous physiological and pathological processes, however, its function in the regulation of blood glucose homeostasis and insulin sensitivity and underlying mechanisms remain unknown. Here, we reveal that miR-155 levels are downregulated in serum from type 2 diabetes (T2D) patients, suggesting that miR-155 might be involved in blood glucose control and diabetes. Gain-of-function and loss-of-function studies in mice demonstrate that miR-155 has no effects on the pancreatic β-cell proliferation and function. Global transgenic overexpression of miR-155 in mice leads to hypoglycaemia, improved glucose tolerance and insulin sensitivity. Conversely, miR-155 deficiency in mice causes hyperglycemia, impaired glucose tolerance and insulin resistance. In addition, consistent with a positive regulatory role of miR-155 in glucose metabolism, miR-155 positively modulates glucose uptake in all cell types examined, while mice overexpressing miR-155 transgene show enhanced glycolysis, and insulin-stimulated AKT and IRS-1 phosphorylation in liver, adipose tissue or skeletal muscle. Furthermore, we reveal these aforementioned phenomena occur, at least partially, through miR-155-mediated repression of important negative regulators (i.e. C/EBPβ, HDAC4 and SOCS1) of insulin signaling. Taken together, these findings demonstrate, for the first time, that miR-155 is a positive regulator of insulin sensitivity with potential applications for diabetes treatment. PMID:27711113

  3. Skeletal muscle phosphatidylcholine and phosphatidylethanolamine are related to insulin sensitivity and respond to acute exercise in humans.

    Science.gov (United States)

    Newsom, Sean A; Brozinick, Joseph T; Kiseljak-Vassiliades, Katja; Strauss, Allison N; Bacon, Samantha D; Kerege, Anna A; Bui, Hai Hoang; Sanders, Phil; Siddall, Parker; Wei, Tao; Thomas, Melissa; Kuo, Ming Shang; Nemkov, Travis; D'Alessandro, Angelo; Hansen, Kirk C; Perreault, Leigh; Bergman, Bryan C

    2016-06-01

    Several recent reports indicate that the balance of skeletal muscle phosphatidylcholine (PC) and phosphatidylethanolamine (PE) is a key determinant of muscle contractile function and metabolism. The purpose of this study was to determine relationships between skeletal muscle PC, PE and insulin sensitivity, and whether PC and PE are dynamically regulated in response to acute exercise in humans. Insulin sensitivity was measured via intravenous glucose tolerance in sedentary obese adults (OB; n = 14), individuals with type 2 diabetes (T2D; n = 15), and endurance-trained athletes (ATH; n = 15). Vastus lateralis muscle biopsies were obtained at rest, immediately after 90 min of cycle ergometry at 50% maximal oxygen consumption (V̇o2 max), and 2-h postexercise (recovery). Skeletal muscle PC and PE were measured via infusion-based mass spectrometry/mass spectrometry analysis. ATH had greater levels of muscle PC and PE compared with OB and T2D (P insulin sensitivity (both P insulin sensitivity among the entire cohort (r = -0.43, P = 0.01). Muscle PC and PE were altered by exercise, particularly after 2 h of recovery, in a highly group-specific manner. However, muscle PC:PE ratio remained unchanged in all groups. In summary, total muscle PC and PE are positively related to insulin sensitivity while PC:PE ratio is inversely related to insulin sensitivity in humans. A single session of exercise significantly alters skeletal muscle PC and PE levels, but not PC:PE ratio. Copyright © 2016 the American Physiological Society.

  4. Insulin sensitivity is reduced in children with high body-fat regardless of BMI

    DEFF Research Database (Denmark)

    Fairchild, Timothy J; Klakk, Heidi; Heidemann, Malene

    2018-01-01

    BF% was measured by dual-energy X-ray absorptiometry (DXA). Fasting plasma glucose and insulin concentrations were measured and the homoeostatic model assessment of insulin resistance (HOMA-IR) used to assess insulin sensitivity. RESULTS: Approximately 8% of children classified as normal weight...... by BMI had high BF% (NW + Adipose). Children with high BF% had significantly higher insulin (NW + adipose: 32.3%; OW/OB + Adipose: 52.2%) and HOMA-IR scores (NW + Adipose: 32.3%; OW/OB + Adipose: 55.3%) than children classified as NW without high BF% (reference group; NW + NonAdipose). Adjusting for CRF...

  5. First results from the MAPS spectrometer at ISIS

    International Nuclear Information System (INIS)

    Frost, C.D.; Perring, T.G.

    2001-01-01

    The scientific commissioning of MAPS, the new state-of-the-art neutron scattering instrument at ISIS, has just begun. The design of MAPS has been optimised for studies of coherent excitations in single-crystals. The principal innovation is the use of position sensitive detectors that provide close to continuos coverage over a large solid angle detector array in the forward direction. The technical description of the spectrometer is presented, and examples from the first scientific experiments are used to illustrate how the position sensitive detectors coupled with easy-to-use visualisation software is already beginning to have an impact in the measurement of excitations in single crystals. (author)

  6. First results from the MAPS spectrometer at ISIS

    Energy Technology Data Exchange (ETDEWEB)

    Frost, C.D.; Perring, T.G. [ISIS Facility, CLRC Rutherford Appleton Laboratory, Didcot, Oxon (United Kingdom)

    2001-03-01

    The scientific commissioning of MAPS, the new state-of-the-art neutron scattering instrument at ISIS, has just begun. The design of MAPS has been optimised for studies of coherent excitations in single-crystals. The principal innovation is the use of position sensitive detectors that provide close to continuos coverage over a large solid angle detector array in the forward direction. The technical description of the spectrometer is presented, and examples from the first scientific experiments are used to illustrate how the position sensitive detectors coupled with easy-to-use visualisation software is already beginning to have an impact in the measurement of excitations in single crystals. (author)

  7. Differentiation of the insulin-sensitive glucose transporter in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Frost, S.C.; Baly, D.L.; Cushman, S.W.; Lane, M.D.; Simpson, I.A.

    1986-01-01

    3T3-L1 fibroblasts differentiate in culture to resemble adipocytes both morphologically and biochemically. Insulin-sensitive glucose transport, as measured by 2-deoxy-[1- 14 C]- glucose uptake in the undifferentiated cell is small (2X). In contrast, the rate of glucose transport in fully differentiated cells is elevated 15-fold over basal in the presence of insulin. To determine if this is due to an increase in the number of transporters/cell or accessibility to the transporters, the number of transporters was measured in subcellular fractions over differentiation using a 3 H-cytochalasin B binding assay. The increase in the rate of insulin-sensitive glucose transport directly parallels an increase in the number of transporters which reside in an insulin-responsive intracellular compartment. This observation was confirmed by identifying the transporters by immunoblotting using an antibody generated against the human erythrocyte transporter. The molecular weight of this transporter increases over differentiation from a single band of 40kDa to a heterogeneous triplet of 40, 44 and 48kDa. These data suggest that the transporter undergoes differential processing and that the functional, insulin-responsive transporter may be different from the insulin-insensitive (basal) transporter

  8. Minor long-term changes in weight have beneficial effects on insulin sensitivity and beta-cell function in obese subjects

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Hendel, Helle Westergren; Rasmussen, M H

    2002-01-01

    To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function.......To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function....

  9. Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome.

    Science.gov (United States)

    Yilmaz, Murat; Bukan, Neslihan; Ersoy, Reyhan; Karakoç, Ayhan; Yetkin, Ilhan; Ayvaz, Göksun; Cakir, Nuri; Arslan, Metin

    2005-09-01

    The aim of the present study was to evaluate insulin resistance (IR), glucose tolerance status and cardiovascular risk factors in first degree relatives of patients with polycystic ovary syndrome (PCOS). A total of 120 family members [Mothers(PCOS) (n = 40), Fathers(PCOS) (n = 38), Sisters(PCOS) (n = 25) and Brothers(PCOS) (n = 17)] of 55 patients with PCOS and 75 unrelated healthy control subjects without a family history of diabetes or PCOS (four age- and weight-matched subgroups, i.e. Control(Mothers), Control(Fathers), Control(Sisters) and Control(Brothers)) were studied. IR was assessed by homeostatic model assessment (HOMA IR), log HOMA, insulin sensivity index (ISI), the quantitative insulin sensitivity check index (QUICKI) and area under the curve for insulin during the oral glucose tolerance test (AUCI, AUCG) in with normal glucose tolerance (NGT) subjects and controls. Serum adiponectin, resistin, homocysteine and lipid levels were measured. The prevalence of any degree of glucose intolerance was 40% in Mothers(PCOS) and 52% in Fathers(PCOS). In total, six (15%) glucose tolerance disorders were identified in the Control(Mothers) and Control(Fathers) in first degree relatives of control subjects. The first degree relatives of PCOS patients had significantly higher serum fasting insulin, HOMA-IR, Log HOMA and AUCI levels in all subgroups than the control subjects. The control subjects had significantly elevated QUCKI, ISI levels and serum adiponectin levels compared to the first degree relatives of PCOS subjects in all subgroups. The serum Hcy and resistin levels increased significantly in both Fathers(PCOS) and Mothers(PCOS) groups but not Brothers(PCOS) and Sister(PCOS). The results of the present study support the finding that the first degree relatives of PCOS patients carry an increased risk of cardiovascular disease, as do PCOS patients.

  10. Effect of Moderate Alcohol Consumption on Adiponectin, Tumor Necrosis Factor-α, and Insulin Sensitivity

    NARCIS (Netherlands)

    Sierksma, A.; Patel, H.; Ouchi, N.; Kihara, S.; Funahashi, T.; Heine, R.J.; Grobbee, D.E.; Kluft, C.; Hendriks, H.F.J.

    2004-01-01

    OBJECTIVE - Epidemiological studies suggest that moderate alcohol consumers have enhanced insulin sensitivity and a reduced risk of type 2 diabetes. Adiponectin, an adipocyte-derived plasma protein, has been found to be negatively associated with adiposity and positively associated with insulin

  11. Serum Is Not Necessary for Prior Pharmacological Activation of AMPK to Increase Insulin Sensitivity of Mouse Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Nicolas O. Jørgensen

    2018-04-01

    Full Text Available Exercise, contraction, and pharmacological activation of AMP-activated protein kinase (AMPK by 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR have all been shown to increase muscle insulin sensitivity for glucose uptake. Intriguingly, improvements in insulin sensitivity following contraction of isolated rat and mouse skeletal muscle and prior AICAR stimulation of isolated rat skeletal muscle seem to depend on an unknown factor present in serum. One study recently questioned this requirement of a serum factor by showing serum-independency with muscle from old rats. Whether a serum factor is necessary for prior AICAR stimulation to increase insulin sensitivity of mouse skeletal muscle is not known. Therefore, we investigated the necessity of serum for this effect of AICAR in mouse skeletal muscle. We found that the ability of prior AICAR stimulation to improve insulin sensitivity of mouse skeletal muscle did not depend on the presence of serum during AICAR stimulation. Although prior AICAR stimulation did not enhance proximal insulin signaling, insulin-stimulated phosphorylation of Tre-2/BUB2/CDC16- domain family member 4 (TBC1D4 Ser711 was greater in prior AICAR-stimulated muscle compared to all other groups. These results imply that the presence of a serum factor is not necessary for prior AMPK activation by AICAR to enhance insulin sensitivity of mouse skeletal muscle.

  12. Drug discovery opportunities and challenges at G protein coupled receptors for long chain free fatty acids

    Directory of Open Access Journals (Sweden)

    Nicholas D Holliday

    2012-01-01

    Full Text Available Discovery of G protein coupled receptors for long chain free fatty acids (FFAs, FFA1 (GPR40 and GPR120, has expanded our understanding of these nutrients as signalling molecules. These receptors have emerged as important sensors for FFA levels in the circulation or the gut lumen, based on evidence from in vitro and rodent models, and an increasing number of human studies. Here we consider their promise as therapeutic targets for metabolic disease, including type 2 diabetes and obesity. FFA1 directly mediates acute FFA-induced glucose-stimulated insulin secretion in pancreatic beta-cells, while GPR120 and FFA1 trigger release of incretins from intestinal endocrine cells, and so indirectly enhance insulin secretion and promote satiety. GPR120 signalling in adipocytes and macrophages also results in insulin sensitizing and beneficial anti-inflammatory effects. Drug discovery has focussed on agonists to replicate acute benefits of FFA receptor signalling, with promising early results for FFA1 agonists in man. Controversy surrounding chronic effects of FFA1 on beta-cells illustrates that long term benefits of antagonists also need exploring. It has proved challenging to generate highly selective potent ligands for FFA1 or GPR120 subtypes, given that both receptors have hydrophobic orthosteric binding sites, which are not completely defined and have modest ligand affinity. Structure activity relationships are also reliant on functional read outs, in the absence of robust binding assays to provide direct affinity estimates. Nevertheless synthetic ligands have already helped dissect specific contributions of FFA1 and GPR120 signalling from the many possible cellular effects of FFAs. Approaches including use of fluorescent ligand binding assays, and targeting allosteric receptor sites, may improve further preclinical ligand development at these receptors, to exploit their unique potential to target multiple facets of diabetes.

  13. P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

    Science.gov (United States)

    Varshney, Pallavi; Dey, Chinmoy Sankar

    2016-07-05

    P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Vitamin D intake is associated with insulin sensitivity in African American, but not European American, women

    Directory of Open Access Journals (Sweden)

    Oster Robert A

    2010-04-01

    Full Text Available Abstract Background The prevalence of type 2 diabetes is higher among African Americans (AA vs European Americans (EA, independent of obesity and other known confounders. Although the reason for this disparity is not known, it is possible that relatively low levels of vitamin D among AA may contribute, as vitamin D has been positively associated with insulin sensitivity in some studies. The objective of this study was to test the hypothesis that dietary vitamin D would be associated with a robust measure of insulin sensitivity in AA and EA women. Methods Subjects were 115 African American (AA and 137 European American (EA healthy, premenopausal women. Dietary intake was determined with 4-day food records; the insulin sensitivity index (SI with a frequently-sampled intravenous glucose tolerance test and minimal modeling; the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR with fasting insulin and glucose; and body composition with dual-energy X-ray absorptiometry. Results Vitamin D intake was positively associated with SI (standardized β = 0.18, P = 0.05 and inversely associated with HOMA-IR (standardized β = -0.26, P = 0.007 in AA, and the relationships were independent of age, total body fat, energy intake, and % kcal from fat. Vitamin D intake was not significantly associated with indices of insulin sensitivity/resistance in EA (standardized β = 0.03, P = 0.74 and standardized β = 0.02, P = 0.85 for SI and HOMA-IR, respectively. Similar to vitamin D, dietary calcium was associated with SI and HOMA-IR among AA but not EA. Conclusions This study provides novel findings that dietary vitamin D and calcium were independently associated with insulin sensitivity in AA, but not EA. Promotion of these nutrients in the diet may reduce health disparities in type 2 diabetes risk among AA, although longitudinal and intervention studies are required.

  15. A low-fat diet improves peripheral insulin sensitivity in patients with Type 1 diabetes

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Almdal, T; Viggers, L

    2006-01-01

    To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes.......To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes....

  16. Lipid droplet size and location in human skeletal muscle fibers are associated with insulin sensitivity

    DEFF Research Database (Denmark)

    Nielsen, Joachim; Christensen, Anders E; Nellemann, Birgitte

    2017-01-01

    In skeletal muscle, an accumulation of lipid droplets (LDs) in the subsarcolemmal space is associated with insulin resistance, but the underlying mechanism is not clear. We aimed to investigate how the size, number and location of LDs are associated with insulin sensitivity and muscle fiber types...... are associated with insulin resistance in skeletal muscle....

  17. Association of oxidative status and insulin sensitivity in periparturient dairy cattle: an observational study.

    Science.gov (United States)

    Abuelo, A; Hernández, J; Benedito, J L; Castillo, C

    2016-04-01

    Post-parturient insulin resistance (IR) is a common feature in all mammalian animals. However, in dairy cows, it can be exacerbated because of high milk yield, leading to excessive negative energy balance, which is related with increased disease incidence, reduced milk production and worsened reproductive performance. IR has been extensively investigated in humans suffering from diabetes mellitus. In these subjects, it is known that oxidative stress (OS) plays a causative role in the onset of IR. Although OS occurs in transitional dairy cattle, there are yet no studies that investigated the association between IR and OS in dairy cattle. Therefore, the aim of this study was to investigate whether there is a relationship between OS and IR in dairy cattle. Serum samples were taken repeatedly from 22 dairy cows from 2 months prior to the expected calving date to 2 months after calving and were analysed for markers of metabolic and redox balance. Surrogate indices of insulin sensitivity were also calculated. Generalised linear mixed models revealed an effect of the oxidative status on peripheral insulin concentration and on indices of insulin sensitivity. Hence, field trials should investigate the effectiveness of antioxidant therapy on insulin sensitivity in peripheral tissues during the transition period of dairy cattle. Journal of Animal Physiology and Animal Nutrition © 2015 Blackwell Verlag GmbH.

  18. pH sensitive thiolated cationic hydrogel for oral insulin delivery.

    Science.gov (United States)

    Sonia, T A; Sharma, Chandra P

    2014-04-01

    The objective of this work is to study the efficacy of pH sensitive thiolated Polydimethylaminoethylmethacrylate for oral delivery of insulin. Synthesis of pH sensitive thiolated Polydimethylaminoethylmethacrylate (PDCPA) was carried out by crosslinking Polymethacrylic acid with thiolated Polydimethylaminoethylmethacrylate (PDCys) via carbodiimide chemistry. Prior to in vivo experiment, various physicochemical and biological characterisation were carried out to evaluate the efficacy of PDCPA. Modification was confirmed by IR and NMR spectroscopy. The particle size was found to be 284 nm with a zeta potential of 37.3+/-1.58 mV. Texture analyser measurements showed that PDCPA is more mucoadhesive than the parent polymer. Transepithelial electrical measurements showed a reduction of greater than 50% on incubation with PDCPA particles. Permeation studies showed that PDCPA is more permeable than the parent polymer. On in vivo evaluation on male diabetic rats, insulin loaded PDCPA exhibited a blood glucose reduction of 19%.

  19. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study

    DEFF Research Database (Denmark)

    Tabák, A.G.; Jokela, M.; Akbaraly, T.N.

    2009-01-01

    BACKGROUND: Little is known about the timing of changes in glucose metabolism before occurrence of type 2 diabetes. We aimed to characterise trajectories of fasting and postload glucose, insulin sensitivity, and insulin secretion in individuals who develop type 2 diabetes. METHODS: We analysed data...... from our prospective occupational cohort study (Whitehall II study) of 6538 (71% male and 91% white) British civil servants without diabetes mellitus at baseline. During a median follow-up period of 9.7 years, 505 diabetes cases were diagnosed (49.1% on the basis of oral glucose tolerance test). We...... assessed retrospective trajectories of fasting and 2-h postload glucose, homoeostasis model assessment (HOMA) insulin sensitivity, and HOMA beta-cell function from up to 13 years before diabetes diagnosis (diabetic group) or at the end of follow-up (non-diabetics). FINDINGS: Multilevel models adjusted...

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

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-12-01

    Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

  1. Normocaloric Diet Restores Weight Gain and Insulin Sensitivity in Obese Mice

    OpenAIRE

    Lombardo, Giovanni Enrico; Arcidiacono, Biagio; De Rose, Roberta Francesca; Lepore, Saverio Massimo; Costa, Nicola; Montalcini, Tiziana; Brunetti, Antonio; Russo, Diego; De Sarro, Giovambattista; Celano, Marilena

    2016-01-01

    An increased incidence of obesity is registered worldwide, and its association with insulin resistance and type 2 diabetes is closely related with increased morbidity and mortality for cardiovascular diseases. A major clinical problem in the management of obesity is the non-adherence or low adherence of patients to a hypo-caloric dietetic restriction. In this study we evaluated in obese mice the effects on insulin sensitivity of shifting from high-calorie foods to normal diet. Male C57BL/6Jol...

  2. Over-expression of Follistatin-like 3 attenuates fat accumulation and improves insulin sensitivity in mice

    DEFF Research Database (Denmark)

    Brandt, Claus; Hansen, Rasmus Hvass; Hansen, Jakob Bondo

    2015-01-01

    -fat feeding. Body weight, food intake, fat accumulation by MR scanning, and glucose, insulin and glucagon tolerance were evaluated, as was the response in body weight and metabolic parameters to 24h fasting. Effects of fstl3 on pancreatic insulin and glucagon content, and pancreatic islet morphology were......OBJECTIVE: Follistatin-like 3 (fstl3), a natural inhibitor of members of the TGF-β family, increases during resistance training in human plasma. Fstl3 primarily binds myostatin and activin A, and thereby inhibits their functions. We hypothesize that blocking myostatin and activin A signalling....../glucagon ratio. Accordingly, fstl3 transfection improved counter-regulation to 24h fasting. CONCLUSION: Fstl3 over-expression regulates insulin and glucagon sensitivities through increased muscular insulin action, as well as increased hepatic glucagon sensitivity and pancreatic glucagon content....

  3. Insulin resistance in drug naive patients with multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Kostić Smiljana

    2017-01-01

    Full Text Available Background/Aim. Due to the fact that there is a relatively small number of data related to systemic insulin abnormalities in the multiple sclerosis (MS, the main objective of our study was to determine whether a dysbalance of glucose and insulin metabolism exist in patients with natural course of MS. Our hypothesis was that the metabolic disorder that characterizes state of the insulin resistance (IR and reduced insulin sensitivity (IS in untreated patients with MS could play a role in disease progression and degree of functional disability. Methods. The study included 31 patients with relapsing-remitting (RR MS and 14 healthy controls from the same geographic area matched by age, ethnicity and number of smokers. The glucose tolerance, IS, and IR were examined using an oral glucose tolerance test (OGTT and using basal plasma glucose and insulin levels. The functional disability and disease progression were evaluated by the Expanded Disability Status Scale (EDSS and Multiple Sclerosis Severity Score (MSSS. Results. The MS patients tolerated glucose equally well as the healthy controls. Basal concentrations of insulin were significantly higher in the MS group (p < 0.05, as well as insulin plasma level 30 min after oral glucose load (p < 0.01. The patients with MS had significantly higher values of homeostasis model assessment indexes of IR (HOMA-IR (p = 0.027; p = 0.028. The percentage of IS (HOMA2 %S and whole body IS index (ISI Matsuda showed significantly lower values in the MS patients than in the controls (p = 0.005; p = 0.001. The insulinogenic index in the first 30 min of OGTT was significantly higher in MS patients (p = 0.005. The measures of functional disability and MS progression did not correlate significantly with the investigated parameters of IR and IS indexes. Conclusion. This study demonstrates for the first time the existence of hyperinsulinemia, reduced insulin sensitivity and normal glucose tolerance that indicate the initial

  4. [Primary study on characteristics of insulin secretion rate, metabolic clearance rate and sensitivity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees].

    Science.gov (United States)

    Ran, J; Cheng, H; Li, F

    2000-01-01

    To investigate the characteristics of insulin secretion rate (ISR), metabolic clearance rate (MCR-I) and sensitivity and to explore their relationship with obesity in non-insulin-dependent diabetic subjects from multiplex diabetic pedigrees (MDP). Fifteen subjects with normal glucose tolerance and 11 non-insulin-dependent diabetic patients from MDP were included in the study. Frequently sampled intravenous glucose tolerance test (FSIVGTT) was performed. Glucose, insulin (INS) and connecting-peptide (C-P) concentrations were measured. A computer procedure devised by our laboratory was used to calculate the value of ISR at each time point, then MCR-I was acquired. Insulin sensitivity index (SI) was calculated according to minimal model technique about glucose in FSIVGTT. The ISR curve in control group was biphasic, while in non-insulin. In non-insulin-dependent diabetic group, areas under the curves of C-P (AUCC) and ISR level (AUCS) measured during 0 approximately 16 min were 7.9 nmol.min(-1).L(-1) +/- 2.8 nmol.min(-1).L(-1), and 6.1 nmol +/- 2.2 nmol, respectively, which were significantly lower than those in control group 17.7 nmol.min(-1).L(-1) +/- 4.92 nmol.min(-1).L(-1) and 12.3 nmol +/- 3.9 nmol (P < 0.01). The two parameters were slightly higher than those in control group 155 nmol.min(-1).L(-1) +/- 44 nmol.min(-1).L(-1) vs 101 nmol.min(-1).L(-1) +/- 30 nmol.min(-1).L(-1) and 76 nmol +/- 26 nmol vs 54 nmol +/- 20.0 nmol (P < 0.05)measured during 16 approximately 180 min. There was no significant difference, between the two groups about the amount of insulin secretion during 3 hours (82 nmol +/- 28nmol vs 68 nmol +/- 21 nmol, P = 0.2). In control group, there were significant positive correlation, between AUCS, waist-hip ratio (WHR), and body surface area, (BSA) and significant negative correlation between MCR-I, SI and WHR, BSA (P < 0.01), and also between MCR-I and SI. In non-insulin-dependent diabetic group, AUCS were significantly correlated with body mass

  5. Subthalamic nucleus stimulation does not influence basal glucose metabolism or insulin sensitivity in patients with Parkinson's disease.

    Science.gov (United States)

    Lammers, Nicolette M; Sondermeijer, Brigitte M; Twickler, Th B Marcel; de Bie, Rob M; Ackermans, Mariëtte T; Fliers, Eric; Schuurman, P Richard; La Fleur, Susanne E; Serlie, Mireille J

    2014-01-01

    Animal studies have shown that central dopamine signaling influences glucose metabolism. As a first step to show this association in an experimental setting in humans, we studied whether deep brain stimulation (DBS) of the subthalamic nucleus (STN), which modulates the basal ganglia circuitry, alters basal endogenous glucose production (EGP) or insulin sensitivity in patients with Parkinson's disease (PD). We studied 8 patients with PD treated with DBS STN, in the basal state and during a hyperinsulinemic euglycemic clamp using a stable glucose isotope, in the stimulated and non-stimulated condition. We measured EGP, hepatic insulin sensitivity, peripheral insulin sensitivity (Rd), resting energy expenditure (REE), glucoregulatory hormones, and Parkinson symptoms, using the Unified Parkinson's Disease Rating Scale (UPDRS). Basal plasma glucose and EGP did not differ between the stimulated and non-stimulated condition. Hepatic insulin sensitivity was similar in both conditions and there were no significant differences in Rd and plasma glucoregulatory hormones between DBS on and DBS off. UPDRS was significantly higher in the non-stimulated condition. DBS of the STN in patients with PD does not influence basal EGP or insulin sensitivity. These results suggest that acute modulation of the motor basal ganglia circuitry does not affect glucose metabolism in humans.

  6. Effects of 7 days of exercise training on insulin sensitivity and responsiveness in type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Kirwan, John P; Solomon, Thomas; Wojta, Daniel M

    2009-01-01

    sensitivity and responsiveness and 2) short-term exercise training results in improved suppression of hepatic glucose production by insulin. Fourteen obese patients with type 2 diabetes, age 64 +/- 2 yr, underwent a two-stage hyperinsulinemic euglycemic clamp procedure, first stage 40 mU.m(-2).min(-1) insulin......The objectives of this study were to determine whether 1) the improvement in insulin action induced by short-term exercise training in patients with type 2 diabetes is due to an improvement in insulin sensitivity, an improvement in insulin responsiveness, or a combination of improved insulin...... infusion, second stage 1,000 mU.m(-2).min(-1) insulin infusion, together with a [3-(3)H]glucose infusion, before and after 7 days of exercise. The training consisted of 30 min of cycling and 30 min of treadmill walking at approximately 70% of maximal aerobic capacity daily for 7 days. The exercise program...

  7. Long-term treatment with losartan versus atenolol improves insulin sensitivity in hypertension: ICARUS, a LIFE substudy

    DEFF Research Database (Denmark)

    Olsen, Michael H; Fossum, Eigil; Høieggen, Aud

    2005-01-01

    Hypertension and insulin resistance might be associated through peripheral vascular hypertrophy/rarefaction which compromises skeletal muscle blood flow and decreases glucose uptake, inducing insulin resistance. We hypothesized that treatment with losartan as compared to atenolol would improve...... insulin sensitivity through regression of peripheral vascular hypertrophy/rarefaction....

  8. Increased abundance of insulin/insulin-like growth factor-I hybrid receptors in skeletal muscle of obese subjects is correlated with in vivo insulin sensitivity.

    Science.gov (United States)

    Federici, M; Porzio, O; Lauro, D; Borboni, P; Giovannone, B; Zucaro, L; Hribal, M L; Sesti, G

    1998-08-01

    We reported that in noninsulin-dependent diabetes melitus (NIDDM) patients expression of insulin/insulin-like growth factor I (IGF-I) hybrid receptors is increased in insulin target tissues. Whether this is a defect associated with NIDDM or represents a generalized abnormality associated with insulin resistant states is still unsettled. To address this, we applied a microwell-based immunoassay to measure abundance of insulin receptors, type 1 IGF receptors, and hybrid receptors in muscle of eight normal and eight obese subjects. Maximal insulin binding to insulin receptors was lower in obese than in control subjects (B/T = 1.8 +/- 0.20 and 2.6 +/- 0.30; P < 0.03, respectively) and was negatively correlated with insulinemia (r = -0.60; P < 0.01). Maximal IGF-I binding to type 1 IGF receptors was higher in obese than in controls (B/T = 1.9 +/- 0.20 and 0.86 +/- 0.10; P < 0.0001, respectively) and was negatively correlated with plasma IGF-I levels (r = -0.69; P < 0.003). Hybrid receptor abundance was higher in obese than in normal subjects (B/T = 1.21 +/- 0.14 and 0.44 +/- 0.06; P < 0.0003, respectively) and was negatively correlated with insulin binding (r = -0.60; P < 0.01) and positively correlated with IGF-I binding (r = 0.92; P < 0.0001). Increased abundance of hybrids was correlated with insulinemia (r = 0.70; P < 0.002) and body mass index (r = 0.71; P < 0.0019), whereas it was negatively correlated with in vivo insulin sensitivity measured by ITT (r = -0.67; P < 0.016). These results indicate that downregulation of insulin receptors or upregulation of type 1 IGF receptors because of changes in plasma insulin and IGF-I levels may result in modifications in hybrid receptor abundance.

  9. [Effects of triterpenoid from Psidium guajava leaves ursolic acid on proliferation, differentiation of 3T3-L1 preadipocyte and insulin resistance].

    Science.gov (United States)

    Lin, Juan-Na; Kuang, Qiao-Ting; Ye, Kai-He; Ye, Chun-Ling; Huang, Yi; Zhang, Xiao-Qi; Ye, Wen-Cai

    2013-08-01

    To investigate the influences of triterpenoid from Psidium guajava Leaves (ursolic acid) on the proliferation, differentiation of 3T3-L1 preadipocyte, and its possible mechanism treat for insulin resistance. 3T3-L1 preadipocyte was cultured in vitro. After adding ursolic acid to the culture medium for 48h, the cell viability was tested by MTT assay. Induced for 6 days, the lipid accumulation of adipocyte was measured by Oil Red O staining. The insulin resistant cell model was established with Dexamethasone. Cellular glucose uptake was determined with GOD-POD assays and FFA concentration was determined at the time of 48h. Secreted adiponectin were measured by ELISA. The protein levels of PPARgamma and PTP1B in insulin resistant adipocyte were measured by Western Blotting. Compared with medium control group, 30, 100 micromol/L ursolic acid could increase its proliferation and differentiation significantly (P 0.05). Ursolic acid can improve the proliferation and differentiation of 3T3-L1 preadipocyte, enhance cellular glucose uptake, inhibit the production of FFA, promote the secretion of adiponectin insulin resistant adipocyte, its mechanism may be related to upregulating the expression of PPARgamma protein.

  10. Effect of High Fat and High Sugar Diet on Glucose Tolerance, Insulin Response to Glucose Load and Insulin Sensitivity in Rats

    OpenAIRE

    岡﨑, 悟

    1987-01-01

    To investigate the precipitating effects of the westernized diet on diabetes mellitus, glucose tolerance and insulin response to oral glucose load (1.5g/kg body weight) and insulin sensitivity to exogenous insulin (0.2U/kg) were studied in rats fed an experimental diet for 8 weeks. Four experimental diets were used : low fat-no sugar diet (energy ratio of 10% fat, 70% starch, a model of the traditional Japanese diet), high fat-high sugar diet (40% fat, 20% starch, 20% sugar, a model of the we...

  11. Synthesis of cytochrome c oxidase 1 (SCO1) inhibits insulin sensitivity by decreasing copper levels in adipocytes.

    Science.gov (United States)

    Wei, Xiang-Bo; Guo, Liang; Liu, Yang; Zhou, Shui-Rong; Liu, Yuan; Dou, Xin; Du, Shao-Yue; Ding, Meng; Peng, Wan-Qiu; Qian, Shu-Wen; Huang, Hai-Yan; Tang, Qi-Qun

    2017-09-23

    Dysregulation of insulin signaling leads to type 2 diabetes mellitus (T2DM) and other metabolic disorders. Obesity is an important contributor to insulin resistance, and although the understanding of this relationship has improved in recent years, the mechanism of obesity-induced insulin resistance is not completely understood. Disorders of copper metabolism tend to accompany the development of obesity, which increases the risk of insulin resistance. Synthesis of cytochrome c oxidase 1 (SCO1) functions in the assembly of cytochrome c oxidase (COX) and cellular copper homeostasis. However, the role of SCO1 in the regulation of metabolism remains unknown. Here, we found that obese mice had higher expression of SCO1 and lower levels of copper in white adipose tissue (WAT) than did the control mice. Overexpression of SCO1 in adipocytes was associated with copper deficiency. Copper increased insulin sensitivity by decreasing the level of phosphatase and tensin homolog (PTEN) protein. Ectopic expression of SCO1 led to insulin resistance and was accompanied by a decrease in intracellular copper level, and addition of copper abolished the inhibitory effect of SCO1 on insulin sensitivity. Our results demonstrated a novel role of SCO1 in modulating insulin sensitivity via the regulation of copper concentration in WAT and suggested a potential therapeutic target for T2DM. Copyright © 2017. Published by Elsevier Inc.

  12. Design and clinical pilot testing of the model-based dynamic insulin sensitivity and secretion test (DISST).

    Science.gov (United States)

    Lotz, Thomas F; Chase, J Geoffrey; McAuley, Kirsten A; Shaw, Geoffrey M; Docherty, Paul D; Berkeley, Juliet E; Williams, Sheila M; Hann, Christopher E; Mann, Jim I

    2010-11-01

    Insulin resistance is a significant risk factor in the pathogenesis of type 2 diabetes. This article presents pilot study results of the dynamic insulin sensitivity and secretion test (DISST), a high-resolution, low-intensity test to diagnose insulin sensitivity (IS) and characterize pancreatic insulin secretion in response to a (small) glucose challenge. This pilot study examines the effect of glucose and insulin dose on the DISST, and tests its repeatability. DISST tests were performed on 16 subjects randomly allocated to low (5 g glucose, 0.5 U insulin), medium (10 g glucose, 1 U insulin) and high dose (20 g glucose, 2 U insulin) protocols. Two or three tests were performed on each subject a few days apart. Average variability in IS between low and medium dose was 10.3% (p=.50) and between medium and high dose 6.0% (p=.87). Geometric mean variability between tests was 6.0% (multiplicative standard deviation (MSD) 4.9%). Geometric mean variability in first phase endogenous insulin response was 6.8% (MSD 2.2%). Results were most consistent in subjects with low IS. These findings suggest that DISST may be an easily performed dynamic test to quantify IS with high resolution, especially among those with reduced IS. © 2010 Diabetes Technology Society.

  13. Developing and testing the density of states FFA method in the SU(3) spin model

    Energy Technology Data Exchange (ETDEWEB)

    Giuliani, Mario; Gattringer, Christof, E-mail: christof.gattringer@uni-graz.at; Törek, Pascal

    2016-12-15

    The Density of States Functional Fit Approach (DoS FFA) is a recently proposed modern density of states technique suitable for calculations in lattice field theories with a complex action problem. In this article we present an exploratory implementation of DoS FFA for the SU(3) spin system at finite chemical potential μ – an effective theory for the Polyakov loop. This model has a complex action problem similar to the one of QCD but also allows for a dual simulation in terms of worldlines where the complex action problem is solved. Thus we can compare the DoS FFA results to the reference data from the dual simulation and assess the performance of the new approach. We find that the method reproduces the observables from the dual simulation for a large range of μ values, including also phase transitions, illustrating that DoS FFA is an interesting approach for exploring phase diagrams of lattice field theories with a complex action problem.

  14. Validation of different measures of insulin sensitivity of glucose metabolism in dairy cows using the hyperinsulinemic euglycemic clamp test as the gold standard.

    Science.gov (United States)

    De Koster, J; Hostens, M; Hermans, K; Van den Broeck, W; Opsomer, G

    2016-10-01

    The aim of the present research was to compare different measures of insulin sensitivity in dairy cows at the end of the dry period. To do so, 10 clinically healthy dairy cows with a varying body condition score were selected. By performing hyperinsulinemic euglycemic clamp (HEC) tests, we previously demonstrated a negative association between the insulin sensitivity and insulin responsiveness of glucose metabolism and the body condition score of these animals. In the same animals, other measures of insulin sensitivity were determined and the correlation with the HEC test, which is considered as the gold standard, was calculated. Measures derived from the intravenous glucose tolerance test (IVGTT) are based on the disappearance of glucose after an intravenous glucose bolus. Glucose concentrations during the IVGTT were used to calculate the area under the curve of glucose and the clearance rate of glucose. In addition, glucose and insulin data from the IVGTT were fitted in the minimal model to derive the insulin sensitivity parameter, Si. Based on blood samples taken before the start of the IVGTT, basal concentrations of glucose, insulin, NEFA, and β-hydroxybutyrate were determined and used to calculate surrogate indices for insulin sensitivity, such as the homeostasis model of insulin resistance, the quantitative insulin sensitivity check index, the revised quantitative insulin sensitivity check index and the revised quantitative insulin sensitivity check index including β-hydroxybutyrate. Correlation analysis revealed no association between the results obtained by the HEC test and any of the surrogate indices for insulin sensitivity. For the measures derived from the IVGTT, the area under the curve for the first 60 min of the test and the Si derived from the minimal model demonstrated good correlation with the gold standard. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Glycine Increases Insulin Sensitivity and Glutathione Biosynthesis and Protects against Oxidative Stress in a Model of Sucrose-Induced Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Mohammed El-Hafidi

    2018-01-01

    Full Text Available Oxidative stress and redox status play a central role in the link between insulin resistance (IR and lipotoxicity in metabolic syndrome. This mechanistic link may involve alterations in the glutathione redox state. We examined the effect of glycine supplementation to diet on glutathione biosynthesis, oxidative stress, IR, and insulin cell signaling in liver from sucrose-fed (SF rats characterized by IR and oxidative stress. Our hypothesis is that the correction of glutathione levels by glycine treatment leads to reduced oxidative stress, a mechanism associated with improved insulin signaling and IR. Glycine treatment decreases the levels of oxidative stress markers in liver from SF rats and increases the concentrations of glutathione (GSH and γ-glutamylcysteine and the amount of γ-glutamylcysteine synthetase (γ-GCS, a key enzyme of GSH biosynthesis in liver from SF rats. In liver from SF rats, glycine also decreases the insulin-induced phosphorylation of insulin receptor substrate-1 (ISR-1 in serine residue and increases the phosphorylation of insulin receptor β-subunit (IR-β in tyrosine residue. Thus, supplementing diets with glycine to correct GSH deficiency and to reduce oxidative stress provides significant metabolic benefits to SF rats by improving insulin sensitivity.

  16. Global transcriptome profiling identifies KLF15 and SLC25A10 as modifiers of adipocytes insulin sensitivity in obese women.

    Directory of Open Access Journals (Sweden)

    Agné Kulyté

    Full Text Available Although the mechanisms linking obesity to insulin resistance (IR and type 2 diabetes (T2D are not entirely understood, it is likely that alterations of adipose tissue function are involved. The aim of this study was to identify new genes controlling insulin sensitivity in adipocytes from obese women with either insulin resistant (OIR or sensitive (OIS adipocytes. Insulin sensitivity was first determined by measuring lipogenesis in isolated adipocytes from abdominal subcutaneous white adipose tissue (WAT in a large observational study. Lipogenesis was measured under conditions where glucose transport was the rate limiting step and reflects in vivo insulin sensitivity. We then performed microarray-based transcriptome profiling on subcutaneous WAT specimen from a subgroup of 9 lean, 21 OIS and 18 obese OIR women. We could identify 432 genes that were differentially expressed between the OIR and OIS group (FDR ≤5%. These genes are enriched in pathways related to glucose and amino acid metabolism, cellular respiration, and insulin signaling, and include genes such as SLC2A4, AKT2, as well as genes coding for enzymes in the mitochondria respiratory chain. Two IR-associated genes, KLF15 encoding a transcription factor and SLC25A10 encoding a dicarboxylate carrier, were selected for functional evaluation in adipocytes differentiated in vitro. Knockdown of KLF15 and SLC25A10 using siRNA inhibited insulin-stimulated lipogenesis in adipocytes. Transcriptome profiling of siRNA-treated cells suggested that KLF15 might control insulin sensitivity by influencing expression of PPARG, PXMP2, AQP7, LPL and genes in the mitochondrial respiratory chain. Knockdown of SLC25A10 had only modest impact on the transcriptome, suggesting that it might directly influence insulin sensitivity in adipocytes independently of transcription due to its important role in fatty acid synthesis. In summary, this study identifies novel genes associated with insulin sensitivity in

  17. A Single Day of Excessive Dietary Fat Intake Reduces Whole-Body Insulin Sensitivity: The Metabolic Consequence of Binge Eating

    Directory of Open Access Journals (Sweden)

    Siôn A. Parry

    2017-07-01

    Full Text Available Consuming excessive amounts of energy as dietary fat for several days or weeks can impair glycemic control and reduce insulin sensitivity in healthy adults. However, individuals who demonstrate binge eating behavior overconsume for much shorter periods of time; the metabolic consequences of such behavior remain unknown. The aim of this study was to determine the effect of a single day of high-fat overfeeding on whole-body insulin sensitivity. Fifteen young, healthy adults underwent an oral glucose tolerance test before and after consuming a high-fat (68% of total energy, high-energy (78% greater than daily requirements diet for one day. Fasting and postprandial plasma concentrations of glucose, insulin, non-esterified fatty acids, and triglyceride were measured and the Matsuda insulin sensitivity index was calculated. One day of high-fat overfeeding increased postprandial glucose area under the curve (AUC by 17.1% (p < 0.0001 and insulin AUC by 16.4% (p = 0.007. Whole-body insulin sensitivity decreased by 28% (p = 0.001. In conclusion, a single day of high-fat, overfeeding impaired whole-body insulin sensitivity in young, healthy adults. This highlights the rapidity with which excessive consumption of calories through high-fat food can impair glucose metabolism, and suggests that acute binge eating may have immediate metabolic health consequences for the individual.

  18. Artemisia Extract Improves Insulin Sensitivity in Women With Gestational Diabetes Mellitus by Up-Regulating Adiponectin.

    Science.gov (United States)

    Sun, Xia; Sun, Hong; Zhang, Jing; Ji, Xianghong

    2016-12-01

    Gestational diabetes mellitus (GDM) has affected a great number of pregnant women worldwide. Artemisia extracts have been found to exhibit a potent antidiabetic effect in the treatment of type 2 diabetes mellitus. We aimed to examine the effects of Artemisia extract on insulin resistance and lipid profiles in pregnant GDM patients. Patients in their second trimester were randomly assigned to the Artemisia extract group (AE) or to a placebo group (PO). They were instructed to consume either AE or PO daily for a period of 10 weeks. Glucose and insulin profiles and adiponectin level were assessed at baseline (week 0) and after the treatment (week 10). Compared to the PO group, fasting plasma glucose, serum insulin levels, homeostasis model of assessment of insulin resistance (HOMA-IR), and β-cell function (HOMA-B) were significantly reduced in the AE group participants. Moreover, levels of circulating adiponectin were also significantly up-regulated in the AE group, which also positively contributed to improved insulin sensitivity. Daily administration of Artemisia extract improves insulin sensitivity by up-regulating adiponectin in women with gestational diabetes mellitus. © 2016, The American College of Clinical Pharmacology.

  19. Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons

    Science.gov (United States)

    Shi, Xuemei; Zhou, Fuguo; Li, Xiaojie; Chang, Benny; Li, Depei; Wang, Yi; Tong, Qingchun; Xu, Yong; Fukuda, Makoto; Zhao, Jean J.; Li, Defa; Burrin, Douglas G.; Chan, Lawrence; Guan, Xinfu

    2013-01-01

    Glucagon-like peptides (GLP-1/2) are co-produced and highlighted as key modulators to improve glucose homeostasis and insulin sensitivity after bariatric surgery. However, it is unknown if CNS GLP-2 plays any physiological role in the control of glucose homeostasis and insulin sensitivity. We show that mice lacking GLP-2 receptor (GLP-2R) in POMC neurons display glucose intolerance and hepatic insulin resistance. GLP-2R activation in POMC neurons is required for GLP-2 to enhance insulin-mediated suppression of hepatic glucose production (HGP) and gluconeogenesis. GLP-2 directly modulates excitability of POMC neurons in GLP-2R- and PI3K-dependent manners. GLP-2 initiates GLP-2R-p85α interaction and facilitates PI3K-Akt-dependent FoxO1 nuclear exclusion in POMC neurons. Central GLP-2 suppresses basal HGP and enhances insulin sensitivity, which are abolished in POMC-p110α KO mice. Thus, CNS GLP-2 plays a key physiological role in the control of hepatic glucose production through activating PI3K-dependent modulation of membrane excitability and nuclear transcription of POMC neurons in the brain. PMID:23823479

  20. Central GLP-2 enhances hepatic insulin sensitivity via activating PI3K signaling in POMC neurons.

    Science.gov (United States)

    Shi, Xuemei; Zhou, Fuguo; Li, Xiaojie; Chang, Benny; Li, Depei; Wang, Yi; Tong, Qingchun; Xu, Yong; Fukuda, Makoto; Zhao, Jean J; Li, Defa; Burrin, Douglas G; Chan, Lawrence; Guan, Xinfu

    2013-07-02

    Glucagon-like peptides (GLP-1/GLP-2) are coproduced and highlighted as key modulators to improve glucose homeostasis and insulin sensitivity after bariatric surgery. However, it is unknown if CNS GLP-2 plays any physiological role in the control of glucose homeostasis and insulin sensitivity. We show that mice lacking GLP-2 receptor (GLP-2R) in POMC neurons display glucose intolerance and hepatic insulin resistance. GLP-2R activation in POMC neurons is required for GLP-2 to enhance insulin-mediated suppression of hepatic glucose production (HGP) and gluconeogenesis. GLP-2 directly modulates excitability of POMC neurons in GLP-2R- and PI3K-dependent manners. GLP-2 initiates GLP-2R-p85α interaction and facilitates PI3K-Akt-dependent FoxO1 nuclear exclusion in POMC neurons. Central GLP-2 suppresses basal HGP and enhances insulin sensitivity, which are abolished in POMC-p110α KO mice. Thus, CNS GLP-2 plays a key physiological role in the control of HGP through activating PI3K-dependent modulation of membrane excitability and nuclear transcription of POMC neurons in the brain. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. A low-fat Diet improves insulin sensitivity in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Rosenfalck, AM; Almdal, Thomas Peter; Viggers, Lone

    2006-01-01

    diet (P = 0.039). The daily protein and carbohydrate intake increased (+4.4% of total energy intake, P = 0.0049 and +2.5%, P = 0.34, respectively), while alcohol intake decreased (-3.2% of total energy intake, P = 0.02). There was a significant improvement in insulin sensitivity on the isocaloric, low-fat......AIMS: To compare the effects on insulin sensitivity, body composition and glycaemic control of the recommended standard weight-maintaining diabetes diet and an isocaloric low-fat diabetes diet during two, 3-month periods in patients with Type 1 diabetes. METHODS: Thirteen Type 1 patients were...... by the insulin clamp technique at baseline and after each of the diet intervention periods. RESULTS: On an isocaloric low-fat diet, Type 1 diabetic patients significantly reduced the proportion of fat in the total daily energy intake by 12.1% (or -3.6% of total energy) as compared with a conventional diabetes...

  2. Researching Effective Strategies to Improve Insulin Sensitivity in Children and Teenagers - RESIST. A randomised control trial investigating the effects of two different diets on insulin sensitivity in young people with insulin resistance and/or pre-diabetes.

    Directory of Open Access Journals (Sweden)

    De Sukanya

    2010-09-01

    Full Text Available Abstract Background Concomitant with the rise in childhood obesity there has been a significant increase in the number of adolescents with clinical features of insulin resistance and prediabetes. Clinical insulin resistance and prediabetes are likely to progress to type 2 diabetes and early atherosclerosis if not targeted for early intervention. There are no efficacy trials of lifestyle intervention in this group to inform clinical practice. The primary aim of this randomised control trial (RCT is to determine the efficacy and effectiveness of two different structured lifestyle interventions differing in diet composition on insulin sensitivity, in adolescents with clinical insulin resistance and/or prediabetes treated with metformin. Methods/design This study protocol describes the design of an ongoing RCT. We are recruiting 108 (54 each treatment arm 10 to 17 year olds with clinical features of insulin resistance and/or prediabetes, through physician referral, into a multi-centred RCT. All participants are prescribed metformin and participate in a diet and exercise program. The lifestyle program is the same for all participants except for diet composition. The diets are a high carbohydrate, low fat diet and a moderate carbohydrate, increased protein diet. The program commences with an intensive 3 month dietary intervention, implemented by trained dietitians, followed by a 3 month intensive gym and home based exercise program, supervised by certified physical trainers. To measure the longer term effectiveness, after the intensive intervention trial participants are managed by either their usual physician or study physician and followed up by the study dietitians for an additional 6 months. The primary outcome measure, change in insulin sensitivity, is measured at 3, 6 and 12 months. Discussion Clinical insulin resistance and prediabetes in the paediatric population are rapidly emerging clinical problems with serious health outcomes. With

  3. Prior AICAR stimulation increases insulin sensitivity in mouse skeletal muscle in an AMPK-dependent manner

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus; Treebak, Jonas Thue; Fentz, Joachim

    2015-01-01

    Acute exercise increases glucose uptake in skeletal muscle by an insulin-independent mechanism. In the period after exercise insulin sensitivity to increase glucose uptake is enhanced. The molecular mechanisms underpinning this phenomenon are poorly understood, but appear to involve an increased ...

  4. Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects.

    Science.gov (United States)

    Reyna, Sara M; Ghosh, Sangeeta; Tantiwong, Puntip; Meka, C S Reddy; Eagan, Phyllis; Jenkinson, Christopher P; Cersosimo, Eugenio; Defronzo, Ralph A; Coletta, Dawn K; Sriwijitkamol, Apiradee; Musi, Nicolas

    2008-10-01

    OBJECTIVE- Tall-like receptor (TLR)4 has been implicated in the pathogenesis of free fatty acid (FFA)-induced insulin resistance by activating inflammatory pathways, including inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB). However, it is not known whether insulin-resistant subjects have abnormal TLR4 signaling. We examined whether insulin-resistant subjects have abnormal TLR4 expression and TLR4-driven (IkappaB/NFkappaB) signaling in skeletal muscle. RESEARCH DESIGN AND METHODS- TLR4 gene expression and protein content were measured in muscle biopsies in 7 lean, 8 obese, and 14 type 2 diabetic subjects. A primary human myotube culture system was used to examine whether FFAs stimulate IkappaB/NFkappaB via TLR4 and whether FFAs increase TLR4 expression/content in muscle. RESULTS- Obese and type 2 diabetic subjects had significantly elevated TLR4 gene expression and protein content in muscle. TLR4 muscle protein content correlated with the severity of insulin resistance. Obese and type 2 diabetic subjects also had lower IkappaBalpha content, an indication of elevated IkappaB/NFkappaB signaling. The increase in TLR4 and NFkappaB signaling was accompanied by elevated expression of the NFkappaB-regulated genes interleukin (IL)-6 and superoxide dismutase (SOD)2. In primary human myotubes, acute palmitate treatment stimulated IkappaB/NFkappaB, and blockade of TLR4 prevented the ability of palmitate to stimulate the IkappaB/NFkappaB pathway. Increased TLR4 content and gene expression observed in muscle from insulin-resistant subjects were reproduced by treating myotubes from lean, normal-glucose-tolerant subjects with palmitate. Palmitate also increased IL-6 and SOD2 gene expression, and this effect was prevented by inhibiting NFkappaB. CONCLUSIONS- Abnormal TLR4 expression and signaling, possibly caused by elevated plasma FFA levels, may contribute to the pathogenesis of insulin resistance in humans.

  5. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease.

    Science.gov (United States)

    Ryan, Marno C; Itsiopoulos, Catherine; Thodis, Tania; Ward, Glenn; Trost, Nicholas; Hofferberth, Sophie; O'Dea, Kerin; Desmond, Paul V; Johnson, Nathan A; Wilson, Andrew M

    2013-07-01

    Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of the Mediterranean diet (MD), a diet high in monounsaturated fatty acids, on steatosis and insulin sensitivity, using gold standard techniques. Twelve non-diabetic subjects (6 Females/6 Males) with biopsy-proven NAFLD were recruited for a randomised, cross-over 6-week dietary intervention study. All subjects undertook both the MD and a control diet, a low fat-high carbohydrate diet (LF/HCD), in random order with a 6-week wash-out period in- between. Insulin sensitivity was determined with a 3-h hyperinsulinemic-euglycemic clamp study and hepatic steatosis was assessed with localized magnetic resonance (1)H spectroscopy ((1)H-MRS). At baseline, subjects were abdominally obese with elevated fasting concentrations of glucose, insulin, triglycerides, ALT, and GGT. Insulin sensitivity at baseline was low (M=2.7 ± 1.0 mg/kg/min(-1)). Mean weight loss was not different between the two diets (p=0.22). There was a significant relative reduction in hepatic steatosis after the MD compared with the LF/HCD: 39 ± 4% versus 7 ± 3%, as measured by (1)H-MRS (p=0.012). Insulin sensitivity improved with the MD, whereas after the LF/HCD there was no change (p=0.03 between diets). Even without weight loss, MD reduces liver steatosis and improves insulin sensitivity in an insulin-resistant population with NAFLD, compared to current dietary advice. This diet should be further investigated in subjects with NAFLD. Copyright © 2013 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice

    Directory of Open Access Journals (Sweden)

    Xiuyuan Zhang

    2016-12-01

    Full Text Available Background/Aims: The endocannabinoid signalling (ECS system has been known to regulate glucose homeostasis. Previous studies have suggested that the cannabinoid 2 (CB2 receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance. Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD/streptozotocin (STZ-induced mice. Methods: Diabetes was induced in male ICR mice by HFD/STZ and exposed to a CB2 receptor agonist, SER601, for 2- or 4-weeks via subcutaneous implantation of osmotic minipumps. Glucose and insulin tolerance tests were performed at the end of treatment. Islets were isolated for assessment of β-cell function. Pancreases and skeletal muscles were also obtained for histological analyses. Results: Despite a lack of impact on glucose tolerance, substantial improvement on insulin sensitivity was observed in SER601-treated mice, which could partly be attributed to improved islet β-cell function, shown as increased glucose-induced insulin secretion and insulin content. No changes on islet macrophage infiltration or skeletal muscle fat deposition were detectable from SER601-treated mice. However, a major decrease in body weight was recorded at the end of 4-week SER601 exposure, accompanied by a lack of epididymal adipose mass in SER601-treated mice. Conclusion: Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity. Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.

  7. The macrophage A2B adenosine receptor regulates tissue insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Hillary Johnston-Cox

    Full Text Available High fat diet (HFD-induced type 2 diabetes continues to be an epidemic with significant risk for various pathologies. Previously, we identified the A2b adenosine receptor (A2bAR, an established regulator of inflammation, as a regulator of HFD-induced insulin resistance. In particular, HFD was associated with vast upregulation of liver A2bAR in control mice, and while mice lacking this receptor showed augmented liver inflammation and tissue insulin resistance. As the A2bAR is expressed in different tissues, here, we provide the first lead to cellular mechanism by demonstrating that the receptor's influence on tissue insulin sensitivity is mediated via its expression in macrophages. This was shown using a newly generated transgenic mouse model expressing the A2bAR gene in the macrophage lineage on an otherwise A2bAR null background. Reinstatement of macrophage A2bAR expression in A2bAR null mice fed HFD restored insulin tolerance and tissue insulin signaling to the level of control mice. The molecular mechanism for this effect involves A2bAR-mediated changes in cyclic adenosine monophosphate in macrophages, reducing the expression and release of inflammatory cytokines, which downregulate insulin receptor-2. Thus, our results illustrate that macrophage A2bAR signaling is needed and sufficient for relaying the protective effect of the A2bAR against HFD-induced tissue inflammation and insulin resistance in mice.

  8. Resistance training associated with the administration of anabolic-androgenic steroids improves insulin sensitivity in ovariectomized rats

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    Urtado CB

    2011-11-01

    Full Text Available Christiano Bertoldo Urtado1,2, Guilherme Borges Pereira3, Marilia Bertoldo Urtado4, Érica Blascovi de Carvalho2, Gerson dos Santos Leite1, Felipe Fedrizzi Donatto1, Claudio de Oliveira Assumpção1, Richard Diego Leite3, Carlos Alberto da Silva1, Marcelo Magalhães de Sales5, Ramires Alsamir Tibana5, Silvia Cristina Crepaldi Alves1, Jonato Prestes51Health Sciences, Methodist University of Piracicaba, Piracicaba, SP, 2Center for Investigation in Pediatrics, Faculty of Medical Sciences, State University of Campinas, Campinas, SP, 3Department of Physiological Sciences, Federal University of São Carlos, São Carlos, SP, 4Laboratory of Orofacial Pain, Division of Oral Physiology, Piracicaba Dental School, State University of Campinas, Campinas, SP, 5Graduation Program in Physical Education, Catholic University of Brasilia, Brasilia, DF, BrazilAbstract: The aim of the present study was to investigate the effects of anabolic-androgenic steroids and resistance training (RT on insulin sensitivity in ovariectomized rats. Adult female Wistar rats were divided into ten experimental groups (n = 5 animals per group: (1 sedentary (Sed-Intact; (2 sedentary ovariectomized (Sed-Ovx; (3 sedentary nandrolone (Sed-Intact-ND; (4 sedentary ovariectomized plus nandrolone (Sed-Ovx-ND; (5 trained (TR-Intact; (6 trained nandrolone (TR-Intact-ND; (7 trained ovariectomized (TR-Ovx; (8 trained ovariectomized plus nandrolone; (9 trained sham; and (10 trained ovariectomized plus sham. Four sessions of RT were used, during which the animals climbed a 1.1 m vertical ladder with weights attached to their tails. The sessions were performed once every 3 days, with between four and nine climbs and with eight to twelve dynamic movements per climb. To test the sensitivity of insulin in the pancreas, glucose and insulin tolerance tests were performed. For insulin sensitivity, there was a statistically significant interaction for the TR-Ovx group, which presented higher sensitivity

  9. Aegeline inspired synthesis of novel β3-AR agonist improves insulin sensitivity in vitro and in vivo models of insulin resistance.

    Science.gov (United States)

    Rajan, Sujith; Satish, Sabbu; Shankar, Kripa; Pandeti, Sukanya; Varshney, Salil; Srivastava, Ankita; Kumar, Durgesh; Gupta, Abhishek; Gupta, Sanchita; Choudhary, Rakhi; Balaramnavar, Vishal M; Narender, Tadigoppula; Gaikwad, Anil N

    2018-03-07

    In our drug discovery program of natural product, earlier we have reported Aegeline that is N-acylated-1-amino-2- alcohol, which was isolated from the leaves of Aeglemarmelos showed anti-hyperlipidemic activity for which the QSAR studies predicted the compound to be the β3-AR agonist, but the mechanism of its action was not elucidated. In our present study, we have evaluated the β3-AR activity of novel N-acyl-1-amino-3-arylopropanol synthetic mimics of aegeline and its beneficial effect in insulin resistance. In this study, we have proposed the novel pharmacophore model using reported molecules for antihyperlipidemic activity. The reported pharmacophore features were also compared with the newly developed pharmacophore model for the observed biological activity. Based on 3D pharmacophore modeling of known β3AR agonist, we screened 20 synthetic derivatives of Aegeline from the literature. From these, the top scoring compound 10C was used for further studies. The in-slico result was further validated in HEK293T cells co-trransfected with human β3-AR and CRE-Luciferase reporter plasmid for β3-AR activity.The most active compound was selected and β3-AR activity was further validated in white and brown adipocytes differentiated from human mesenchymal stem cells (hMSCs). Insulin resistance model developed in hMSC derived adipocytes was used to study the insulin sensitizing property. 8 week HFD fed C57BL6 mice was given 50 mg/Kg of the selected compound and metabolic phenotyping was done to evaluate its anti-diabetic effect. As predicted by in-silico 3D pharmacophore modeling, the compound 10C was found to be the most active and specific β3-AR agonist with EC 50 value of 447 nM. The compound 10C activated β3AR pathway, induced lipolysis, fatty acid oxidation and increased oxygen consumption rate (OCR) in human adipocytes. Compound 10C induced expression of brown adipocytes specific markers and reverted chronic insulin induced insulin resistance in white

  10. Aerobic Exercise Increases Peripheral and Hepatic Insulin Sensitivity in Sedentary Adolescents

    NARCIS (Netherlands)

    van der Heijden, Gert-Jan; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    2009-01-01

    Context: Data are limited on the effects of controlled aerobic exercise programs (without weight loss) on insulin sensitivity and glucose metabolism in children and adolescents. Objective: To determine whether a controlled aerobic exercise program (without weight loss) improves peripheral and

  11. Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

    Science.gov (United States)

    Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

    2014-08-01

    Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

  12. ROLE OF INSULIN SENSITIZERS ON CARDIOVASCULAR RISK FACTORS IN POLYCYSTIC OVARIAN SYNDROME: A META-ANALYSIS.

    Science.gov (United States)

    Thethi, Tina K; Katalenich, Bonnie; Nagireddy, Prathima; Chabbra, Pankdeep; Kuhadiya, Nitesh; Fonseca, Vivian

    2015-06-01

    Polycystic ovarian syndrome (PCOS) is associated with an increase in cardiovascular (CV) risk factors such as insulin resistance, with accompanying hyperinsulinemia and hyperlipidemia, which are predisposing factors for type 2 diabetes mellitus and CV disease. The aim of this meta-analysis is to examine the effect of insulin sensitizers on clinical and biochemical features of PCOS and risk factors for CV disease. A systematic literature review was conducted, and randomized controlled clinical trials were identified by a search of bibliographic databases: Medline database (from 1966 forward), EMBASE (January 1985 forward), and Cochrane Central Register of Controlled Trials. Reviews of reference lists further identified candidate trials. Data was independently abstracted in duplicate by 2 investigators using a standardized data-collection form. Articles without a comparison group and randomization allocation were excluded. Reviewers worked independently and in duplicate to determine the methodological quality of trials, then collected data on patient characteristics, interventions, and outcomes. Of 455 studies, 44 trials were eligible. A random effects model was used. Significant unadjusted results favoring treatment with insulin sensitizers were obtained for body mass index (BMI) (effect size [ES] of 0.58), waist to hip ratio (WHR) (ES of 0.02), low-density-lipoprotein cholesterol (LDL-C) (ES of 0.11), fasting insulin (ES of 2.82), fasting glucose (ES of 0.10), free testosterone (ES of 1.88), and androstenedione level (ES of 0.76). Treatment with insulin sensitizers in women with PCOS results in improvement in CV factors such as BMI, WHR, LDL-C, fasting insulin, glucose, free testosterone, and androstenedione.

  13. Functional organization of the face-sensitive areas in human occipital-temporal cortex.

    Science.gov (United States)

    Shao, Hanyu; Weng, Xuchu; He, Sheng

    2017-08-15

    Human occipital-temporal cortex features several areas sensitive to faces, presumably forming the biological substrate for face perception. To date, there are piecemeal insights regarding the functional organization of these regions. They have come, however, from studies that are far from homogeneous with regard to the regions involved, the experimental design, and the data analysis approach. In order to provide an overall view of the functional organization of the face-sensitive areas, it is necessary to conduct a comprehensive study that taps into the pivotal functional properties of all the face-sensitive areas, within the context of the same experimental design, and uses multiple data analysis approaches. In this study, we identified the most robustly activated face-sensitive areas in bilateral occipital-temporal cortices (i.e., AFP, aFFA, pFFA, OFA, pcSTS, pSTS) and systemically compared their regionally averaged activation and multivoxel activation patterns to 96 images from 16 object categories, including faces and non-faces. This condition-rich and single-image analysis approach critically samples the functional properties of a brain region, allowing us to test how two basic functional properties, namely face-category selectivity and face-exemplar sensitivity are distributed among these regions. Moreover, by examining the correlational structure of neural responses to the 96 images, we characterize their interactions in the greater face-processing network. We found that (1) r-pFFA showed the highest face-category selectivity, followed by l-pFFA, bilateral aFFA and OFA, and then bilateral pcSTS. In contrast, bilateral AFP and pSTS showed low face-category selectivity; (2) l-aFFA, l-pcSTS and bilateral AFP showed evidence of face-exemplar sensitivity; (3) r-OFA showed high overall response similarities with bilateral LOC and r-pFFA, suggesting it might be a transitional stage between general and face-selective information processing; (4) r-aFFA showed high

  14. The effects of insulin sensitizers on the cardiovascular risk factors in women with polycystic ovary syndrome.

    Science.gov (United States)

    Kassi, E; Diamanti-Kandarakis, E

    2008-12-01

    Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in pre-menopausal women characterized by menstrual cycle disturbances, chronic anovulation, and clinical and/or biochemical hyperandrogenism. Although, the primary etiology of PCOS remains unknown, insulin resistance/hyperinsulinemia plays a pivotal role in the pathogenesis of the syndrome. A growing body of recent data support that women with PCOS have displayed an increased prevelance of cardiovascular disease (CVD) risk factors putting potentially at a hight risk for heart disease. Most of these CVD risk factors are etiologically correlated with insulin resistance/hyperinsulinemia, highlighting the role of insulin sensitizers in the therapeutic quiver for the chronic treatment of PCOS. In this review, we discuss the current literature on the CVD risk factors in PCOS and the influence of insulin sensitizers upon these risk factors.

  15. Proof of Concept: Matrix metalloproteinase inhibitor decreases inflammation and improves muscle insulin sensitivity in people with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Frankwich Karen

    2012-10-01

    Full Text Available Abstract Background Obesity is a state of subclinical inflammation resulting in loss of function of insulin receptors and decreased insulin sensitivity. Inhibition of the inflammatory enzymes, matrix metalloproteinases (MMPs, for 6 months in rodent models restores insulin receptor function and insulin sensitivity. Methods This 12-week double-blind, randomized, placebo (PL-controlled proof-of-concept study was performed to determine if the MMP inhibitor (MMPI, doxycycline, decreased global markers of inflammation and enhanced muscle insulin sensitivity in obese people with type 2 diabetes (DM2. The study included non-DM2 controls (n = 15, and DM2 subjects randomized to PL (n = 13 or doxycycline 100 mg twice daily (MMPI; n = 11. All participants were evaluated on Day 1; MMPI and PL groups were also evaluated after 84 days of treatment. Results There was a significant decrease in inflammatory markers C-reactive protein (P  Conclusions This study demonstrated short term treatment of people with diabetes with an MMPI resulted in decreased inflammation and improved insulin sensitivity. Larger, longer studies are warranted to determine if doxycycline can improve glucose control in people with diabetes. Trial Registration Clinicaltrials.gov NCT01375491

  16. Acute insulin resistance stimulates and insulin sensitization attenuates vascular smooth muscle cell migration and proliferation.

    Science.gov (United States)

    Cersosimo, Eugenio; Xu, Xiaojing; Upala, Sikarin; Triplitt, Curtis; Musi, Nicolas

    2014-08-01

    Differential activation/deactivation of insulin signaling, PI-3K and MAP-K pathways by high glucose and palmitate, with/out the insulin sensitizer pioglitazone (PIO), have been previously shown in vascular smooth muscle cells (VSMCs). To determine the biological impact of these molecular changes, we examined VSMC migration and proliferation ("M"&"P") patterns in similar conditions. VSMCs from healthy human coronary arteries were incubated in growth medium and "M"&"P" were analyzed after exposure to high glucose (25 mmol/L) ± palmitate (200 μmol/L) and ± PIO (8 μmol/L) for 5 h. "M"&"P" were assessed by: (1) polycarbonate membrane barrier with chemo-attractants and extended cell protrusions quantified by optical density (OD595 nm); (2) % change in radius area (2D Assay) using inverted microscopy images; and (3) cell viability assay expressed as cell absorbance (ABS) in media. "M" in 25 mmol/L glucose media increased by ~25% from baseline and % change in radius area rose from ~20% to ~30%. The addition of PIO was accompanied by a significant decrease in "M" from 0.25 ± 0.02 to 0.19 ± 0.02; a comparable decline from 0.25 ± 0.02 to 0.18 ± 0.02 was also seen with 25 mmol/L of glucose +200 μmol/L of palmitate. When PIO was coincubated with high glucose plus palmitate there was a 50% reduction in % change in radius. A ~10% increase in ABS, reflecting augmented "P" in media with 25 mmol/L glucose versus control was documented. The addition of PIO reduced ABS from 0.208 ± 0.03 to 0.183 ± 0.06. Both high glucose and palmitate showed ABS of ~0.140 ± 0.02, which decreased with PIO to ~0.120 ± 0.02, indicating "P" was reduced. These results confirm that high glucose and palmitate stimulate VSMCs migration and proliferation in vitro, which is attenuated by coincubation with the insulin sensitizer PIO. Although, we cannot ascertain whether these functional changes are coincident with the activation/deactivation of signal molecules, our findings are consistent with the

  17. Education and Training on ISIS Research Reactor

    International Nuclear Information System (INIS)

    Foulon, F.; Badeau, G.; Lescop, B.; Wohleber, X.

    2013-01-01

    In the frame of academic and vocational programs the National Institute for Nuclear Science and Technology uses the ISIS research reactor as a major tool to ensure a practical and comprehensive understanding of the nuclear reactor physics, principles and operation. A large set of training courses have been developed on ISIS, optimising both the content of the courses and the pedagogical approach. Programs with duration ranging from 3 hours (introduction to reactor operation) to 24 hours (full program for the future operators of research reactors) are carried out on ISIS reactor. The reactor is operated about 350 hours/year for education and training, about 40 % of the courses being carried out in English. Thus, every year about 400 trainees attend training courses on ISIS reactor. We present here the ISIS research reactor and the practical courses that have been developed on ISIS reactor. Emphasis is given to the pedagogical method which is used to focus on the operational and safety aspects, both in normal and incidental operation. We will present the curricula of the academic and vocational courses in which the practical courses are integrated, the courses being targeted to a wide public, including operators of research reactors, engineers involved in the design and operation of nuclear reactors as well as staff of the regulatory body. We address the very positive impact of the courses on the development of the competences and skills of participants. Finally, we describe the Internet Reactor Laboratories (IRL) that are under development and will consist in broadcasting the training courses via internet to remote facilities or institutions

  18. Education and Training on ISIS Research Reactor

    Energy Technology Data Exchange (ETDEWEB)

    Foulon, F.; Badeau, G.; Lescop, B.; Wohleber, X. [French Atomic Energy and Alternative Energies Commission, Paris (France)

    2013-07-01

    In the frame of academic and vocational programs the National Institute for Nuclear Science and Technology uses the ISIS research reactor as a major tool to ensure a practical and comprehensive understanding of the nuclear reactor physics, principles and operation. A large set of training courses have been developed on ISIS, optimising both the content of the courses and the pedagogical approach. Programs with duration ranging from 3 hours (introduction to reactor operation) to 24 hours (full program for the future operators of research reactors) are carried out on ISIS reactor. The reactor is operated about 350 hours/year for education and training, about 40 % of the courses being carried out in English. Thus, every year about 400 trainees attend training courses on ISIS reactor. We present here the ISIS research reactor and the practical courses that have been developed on ISIS reactor. Emphasis is given to the pedagogical method which is used to focus on the operational and safety aspects, both in normal and incidental operation. We will present the curricula of the academic and vocational courses in which the practical courses are integrated, the courses being targeted to a wide public, including operators of research reactors, engineers involved in the design and operation of nuclear reactors as well as staff of the regulatory body. We address the very positive impact of the courses on the development of the competences and skills of participants. Finally, we describe the Internet Reactor Laboratories (IRL) that are under development and will consist in broadcasting the training courses via internet to remote facilities or institutions.

  19. A simple method for measuring glucose utilization of insulin-sensitive tissues by using the brain as a reference

    International Nuclear Information System (INIS)

    Namba, Hiroki; Nakagawa, Keiichi; Iyo, Masaomi; Fukushi, Kiyoshi; Irie, Toshiaki

    1994-01-01

    A simple method, without measurement of the plasma input function, to obtain semiquantitative values of glucose utilization in tissues other than the brain with radioactive deoxyglucose is reported. The brain, in which glucose utilization is essentially insensitive to plasma glucose and insulin concentrations, was used as an internal reference. The effects of graded doses of oral glucose loading (0.5, 1 and 2 mg/g body weight) on insulin-sensitive tissues (heart, muscle and fat tissue) were studied in the rat. By using the brain-reference method, dose-dependent increases in glucose utilization were clearly shown in all the insulin-sensitive tissues examined. The method seems to be of value for measurement of glucose utilization using radioactive deoxyglucose and positron emission tomography in the heart or other insulin-sensitive tissues, especially during glucose loading. (orig.)

  20. Partial disruption of lipolysis increases postexercise insulin sensitivity in skeletal muscle despite accumulation of DAG

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck; Alsted, Thomas Junker; Jordy, Andreas Børsting

    2016-01-01

    reactivity in vitro, we investigated if the described function of DAGs as mediators of lipid-induced insulin resistance was depending on the different DAG-isomers. We measured insulin stimulated glucose uptake in hormone sensitive lipase (HSL) knock out (KO) mice after treadmill exercise to stimulate...

  1. Interaction between leucine and phosphodiesterase 5 inhibition in modulating insulin sensitivity and lipid metabolism

    Directory of Open Access Journals (Sweden)

    Fu L

    2015-05-01

    Full Text Available Lizhi Fu,1 Fenfen Li,1 Antje Bruckbauer,2 Qiang Cao,1 Xin Cui,1 Rui Wu,1 Hang Shi,1 Bingzhong Xue,1 Michael B Zemel21Department of Biology, Center for Obesity Reversal, Georgia State University, Atlanta, GA, 2NuSirt Biopharma Inc., Nashville, TN, USA Purpose: Leucine activates SIRT1/AMP-activated protein kinase (AMPK signaling and markedly potentiates the effects of other sirtuin and AMPK activators on insulin signaling and lipid metabolism. Phosphodiesterase 5 inhibition increases nitric oxide–cGMP signaling, which in turn exhibits a positive feedback loop with both SIRT1 and AMPK, thus amplifying peroxisome proliferator-activated receptor γ co-activator α (PGC1α-mediated effects. Methods: We evaluated potential synergy between leucine and PDE5i on insulin sensitivity and lipid metabolism in vitro and in diet-induced obese (DIO mice. Results: Leucine (0.5 mM exhibited significant synergy with subtherapeutic doses (0.1–10 nM of PDE5-inhibitors (sildenafil and icariin on fat oxidation, nitric oxide production, and mitochondrial biogenesis in hepatocytes, adipocytes, and myotubes. Effects on insulin sensitivity, glycemic control, and lipid metabolism were then assessed in DIO-mice. DIO-mice exhibited fasting and postprandial hyperglycemia, insulin resistance, and hepatic steatosis, which were not affected by the addition of leucine (24 g/kg diet. However, the combination of leucine and a subtherapeutic dose of icariin (25 mg/kg diet for 6 weeks reduced fasting glucose (38%, P<0.002, insulin (37%, P<0.05, area under the glucose tolerance curve (20%, P<0.01, and fully restored glucose response to exogenous insulin challenge. The combination also inhibited hepatic lipogenesis, stimulated hepatic and muscle fatty acid oxidation, suppressed hepatic inflammation, and reversed high-fat diet-induced steatosis. Conclusion: These robust improvements in insulin sensitivity, glycemic control, and lipid metabolism indicate therapeutic potential for

  2. Alternative translation initiation of Caveolin-2 desensitizes insulin signaling through dephosphorylation of insulin receptor by PTP1B and causes insulin resistance.

    Science.gov (United States)

    Kwon, Hayeong; Jang, Donghwan; Choi, Moonjeong; Lee, Jaewoong; Jeong, Kyuho; Pak, Yunbae

    2018-06-01

    Insulin resistance, defined as attenuated sensitivity responding to insulin, impairs insulin action. Direct causes and molecular mechanisms of insulin resistance have thus far remained elusive. Here we show that alternative translation initiation (ATI) of Caveolin-2 (Cav-2) regulates insulin sensitivity. Cav-2β isoform yielded by ATI desensitizes insulin receptor (IR) via dephosphorylation by protein-tyrosine phosphatase 1B (PTP1B), and subsequent endocytosis and lysosomal degradation of IR, causing insulin resistance. Blockage of Cav-2 ATI protects against insulin resistance by preventing Cav-2β-PTP1B-directed IR desensitization, thereby normalizing insulin sensitivity and glucose uptake. Our findings show that Cav-2β is a negative regulator of IR signaling, and identify a mechanism causing insulin resistance through control of insulin sensitivity via Cav-2 ATI. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Clustering effects on postprandial insulin secretion and sensitivity in response to meals with different fatty acid compositions.

    Science.gov (United States)

    Bermudez, Beatriz; Ortega-Gomez, Almudena; Varela, Lourdes M; Villar, Jose; Abia, Rocio; Muriana, Francisco J G; Lopez, Sergio

    2014-07-25

    Dietary fatty acids play a role in glucose homeostasis. The aim of this study was to assess the individual relationship between dietary saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids with postprandial β-cell function and insulin sensitivity in subjects with normal and high fasting triglycerides. We assessed postprandial β-cell function (by the insulinogenic index and the ratio of the insulin to glucose areas under the time-concentration curve) and insulin sensitivity (by the oral glucose and the minimal model insulin sensitivity indices) over four nonconsecutive, randomly assigned, high-fat meals containing a panel of SFA (palmitic and stearic acids), MUFA (palmitoleic and oleic acids) and PUFA (linoleic and α-linolenic acids) in 14 subjects with normal and in 14 subjects with high fasting triglycerides. The proportions of each fatty acid in the meals and the values for surrogate measures of postprandial β-cell function and insulin sensitivity were subjected to a Pearson correlation and hierarchical cluster analysis, which revealed two classes of dietary fatty acids for regulating postprandial glucose homeostasis. We successfully discriminated the adverse effects of SFA palmitic acid from the beneficial effects of MUFA oleic acid on postprandial β-cell function (r ≥ 0.84 for SFA palmitic acid and r ≥ -0.71 for MUFA oleic acid; P < 0.05) and insulin sensitivity (r ≥ -0.92 for SFA palmitic acid and r ≥ 0.89 for MUFA oleic acid; P < 0.001) both in subjects with normal and high fasting triglycerides. In conclusion, dietary MUFA oleic acid, in contrast to SFA palmitic acid, favours the tuning towards better postprandial glycaemic control in subjects with normal and high fasting triglycerides.

  4. An intense transmission spectrometer for ISIS

    International Nuclear Information System (INIS)

    Newport, R.J.; Howells, W.S.

    1986-07-01

    The report seeks to outline a design for an intense transmission spectrometer (ITS) suitable for installation on the pulsed neutron source ISIS. The performance of the instrument is evaluated and several examples of the areas of science made accessible are discussed. It is shown that the proposed design will represent a scientifically valuable and cost-effective addition to the present suite of ISIS instruments. (author)

  5. Effects of High Fat Diet and Physical Exercise on Glucose Tolelance and Insulin Sensitivity in Rats

    OpenAIRE

    福田,哲也

    1987-01-01

    To investigate the interrelationships between the westernized diet and physical exercise as they affect the development of non-insulin-dependent diabetes mellitus (NIDDM), adiposity, glucose tolerance and insulin response to an intraperitoneal glucose load (1.5g/kg bw) and insulin sensitivity to exogenous insulin (0.2U/kg bw) were studied in spontaneously exercised and sedentary rats fed either a high fat diet (40% fat, modern western type) or a low fat diet (10% fat, traditional Japanese typ...

  6. Conceptional design and some application for ISI systems of 'Monju'

    International Nuclear Information System (INIS)

    Nakamura, Takashi; Rindo, Hiroshi; Ara, Kuniaki; Kamimura, Takeo; Tsuzuki, Satoshi; Morimoto, Kazuo; Nagaoka, Etsuo; Ikeda, Naoaki.

    1987-01-01

    In order to fit the Monju system for inspection during use of the (prototype FBR) ''Monju'' plant, a system concept necessary for this plant has been established and part of the machinery has been tested, on the basis of ISI light water reactor and thermal plant technology. Electromagnetic acoustic testing equipment (EMAT), which is drawing attention for the volumetric examination without contact, and also a wall-to-wall four-wheel self-propelled vehicle, as an ISI tool for R/V of FBR, are both being developed. Contents are the following: basic concept and development of ISI system - reactor vessel proper and inlet piping ISI system, and concept of steam generator evaporator heat exchanger tube ISI system; development of ISI systems - experimental self-propelled four-wheel tool, and EMAT signal processing unit. (Mori, K.)

  7. Developmental Programming: Impact of Gestational Steroid and Metabolic Milieus on Mediators of Insulin Sensitivity in Prenatal Testosterone-Treated Female Sheep.

    Science.gov (United States)

    Puttabyatappa, Muraly; Andriessen, Victoria; Mesquitta, Makeda; Zeng, Lixia; Pennathur, Subramaniam; Padmanabhan, Vasantha

    2017-09-01

    Prenatal testosterone (T) excess in sheep leads to peripheral insulin resistance (IR), reduced adipocyte size, and tissue-specific changes, with liver and muscle but not adipose tissue being insulin resistant. To determine the basis for the tissue-specific differences in insulin sensitivity, we assessed changes in negative (inflammation, oxidative stress, and lipotoxicity) and positive mediators (adiponectin and antioxidants) of insulin sensitivity in the liver, muscle, and adipose tissues of control and prenatal T-treated sheep. Because T excess leads to maternal hyperinsulinemia, fetal hyperandrogenism, and functional hyperandrogenism and IR in their female offspring, prenatal and postnatal interventions with antiandrogen, flutamide, and the insulin sensitizer rosiglitazone were used to parse out the contribution of androgenic and metabolic pathways in programming and maintaining these defects. Results showed that (1) peripheral IR in prenatal T-treated female sheep is related to increases in triglycerides and 3-nitrotyrosine, which appear to override the increase in high-molecular-weight adiponectin; (2) liver IR is a function of the increase in oxidative stress (3-nitrotyrosine) and lipotoxicity; (3) muscle IR is related to lipotoxicity; and (4) the insulin-sensitive status of visceral adipose tissue appears to be a function of the increase in antioxidants that likely overrides the increase in proinflammatory cytokines, macrophages, and oxidative stress. Prenatal and postnatal intervention with either antiandrogen or insulin sensitizer had partial effects in preventing or ameliorating the prenatal T-induced changes in mediators of insulin sensitivity, suggesting that both pathways are critical for the programming and maintenance of the prenatal T-induced changes and point to potential involvement of estrogenic pathways. Copyright © 2017 Endocrine Society.

  8. Endurance training improves insulin sensitivity and body composition in prostate cancer patients treated with androgen deprivation therapy.

    Science.gov (United States)

    Hvid, Thine; Winding, Kamilla; Rinnov, Anders; Dejgaard, Thomas; Thomsen, Carsten; Iversen, Peter; Brasso, Klaus; Mikines, Kari J; van Hall, Gerrit; Lindegaard, Birgitte; Solomon, Thomas P J; Pedersen, Bente K

    2013-10-01

    Insulin resistance and changes in body composition are side effects of androgen deprivation therapy (ADT) given to prostate cancer patients. The present study investigated whether endurance training improves insulin sensitivity and body composition in ADT-treated prostate cancer patients. Nine men undergoing ADT for prostate cancer and ten healthy men with normal testosterone levels underwent 12 weeks of endurance training. Primary endpoints were insulin sensitivity (euglycemic-hyperinsulinemic clamps with concomitant glucose-tracer infusion) and body composition (dual-energy X-ray absorptiometry and magnetic resonance imaging). The secondary endpoint was systemic inflammation. Statistical analysis was carried out using two-way ANOVA. Endurance training increased VO2max (ml(O2)/min per kg) by 11 and 13% in the patients and controls respectively (PBody weight (Pbody fat mass (FM) (Pbody mass (P=0.99) was unchanged. Additionally, reductions were observed in abdominal (Pcancer patients exhibited improved insulin sensitivity and body composition to a similar degree as eugonadal men.

  9. Anti-hyperglycemic and insulin sensitizer effects of turmeric and its principle constituent curcumin.

    Science.gov (United States)

    Ghorbani, Zeinab; Hekmatdoost, Azita; Mirmiran, Parvin

    2014-10-01

    Turmeric is obtained from the plant Curcuma longa L; its major constituent, curcumin, is a polyphenol with multiple effects which can modulate some signaling pathways. Insulin resistance is a major risk factor for chronic diseases such as type 2 diabetes, atherosclerotic, metabolic syndrome and cardiovascular disease. In addition, Insulin resistance in peripheral tissue is one of the most important reasons of hyperglycemia which can cause global or systemic effects. The present study reviewed studies published in PubMed from 1998 to 2013, indicating the role of curcumin in attenuation of many pathophysiological processes involved in development and progression of hyperglycemia and insulin resistance. Curcumin can reduce blood glucose level by reducing the hepatic glucose production, suppression of hyperglycemia-induced inflammatory state, stimulation of glucose uptake by up-regulation of GLUT4, GLUT2 and GLUT3 genes expressions, activation of AMP kinase, promoting the PPAR ligand-binding activity, stimulation of insulin secretion from pancreatic tissues, improvement in pancreatic cell function, and reduction of insulin resistance. Curcumin has antihyperglycemic and insulin sensitizer effects. Thereby, more studies evaluating the effects of curcumin on hyperglycemic state and insulin resistance in related disorders such as diabetes are recommended.

  10. Infection with Soil-Transmitted Helminths Is Associated with Increased Insulin Sensitivity

    NARCIS (Netherlands)

    Wiria, A.E.; Hamid, F.; Wammes, L.J.; Prasetyani, M.A.; Dekkers, O.M.; May, L.; Kaisar, M.M.; Verweij, J.J.; Guigas, B.; Partono, F.; Sartono, E.; Supali, T.; Yazdanbakhsh, M.; Smit, J.W.A.

    2015-01-01

    OBJECTIVE: Given that helminth infections have been shown to improve insulin sensitivity in animal studies, which may be explained by beneficial effects on energy balance or by a shift in the immune system to an anti-inflammatory profile, we investigated whether soil-transmitted helminth

  11. Leptin rapidly improves glucose homeostasis in obese mice by increasing hypothalamic insulin sensitivity.

    Science.gov (United States)

    Koch, Christiane; Augustine, Rachael A; Steger, Juliane; Ganjam, Goutham K; Benzler, Jonas; Pracht, Corinna; Lowe, Chrishanthi; Schwartz, Michael W; Shepherd, Peter R; Anderson, Greg M; Grattan, David R; Tups, Alexander

    2010-12-01

    Obesity is associated with resistance to the actions of both leptin and insulin via mechanisms that remain incompletely understood. To investigate whether leptin resistance per se contributes to insulin resistance and impaired glucose homeostasis, we investigated the effect of acute leptin administration on glucose homeostasis in normal as well as leptin- or leptin receptor-deficient mice. In hyperglycemic, leptin-deficient Lep(ob/ob) mice, leptin acutely and potently improved glucose metabolism, before any change of body fat mass, via a mechanism involving the p110α and β isoforms of phosphatidylinositol-3-kinase (PI3K). Unlike insulin, however, the anti-diabetic effect of leptin occurred independently of phospho-AKT, a major downstream target of PI3K, and instead involved enhanced sensitivity of the hypothalamus to insulin action upstream of PI3K, through modulation of IRS1 (insulin receptor substrate 1) phosphorylation. These data suggest that leptin resistance, as occurs in obesity, reduces the hypothalamic response to insulin and thereby impairs peripheral glucose homeostasis, contributing to the development of type 2 diabetes.

  12. Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation.

    Directory of Open Access Journals (Sweden)

    J Eduardo Rico

    Full Text Available Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition. Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in

  13. Temporal changes in sphingolipids and systemic insulin sensitivity during the transition from gestation to lactation

    Science.gov (United States)

    Rico, J. Eduardo; Saed Samii, Sina; Mathews, Alice T.; Lovett, Jacqueline; Haughey, Norman J.; McFadden, Joseph W.

    2017-01-01

    Reduced insulin action develops naturally during the peripartum to ensure maternal nutrient delivery to the fetus and neonate. However, increased insulin resistance can facilitate excessive lipolysis which in turn promotes metabolic disease in overweight dairy cattle. Increased fatty acid availability favors the accumulation of the sphingolipid ceramide and is implicated in the pathogenesis of insulin resistance, however, the relationship between sphingolipid metabolism and insulin resistance during the peripartum remains largely unknown. Our objectives were to characterize temporal responses in plasma and tissue sphingolipids in lean and overweight peripartal cows and to establish the relationships between sphingolipid supply and lipolysis, hepatic lipid deposition, and systemic insulin action. Twenty-one multiparous lean and overweight Holstein cows were enrolled in a longitudinal study spanning the transition from gestation to lactation (d -21 to 21, relative to parturition). Plasma, liver, and skeletal muscle samples were obtained, and sphingolipids were profiled using LC/MS/MS. Insulin sensitivity was assessed utilizing intravenous insulin and glucose challenges. Our results demonstrated the following: first, insulin resistance develops postpartum concurrently with increased lipolysis and hepatic lipid accumulation; second, ceramides and glycosylated ceramides accumulate during the transition from gestation to lactation and are further elevated in overweight cows; third, ceramide accrual is associated with lipolysis and liver lipid accumulation, and C16:0- and C24:0-ceramide are inversely associated with systemic insulin sensitivity postpartum; fourth, plasma sphingomyelin, a potential source of ceramides reaches a nadir at parturition and is closely associated with feed intake; fifth, select sphingomyelins are lower in the plasma of overweight cows during the peripartal period. Our results demonstrate that dynamic changes occur in peripartal sphingolipids

  14. Intersections of two isiZulu genderlects and the construction of ...

    African Journals Online (AJOL)

    Kate H

    The isiNgqumo lexicon is characterised largely by what Zulu speakers ... isiNgqumo offers a sense of community and an opportunity to escape public .... isiNgqumo use seems more prevalent in lower socioeconomic “gay” circles and semi-.

  15. Tin (II Chloride Catalyzed Esterification of High FFA Jatropha Oil: Experimental and Kinetics Study

    Directory of Open Access Journals (Sweden)

    Ratna Dewi Kusumaningtyas

    2014-05-01

    Full Text Available Biodiesel is one of the promising energy source alternatives to fossil fuel. To produce biodiesel in a more economical way, the employment of the low-cost feed stocks, such as non-edible oils with high free fatty acid (FFA, is necessary. Accordingly, the esterification reaction of FFA in vegetable oils plays an important role in the biodiesel production. In this work, esterification of FFA contained in Crude Jatropha Oil (CJO in the presence of tin (II chloride catalyst in a batch reactor has been carried out. The esterification reaction was conducted using methanol at the temperature of 40-60 °C for 4 hours. The effect of molar ratio of methanol to oil was studied in the range 15:1 to 120:1. The influence of catalyst loading was investigated in the range of 2.5 to 15% w/w oil. The optimum reaction conversion was obtained at 60 °C with the catalyst loading of 10% w/w oil and molar ratio of methanol to oil of 120:1. A pseudo-homogeneous reversible second order kinetic model for describing the esterification of FFA contained in CJO with methanol over tin (II chloride catalyst was developed based on the experimental data. The kinetic model can fit the data very well.

  16. ISI PUBLICATIONS MANAGEMENT THROUGH PERFORMANCE INDICATORS

    Directory of Open Access Journals (Sweden)

    Victor VELTER

    2010-09-01

    Full Text Available The paper proposes to describe the ways in which the research management and administration department from a certain institution can interfere with specific policies in order to increase the visibility of scientific publications. Scientometric analysis is made on ISI publications of “Constantin Brancsi” University from Targu Jiu and wants to reveal performance indicators able to monitor the visibility of the papers indexed in ThomsonReuters ISI base.

  17. Maternal Fructose Intake Induces Insulin Resistance and Oxidative Stress in Male, but Not Female, Offspring

    Directory of Open Access Journals (Sweden)

    Lourdes Rodríguez

    2015-01-01

    Full Text Available Objective. Fructose intake from added sugars correlates with the epidemic rise in metabolic syndrome and cardiovascular diseases. However, consumption of beverages containing fructose is allowed during gestation. Recently, we found that an intake of fructose (10% wt/vol throughout gestation produces an impaired fetal leptin signalling. Therefore, we have investigated whether maternal fructose intake produces subsequent changes in their progeny. Methods. Blood samples from fed and 24 h fasted female and male 90-day-old rats born from fructose-fed, glucose-fed, or control mothers were used. Results. After fasting, HOMA-IR and ISI (estimates of insulin sensitivity were worse in male descendents from fructose-fed mothers in comparison to the other two groups, and these findings were also accompanied by a higher leptinemia. Interestingly, plasma AOPP and uricemia (oxidative stress markers were augmented in male rats from fructose-fed mothers compared to the animals from control or glucose-fed mothers. In contrast, female rats did not show any differences in leptinemia between the three groups. Further, insulin sensitivity was significantly improved in fasted female rats from carbohydrate-fed mothers. In addition, plasma AOPP levels tended to be diminished in female rats from carbohydrate-fed mothers. Conclusion. Maternal fructose intake induces insulin resistance, hyperleptinemia, and plasma oxidative stress in male, but not female, progeny.

  18. Inactivation of the Class II PI3K-C2β Potentiates Insulin Signaling and Sensitivity

    Directory of Open Access Journals (Sweden)

    Samira Alliouachene

    2015-12-01

    Full Text Available In contrast to the class I phosphoinositide 3-kinases (PI3Ks, the organismal roles of the kinase activity of the class II PI3Ks are less clear. Here, we report that class II PI3K-C2β kinase-dead mice are viable and healthy but display an unanticipated enhanced insulin sensitivity and glucose tolerance, as well as protection against high-fat-diet-induced liver steatosis. Despite having a broad tissue distribution, systemic PI3K-C2β inhibition selectively enhances insulin signaling only in metabolic tissues. In a primary hepatocyte model, basal PI3P lipid levels are reduced by 60% upon PI3K-C2β inhibition. This results in an expansion of the very early APPL1-positive endosomal compartment and altered insulin receptor trafficking, correlating with an amplification of insulin-induced, class I PI3K-dependent Akt signaling, without impacting MAPK activity. These data reveal PI3K-C2β as a critical regulator of endosomal trafficking, specifically in insulin signaling, and identify PI3K-C2β as a potential drug target for insulin sensitization.

  19. Insulin resistance in obesity can be reliably identified from fasting plasma insulin.

    Science.gov (United States)

    ter Horst, K W; Gilijamse, P W; Koopman, K E; de Weijer, B A; Brands, M; Kootte, R S; Romijn, J A; Ackermans, M T; Nieuwdorp, M; Soeters, M R; Serlie, M J

    2015-12-01

    Insulin resistance is the major contributor to cardiometabolic complications of obesity. We aimed to (1) establish cutoff points for insulin resistance from euglycemic hyperinsulinemic clamps (EHCs), (2) identify insulin-resistant obese subjects and (3) predict insulin resistance from routinely measured variables. We assembled data from non-obese (n=112) and obese (n=100) men who underwent two-step EHCs using [6,6-(2)H2]glucose as tracer (insulin infusion dose 20 and 60 mU m(-2) min(-1), respectively). Reference ranges for hepatic and peripheral insulin sensitivity were calculated from healthy non-obese men. Based on these reference values, obese men with preserved insulin sensitivity or insulin resistance were identified. Cutoff points for insulin-mediated suppression of endogenous glucose production (EGP) and insulin-stimulated glucose disappearance rate (Rd) were 46.5% and 37.3 μmol kg(-)(1) min(-)(1), respectively. Most obese men (78%) had EGP suppression within the reference range, whereas only 12% of obese men had Rd within the reference range. Obese men with Rd obese men in age, body mass index (BMI), body composition, fasting glucose or cholesterol, but did have higher fasting insulin (110±49 vs 63±29 pmol l(-1), Pobese men could be identified with good sensitivity (80%) and specificity (75%) from fasting insulin >74 pmol l(-1). Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

  20. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves

    International Nuclear Information System (INIS)

    Kamal, M.M.; Van Eetvelde, M.; Bogaert, H.; Hostens, M.; Vandaele, L.; Shamsuddin, M.; Opsomer, G.

    2016-01-01

    Full text: The objective of the present retrospective cohort study was to evaluate potential associations between environmental factors and dam characteristics, including level of milk production during gestation, and insulin traits in newborn Holstein calves. Birth weight and gestational age of the calves at delivery were determined. On the next day, heart girth, wither height and diagonal length of both the calves and their dams were measured. Parity, body condition score and age at calving were recorded for all dams. For the cows, days open before last gestation, lactation length (LL), lenght of dry period (DP) and calving interval were also calculated. The magnitude and shape of the lactation curve both quantified using the MilkBot model based on monthly milk weights, were used to calculate the amount of milk produced during gestation. Using the same procedure, cumulative milk production from conception to drying off (MGEST) was calculated. A blood sample was collected from all calves (n=481; 169 born to heifers and 312 born to cows) at least 5 h after a milk meal on day 3 of life to measure basal glucose and insulin levels. In addition, an intravenous glucose-stimulated insulin secretion test was performed in a subset of the calves (n=316). After descriptive analysis, generalized linear mixed models were used to identify factors that were significantly associated with the major insulin traits (Insb, basal insulin level; QUICKI, quantitative insulin sensitivity check index; AIR, acute insulin response; DI, disposition index) of the newborn calves. The overall average birth weight of the calves was 42.7 ± 5.92 kg. The insulin traits were significantly associated with MGEST (P=0.076) and longer DP (P=0.034). The QUICKI was estimated to be lower in calves born to the cows having passed a higher MGEST (P=0.030) and longer DP (P=0.058). Moreover, the AIR (P=0.009) and DI (P=0.049) were estimated to be lower in male compared with female calves. Furthermore, the AIR

  1. Fibroblast growth factor 21 improves insulin sensitivity and synergizes with insulin in human adipose stem cell-derived (hASC adipocytes.

    Directory of Open Access Journals (Sweden)

    Darwin V Lee

    Full Text Available Fibroblast growth factor 21 (FGF21 has evolved as a major metabolic regulator, the pharmacological administration of which causes weight loss, insulin sensitivity and glucose control in rodents and humans. To understand the molecular mechanisms by which FGF21 exerts its metabolic effects, we developed a human in vitro model of adipocytes to examine crosstalk between FGF21 and insulin signaling. Human adipose stem cell-derived (hASC adipocytes were acutely treated with FGF21 alone, insulin alone, or in combination. Insulin signaling under these conditions was assessed by measuring tyrosine phosphorylation of insulin receptor (InsR, insulin receptor substrate-1 (IRS-1, and serine 473 phosphorylation of Akt, followed by a functional assay using 14C-2-deoxyglucose [14C]-2DG to measure glucose uptake in these cells. FGF21 alone caused a modest increase of glucose uptake, but treatment with FGF21 in combination with insulin had a synergistic effect on glucose uptake in these cells. The presence of FGF21 also effectively lowered the insulin concentration required to achieve the same level of glucose uptake compared to the absence of FGF21 by 10-fold. This acute effect of FGF21 on insulin signaling was not due to IR, IGF-1R, or IRS-1 activation. Moreover, we observed a substantial increase in basal S473-Akt phosphorylation by FGF21 alone, in contrast to the minimal shift in basal glucose uptake. Taken together, our data demonstrate that acute co-treatment of hASC-adipocytes with FGF21 and insulin can result in a synergistic improvement in glucose uptake. These effects were shown to occur at or downstream of Akt, or separate from the canonical insulin signaling pathway.

  2. Sensitive double-antibody method for simultaneous determination of insulin and growth hormone

    International Nuclear Information System (INIS)

    Koparanova, O.; Sotirov, G.; Tyrkolev, N.

    1982-01-01

    A method is described for simultaneous determination of insulin and growth hormone in one sample, using double-antibody technique. The method is characterized by appreciable sensitivity (2.5 μE/ml for insulin and a.2 ng/ml for growth hormone), exactness (variation quotient 6-16 per cent) and reproducibility (96.9-117 per cent). There was no statistically significant difference in the insulin and growth hormone values of the same sera, determined by the here suggested and the standard methods. The necessary test material for examination of either hormone is minimal (0.2 ml). One may thus extend the possibilities for radioimmunologic determination of insulin and growth hormone, when only minor amounts of serum or other biological fluid are available. The method is also less time consuming. Results are reported of statistical processing of an experimental model and different sera determined by the standard method and the one described by the authors. (author)

  3. Early insulin sensitivity after restrictive bariatric surgery, inconsistency between HOMA-IR and steady-state plasma glucose levels.

    Science.gov (United States)

    van Dielen, Francois M H; Nijhuis, Jeroen; Rensen, Sander S M; Schaper, Nicolaas C; Wiebolt, Janneke; Koks, Afra; Prakken, Fred J; Buurman, Wim A; Greve, Jan Willem M

    2010-01-01

    The low-grade inflammatory condition present in morbid obesity is thought to play a causative role in the pathophysiology of insulin resistance (IR). Bariatric surgery fails to improve this inflammatory condition during the first months after surgery. Considering the close relation between inflammation and IR, we conducted a study in which insulin sensitivity was measured during the first months after bariatric surgery. Different methods to measure IR shortly after bariatric surgery have given inconsistent data. For example, the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels have been reported to decrease rapidly after bariatric surgery, although clamp techniques have shown sustained insulin resistance. In the present study, we evaluated the use of steady-state plasma glucose (SSPG) levels to assess insulin sensitivity 2 months after bariatric surgery. Insulin sensitivity was measured using HOMA-IR and SSPG levels in 11 subjects before surgery and at 26% excess weight loss (approximately 2 months after restrictive bariatric surgery). The SSPG levels after 26% excess weight loss did not differ from the SSPG levels before surgery (14.3 +/- 5.4 versus 14.4 +/- 2.7 mmol/L). In contrast, the HOMA-IR values had decreased significantly (3.59 +/- 1.99 versus 2.09 +/- 1.02). During the first months after restrictive bariatric surgery, we observed a discrepancy between the HOMA-IR and SSPG levels. In contrast to the HOMA-IR values, the SSPG levels had not improved, which could be explained by the ongoing inflammatory state after bariatric surgery. These results suggest that during the first months after restrictive bariatric surgery, HOMA-IR might not be an adequate marker of insulin sensitivity. Copyright 2010 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  4. Resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin.

    Science.gov (United States)

    Yuan, Hong; Weng, Chunyan; Yang, Youbo; Huang, Lihua; Xing, Xiaowei

    2013-12-01

    The metabolic syndrome (MS) is a cluster of metabolic disorders arising from insulin resistance, characterized by the presence of central obesity, impaired fasting glucose level, dyslipidemia and hypertension. As the first-line medication, metformin is commonly used for MS to reduce insulin resistance. Comparing with rosiglitazone, metformin does not increase cardiovascular mortality risk in patients with MS. However, metformin is not good enough in improving insulin sensitivity. Its molecular mechanism is still not clear. Recent studies have demonstrated that resistin, an adipokine, could induce IR by both AMPK-dependent and AMPK-independent pathways. Though there were conflicting findings of resistin in metabolic syndrome or type 2 diabetes mellitus in different studies, resistin was significant decreased in the rosiglitazone treated patients than in the metformin-treated patients in most of studies. Here, we hypothesized that resistin, an adipokine, may affect the improvement of insulin sensitivity in the metabolic syndrome patient treated with metformin. This hypothesis could explain why rosiglitazone is superior to metformin in enhancement of insulin sensitivity. Copyright © 2013. Published by Elsevier Ltd.

  5. A Role for IR-β in the Free Fatty Acid Mediated Development of Hepatic Insulin Resistance?

    Directory of Open Access Journals (Sweden)

    Arthur G. Cox

    2009-10-01

    Full Text Available Several studies have been conducted to elucidate the role of free fatty acids (FFAs in the pathogenesis of type 2 diabetes, but the exact molecular mechanism by which FFAs alter glucose metabolism in the liver is still not completely understood.1-4 In a recent publication, Ragheb and co-workers have examined the effect of free fatty acid (FFA treatment on insulin signaling and insulin resistance by using immunoprecipitation and immunoblotting to study the effect of high concentrations of insulin and FFAs on insulin receptor-beta (IR-β and downstream elements in the PI3K pathway using the fructose-fed hamster model.5 Their results clearly show that free fatty acids have an insignificant effect on IR-β and supports previous findings that FFAs lead to insulin resistance in the liver via the PKC-NFĸB pathway.2,3

  6. Total adiponectin and adiponectin multimeric complexes in relation to weight loss-induced improvements in insulin sensitivity in obese women

    DEFF Research Database (Denmark)

    Polak, J.; Kovacova, Z.; Holst, C.

    2008-01-01

    , and LMW). The HMW form was suggested to be closely associated with insulin sensitivity. This study investigated whether diet-induced changes in insulin sensitivity were associated with changes in adiponectin multimeric complexes. SUBJECTS: Twenty obese women with highest and twenty obese women with lowest...... diet induced changes in insulin sensitivity (responders and non-responders respectively), matched for weight loss (body mass index (BMI)=34.5 (s.d. 2.9) resp. 36.5 kg/m(2) (s.d. 4.0) for responders and non-responders), were selected from 292 women who underwent a 10-week low-caloric diet (LCD; 600 kcal...

  7. Effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin in the soleus muscle of the rat.

    Science.gov (United States)

    Dimitriadis, G D; Leighton, B; Parry-Billings, M; West, D; Newsholme, E A

    1989-01-01

    1. The effects of hypothyroidism on the sensitivity of glycolysis and glycogen synthesis to insulin were investigated in the isolated, incubated soleus muscle of the rat. 2. Hypothyroidism, which was induced by administration of propylthiouracil to the rats, decreased fasting plasma levels of free fatty acids and increased plasma levels of glucose but did not significantly change plasma levels of insulin. 3. The sensitivity of the rates of glycogen synthesis to insulin was increased at physiological, but decreased at supraphysiological, concentrations of insulin. 4. The rates of glycolysis in the hypothyroid muscles were decreased at all insulin concentrations studied and the EC50 for insulin was increased more than 8-fold; the latter indicates decreased sensitivity of this process to insulin. However, at physiological concentrations of insulin, the rates of glucose phosphorylation in the soleus muscles of hypothyroid rats were not different from controls. This suggests that hypothyroidism affects glucose metabolism in muscle not by affecting glucose transport but by decreasing the rate of glucose 6-phosphate conversion to lactate and increasing the rate of conversion of glucose 6-phosphate to glycogen. 5. The rates of glucose oxidation were decreased in the hypothyroid muscles at all insulin concentrations. PMID:2649073

  8. Treatment of type 2 diabetes by free Fatty Acid receptor agonists

    DEFF Research Database (Denmark)

    Watterson, Kenneth R; Hudson, Brian D; Ulven, Trond

    2014-01-01

    been developed as potential treatments for type 2 diabetes (T2D). In particular, clinical studies show that Fasiglifam, an agonist of the long-chain FFA receptor, FFA1, improved glycemic control and reduced HbA1c levels in T2D patients, with a reduced risk of hypoglycemia. However, this ligand...... was removed from clinical trials due to potential liver toxicity and determining if this is a target or a ligand-specific feature is now of major importance. Pre-clinical studies also show that FFA4 agonism increases insulin sensitivity, induces weight loss, and reduces inflammation and the metabolic and anti...

  9. Involvement of insulin-degrading enzyme in insulin- and atrial natriuretic peptide-sensitive internalization of amyloid-β peptide in mouse brain capillary endothelial cells.

    Science.gov (United States)

    Ito, Shingo; Ohtsuki, Sumio; Murata, Sho; Katsukura, Yuki; Suzuki, Hiroya; Funaki, Miho; Tachikawa, Masanori; Terasaki, Tetsuya

    2014-01-01

    Cerebral clearance of amyloid-β peptide (Aβ), which is implicated in Alzheimer's disease, involves elimination across the blood-brain barrier (BBB), and we previously showed that an insulin-sensitive process is involved in the case of Aβ1-40. The purpose of this study was to clarify the molecular mechanism of the insulin-sensitive Aβ1-40 elimination across mouse BBB. An in vivo cerebral microinjection study demonstrated that [125I]hAβ1-40 elimination from mouse brain was inhibited by human natriuretic peptide (hANP), and [125I]hANP elimination was inhibited by hAβ1-40, suggesting that hAβ1-40 and hANP share a common elimination process. Internalization of [125I]hAβ1-40 into cultured mouse brain capillary endothelial cells (TM-BBB4) was significantly inhibited by either insulin, hANP, other natriuretic peptides or insulin-degrading enzyme (IDE) inhibitors, but was not inhibited by phosphoramidon or thiorphan. Although we have reported the involvement of natriuretic peptide receptor C (Npr-C) in hANP internalization, cells stably expressing Npr-C internalized [125I]hANP but not [125I]hAβ1-40, suggesting that there is no direct interaction between Npr-C and hAβ1-40. IDE was detected in plasma membrane of TM-BBB4 cells, and internalization of [125I]hAβ1-40 by TM-BBB4 cells was reduced by IDE-targeted siRNAs. We conclude that elimination of hAβ1-40 from mouse brain across the BBB involves an insulin- and ANP-sensitive process, mediated by IDE expressed in brain capillary endothelial cells.

  10. GPR119 - a major Enteroendocrine Sensor of Dietary Triglyceride Metabolites Co-acting in Synergy with FFA1 (GPR40)

    DEFF Research Database (Denmark)

    Ekberg, Jeppe H; Pedersen, Maria Hauge; Kristensen, Line V

    2016-01-01

    the FFA1 agonist was administered on top of appropriately low doses of the GPR119 agonist a clear synergistic, i.e. more than additive effect was observed. It is concluded that the 2-MAG receptor GPR119 is at least as important as the LCFA receptor FFA1 in mediating the triglyceride-induced secretion......Triglycerides are among the most efficacious stimulators of incretin secretion; however the relative importance of FFA1 (GPR40), FFA4 (GPR120) and GPR119 which all recognize triglyceride metabolites, i.e. LCFA and 2-MAG respectively, is still unclear. Here, we find all three receptors to be highly...... the synthetic FFA1 agonists, TAK-875 stimulated GLP-1 secretion to a similar extent as the prototype GLP-1 secretagogue neuromedin C, this however only corresponded to approx. half the maximal efficiency of the GPR119 agonist AR231453 whereas the GPR120 agonist Metabolix-209 had no effect. Importantly, when...

  11. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation.

    Directory of Open Access Journals (Sweden)

    Gesine Flehmig

    Full Text Available In obesity, elevated fat mass and ectopic fat accumulation are associated with changes in adipokine secretion, which may link obesity to inflammation and the development of insulin resistance. However, relationships among individual adipokines and between adipokines and parameters of obesity, glucose metabolism or inflammation are largely unknown. Serum concentrations of 20 adipokines were measured in 141 Caucasian obese men (n = 67 and women (n = 74 with a wide range of body weight, glycemia and insulin sensitivity. Unbiased, distance-based hierarchical cluster analyses were performed to recognize patterns among adipokines and their relationship with parameters of obesity, glucose metabolism, insulin sensitivity and inflammation. We identified two major adipokine clusters related to either (1 body fat mass and inflammation (leptin, ANGPTL3, DLL1, chemerin, Nampt, resistin or insulin sensitivity/hyperglycemia, and lipid metabolism (vaspin, clusterin, glypican 4, progranulin, ANGPTL6, GPX3, RBP4, DLK1, SFRP5, BMP7, adiponectin, CTRP3 and 5, omentin. In addition, we found distinct adipokine clusters in subgroups of patients with or without type 2 diabetes (T2D. Logistic regression analyses revealed ANGPTL6, DLK1, Nampt and progranulin as strongest adipokine correlates of T2D in obese individuals. The panel of 20 adipokines predicted T2D compared to a combination of HbA1c, HOMA-IR and fasting plasma glucose with lower sensitivity (78% versus 91% and specificity (76% versus 94%. Therefore, adipokine patterns may currently not be clinically useful for the diagnosis of metabolic diseases. Whether adipokine patterns are relevant for the predictive assessment of intervention outcomes needs to be further investigated.

  12. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Science.gov (United States)

    Sartorius, Tina; Peter, Andreas; Schulz, Nadja; Drescher, Andrea; Bergheim, Ina; Machann, Jürgen; Schick, Fritz; Siegel-Axel, Dorothea; Schürmann, Annette; Weigert, Cora; Häring, Hans-Ulrich; Hennige, Anita M

    2014-01-01

    Treatment of diabetic subjects with cinnamon demonstrated an improvement in blood glucose concentrations and insulin sensitivity but the underlying mechanisms remained unclear. This work intends to elucidate the impact of cinnamon effects on the brain by using isolated astrocytes, and an obese and diabetic mouse model. Cinnamon components (eugenol, cinnamaldehyde) were added to astrocytes and liver cells to measure insulin signaling and glycogen synthesis. Ob/ob mice were supplemented with extract from cinnamomum zeylanicum for 6 weeks and cortical brain activity, locomotion and energy expenditure were evaluated. Insulin action was determined in brain and liver tissues. Treatment of primary astrocytes with eugenol promoted glycogen synthesis, whereas the effect of cinnamaldehyde was attenuated. In terms of brain function in vivo, cinnamon extract improved insulin sensitivity and brain activity in ob/ob mice, and the insulin-stimulated locomotor activity was improved. In addition, fasting blood glucose levels and glucose tolerance were greatly improved in ob/ob mice due to cinnamon extracts, while insulin secretion was unaltered. This corresponded with lower triglyceride and increased liver glycogen content and improved insulin action in liver tissues. In vitro, Fao cells exposed to cinnamon exhibited no change in insulin action. Together, cinnamon extract improved insulin action in the brain as well as brain activity and locomotion. This specific effect may represent an important central feature of cinnamon in improving insulin action in the brain, and mediates metabolic alterations in the periphery to decrease liver fat and improve glucose homeostasis.

  13. Immunohistochemical expression of insulin, glucagon, and somatostatin in pancreatic islets of horses with and without insulin resistance.

    Science.gov (United States)

    Newkirk, Kim M; Ehrensing, Gordon; Odoi, Agricola; Boston, Raymond C; Frank, Nicholas

    2018-02-01

    OBJECTIVE To assess insulin, glucagon, and somatostatin expression within pancreatic islets of horses with and without insulin resistance. ANIMALS 10 insulin-resistant horses and 13 insulin-sensitive horses. PROCEDURES For each horse, food was withheld for at least 10 hours before a blood sample was collected for determination of serum insulin concentration. Horses with a serum insulin concentration horses with a serum insulin concentration > 20 μU/mL underwent a frequently sampled IV glucose tolerance test to determine sensitivity to insulin by minimal model analysis. Horses with a sensitivity to insulin horses were euthanized with a barbiturate overdose, and pancreatic specimens were harvested and immunohistochemically stained for determination of insulin, glucagon, and somatostatin expression in pancreatic islets. Islet hormone expression was compared between insulin-resistant and insulin-sensitive horses. RESULTS Cells expressing insulin, glucagon, and somatostatin made up approximately 62%, 12%, and 7%, respectively, of pancreatic islet cells in insulin-resistant horses and 64%, 18%, and 9%, respectively, of pancreatic islet cells in insulin-sensitive horses. Expression of insulin and somatostatin did not differ between insulin-resistant and insulin-sensitive horses, but the median percentage of glucagon-expressing cells in the islets of insulin-resistant horses was significantly less than that in insulin-sensitive horses. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that, in insulin-resistant horses, insulin secretion was not increased but glucagon production might be downregulated as a compensatory response to hyperinsulinemia.

  14. Adipose tissue (PRR regulates insulin sensitivity, fat mass and body weight

    Directory of Open Access Journals (Sweden)

    Zulaykho Shamansurova

    2016-10-01

    Full Text Available Objective: We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(PRR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (PRR gene would prevent weight gain and insulin resistance. Methods: An adipose tissue-specific (PRR knockout (KO mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (PRR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. Results: KO mice had lower body weights compared to wild-types (WT. Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (PRR. Conclusions: (PRR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes. Keywords: (Prorenin receptor, Renin-angiotensin system, Adipose

  15. Plasma lipid fatty acid composition, desaturase activities and insulin sensitivity in Amerindian women.

    Science.gov (United States)

    Vessby, B; Ahrén, B; Warensjö, E; Lindgärde, F

    2012-03-01

    Two Amerindian populations--Shuar women living in the Amazonian rain forest under traditional conditions and urbanized women in a suburb of Lima were studied. The fatty acid composition in plasma lipids and the relationships between fatty acid composition and metabolic variables were studied, as well as in a reference group of Swedish women. Fasting plasma was used for analyses of glucose, insulin, leptin and fatty acid composition. Women in Lima had more body fat, higher fasting insulin and leptin and lower insulin sensitivity than the Shuar women, who had insulin sensitivity similar to Swedish women. Shuar women had very high proportions (mean; SD) of palmitoleic (13.2; 3.9%) and oleic (33.9; 3.7%) acids in the plasma cholesteryl esters with very low levels of linoleic acid (29.1; 6.1 3%), as expected on a low fat, high carbohydrate diet. The estimated activity of delta 9 (SCD-1) desaturase was about twice as high in the Shuar compared with Lima women, suggesting neo lipogenesis, while the delta 5 desaturase activity did not differ. The Lima women, as well as the Swedish, showed strong positive correlations between SCD-1 activity on the one hand and fasting insulin and HOMA index on the other. These associations were absent in the Shuar women. The high SCD-1 activity in the Shuar women may reflect increased lipogenesis in adipose tissue. It also illustrates how a low fat diet rich in non-refined carbohydrates can be linked to a good metabolic situation. Copyright © 2010. Published by Elsevier B.V.

  16. Acute High-intensity Interval Exercise-induced Redox Signaling is Associated with Enhanced Insulin Sensitivity in Obese Middle-aged Men.

    Directory of Open Access Journals (Sweden)

    Lewan Parker

    2016-09-01

    Full Text Available Background. Obesity and ageing are associated with increased oxidative stress, activation of stress and mitogen activated protein kinases (SAPK, and the development of insulin resistance and metabolic disease. In contrast, acute exercise also increases oxidative stress and SAPK signaling, yet is reported to enhance insulin sensitivity and reduce the risk of metabolic disease. This study explored this paradox by investigating the effect of a single session of high-intensity interval-exercise (HIIE on redox status, muscle SAPK and insulin protein signaling in eleven middle-aged obese men. Methods. Participants completed a 2 hour hyperinsulinaemic-euglycaemic clamp at rest, and 60 minutes after HIIE (4x4 mins at 95% HRpeak; 2 min recovery periods, separated by 1-3 weeks. Results. Irrespective of exercise-induced changes to redox status, insulin stimulation both at rest and after HIIE similarly increased plasma superoxide dismutase activity, plasma catalase activity, and skeletal muscle 4-HNE; and significantly decreased plasma TBARS and hydrogen peroxide. The SAPK signaling pathways of p38 MAPK, NF-κB p65, and JNK, and the distal insulin signaling protein AS160Ser588, were activated with insulin stimulation at rest and to a greater extent with insulin stimulation after a prior bout of HIIE. Higher insulin sensitivity after HIIE was associated with higher insulin-stimulated SAPK phosphorylation (JNK, p38 MAPK and NF-κB and SOD activity (p<0.05. Conclusion. These findings support a role for redox homeostasis and SAPK signaling in insulin-stimulated glucose uptake which may contribute to the enhancement of insulin sensitivity in obese men 3 hours after HIIE.

  17. Characterization of the insulin-sensitive low Km cAMP phosphodiesterase from rat adipose tissue

    International Nuclear Information System (INIS)

    Degerman, E.; Belfrage, P.; Manganiello, V.C.

    1986-01-01

    Particulate, but not soluble, low K/sub m/ cAMP phosphodiesterase (PDE) activity of rat adipocytes was increased 50-100% during incubation (10 min) of intact cells with 1-3 nM insulin; activation was less with higher or lower insulin concentrations. Activation was maintained during solubilization with an alkyl polyoxyethylene non-ionic detergent C 13 , E 12 and NaBr and chromatography on DEAE. Enzyme from DEAE was further purified by chromatography on Sepahadex G-200 and Blue-Sepharose. Activity (with 0.5 μM [ 3 H]cAMP) was rather sensitive to inhibition by p-chloromercuribenzoate (IC 50 , 1 μM) and less so by 2,2'-dithiobis-(5-nitropyridine) (160 μM), N-ethylmaleimide (525 μM) and iodoacetamide (750 μM). PDE activity was also rather sensitive to inhibition by cilostamide (IC 50 , ∼40 nM) and the cardiotonic drugs CI 930 (450 nM) and milrinone (630 nM) but rather insensitive to RO 20-1724 (190 μM). Based on effects of these inhibitors, the hormone-sensitive low K/sub m/ particulate cAMP PDE from rat adipocytes seems to be analogous to the insulin-activated particulate PDE from 3T3-L1 adipocytes and the cilostamide-sensitive soluble low K/sub m/ cAMP PDE from bovine liver (designated as III-C), platelets, heart, and other tissues

  18. Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Carstensen, Steen; Hove, Jens D

    2002-01-01

    patients with ischaemic heart disease and impaired LV ejection fraction (EF) and age-matched healthy volunteers ( n = 30). As assessed by euglycaemic glucose-insulin clamp, 15 patients had a low and 14 a normal whole-body insulin sensitivity. Using positron emission tomography, patterns of fluorine-18......We tested the hypothesis that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired left ventricular (LV) function is associated with abnormalities of insulin-mediated myocardial glucose uptake affecting outcome after coronary bypass surgery (CABG). We studied 29......-normal myocardium was found to be higher in patients with normal whole-body insulin sensitivity ( P body insulin sensitivity more segments displayed a pattern of reduced glucose uptake in normoperfused myocardium (PET-reverse mismatch) ( P

  19. Intrauterine growth-restricted sheep fetuses exhibit smaller hindlimb muscle fibers and lower proportions of insulin-sensitive Type I fibers near term.

    Science.gov (United States)

    Yates, Dustin T; Cadaret, Caitlin N; Beede, Kristin A; Riley, Hannah E; Macko, Antoni R; Anderson, Miranda J; Camacho, Leticia E; Limesand, Sean W

    2016-06-01

    Intrauterine growth restriction (IUGR) reduces muscle mass and insulin sensitivity in offspring. Insulin sensitivity varies among muscle fiber types, with Type I fibers being most sensitive. Differences in fiber-type ratios are associated with insulin resistance in adults, and thus we hypothesized that near-term IUGR sheep fetuses exhibit reduced size and proportions of Type I fibers. Placental insufficiency-induced IUGR fetuses were ∼54% smaller (P fetal muscles develop smaller fibers and have proportionally fewer Type I fibers, which is indicative of developmental adaptations that may help explain the link between IUGR and adulthood insulin resistance. Copyright © 2016 the American Physiological Society.

  20. Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome.

    Science.gov (United States)

    Derkach, K V; Ivantsov, A O; Chistyakova, O V; Sukhov, I B; Buzanakov, D M; Kulikova, A A; Shpakov, A O

    2017-06-01

    We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

  1. pH-sensitive chitosan/alginate core-shell nanoparticles for efficient and safe oral insulin delivery.

    Science.gov (United States)

    Mukhopadhyay, Piyasi; Chakraborty, Souma; Bhattacharya, Sourav; Mishra, Roshnara; Kundu, P P

    2015-01-01

    Chitosan-alginate (CS/ALG) nanoparticles were prepared by formation of an ionotropic pre-gelation of an alginate (ALG) core entrapping insulin, followed by chitosan (CS) polyelectrolyte complexation, for successful oral insulin administration. Mild preparation process without harsh chemicals is aimed at improving insulin bio-efficiency in in vivo model. The nanoparticles showed an average particle size of 100-200 nm in dynamic light scattering (DLS), with almost spherical or sub-spherical shape and ∼ 85% of insulin encapsulation. Again, retention of almost entire amount of encapsulated insulin in simulated gastric buffer followed by its sustained release in simulated intestinal condition proved its pH sensitivity in in vitro release studies. Significant hypoglycemic effects with improved insulin-relative bioavailability (∼ 8.11%) in in vivo model revealed the efficacy of these core-shell nanoparticles of CS/ALG as an oral insulin carrier. No systemic toxicity was found after its peroral treatment, suggesting these core-shell nanoparticles as a promising device for potential oral insulin delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. One week treatment with the IL-1 receptor antagonist anakinra leads to a sustained improvement in insulin sensitivity in insulin resistant patients with type 1 diabetes mellitus

    NARCIS (Netherlands)

    Asseldonk, van E.J.P.; Poppel, van P.C.M.; Ballak, D.B.; Stienstra, Rinke; Netea, M.G.; Tack, C.J.

    2015-01-01

    Inflammation associated with obesity is involved in the development of insulin resistance. We hypothesized that anti-inflammatory treatment with the Interleukin-1 receptor antagonist anakinra would improve insulin sensitivity.In an open label proof-of-concept study, we included overweight

  3. The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

    DEFF Research Database (Denmark)

    Henstridge, Darren C; Forbes, Josephine M; Penfold, Sally A

    2010-01-01

    Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young...... healthy human population free of hyperglycemia. Healthy participants (N = 17; age, 30 ± 3 years) underwent measurement of body composition (dual-energy x-ray absorptiometry), a maximum aerobic capacity test (VO(2max)), an oral glucose tolerance test, and a hyperinsulinemic-euglycemic clamp (M) to access...... insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat (r = -0.54, P

  4. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    DEFF Research Database (Denmark)

    Lundsgaard, Annemarie; Kiens, Bente

    2014-01-01

    higher insulin sensitivity of female skeletal muscle can be related to gender-specific regulation of molecular metabolism will be topic for discussion. Gender differences in muscle fiber type distribution and substrate availability to and in skeletal muscle are highly relevant for substrate metabolism...

  5. The use of CDS/ISIS software in Africa | Abboy | Innovation

    African Journals Online (AJOL)

    CDS/ISIS is free-of-charge software that has been developed by UNESCO and is distributed through a network of country distributors and more recently through the World Wide Web. CDS/ISIS is ideally suited for the manipulation of bibliographic data. Literature sources reveal that the use of CDS/ISIS is widespread in Africa ...

  6. Correlation of urodynamic characteristics with insulin resistance and serum damage media in diabetic patients with benign prostatic hyperplasia

    Directory of Open Access Journals (Sweden)

    Zhong-Ping Jiang

    2017-03-01

    Full Text Available Objective: To study the correlation of urodynamic characteristics with insulin resistance and serum damage media in patients with diabetes and benign prostatic hyperplasia (BPH. Methods: 45 patients with type 2 diabetes mellitus and BPH treated in our hospital between May 2014 and August 2016 were selected as DM+BPH group, 58 patients with BPH alone were selected as BPH group, and 50 healthy volunteers were selected as control group. Urodynamic tester was used to measure the maximum flow rate (MFR, postvoid residual (PVR and detrusor pressure at maximum flow rate (Pdet, and serum was collected to determine insulin resistance indexes and oxidative stress indexes. Results: MFR and Pdet of DM+BPH group were significantly lower than those of control group (P<0.05 while PVR was significantly higher than that of control group (P<0.05; MFR of BPH group was significantly lower than that of control group (P<0.05 while PVR and Pdet were significantly higher than those of control group (P<0.05; MFR and Pdet of DM+BPH group were significantly lower than those of BPH group (P<0.05 while PVR was significantly higher than that of BPH group (P<0.05; insulin secretion index (HOMA-β, insulin sensitive index (ISI as well as serum manganese superoxide dismutase (MnSOD, copper-zinc superoxide dismutase (CuZnSOD and glutathione peroxidase (GPx levels of DM+BPH group and BPH group were significantly lower than those of control group (P<0.05 while insulin resistance index (HOMA-IR as well as serum thioredoxin (Trx and thioredoxin-interacting protein (TXNIP levels was significantly higher than those of control group (P<0.05; HOMA-β, ISI as well as serum MnSOD, CuZnSOD and GPx levels of DM+BPH group were significantly lower than those of BPH group (P<0.05, positively correlated with MFR and Pdet, and negatively correlated with MFR, and HOMA-IR as well as serum Trx and TXNIP levels was significantly higher than those of BPH group (P<0.05, negatively correlated with MFR

  7. Fat distribution and glucose intolerance among Greenland inuit

    DEFF Research Database (Denmark)

    Jørgensen, Marit Eika; Borch-Johnsen, Knut; Stolk, Ronald

    2013-01-01

    circumference [WC], and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment [HOMA-IR], and the insulin sensitivity index [ISI0,120]) among Greenland Inuit. RESEARCH DESIGN AND METHODS A total of 3,108 adult Inuit...... associated with glucose intolerance, fasting and 2-h plasma glucose levels, HOMA-IR, and ISI0,120. VAT was more strongly associated with all outcomes than was SAT. After further adjustment for BMI or WC, VAT was associated with glucose intolerance and insulin resistance, whereas there was a trend toward...

  8. Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity.

    Science.gov (United States)

    Vieira Potter, Victoria J; Strissel, Katherine J; Xie, Chen; Chang, Eugene; Bennett, Grace; Defuria, Jason; Obin, Martin S; Greenberg, Andrew S

    2012-09-01

    Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (≈ 31 g) became fatter than SHM mice (≈ 26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-MΦ (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (-20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (+2-fold), IL12p40 (+2-fold), and interferon-γ (+78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity.

  9. The Relationship between Adiposity and Insulin Sensitivity in African Women Living with the Polycystic Ovarian Syndrome: A Clamp Study

    Directory of Open Access Journals (Sweden)

    Emmanuella Doh

    2016-01-01

    Full Text Available Objectives. We aimed to assess the variation of insulin sensitivity in relation to obesity in women living with PCOS in a sub-Sahara African setting. Methods. We studied body composition, insulin sensitivity, and resting energy expenditure in 14 PCOS patients (6 obese and 8 nonobese compared to 10 matched nonobese non-PCOS subjects. Insulin sensitivity was assessed using the gold standard 80 mU/m2/min euglycemic-hyperinsulinemic clamp and resting energy expenditure was measured by indirect calorimetry. Results. Insulin sensitivity adjusted to lean mass was lowest in obese PCOS subjects and highest in healthy subjects (11.2 [10.1–12.4] versus 12.9 [12.1–13.8] versus 16.6 [13.8–17.9], p=0.012; there was a tendency for resting energy expenditure adjusted for total body mass to decrease across the groups highest in obese PCOS subjects (1411 [1368–1613] versus 1274 [1174–1355] versus 1239 [1195–1454], p=0.306. Conclusion. In this sub-Saharan population, insulin resistance is associated with PCOS per se but is further aggravated by obesity. Obesity did not seem to be explained by low resting energy expenditure suggesting that dietary intake may be a determinant of the obesity in this context.

  10. Exercise increases human skeletal muscle insulin sensitivity via coordinated increases in microvascular perfusion and molecular signaling

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Frøsig, Christian; Kjøbsted, Rasmus

    2017-01-01

    and increased similarly in both legs during the clamp and L-NMMA had no effect on these insulin-stimulated signaling pathways. Therefore, acute exercise increases insulin sensitivity of muscle by a coordinated increase in insulin-stimulated microvascular perfusion and molecular signaling at the level of TBC1D4...... and glycogen synthase in muscle. This secures improved glucose delivery on the one hand and increased ability to take up and dispose of the delivered glucose on the other hand....

  11. EGb761, an extract of Ginkgo biloba leaves, reduces insulin resistance in a high-fat-fed mouse model

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    2011-06-01

    Full Text Available EGb761, a standardized and well-defined product extract of Ginkgo biloba leaves, has beneficial effects on the treatment of multiple diseases, including diabetes and dyslipidemia. However, it is still unclear whether EGb761 can increase insulin sensitivity. The objectives of the present study are to evaluate the effects of EGb761 on insulin sensitivity in an obese and insulin-resistant mouse model, established through chronic feeding of C57BL/6J mice with a high-fat diet (HFD, and to explore potential mechanisms. Mice fed with HFD for 18 weeks (starting from 4 weeks of age developed obesity, dyslipidemia (as indicated by biochemical measurements of blood glucose, triglyceride (TG, total cholesterol (TC, and free fatty acids (FFA, and insulin resistance (as determined by the oral glucose tolerance test (OGTT and the homeostasis model assessment of insulin resistance (HOMA-IR index, compared to control mice fed with a standard laboratory chow. Oral treatment of the HFD-fed mice with EGb761, at low (100 mg/kg, medium (200 mg/kg, or high (400 mg/kg doses, via oral gavage (once daily for 8 weeks (starting from 26 weeks of age dose-dependently enhanced glucose tolerance in OGTT, and decreased both the insulin levels (by 29%, 55%, and 70%, respectively, and the HOMA-IR index values (by 50%, 69%, and 80%, respectively. EGb761 treatment also ameliorated HFD-induced obesity, dyslipidemia, and liver injury, as indicated by decreases in body weight (by 4%, 11%, and 16%, respectively, blood TC levels (by 23%, 32%, and 37%, respectively, blood TG levels (by 17%, 23%, and 33%, respectively, blood FAA levels (by 35%, 38%, and 46%, respectively, and liver index (liver weight/body weight values (by 12.8%, 25%, and 28%, respectively in the low, medium, and high EGb761 dose groups, respectively. In further mechanism studies, EGb761 was found to protect hepatic insulin receptor β and insulin receptor substrate 1 from HFD-induced degradation, and to keep the AMP

  12. Impact of Diabetes-Specific Nutritional Formulas versus Oatmeal on Postprandial Glucose, Insulin, GLP-1 and Postprandial Lipidemia

    Directory of Open Access Journals (Sweden)

    Adham Mottalib

    2016-07-01

    Full Text Available Diabetes-specific nutritional formulas (DSNFs are frequently used as part of medical nutrition therapy for patients with diabetes. This study aims to evaluate postprandial (PP effects of 2 DSNFs; Glucerna (GL and Ultra Glucose Control (UGC versus oatmeal (OM on glucose, insulin, glucagon-like peptide-1 (GLP-1, free fatty acids (FFA and triglycerides (TG. After an overnight fast, 22 overweight/obese patients with type 2 diabetes were given 200 kcal of each of the three meals on three separate days in random order. Blood samples were collected at baseline and at 30, 60, 90, 120, 180 and 240 min. Glucose area under the curve (AUC0–240 after GL and UGC was lower than OM (p < 0.001 for both. Insulin positive AUC0–120 after UGC was higher than after OM (p = 0.02. GLP-1 AUC0–120 and AUC0–240 after GL and UGC was higher than after OM (p < 0.001 for both. FFA and TG levels were not different between meals. Intake of DSNFs improves PP glucose for 4 h in comparison to oatmeal of similar caloric level. This is achieved by either direct stimulation of insulin secretion or indirectly by stimulating GLP-1 secretion. The difference between their effects is probably related to their unique blends of amino acids, carbohydrates and fat.

  13. The impact of pegvisomant treatment on substrate metabolism and insulin sensitivity in patients with acromegaly

    DEFF Research Database (Denmark)

    Lindberg-Larsen, Rune; Møller, Niels; Schmitz, Ole

    2007-01-01

    CONTEXT: Pegvisomant is a specific GH receptor antagonist that is able to normalize serum IGF-I concentrations in most patients with acromegaly. The impact of pegvisomant on insulin sensitivity and substrate metabolism is less well described. PATIENTS AND METHODS: We assessed basal and insulin......-stimulated (euglycemic clamp) substrate metabolism in seven patients with active acromegaly before and after 4-wk pegvisomant treatment (15 mg/d) in an open design. RESULTS: After pegvisomant, IGF-I decreased, whereas GH increased (IGF-I, 621 +/- 82 vs. 247 +/- 33 microg/liter, P = 0.02; GH, 5.3 +/- 1.5 vs. 10.8 +/- 3...... vs. 1563 +/- 101 kcal/24 h, P = 0.03), but the rate of lipid oxidation did not change significantly. CONCLUSIONS: 1) Pegvisomant treatment for 4 wk improves peripheral and hepatic insulin sensitivity in acromegaly. 2) This is associated with a decrease in resting energy expenditure, whereas free...

  14. Evaluatie van ISIS-MML

    NARCIS (Netherlands)

    Benthem BHB van; EPI

    2007-01-01

    The Infectious Diseases Surveillance Information system that collects data of medical microbiology laboratories in the Netherlands (ISIS-MML) is not suitable for early warning of infectious diseases outbreaks. However, the system is appropriate for monitoring trends in antimicrobial resistance.

  15. Modification and Validation of the Triglyceride-to-HDL Cholesterol Ratio as a Surrogate of Insulin Sensitivity in White Juveniles and Adults without Diabetes Mellitus

    DEFF Research Database (Denmark)

    Paulmichl, Katharina; Hatunic, Mensud; Højlund, Kurt

    2016-01-01

    BACKGROUND: The triglyceride-to-HDL cholesterol (TG/HDL-C) ratio was introduced as a tool to estimate insulin resistance, because circulating lipid measurements are available in routine settings. Insulin, C-peptide, and free fatty acids are components of other insulin-sensitivity indices...... but their measurement is expensive. Easier and more affordable tools are of interest for both pediatric and adult patients. METHODS: Study participants from the Relationship Between Insulin Sensitivity and Cardiovascular Disease [43.9 (8.3) years, n = 1260] as well as the Beta-Cell Function in Juvenile Diabetes...... and Obesity study cohorts [15 (1.9) years, n = 29] underwent oral-glucose-tolerance tests and euglycemic clamp tests for estimation of whole-body insulin sensitivity and calculation of insulin sensitivity indices. To refine the TG/HDL ratio, mathematical modeling was applied including body mass index (BMI...

  16. Characterization of the insulin-sensitive low Km cAMP phosphodiesterase from rat adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Degerman, E.; Belfrage, P.; Manganiello, V.C.

    1986-05-01

    Particulate, but not soluble, low K/sub m/ cAMP phosphodiesterase (PDE) activity of rat adipocytes was increased 50-100% during incubation (10 min) of intact cells with 1-3 nM insulin; activation was less with higher or lower insulin concentrations. Activation was maintained during solubilization with an alkyl polyoxyethylene non-ionic detergent C/sub 13/, E/sub 12/ and NaBr and chromatography on DEAE. Enzyme from DEAE was further purified by chromatography on Sepahadex G-200 and Blue-Sepharose. Activity (with 0.5 ..mu..M (/sup 3/H)cAMP) was rather sensitive to inhibition by p-chloromercuribenzoate (IC/sub 50/, 1 ..mu..M) and less so by 2,2'-dithiobis-(5-nitropyridine) (160 ..mu..M), N-ethylmaleimide (525 ..mu..M) and iodoacetamide (750 ..mu..M). PDE activity was also rather sensitive to inhibition by cilostamide (IC/sub 50/, approx.40 nM) and the cardiotonic drugs CI 930 (450 nM) and milrinone (630 nM) but rather insensitive to RO 20-1724 (190 ..mu..M). Based on effects of these inhibitors, the hormone-sensitive low K/sub m/ particulate cAMP PDE from rat adipocytes seems to be analogous to the insulin-activated particulate PDE from 3T3-L1 adipocytes and the cilostamide-sensitive soluble low K/sub m/ cAMP PDE from bovine liver (designated as III-C), platelets, heart, and other tissues.

  17. Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity

    DEFF Research Database (Denmark)

    Vigelsø Hansen, Andreas; Prats Gavalda, Clara; Ploug, Thorkil

    2013-01-01

    Background: Impaired insulin sensitivity may partly arise from a dysregulated lipid metabolism in human skeletal muscle. This study investigates the expression levels of perilipin 2, 3, and 5, and four key lipases in human skeletal muscle from the subjects that exhibit a range from normal to very...

  18. Spirulina vesicolor Improves Insulin Sensitivity and Attenuates Hyperglycemia-Mediated Oxidative Stress in Fructose-Fed Rats

    Directory of Open Access Journals (Sweden)

    Walaa Hozayen

    2016-03-01

    Full Text Available Aim: The current study aimed to investigate the anti-hyperglycemic, anti-hyperlipidemic and insulin sensitizing effects of the cyanobacterium Spirulina vesicolor extract in fructose-fed rats. Materials and Methods: Rats were fed 30% fructose solution in drinking water for 4 weeks. Animals exhibited hyperglycemia and hyperinsulinemia were selected for further investigations. Diabetic and control rats were orally supplemented with 50 mg/kg body weight S. vesicolor extract for 4 weeks. Results: At the end of 8 weeks, fructose-fed rats showed significant increase in serum glucose, insulin, cholesterol, triglycerides, cardiovascular risk indices and insulin resistance. Treatment of the fructose-fed rats with S. vesicolor extract improved this metabolic profile. Fructose feeding produced a significant increase in serum tumor necrosis factor alpha (TNF-α and a decrease in adiponectin levels. In addition, fructose-fed rats exhibited a significant increase in liver, kidney and heart lipid peroxidation levels, and declined antioxidant defenses. Supplementation of the fructose-fed rats with S. vesicolor extract reversed these alterations. Conclusion: S. vesicolor attenuates hyperglycemia-mediated oxidative stress and inflammation, and is thus effective in improving insulin sensitivity in fructose-fed rats. [J Complement Med Res 2016; 5(1.000: 57-64

  19. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation and ceramide content in skeletal muslce of men, but not women

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas; Sjøberg, Kim Anker; Lundsgaard, Annemarie

    2013-01-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin sensitizing effect have been investigated in rodents, but little is known in humans especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men...

  20. Pioglitazone improves insulin sensitivity, reduces visceral fat and stimulates lipolysis in non diabetic dialyzed patients

    Directory of Open Access Journals (Sweden)

    Anne Zanchi

    2012-06-01

    Full Text Available Insulin resistance is common in dialyzed patients and is associated with increased mortality and protein-energy wasting. The aim of this study was to investigate the effect of pioglitazone (PIO, a powerful insulin sensitizer, on insulin sensitivity, body composition and adipose tissue metabolism, in dialyzed patients. A double blind randomized cross-over study was performed in non diabetic dialysis patients. Each patient followed 2 treatment phases of 16 weeks, starting either with oral PIO 45 mg/d or placebo (PL, and then switched to the other phase. At the end of each phase, patients underwent hyperinsulinemic euglycemic clamps, dual energy X-ray absorptiometry, an abdominal CT, and extensive plasma biochemical analysis. Twelve patients including 8 HD (59.6±4.4 y and 4 PD patients (43.5±3.6 y were recruited. Nine patients completed both phases and 3 patients dropped out (renal transplantation/2 HD and peritonitis/1 PD. PIO was safe and well tolerated. Under PIO, insulin sensitivity improved, as assessed by increased total glucose disposal rate (1.98±0.24 for PIO versus 1.58±0.12 umol/kg/min for PL, p<0.05, and reduced glucose endogenous hepatic production. PIO did not affect post-dialysis body weight, total fat and lean body mass, but significantly reduced visceral adipose tissue (VAT area and the VAT/SAT (subcutaneous adipose tissue ratio. HDL-cholesterol significantly increased. PIO decreased CRP (3.96±1.44 mg/l vs 7.88±2.56, p<0.05, plasma leptin, and dramatically reduced leptin/adiponectin ratio. Glycerol turnover, circulating glycerol and non esterified fatty acids were paradoxically increased. In conclusion, the improvement in insulin sensitivity by PIO, in non diabetic dialyzed patients, was associated with favorable metabolic effects, reduction in inflammation and body fat redistribution. The stimulation of systemic lipolysis was a surprising finding which may reflect adipose tissue remodeling and/or a paradoxical lypolitic

  1. Replacement of the ISIS control system

    International Nuclear Information System (INIS)

    Mannix, R.P.; Barton, C.J.; Brownless, D.M.; Kerr, J.C.

    1992-01-01

    In operation since 1985, ISIS is the world's most powerful pulsed spallation neutron source. The decision has been taken to replace the existing ISIS control system, which has been in use for over ten years. The problems of such a project, given the legacy of processor specific hardware and software are discussed, a long with the problems associated with incorporating existing interface hardware into any new system. Present progress using commercial workstation based control software is presented with, an assessment of the benefits and pitfalls of such an approach. (author)

  2. Effects of Rosiglitazone, Glyburide, and Metformin on β-Cell Function and Insulin Sensitivity in ADOPT

    Science.gov (United States)

    Kahn, Steven E.; Lachin, John M.; Zinman, Bernard; Haffner, Steven M.; Aftring, R. Paul; Paul, Gitanjali; Kravitz, Barbara G.; Herman, William H.; Viberti, Giancarlo; Holman, Rury R.

    2011-01-01

    OBJECTIVE ADOPT (A Diabetes Outcome Progression Trial) demonstrated that initial monotherapy with rosiglitazone provided superior durability of glycemic control compared with metformin and glyburide in patients with recently diagnosed type 2 diabetes. Herein, we examine measures of β-cell function and insulin sensitivity from an oral glucose tolerance test (OGTT) over a 4-year period among the three treatments. RESEARCH DESIGN AND METHODS Recently diagnosed, drug-naïve patients with type 2 diabetes (4,360 total) were treated for a median of 4.0 years with rosiglitazone, metformin, or glyburide and were examined with periodic metabolic testing using an OGTT. RESULTS Measures of β-cell function and insulin sensitivity from an OGTT showed more favorable changes over time with rosiglitazone versus metformin or glyburide. Persistent improvements were seen in those who completed 4 years of monotherapy and marked deterioration of β-cell function in those who failed to maintain adequate glucose control with initial monotherapy. CONCLUSIONS The favorable combined changes in β-cell function and insulin sensitivity over time with rosiglitazone appear to be responsible for its superior glycemic durability over metformin and glyburide as initial monotherapy in type 2 diabetes. PMID:21415383

  3. A common polymorphism near the interleukin-6 gene modifies the association between dietary fat intake and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Cuda C

    2012-01-01

    Full Text Available Cristina Cuda1, Bibiana Garcia-Bailo1,2, Mohamed Karmali1,2, Ahmed El-Sohemy1, Alaa Badawi21Department of Nutritional Sciences, University of Toronto, 2Office of Biotechnology, Genomics and Population Health, Public Health Agency of Canada, Toronto, Ontario, CanadaBackground: Increasing evidence suggests a role for inflammation in the development of type 2 diabetes. Elevated levels of inflammatory cytokines, including interleukin-6, have been associated with insulin resistance, and dietary lipids can increase cytokine production. The objective of this study was to determine whether a single nucleotide polymorphism near the IL6 gene (rs7801406 modifies the relationship between dietary fat and markers of insulin sensitivity.Methods: Subjects were healthy men and women aged 20–29 years from the Toronto Nutrigenomics and Health Study. Dietary intake was estimated using a one-month semiquantitative food frequency questionnaire. Fasting blood samples were taken for genotyping and biomarker measurement.Results: The single nucleotide polymorphism was not associated with any of the measures of insulin sensitivity. However, it modified the relationship between total dietary fat and the homeostasis model assessment of insulin resistance (P = 0.053 for interaction. Total fat intake was positively related to HOMA-IR in individuals homozygous for the G allele (ß = 0.005 ± 0.002, P = 0.03, but not among heterozygotes. There was an inverse relationship between total fat intake and HOMA-IR in individuals who were homozygous for the A allele (β= –0.012 ± 0.006, P = 0.047.Conclusion: These findings suggest that dietary fat influences insulin sensitivity differently depending on genotype.Keywords: interleukin-6, insulin sensitivity, nutrigenomics, dietary fat

  4. Exercise Increases Insulin Sensitivity and Skeletal Muscle AMPK Expression in Systemic Lupus Erythematosus: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Fabiana B. Benatti

    2018-04-01

    Full Text Available Systemic lupus erythematosus (SLE patients may show increased insulin resistance (IR when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-week, randomized controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n = 9 and non-trained (SLE-NT, n = 10. Before and after 12 weeks of the exercise training program, patients underwent a meal test (MT, from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling [Akt and AMP-activated protein kinase (AMPK]. SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin [−39 vs. +14%, p = 0.009, effect size (ES = −1.0] and in the insulin response to MT (−23 vs. +21%, p = 0.007, ES = −1.1, homeostasis model assessment IR (−30 vs. +15%, p = 0.005, ES = −1.1, a tendency toward decreased proinsulin response to MT (−19 vs. +6%, p = 0.07, ES = −0.9 and increased glucagon response to MT (+3 vs. −3%, p = 0.09, ES = 0.6, and significant increases in the Matsuda index (+66 vs. −31%, p = 0.004, ES = 0.9 and fasting glucagon (+4 vs. −8%, p = 0.03, ES = 0.7. No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT, and insulinogenic index (all p > 0.05. SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73 vs. −12%, p = 0.014, ES = 1.3, whereas no

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

    DEFF Research Database (Denmark)

    Mandrup, Camilla M; Egelund, Jon; Nyberg, Michael

    2018-01-01

    To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n...

  6. The Isis project: Fault-tolerance in large distributed systems

    Science.gov (United States)

    Birman, Kenneth P.; Marzullo, Keith

    1993-01-01

    This final status report covers activities of the Isis project during the first half of 1992. During the report period, the Isis effort has achieved a major milestone in its effort to redesign and reimplement the Isis system using Mach and Chorus as target operating system environments. In addition, we completed a number of publications that address issues raised in our prior work; some of these have recently appeared in print, while others are now being considered for publication in a variety of journals and conferences.

  7. DNA methylation and histone deacetylation regulating insulin sensitivity due to chronic cold exposure.

    Science.gov (United States)

    Wang, Xiaoqing; Wang, Lai; Sun, Yizheng; Li, Ruiping; Deng, Jinbo; Deng, Jiexin

    2017-02-01

    In this study, we investigated the causal relationship between chronic cold exposure and insulin resistance and the mechanisms of how DNA methylation and histone deacetylation regulate cold-reduced insulin resistance. 46 adult male mice from postnatal day 90-180 were randomly assigned to control group and cold-exposure group. Mice in cold-exposure group were placed at temperature from -1 to 4 °C for 30 days to mimic chronic cold environment. Then, fasting blood glucose, blood insulin level and insulin resistance index were measured with enzymatic methods. Immunofluorescent labeling was carried out to visualize the insulin receptor substrate 2 (IRS2), Obese receptor (Ob-R, a leptin receptor), voltage-dependent anion channel protein 1 (VDAC1), cytochrome C (cytC), 5-methylcytosine (5-mC) positive cells in hippocampal CA1 area. Furthermore, the expressions of some proteins mentioned above were detected with Western blot. The results showed: ① Chronic cold exposure could reduce the insulin resistance index (P cold-exposure group than in control group with both immunohistochemical staining and Western blot (P cold exposure increased DNA methylation and histone deacetylation in the pyramidal cells of CA1 area and led to an increase in the expression of histone deacetylase 1 (HDAC1) and DNA methylation relative enzymes (P cold exposure can improve insulin sensitivity, with the involvement of DNA methylation, histone deacetylation and the regulation of mitochondrial energy metabolism. These epigenetic modifications probably form the basic mechanism of cold-reduced insulin resistance. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. BEATING ISIS IN THE DIGITAL SPACE: FOCUS TESTING ISIS DEFECTOR COUNTER-NARRATIVE VIDEOS WITH AMERICAN COLLEGE STUDENTS

    OpenAIRE

    Allision McDowell-Smith; Anne Speckhard; Ahmet S. Yayla

    2017-01-01

    ISIS recruits on a 24/7 basis in over 21 languages over the Internet using videos, memes, tweets and other social media postings and swarming in on anyone that retweets, likes or endorses their materials to try to seduce them into the group. Their unprecedented social media drive has resulted in over 30,000 foreign fighters from more than 100 countries migrating to Syria and Iraq. ISIS recruitment in the U.S. is for the most part Internet based and has resulted in the actual and attempted r...

  9. New Onset Diabetes Mellitus after Kidney Transplantation in Denmark

    DEFF Research Database (Denmark)

    Hornum, Mette; Jørgensen, Kaj Anker; Hansen, Jesper Melchior

    2010-01-01

    patients remaining on the waiting list for kidney transplantation (uremic controls, age 47 11 years). All were examined at baseline before possible transplantation and after 12 months. The prevalence of diabetes, prediabetes, insulin sensitivity index (ISI), and insulin secretion index (Isecr) were...

  10. Development and Characterization of a Fluorescent Tracer for the Free Fatty Acid Receptor 2 (FFA2/GPR43)

    DEFF Research Database (Denmark)

    Hansen, Anders Højgaard; Sergeev, Eugenia; Pandey, Sunil K.

    2017-01-01

    The free fatty acid receptor 2 (FFA2/GPR43) is considered a potential target for treatment of metabolic and inflammatory diseases. Here we describe the development of the first fluorescent tracer for FFA2 intended as a tool for assessment of thermodynamic and kinetic binding parameters of unlabel...

  11. Plasma glycosylphosphatidylinositol-specific phospholipase D predicts the change in insulin sensitivity in response to a low-fat but not a low-carbohydrate diet in obese women.

    Science.gov (United States)

    Gray, Dona L; O'Brien, Kevin D; D'Alessio, David A; Brehm, Bonnie J; Deeg, Mark A

    2008-04-01

    Although circulating glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD), a minor high-density lipoprotein-associated protein, is elevated in patients with insulin resistance or high triglycerides, no information is available on the effect of weight loss or changes in insulin sensitivity on circulating GPI-PLD levels. The objective of the study was to determine the effect of weight loss and changes in insulin sensitivity on plasma GPI-PLD levels. Forty-two nondiabetic obese women were included in the study, which involved a 3-month dietary intervention randomizing patients to a low-fat or a low-carbohydrate diet. The study's main outcome measures were plasma GPI-PLD levels and insulin sensitivity as estimated by the homeostasis model assessment. The very low carbohydrate diet group lost more weight after 3 months (-7.6 +/- 3.2 vs -4.2 +/- 3.5 kg, P low-fat diet, whereas baseline insulin sensitivity correlated with the change in insulin sensitivity in response to the low-carbohydrate diet. Plasma GPI-PLD may serve as a clinical tool to determine the effect of a low-fat diet on insulin sensitivity.

  12. High-fat diet induced insulin resistance in pregnant rats through pancreatic pax6 signaling pathway.

    Science.gov (United States)

    Wu, Hao; Liu, Yunyun; Wang, Hongkun; Xu, Xianming

    2015-01-01

    To explore the changes in pancreas islet function of pregnant rats after consumption of high-fat diet and the underlying mechanism. Thirty pregnant Wistar rats were randomly divided into two groups: high-fat diet group and normal control group. Twenty days after gestation, fasting blood glucose concentration (FBG) and fasting serum insulin concentration (FINS) were measured. Then, oral glucose tolerance test (OGTT) and insulin release test (IRT) were performed. Finally, all the rats were sacrificed and pancreas were harvested. Insulin sensitivity index (ISI) and insulin resistance index (HOMA-IR) were calculated according to FBG and FINS. RT-PCR and Real-time PCR were performed to study the expression of paired box 6 transcription factor (Pax6) and its target genes in pancreatic tissues. The body weight was significantly increased in the high-fat diet group compared with that of normal control rats (Pinsulin concentration between the two groups. OGTT and IRT were abnormal in the high-fat diet group. The high-fat diet rats were more prone to impaired glucose tolerance and insulin resistance. The level of the expression of Pax6 transcription factor and its target genes in pancreas, such as pancreatic and duodenal homeobox factor-1 (Pdx1), v-maf musculoaponeurotic fibrosarcoma oncogene homolog A (MafA) and glucose transporter 2 (Glut2) were decreased significantly compared with those of normal control group. High-fat diet feeding during pregnancy may induce insulin resistance in maternal rats by inhibiting pancreatic Pax6 and its target genes expression.

  13. Effect of fructose consumption on insulin sensitivity in nondiabetic subjects: a systematic review and meta-analysis of diet-intervention trials.

    Science.gov (United States)

    Ter Horst, Kasper W; Schene, Merle R; Holman, Rebecca; Romijn, Johannes A; Serlie, Mireille J

    2016-12-01

    High fructose consumption has been suggested to contribute to several features of metabolic syndrome including insulin resistance, but to our knowledge, no previous meta-analyses have investigated the effect of fructose on insulin sensitivity in nondiabetic subjects. We performed a systematic review and meta-analysis of controlled diet-intervention studies in nondiabetic subjects to determine the effect of fructose on insulin sensitivity. We searched MEDLINE, EMBASE, and the Cochrane Library for relevant trials on the basis of predetermined eligibility criteria. Two investigators independently performed the study selection, quality assessment, and data extraction. Results were pooled with the use of the generic inverse-variance method with random effects weighting and were expressed as mean differences (MDs) or standardized mean differences (SMDs) with 95% CIs. Twenty-nine articles that described 46 comparisons in 1005 normal-weight and overweight or obese participants met the eligibility criteria. An energy-matched (isocaloric) exchange of dietary carbohydrates by fructose promoted hepatic insulin resistance (SMD: 0.47; 95% CI: 0.03, 0.91; P = 0.04) but had no effect on fasting plasma insulin concentrations (MD: -0.79 pmol/L; 95% CI: -6.41, 4.84 pmol/L; P = 0.78), the homeostasis model assessment of insulin resistance (HOMA-IR) (MD: 0.13; 95% CI: -0.07, 0.34; P = 0.21), or glucose disposal rates under euglycemic hyperinsulinemic clamp conditions (SMD: 0.00; 95% CI: 20.41, 0.41; P = 1.00). Hypercaloric fructose (∼25% excess of energy compared with that of the weight-maintenance control diet) raised fasting plasma insulin concentrations (MD: 3.38 pmol/L; 95% CI: 0.03, 6.73 pmol/L; P fructose consumption, in isocaloric exchange or in hypercaloric supplementation, promotes the development of hepatic insulin resistance in nondiabetic adults without affecting peripheral or muscle insulin sensitivity. Larger and longer-term studies are needed to assess whether real

  14. Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

    Directory of Open Access Journals (Sweden)

    Angela Cassese

    Full Text Available Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15 causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1. Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4 restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15 by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance.

  15. [Mechanism of action of insulin sensitizer agents in the treatment of polycystic ovarian syndrome].

    Science.gov (United States)

    Galindo García, Carlos G; Vega Arias, Maria de Jesús; Hernández Marín, Imelda; Ayala, Aquiles R

    2007-03-01

    Polycystic ovarian disease (PCOD) is the most important endocrine abnormality that affects women in reproductive age. It is characterized by chronic anovulation and hyperandrogenemia probably secondary to insulin resistance. Hence insulin sensitizers agents had been used in PCOD. Metformin is a biguanide used in the treatment of PCOD via decrease of hepatic gluconeogenesis and insulinemia; improvement peripheral glucose utilization, oxidative glucose metabolism, nonoxidative glucose metabolism and intracellular glucose transport. Such effects, when this drug is administered alone during 3 to 6 months, increase sex hormone binding globulin (SHBG), reduce free androgens index and hirsutism, decrease insulin resistance, and regulate menses in 60 to 70% of cases. Thiazolidinodiones are drugs that decrease insulin resistance in the liver with hepatic glucose production. Their mechanism of action is through the peroxisome proliferator-activated receptors gamma (PPAR-gamma), that help to decrease plasmatic concentrations of free fatty acids, pre and postprandial glucose, insulin, triglycerides, increased HDL cholesterol and decreased LDL, menses return to normality, with improvement of ovulation and decreased hirsutism. It seems that by modulation and attenuation of insulin resistance, hypoglucemic agents such as metfomin and thiazolidinodiones can be used effectively to treat anovulation, infertility and hyperandrogenemia.

  16. Myostatin inhibition in muscle, but not adipose tissue, decreases fat mass and improves insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Tingqing Guo

    Full Text Available Myostatin (Mstn is a secreted growth factor expressed in skeletal muscle and adipose tissue that negatively regulates skeletal muscle mass. Mstn(-/- mice have a dramatic increase in muscle mass, reduction in fat mass, and resistance to diet-induced and genetic obesity. To determine how Mstn deletion causes reduced adiposity and resistance to obesity, we analyzed substrate utilization and insulin sensitivity in Mstn(-/- mice fed a standard chow. Despite reduced lipid oxidation in skeletal muscle, Mstn(-/- mice had no change in the rate of whole body lipid oxidation. In contrast, Mstn(-/- mice had increased glucose utilization and insulin sensitivity as measured by indirect calorimetry, glucose and insulin tolerance tests, and hyperinsulinemic-euglycemic clamp. To determine whether these metabolic effects were due primarily to the loss of myostatin signaling in muscle or adipose tissue, we compared two transgenic mouse lines carrying a dominant negative activin IIB receptor expressed specifically in adipocytes or skeletal muscle. We found that inhibition of myostatin signaling in adipose tissue had no effect on body composition, weight gain, or glucose and insulin tolerance in mice fed a standard diet or a high-fat diet. In contrast, inhibition of myostatin signaling in skeletal muscle, like Mstn deletion, resulted in increased lean mass, decreased fat mass, improved glucose metabolism on standard and high-fat diets, and resistance to diet-induced obesity. Our results demonstrate that Mstn(-/- mice have an increase in insulin sensitivity and glucose uptake, and that the reduction in adipose tissue mass in Mstn(-/- mice is an indirect result of metabolic changes in skeletal muscle. These data suggest that increasing muscle mass by administration of myostatin antagonists may be a promising therapeutic target for treating patients with obesity or diabetes.

  17. Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids.

    Science.gov (United States)

    Rasmussen, Jon Jarløv; Schou, Morten; Selmer, Christian; Johansen, Marie Louise; Gustafsson, Finn; Frystyk, Jan; Dela, Flemming; Faber, Jens; Kistorp, Caroline

    2017-09-01

    Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current and former AAS abusers compared with controls. Cross-sectional study among men involved in recreational strength training. Current and former AAS abusers (n=37 and n=33) and controls (n=30) volunteered from the community. We assessed insulin sensitivity by Matsuda index (oral glucose tolerance test). Using overnight fasting blood samples, adiponectin and leptin were measured. Body composition and fat distribution, including visceral adipose tissue (VAT), were assessed by dual energy X-ray absorptiometry. Current and former AAS abusers displayed lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45; -1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS abusers and subnormal among former AAS abusers compared with controls. Current AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm 3 , P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In contrast, former AAS abusers showed highest leptin concentrations and body fat %. Multivariate linear regressions identified VAT as independent predictor of lower Matsuda index among current AAS abusers compared with controls; while body fat % independently predicted lower Matsuda index among former AAS abusers. Both current and former AAS abusers displayed lower insulin sensitivity which could be mediated by higher VAT and total body fat %, respectively. © 2017 John Wiley & Sons Ltd.

  18. IsiZulu as a vehicle towards teaching and conducting research in ...

    African Journals Online (AJOL)

    Results indicate that lecturers use isiZulu successfully for purposes of research and teaching, but there are some challenges which need to be considered. These challenges include isiZulu as language of instruction in some study programmes, and reporting research outputs through the use of an African language, isiZulu.

  19. Assessment of insulin sensitivity/resistance and their relations with leptin concentrations and anthropometric measures in a pregnant population with and without gestational diabetes mellitus.

    Science.gov (United States)

    Yilmaz, Ozgur; Kucuk, Mert; Ilgin, Aydin; Dagdelen, Muride

    2010-01-01

    Fifty-six pregnant women with gestational diabetes mellitus (GDM) and 42 normal glucose tolerant (NGT) pregnant women between 26 and 36 gestational weeks were included in the study prospectively. The body fat percentage (BFP) was calculated using the Siri formula from skinfold thickness (SFT) measurements. Both groups were comparable for gestational age, height, weight, and body mass index (P>.05). Insulin resistance assessed by homeostasis model assessment for insulin resistance (HOMA-IR) method was significantly higher in GDM patients compared to their NGT weight-matched control group. In contrast, the insulin sensitivity calculated from quantitative insulin sensitivity check index (QUICKI-IS) equation was significantly lower in GDM group. Calculated lean body mass was found to be similar in between both groups. Body fat percentage derived from SFT parameters was significantly higher in women with GDM. Women with GDM had significantly higher levels of serum insulin and leptin concentrations when compared with the NGT group. All SFT measurements were higher in GDM group when compared to those in NGT women. We did not find any correlation between leptin levels and insulin resistance; we found negative correlation between leptin levels and insulin sensitivity. Thus, we observed that leptin may contribute development of GDM by decreasing insulin sensitivity but not increasing insulin resistance. Also, we observed that the BFP estimated by the Siri formula from SFT measurements correlated significantly with HOMA-IR and QUICKI-IS and leptin concentrations in pregnant women. We suggest that by simply evaluating SFT, we may hold a view about BFP and leptin concentrations and insulin sensitivity in pregnant women.

  20. Effects of weight loss in metabolically healthy obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet.

    Directory of Open Access Journals (Sweden)

    Giorgio Sesti

    Full Text Available Weight loss in metabolically healthy obese (MHO subjects may result in deterioration of cardio-metabolic risk profile. We analyzed the effects of weight loss induced by laparoscopic adjustable gastric banding (LAGB on cardio-metabolic risk factors in MHO and insulin resistant obese (IRO individuals. This study included 190 morbidly obese non-diabetic subjects. Obese individuals were stratified on the basis of their insulin sensitivity index (ISI, estimated from an OGTT, into MHO (ISI index in the upper quartile and IRO (ISI in the three lower quartiles. Anthropometric and cardio-metabolic variables were measured at baseline and 6-months after LAGB. Six months after LAGB, anthropometric measures were significantly reduced in both MHO and IRO. Percent changes in body weight, BMI, and waist circumference did not differ between the two groups. Fasting glucose and insulin levels, triglycerides, AST, and ALT were significantly reduced, and HDL cholesterol significantly increased, in both MHO and IRO subjects with no differences in percent changes from baseline. Insulin sensitivity increased in both MHO and IRO group. Insulin secretion was significantly reduced in the IRO group only. However, the disposition index significantly increased in both MHO and IRO individuals with no differences in percent changes from baseline between the two groups. The change in insulin sensitivity correlated with the change in BMI (r = -0.43; P<0.0001. In conclusion, our findings reinforce the recommendation that weight loss in response to LAGB intervention should be considered an appropriate treatment option for morbidly obese individuals regardless of their metabolic status, i.e. MHO vs. IRO subjects.

  1. Effects of combined calcium and vitamin D supplementation on insulin secretion, insulin sensitivity and β-cell function in multi-ethnic vitamin D-deficient adults at risk for type 2 diabetes: a pilot randomized, placebo-controlled trial.

    Directory of Open Access Journals (Sweden)

    Claudia Gagnon

    Full Text Available To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers.6-month randomized, placebo-controlled trial.Ninety-five adults with serum 25-hydroxyvitamin D [25(OHD] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15 were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45.Daily calcium carbonate (1,200 mg and cholecalciferol [2,000-6,000 IU to target 25(OHD >75 nmol/L] or matching placebos for 6 months.Insulin sensitivity (HOMA2%S, Matsuda index, insulin secretion (insulinogenic index, area under the curve (AUC for C-peptide and β-cell function (Matsuda index x AUC for C-peptide derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin.Participants were middle-aged adults (mean age 54 years; 69% Europid at risk of type 2 diabetes (48% with prediabetes. Compliance was >80% for calcium and vitamin D. Mean serum 25(OHD concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L, but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda was observed.Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes

  2. A novel hybrid catalyst for the esterification of high FFA in Jatropha oil for biodiesel production

    International Nuclear Information System (INIS)

    Mushtaq, M.; Tan, I.M.; Sagir, M.; Suleman Tahir, M.; Pervaiz, M.

    2016-01-01

    The synthesis and application of a hybrid catalyst for the esterification of free fatty acids (FFA) in Jatropha oil is reported. Three catalysts, namely silica sulfuric acid, silica supported boron trifluoride and a combination of the two in the weight ratio of 1:1, the hybrid catalyst, were investigated. Jatropha oil samples with a wide range of FFA values i.e. 6.64 to 45.64% were prepared and utilized for the experimental work. This study revealed that silica sulfuric acid and silica supported boron trifluoride were not very effective when used independently. However, a strong synergistic effect was noted in the catalytic activity of the hybrid catalyst which reduced the FFA value from 45.64 to 0.903% with a conversion efficiency of 98%. Reusability of the catalyst was also tested and the results were promising in up to three cycles of use when used with lower amounts of FFA (6.64%) in the oil. Under the influence of the catalyst, the reaction was found to follow first order kinetics. Activation energy was calculated to be 45.42 KJ·mol−1 for 2 wt.% of hybrid catalyst. The products were analyzed by FT-IR and NMR spectroscopic techniques and the results are reported. [es

  3. KARMEN: neutrino spectroscopy at ISIS

    Energy Technology Data Exchange (ETDEWEB)

    Drexlin, G [Forschungszentrum Karlsruhe GmbH Technik und Umwelt (Germany). Inst. fuer Kernphysik

    1996-11-01

    The Karlsruhe-Rutherford Neutrino Experiment KARMEN at the spallation neutron facility ISIS investigates fundamental properties of neutrinos as well as their interactions with matter. Low energy neutrinos with energies up to 50 MeV emitted by the pulsed {nu}-source ISIS are detected by a 56 tonne high resolution liquid scintillation calorimeter. Clear {nu}-signatures allow a reliable search for neutrino oscillations of the type {nu}{sub {mu}}{yields}{nu}{sub e} and {nu}{sub {mu}}{yields}{nu}{sub e} as well as a detailed investigation of neutrino-nucleus interactions in an energy range important for astrophysics. We present the results of the KARMEN experiment from data taking in the period from June 1990 - December 1995. (author) 9 figs., 10 refs.

  4. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    OpenAIRE

    Messier, Claude; Teutenberg, Kevin

    2005-01-01

    Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

  5. A high-fat, high-saturated fat diet decreases insulin sensitivity without changing intra-abdominal fat in weight-stable overweight and obese adults.

    Science.gov (United States)

    von Frankenberg, Anize D; Marina, Anna; Song, Xiaoling; Callahan, Holly S; Kratz, Mario; Utzschneider, Kristina M

    2017-02-01

    We sought to determine the effects of dietary fat on insulin sensitivity and whether changes in insulin sensitivity were explained by changes in abdominal fat distribution or very low-density lipoprotein (VLDL) fatty acid composition. Overweight/obese adults with normal glucose tolerance consumed a control diet (35 % fat/12 % saturated fat/47 % carbohydrate) for 10 days, followed by a 4-week low-fat diet (LFD, n = 10: 20 % fat/8 % saturated fat/62 % carbohydrate) or high-fat diet (HFD, n = 10: 55 % fat/25 % saturated fat/27 % carbohydrate). All foods and their eucaloric energy content were provided. Insulin sensitivity was measured by labeled hyperinsulinemic-euglycemic clamps, abdominal fat distribution by MRI, and fasting VLDL fatty acids by gas chromatography. The rate of glucose disposal (Rd) during low- and high-dose insulin decreased on the HFD but remained unchanged on the LFD (Rd-low: LFD: 0.12 ± 0.11 vs. HFD: -0.37 ± 0.15 mmol/min, mean ± SE, p vs. HFD: -0.71 ± 0.26 mmol/min, p = 0.08). Hepatic insulin sensitivity did not change. Changes in subcutaneous fat were positively associated with changes in insulin sensitivity on the LFD (r = 0.78, p fat. The LFD led to an increase in VLDL palmitic (16:0), stearic (18:0), and palmitoleic (16:1n7c) acids, while no changes were observed on the HFD. Changes in VLDL n-6 docosapentaenoic acid (22:5n6) were strongly associated with changes in insulin sensitivity on both diets (LFD: r = -0.77; p fat and saturated fat adversely affects insulin sensitivity and thereby might contribute to the development of type 2 diabetes. CLINICALTRIALS. NCT00930371.

  6. Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.

    Science.gov (United States)

    Oakes, Nicholas D; Thalén, Pia; Hultstrand, Therese; Jacinto, Severina; Camejo, Germán; Wallin, Boel; Ljung, Bengt

    2005-10-01

    Insulin resistance, impaired glucose tolerance, high circulating levels of free fatty acids (FFA), and postprandial hyperlipidemia are associated with the metabolic syndrome, which has been linked to increased risk of cardiovascular disease. We studied the metabolic responses to an oral glucose/triglyceride (TG) (1.7/2.0 g/kg lean body mass) load in three groups of conscious 7-h fasted Zucker rats: lean healthy controls, obese insulin-resistant/dyslipidemic controls, and obese rats treated with the dual peroxisome proliferator-activated receptor alpha/gamma agonist, tesaglitazar, 3 mumol.kg(-1).day(-1) for 4 wk. Untreated obese Zucker rats displayed marked insulin resistance, as well as glucose and lipid intolerance in response to the glucose/TG load. The 2-h postload area under the curve values were greater for glucose (+19%), insulin (+849%), FFA (+53%), and TG (+413%) compared with untreated lean controls. Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance. Fasting FFA were not affected, but postprandial FFA suppression was restored to levels seen in lean controls. Mechanisms of tesaglitazar-induced lowering of plasma TG were studied separately using the Triton WR1339 method. In anesthetized, 5-h fasted, obese Zucker rats, tesaglitazar reduced hepatic TG secretion by 47%, increased plasma TG clearance by 490%, and reduced very low-density lipoprotein (VLDL) apolipoprotein CIII content by 86%, compared with obese controls. In conclusion, the glucose/lipid tolerance test in obese Zucker rats appears to be a useful model of the metabolic syndrome that can be used to evaluate therapeutic effects on impaired postprandial glucose and lipid metabolism. The present work demonstrates that tesaglitazar ameliorates these abnormalities and enhances insulin sensitivity in this animal model.

  7. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lepob/ob mice

    International Nuclear Information System (INIS)

    Sekiya, Motohiro; Yahagi, Naoya; Tamura, Yoshiaki; Okazaki, Hiroaki; Igarashi, Masaki; Ohta, Keisuke; Takanashi, Mikio; Kumagai, Masayoshi; Takase, Satoru; Nishi, Makiko; Takeuchi, Yoshinori; Izumida, Yoshihiko; Kubota, Midori; Ohashi, Ken; Iizuka, Yoko; Yagyu, Hiroaki; Gotoda, Takanari; Nagai, Ryozo; Shimano, Hitoshi; Yamada, Nobuhiro

    2009-01-01

    It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lep ob/ob /HSL -/- ) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lep ob/ob /HSL -/- developed elevated blood glucose levels and reduced plasma insulin levels compared with Lep ob/ob /HSL +/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep +/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lep ob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lep ob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

  8. Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity

    DEFF Research Database (Denmark)

    Skovbro, M; Baranowski, M; Skov-Jensen, C

    2008-01-01

    -hyperinsulinaemic clamp was performed for 120 and 90 min for step 1 and step 2, respectively. Muscle biopsies were obtained from vastus lateralis at baseline, and after steps 1 and 2. RESULTS: Glucose infusion rates increased in response to insulin infusion, and significant differences were present between groups (T2D......AIMS/HYPOTHESIS: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. This study investigated total skeletal muscle ceramide fatty acid content in participants exhibiting a wide range of insulin sensitivities. METHODS......: The middle-aged male participants (n=33) were matched for lean body mass and divided into four groups: type 2 diabetes (T2D, n=8), impaired glucose tolerance (IGT, n=9), healthy controls (CON, n=8) and endurance-trained (TR, n=8). A two step (28 and 80 mU m(-2) min(-1)) sequential euglycaemic...

  9. Maternal Rat Diabetes Mellitus Deleteriously Affects Insulin Sensitivity and Beta-Cell Function in the Offspring

    Directory of Open Access Journals (Sweden)

    Abdel-Baset M. Aref

    2013-01-01

    Full Text Available This study was designed to assess the effect of maternal diabetes in rats on serum glucose and insulin concentrations, insulin resistance, histological architecture of pancreas and glycogen content in liver of offspring. The pregnant rat females were allocated into two main groups: normal control group and streptozotocin-induced diabetic group. After birth, the surviving offspring were subjected to biochemical and histological examination immediately after delivery and at the end of the 1st and 2nd postnatal weeks. In comparison with the offspring of normal control dams, the fasting serum glucose level of offspring of diabetic mothers was significantly increased at the end of the 1st and 2nd postnatal weeks. Serum insulin level of offspring of diabetic dams was significantly higher at birth and decreased significantly during the following 2 postnatal weeks, while in normal rat offspring, it was significantly increased with progress of time. HOMA Insulin Resistance (HOMA-IR was significantly increased in the offspring of diabetic dams at birth and after 1 week than in normal rat offspring, while HOMA insulin sensitivity (HOMA-IS was significantly decreased. HOMA beta-cell function was significantly decreased at all-time intervals in offspring of diabetic dams. At birth, islets of Langerhans as well as beta cells in offspring of diabetic dams were hypertrophied. The cells constituting islets seemed to have a high division rate. However, beta-cells were degenerated during the following 2 post-natal weeks and smaller insulin secreting cells predominated. Vacuolation and necrosis of the islets of Langerhans were also observed throughout the experimental period. The carbohydrate content in liver of offspring of diabetic dams was at all-time intervals lower than that in control. The granule distribution was more random. Overall, the preexisting maternal diabetes leads to glucose intolerance, insulin resistance, and impaired insulin sensitivity and

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

    Science.gov (United States)

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

    2018-02-01

    To investigate peripheral insulin sensitivity and skeletal muscle glucose metabolism in premenopausal and postmenopausal women, and evaluate whether exercise training benefits are maintained after menopause. Sedentary, healthy, normal-weight, late premenopausal (n = 21), and early postmenopausal (n = 20) women were included in a 3-month high-intensity exercise training intervention. Body composition was assessed by magnetic resonance imaging and dual-energy x-ray absorptiometry, whole body glucose disposal rate (GDR) by hyperinsulinemic euglycemic clamp (40 mU/m/min), and femoral muscle glucose uptake by positron emission tomography/computed tomography, using the glucose analog fluorodeoxyglucose, expressed as estimated metabolic rate (eMR). Insulin signaling was investigated in muscle biopsies. Age difference between groups was 4.5 years, and no difference was observed in body composition. Training increased lean body mass (estimate [95% confidence interval] 0.5 [0.2-0.9] kg, P training (eMR vastus lateralis muscle: 27.8 [19.6-36.0] μmol/min/kg, P training-induced increases in insulin sensitivity included increased expression of hexokinase (19.2 [5.0-24.7] AU, P = 0.02) and glycogen synthase (32.4 [15.0-49.8] AU, P high-intensity exercise training.

  11. Relationship between red cell membrane fatty acids and adipokines in individuals with varying insulin sensitivity.

    Science.gov (United States)

    Min, Y; Lowy, C; Islam, S; Khan, F S; Swaminathan, R

    2011-06-01

    Plasma leptin and adiponectin, and membrane phospholipid fatty acid composition are implicated into the mechanism of insulin resistance but no clear pattern has emerged. Hence, this study examined these variables in subjects presenting to the diabetic clinic for a diagnostic glucose tolerance test. Body composition, glucose, glycated hemoglobin, insulin, leptin, adiponectin, and red cell and plasma phospholipid fatty acids were assessed from 42 normal and 28 impaired glucose tolerant subjects. Insulin sensitivity was determined by homeostatic model assessment. The plasma phosphatidylcholine fatty acid composition of the impaired glucose tolerant subjects was similar to that of normal subjects. However, the impaired glucose tolerant subjects had significantly lower linoleic (Pphosphatidylcholine and phosphatidylethanolamine compared with the normal subjects. Moreover, red cell phosphatidylcholine docosahexaenoic acid correlated positively with adiponectin (r=0.290, Pinsulin (r=-0.335, Pinsulin resistance (r=-0.322, Pinsulin level whereas insulin was the only component that predicted the membrane fatty acids. We postulate that membrane phospholipids fatty acids have an indirect role in determining insulin concentration but insulin has a major role in determining membrane fatty acid composition.

  12. Isis, la Gran Maga

    Directory of Open Access Journals (Sweden)

    Hipólito Pecci Tenrero

    2002-01-01

    Full Text Available La diosa Isis es una de las divinidades más importantes de Egipto, al extenderse por el Mediterráneo continúa manteniendo esta significación. En el texto siguiente se intenta tratar de una forma sucinta como se ha producido esta expansión, la rapidez en conseguir adeptos fuera de Egipto y la influencia no solo dentro de la sociedad, sino también dentro de la política, así como su desaparición final.The goddess Isis is one of the most important divinities of Egypt, on having spread over the Mediterranean she continúes supporting this significance. In the next text one is tried to treat as a succinct form since this expansión, the rapidity has taken place in followers obtained out of Egypt and the influence not only inside the society, but also inside the politics, asweil as his final disappearance.

  13. Insulin sensitivity and beta-cell function after carbohydrate oral loading in hip replacement surgery: a double-blind, randomised controlled clinical trial.

    Science.gov (United States)

    Ljunggren, Stefan; Hahn, Robert G; Nyström, Thomas

    2014-06-01

    Surgery initiates a series of physiological stress processes in the body, inducing transient insulin resistance. Preoperative carbohydrate treatment can reduce the latter phenomenon. We investigated the effects of carbohydrate loading on insulin sensitivity and beta-cell function after elective hip replacement. Twenty-three nondiabetic patients (mean age of 68 years) who underwent elective hip replacement surgery participated in this double-blind controlled study. The patients were randomised to a nutrition group, which ingested a carbohydrate-rich fluid (50 kcal/100 ml) (Preop(®)), or a control group (tap water flavoured with lemon) 800 ml + 400 ml before the surgery. The insulin response (beta-cell function) and the insulin sensitivity were measured with an intravenous glucose tolerance test (IVGTT) and a hyperinsulinaemic euglycaemic glucose clamp, respectively, one day before and two days after the surgery. Insulin sensitivity decreased by 51% (median; 25-75th percentiles 35-61) after ingesting Preop(®) and by 39% (21-51) after ingesting in the control group (n.s.). The postoperative IVGTT in the nutrition group was followed by a significantly larger area under the curve (AUC) for plasma insulin (+54% versus the preoperative IVGTT) compared to the control group (+7%). This difference was already apparent during the first phase (0-10 min) of insulin secretion (+20 and -21%, respectively; P water prior to the surgery demonstrated a significant but similar decrease in insulin sensitivity. The carbohydrates increased the beta-cell function as a compensatory response to the disposition index, resulting in a smaller reduction in surgery-induced insulin resistance compared to the tap water. The study was registered at http://www.clinicaltrials.gov (NCT01774084). Copyright © 2013 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  14. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth

    NARCIS (Netherlands)

    Van Der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    VAN DER HEIJDEN, G.-J., Z. J. WANG, Z. CHU, G. TOFFOLO, E. MANESSO, P. J. J. SAUER, and A. L. SUNEHAG. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth. Med. Sci. Sports Exerc., Vol. 42, No. 11, pp. 1973-1980, 2010. Introduction: Data on the metabolic effects of

  15. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth

    NARCIS (Netherlands)

    Van Der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J. J.; Sunehag, Agneta L.

    2010-01-01

    VAN DER HEIJDEN, G.-J., Z. J. WANG, Z. CHU, G. TOFFOLO, E. MANESSO, P. J. J. SAUER, and A. L. SUNEHAG. Strength Exercise Improves Muscle Mass and Hepatic Insulin Sensitivity in Obese Youth. Med. Sci. Sports Exerc., Vol. 42, No. 11, pp. 1973-1980, 2010. Introduction: Data on the metabolic effects of

  16. Tumor necrosis factor alpha is associated with insulin-mediated suppression of free fatty acids and net lipid oxidation in HIV-infected patients with lipodystrophy

    DEFF Research Database (Denmark)

    Haugaard, SB; Andersen, O; Pedersen, Steen Bønløkke

    2006-01-01

    Tumor necrosis factor alpha (TNF-alpha) stimulates lipolysis in man. We examined whether plasma TNF-alpha is associated with the degree by which insulin suppresses markers of lipolysis, for example, plasma free fatty acid (FFA) and net lipid oxidation (LIPOX) rate in HIV-infected patients...... with lipodystrophy (LIPO) and those without (controls). LIPOX was estimated by indirect calorimetry during fasting and steady state of a hyperinsulinemic euglycemic clamp in 36 (18 LIPO and 18 controls) normoglycemic HIV-infected men on highly active antiretroviral therapy. In LIPO, TNF-alpha correlated with clamp...... were significant in controls. In all patients, TNF-alpha correlated with clamp FFA (r = 0.61, P

  17. Adipose tissue (P)RR regulates insulin sensitivity, fat mass and body weight.

    Science.gov (United States)

    Shamansurova, Zulaykho; Tan, Paul; Ahmed, Basma; Pepin, Emilie; Seda, Ondrej; Lavoie, Julie L

    2016-10-01

    We previously demonstrated that the handle-region peptide, a prorenin/renin receptor [(P)RR] blocker, reduces body weight and fat mass and may improve insulin sensitivity in high-fat fed mice. We hypothesized that knocking out the adipose tissue (P)RR gene would prevent weight gain and insulin resistance. An adipose tissue-specific (P)RR knockout (KO) mouse was created by Cre-loxP technology using AP2-Cre recombinase mice. Because the (P)RR gene is located on the X chromosome, hemizygous males were complete KO and had a more pronounced phenotype on a normal diet (ND) diet compared to heterozygous KO females. Therefore, we challenged the female mice with a high-fat diet (HFD) to uncover certain phenotypes. Mice were maintained on either diet for 9 weeks. KO mice had lower body weights compared to wild-types (WT). Only hemizygous male KO mice presented with lower total fat mass, higher total lean mass as well as smaller adipocytes compared to WT mice. Although food intake was similar between genotypes, locomotor activity during the active period was increased in both male and female KO mice. Interestingly, only male KO mice had increased O2 consumption and CO2 production during the entire 24-hour period, suggesting an increased basal metabolic rate. Although glycemia during a glucose tolerance test was similar, KO males as well as HFD-fed females had lower plasma insulin and C-peptide levels compared to WT mice, suggesting improved insulin sensitivity. Remarkably, all KO animals exhibited higher circulating adiponectin levels, suggesting that this phenotype can occur even in the absence of a significant reduction in adipose tissue weight, as observed in females and, thus, may be a specific effect related to the (P)RR. (P)RR may be an important therapeutic target for the treatment of obesity and its associated complications such as type 2 diabetes.

  18. Plasma adiponectin concentration is associated with skeletal muscle insulin receptor tyrosine phosphorylation, and low plasma concentration precedes a decrease in whole-body insulin sensitivity in humans

    DEFF Research Database (Denmark)

    Stefan, Norbert; Vozarova, Barbora; Funahashi, Tohru

    2002-01-01

    (insulin-stimulated glucose disposal, hyperinsulinemic clamp), and glucose tolerance (75-g oral glucose tolerance test) were measured in 55 Pima Indians (47 men and 8 women, aged 31 +/- 8 years, body fat 29 +/- 8% [mean +/- SD]; 50 with normal glucose tolerance, 3 with impaired glucose tolerance, and 2......Adiponectin, the most abundant adipose-specific protein, has been found to be negatively associated with degree of adiposity and positively associated with insulin sensitivity in Pima Indians and other populations. Moreover, adiponectin administration to rodents has been shown to increase insulin...

  19. Adiponectin in mice with altered GH action: links to insulin sensitivity and longevity?

    Science.gov (United States)

    Lubbers, Ellen R; List, Edward O; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D; Kineman, Rhonda D; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J; Berryman, Darlene E

    2013-03-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high-molecular-weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered GH signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH vs IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying that the effects of GH on adiponectin are depot specific. Interestingly, rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity.

  20. Insulin secretion and insulin resistance in Korean women with gestational diabetes mellitus and impaired glucose tolerance.

    Science.gov (United States)

    Yang, Sae Jeong; Kim, Tae Nyun; Baik, Sei Hyun; Kim, Tae Sun; Lee, Kwan Woo; Nam, Moonsuk; Park, Yong Soo; Woo, Jeong-Teak; Kim, Young Seol; Kim, Sung-Hoon

    2013-05-01

    The aim was to compare the insulin sensitivity and secretion index of pregnant Korean women with normal glucose tolerance (NGT), gestational impaired glucose tolerance (GIGT; only one abnormal value according to the Carpenter and Coustan criteria), and gestational diabetes mellitus (GDM). A cross-sectional study was performed with 1,163 pregnant women with positive (1-hour plasma glucose ≥ 7.2 mmol/L) in a 50-g oral glucose challenge test (OGCT). The 100-g oral glucose tolerance test (OGTT) was used to stratify the participants into three groups: NGT (n = 588), GIGT (n = 294), and GDM (n = 281). The GDM group had higher homeostasis model assessment of insulin resistance and lower insulin sensitivity index (ISOGTT), quantitative insulin sensitivity check index, homeostasis model assessment for estimation of index β-cell secretion (HOMA-B), first and second phase insulin secretion, and insulin secretion-sensitivity index (ISSI) than the NGT group (p ≤ 0.001 for all). Moreover, the GIGT group had lower ISOGTT, HOMA-B, first and second phase insulin secretion, and ISSI than the NGT group (p insulin secretion status than the 3-hour abnormal levels group. Korean women with GDM show impairments of both insulin secretion and insulin sensitivity. In addition, GIGT is associated with both β-cell dysfunction and insulin resistance.

  1. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats.

    Science.gov (United States)

    Begg, Denovan P; Mul, Joram D; Liu, Min; Reedy, Brianne M; D'Alessio, David A; Seeley, Randy J; Woods, Stephen C

    2013-03-01

    Diet-induced obesity (DIO) reduces the ability of centrally administered insulin to reduce feeding behavior and also reduces the transport of insulin from the periphery to the central nervous system (CNS). The current study was designed to determine whether reversal of high-fat DIO restores the anorexic efficacy of central insulin and whether this is accompanied by restoration of the compromised insulin transport. Adult male Long-Evans rats were initially maintained on either a low-fat chow diet (LFD) or a high-fat diet (HFD). After 22 weeks, half of the animals on the HFD were changed to the LFD, whereas the other half continued on the HFD for an additional 8 weeks, such that there were 3 groups: 1) a LFD control group (Con; n = 18), 2) a HFD-fed, DIO group (n = 17), and 3) a HFD to LFD, DIO-reversal group (DIO-rev; n = 18). The DIO reversal resulted in a significant reduction of body weight and epididymal fat weight relative to the DIO group. Acute central insulin administration (8 mU) reduced food intake and caused weight loss in Con and DIO-rev but not DIO rats. Fasting cerebrospinal fluid insulin was higher in DIO than Con animals. However, after a peripheral bolus injection of insulin, cerebrospinal fluid insulin increased in Con and DIO-rev rats but not in the DIO group. These data provide support for previous reports that DIO inhibits both the central effects of insulin and insulin's transport to the CNS. Importantly, DIO-rev restored sensitivity to the effects of central insulin on food intake and insulin transport into the CNS.

  2. Insulin-Sensitizer Effects of Fenugreek Seeds in Parallel with Changes in Plasma MCH Levels in Healthy Volunteers

    Directory of Open Access Journals (Sweden)

    Rita Kiss

    2018-03-01

    Full Text Available In developed, developing and low-income countries alike, type 2 diabetes mellitus (T2DM is one of the most common chronic diseases, the severity of which is substantially a consequence of multiple organ complications that occur due to long-term progression of the disease before diagnosis and treatment. Despite enormous investment into the characterization of the disease, its long-term management remains problematic, with those afflicted enduring significant degradation in quality-of-life. Current research efforts into the etiology and pathogenesis of T2DM, are focused on defining aberrations in cellular physiology that result in development of insulin resistance and strategies for increasing insulin sensitivity, along with downstream effects on T2DM pathogenesis. Ongoing use of plant-derived naturally occurring materials to delay the onset of the disease or alleviate symptoms is viewed by clinicians as particularly desirable due to well-established efficacy and minimal toxicity of such preparations, along with generally lower per-patient costs, in comparison to many modern pharmaceuticals. A particularly attractive candidate in this respect, is fenugreek, a plant that has been used as a flavouring in human diet through recorded history. The present study assessed the insulin-sensitizing effect of fenugreek seeds in a cohort of human volunteers, and tested a hypothesis that melanin-concentrating hormone (MCH acts as a critical determinant of this effect. A test of the hypothesis was undertaken using a hyperinsulinemic euglycemic glucose clamp approach to assess insulin sensitivity in response to oral administration of a fenugreek seed preparation to healthy subjects. Outcomes of these evaluations demonstrated significant improvement in glucose tolerance, especially in patients with impaired glucose responses. Outcome data further suggested that fenugreek seed intake-mediated improvement in insulin sensitivity correlated with reduction in MCH

  3. No Weight Catch-Up Growth of SGA Infants Is Associated with Impaired Insulin Sensitivity during the Early Postnatal Period

    Directory of Open Access Journals (Sweden)

    Tong-yan Han

    2010-01-01

    Full Text Available Objective. To investigate the relationship between weight catch-up growth and insulin sensitivity in small for gestational age (SGA infants. Methods. Forty-four singleton SGA subjects met the inclusion criteria and finished-3-month followup. Body weight, length, fasting glucose, and fasting insulin (FI levels were measured at 3 days and 3 months. Insulin sensitivity was evaluated by FI and homeostasis model assessment (HOMA. Results. According to the change of weight Z-score, forty-four subjects were divided into two groups: noncatch-up growth (NCUG and catch-up growth (CUG. By 3 months of age, the body weight, body length and BMI of NCUG group were significantly lower than those of CUG group. The FI and HOMA were significantly higher in NCUG group. The change of weight Z-score during 3 months was inversely related to the HOMA at 3 months. Conclusion. Our data exemplified that no weight catch-up growth during the first 3 months was associated with impaired insulin sensitivity in SGA infants.

  4. Normal sweat secretion despite impaired growth hormone-insulin-like growth factor-I axis in obese subjects

    DEFF Research Database (Denmark)

    Rasmussen, Michael Højby; Juul, Anders; Main, Katharina M

    2011-01-01

    Adults with GH deficiency are known to exhibit reduced sweating. Whether sweating capacity is impacted in obese subjects with impaired GH secretion have not previously been investigated. The main objective was to investigate sweat secretion rate and the GH-IGF-I axis in obese subjects before...... and after weight loss. Sixteen severely obese women (BMI, 40.6 ± 1.1 kg/m(2)) were investigated before and after a diet-induced weight loss. Sixteen age-matched nonobese women served as controls. The obese subjects presented the characteristic decreased GH release, hyperinsulinaemia, increased FFA levels......, and impaired insulin sensitivity, which all were normalised after diet-induced weight loss of 30 ± 5 kg. Sweat secretion rates were similar comparing obese and nonobese subjects (78 ± 10 versus 82 ± 9 mg/30 minutes) and sweat secretion did not change after a diet-induced weight loss in obese subjects. We...

  5. Treatment with insulin (analogues) and breast cancer risk in diabetics; a systematic review and meta-analysis of in vitro, animal and human evidence

    DEFF Research Database (Denmark)

    Bronsveld, Heleen K; ter Braak, Bas; Karlstad, Øystein

    2015-01-01

    INTRODUCTION: Several studies have suggested that anti-diabetic insulin analogue treatment might increase cancer risk. The aim of this study was to review the postulated association between insulin and insulin analogue treatment and breast cancer development, and plausible mechanisms. METHOD......: A systematic literature search was performed on breast cell-line, animal and human studies using the key words 'insulin analogue' and 'breast neoplasia' in MEDLINE at PubMed, EMBASE, and ISI Web of Science databases. A quantitative and qualitative review was performed on the epidemiological data; due...

  6. GLP-1 does not not acutely affect insulin sensitivity in healthy man

    DEFF Research Database (Denmark)

    Orskov, L; Holst, J J; Møller, J

    1996-01-01

    Previous studies have suggested that glucagon-like peptide-1 (GLP-1) (7-36 amide) may have the direct effect of increasing insulin sensitivity in healthy man. To evaluate this hypothesis we infused GLP-1 in seven lean healthy men during a hyper insulinaemic (0.8 mU.kg-1.min-1), euglycaemic (5 mmo...

  7. Epithermal neutron instrumentation at ISIS

    International Nuclear Information System (INIS)

    Gorini, G; Festa, G; Andreani, C

    2014-01-01

    The advent of pulsed neutron sources makes available high epithermal neutron fluxes (in the energy range between 500 meV and 100 eV). New dedicated instrumentation, such as Resonance Detectors, was developed at ISIS spallation neutron source in the last years to apply the specific properties of this kind of neutron beam to the study of condensed matter. New detection strategies like Filter Difference method and Foil Cycling Technique were also developed in parallel to the detector improvement at the VESUVIO beamline. Recently, epithermal neutron beams were also used at the INES beamline to study elemental and isotopic composition of materials, with special application to cultural heritage studies. In this paper we review a series of epithermal neutron instrumentation developed at ISIS, their evolution over time and main results obtained

  8. The ISIS Open GENIE user manual

    International Nuclear Information System (INIS)

    Akeroyd, F.A.; Ashworth, R.L.; Campbell, S.I.; Johnston, S.D.; Martin, J.M.; Moreton-Smith, C.M.; Sivia, D.S.

    2000-01-01

    This manual should enable you to become familiar with Open GENIE quickly and easily. It therefore complements the Open GENIE Reference Manual which should be used to understand the full meaning of Open GENIE commands. The reference manual is accessible on the ISIS web server at: http://www.isis.rl.ac.uk/GENIEReferenceManual/ and the user manual is planned to be accessible by January '98 at http://www.isis.rl.ac.ukIGENIEUserManual/. The Open GENIE User Manual is separated into two parts: Part A. The User Manual. An introduction to the use of Open GENIE. Part B. The Installation Guide. General information on how to install and run Open GENIE. Assuming that you are new to Open GENIE and have just downloaded a copy you will need to consult the Installation Guide to get Open GENIE installed on your machine. After this we recommend you experiment with some of the example files to get an idea of the capabilities of Open GENIE. For further information, comments, additions of routines that you feel should be included, please contact us at genie at isise.rl.ac.uk

  9. Effects of a 12-week exercise training on insulin sensitivity, quality of life, and depression status in patients with type 2 diabetes

    Directory of Open Access Journals (Sweden)

    Chia-Huei Lin

    2017-01-01

    Full Text Available Background: Exercise is one of the optimal and alternative treatments for type 2 diabetes (T2DM. Although the effect of a single bout of exercise on insulin sensitivity is reported to persist only for 2–3 days, effects remain unclear of a 12-week aerobic exercise training on insulin sensitivity, quality of life (QOL, and depression status over time as exercise training duration increases in patients with T2DM. Objectives: To investigate the effects over time in patients with T2DM of a 12-week aerobic exercise training on insulin sensitivity, QOL, and depression status. Materials and Methods: Purposive sampling was used to recruit 17 T2DM patients. Participants underwent a 12-week, supervised, moderate-intensity aerobic exercise training three times per week, 30 min per session. Outcome indicators including insulin sensitivity (measured by a 2-h oral glucose tolerance test [OGTT] and homeostatic model assessment-insulin resistance [HOMA-IR], QOL (Medical Outcomes Study Short Form 36, and depression status (beck depression inventory scale were evaluated at baseline and at 4-week intervals. Results: A final 13 eligible participants completed the study. For every 4-week increase in duration of exercise training, there was an increase over time in insulin sensitivity, including a decrease over time in OGTT glucose area under the curve of 66.92 min/mmol/L. Glucose concentrations decreased over time at 60, 90, and 120 min after an oral glucose challenge. Further, the HOMA-IR decreased over time as the duration of exercise training increased. QOL and depression status improved significantly during the training. Conclusions: Moderate-intensity exercise training improves insulin sensitivity, QOL, and depression status in T2DM patients, particularly over time within a 12-week exercise training course.

  10. Probiotics modulate gut microbiota and improve insulin sensitivity in DIO mice.

    Science.gov (United States)

    Bagarolli, Renata A; Tobar, Natália; Oliveira, Alexandre G; Araújo, Tiago G; Carvalho, Bruno M; Rocha, Guilherme Z; Vecina, Juliana F; Calisto, Kelly; Guadagnini, Dioze; Prada, Patrícia O; Santos, Andrey; Saad, Sara T O; Saad, Mario J A

    2017-12-01

    Obesity and type 2 diabetes are characterized by subclinical inflammatory process. Changes in composition or modulation of the gut microbiota may play an important role in the obesity-associated inflammatory process. In the current study, we evaluated the effects of probiotics (Lactobacillus rhamnosus, L. acidophilus and Bifidobacterium bifidumi) on gut microbiota, changes in permeability, and insulin sensitivity and signaling in high-fat diet and control animals. More importantly, we investigated the effects of these gut modulations on hypothalamic control of food intake, and insulin and leptin signaling. Swiss mice were submitted to a high-fat diet (HFD) with probiotics or pair-feeding for 5 weeks. Metagenome analyses were performed on DNA samples from mouse feces. Blood was drawn to determine levels of glucose, insulin, LPS, cytokines and GLP-1. Liver, muscle, ileum and hypothalamus tissue proteins were analyzed by Western blotting and real-time polymerase chain reaction. In addition, liver and adipose tissues were analyzed using histology and immunohistochemistry. The HFD induced huge alterations in gut microbiota accompanied by increased intestinal permeability, LPS translocation and systemic low-grade inflammation, resulting in decreased glucose tolerance and hyperphagic behavior. All these obesity-related features were reversed by changes in the gut microbiota profile induced by probiotics. Probiotics also induced an improvement in hypothalamic insulin and leptin resistance. Our data demonstrate that the intestinal microbiome is a key modulator of inflammatory and metabolic pathways in both peripheral and central tissues. These findings shed light on probiotics as an important tool to prevent and treat patients with obesity and insulin resistance. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. ISIS status report

    International Nuclear Information System (INIS)

    Finney, J.L.; Gray, D.A.

    1989-01-01

    The authors review the progress on ISIS, the pulsed neutron source at the Rutherford-Appleton Laboratory, since the last ICANS meeting. The machine is now running regularly at 100 μA at 750 MeV, and delivering neutrons for an increasing UK and international neutron scattering program. The current status of the operating and development instruments is summarized, and some examples given of recent science. 3 refs., 11 figs., 3 tabs

  12. Defeating ISIS by Winning the War of Ideas

    Science.gov (United States)

    2017-03-17

    Partial Fulfillment of the Graduation Requirements Advisor: Lt Col Brande Walton Maxwell Air Force Base, Alabama 17 March 2017 DISTRIBUTION A...with their lives due to economic or emotional struggle could fall victim to ISIS messaging. ISIS messaging is sophisticated, attracting several...slavery, denying women’s rights, rape, torture, and jihadi groups are all forbidden.53 Though many Muslims have been branded as “radical extremists

  13. Plasma Taurine, Diabetes Genetic Predisposition, and Changes of Insulin Sensitivity in Response to Weight-Loss Diets.

    Science.gov (United States)

    Zheng, Yan; Ceglarek, Uta; Huang, Tao; Wang, Tiange; Heianza, Yoriko; Ma, Wenjie; Bray, George A; Thiery, Joachim; Sacks, Frank M; Qi, Lu

    2016-10-01

    Taurine metabolism disturbance is closely linked to obesity, insulin resistance, and diabetes. Previous evidence suggested that the preventative effects of taurine on diabetes might be through regulating the expression levels of diabetes-related genes. We estimated whether blood taurine levels modified the overall genetic susceptibility to diabetes on improvement of insulin sensitivity in a randomized dietary trial. We genotyped 31 diabetes-associated variants to calculate a genetic risk score (GRS) and measured plasma taurine levels and glycemic traits among participants from the Preventing Overweight Using Novel Dietary Strategies (POUNDS Lost) trial. Seven-hundred eleven overweight or obese participants (age 30-70 y; 60% females) had genetic variants genotyped and blood taurine levels measured. Participants went on 2-year weight-loss diets, which were different in macronutrient composition. Improvements in glycemic traits were measured. We found that baseline taurine levels significantly modified the effects of diabetes GRS on changes in fasting glucose, insulin, and homeostatic model assessment of insulin resistance (HOMA-IR) during the 2-year diet intervention (P-interaction = .04, .01, .002, respectively), regardless of weight loss. High baseline taurine levels were associated with a less reduction in both glucose and HOMA-IR among the participants with the lowest tertile of diabetes GRS (both P = .02), and with a greater reduction in both insulin and HOMA-IR among those with the highest tertile of diabetes GRS (both P = .04). Our data suggest that blood taurine levels might differentially modulate the effects of diabetes-related genes on improvement of insulin sensitivity among overweight/obese patients on weight-loss diets.

  14. Adipokine zinc-α2-glycoprotein regulated by growth hormone and linked to insulin sensitivity.

    Science.gov (United States)

    Balaz, Miroslav; Ukropcova, Barbara; Kurdiova, Timea; Gajdosechova, Lucia; Vlcek, Miroslav; Janakova, Zuzana; Fedeles, Jozef; Pura, Mikulas; Gasperikova, Daniela; Smith, Steven R; Tkacova, Ruzena; Klimes, Iwar; Payer, Juraj; Wolfrum, Christian; Ukropec, Jozef

    2015-02-01

    Hypertrophic obesity is associated with impaired insulin sensitivity and lipid-mobilizing activity of zinc-α2-glycoprotein. Adipose tissue (AT) of growth hormone (GH) -deficient patients is characterized by extreme adipocyte hypertrophy due to defects in AT lipid metabolism. It was hypothesized that zinc-α2-glycoprotein is regulated by GH and mediates some of its beneficial effects in AT. AT from patients with GH deficiency and individuals with obesity-related GH deficit was obtained before and after 5-year and 24-month GH supplementation therapy. GH action was tested in primary human adipocytes. Relationships of GH and zinc-α2-glycoprotein with adipocyte size and insulin sensitivity were evaluated in nondiabetic patients with noncancerous cachexia and hypertrophic obesity. AT in GH-deficient adults displayed a substantial reduction of zinc-α2-glycoprotein. GH therapy normalized AT zinc-α2-glycoprotein. Obesity-related relative GH deficit was associated with almost 80% reduction of zinc-α2-glycoprotein mRNA in AT. GH increased zinc-α2-glycoprotein mRNA in both AT of obese men and primary human adipocytes. Interdependence of GH and zinc-α2-glycoprotein in regulating AT morphology and metabolic phenotype was evident from their relationship with adipocyte size and AT-specific and whole-body insulin sensitivity. The results demonstrate that GH is involved in regulation of AT zinc-α2-glycoprotein; however, the molecular mechanism linking GH and zinc-α2-glycoprotein in AT is yet unknown. © 2014 The Obesity Society.

  15. Insulin resistance in dairy cows.

    Science.gov (United States)

    De Koster, Jenne D; Opsomer, Geert

    2013-07-01

    Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows. Copyright © 2013 Elsevier Inc. All rights reserved.

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

    Science.gov (United States)

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

    2016-09-01

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

  17. Framework for applying RI-ISI methodology for Indian PHWRs

    International Nuclear Information System (INIS)

    Vinod, Gopika; Saraf, R.K.; Ghosh, A.K.; Kushwaha, H.S.

    2006-01-01

    Risk Informed In-Service Inspection (RI-ISI) aims at categorizing the components for In-Service inspection based on their contribution to Risk. For defining the contribution of risk from components, their failure probabilities and its subsequent effect on Core Damage Frequency (CDF) needs to be evaluated using Probabilistic Safety Assessment methodology. During the last several years, both the U.S. Nuclear Regulatory Commission (NRC) and the nuclear industry have recognized that Probabilistic Safety Assessment (PSA) has evolved to be more useful in supplementing traditional engineering approaches in reactor regulation. The paper highlights the various stages involved in applying RI-ISI and then compares the findings with existing ISI practices. (author)

  18. Association of NEFA composition with insulin sensitivity and beta cell function in the Prospective Metabolism and Islet Cell Evaluation (PROMISE) cohort.

    Science.gov (United States)

    Johnston, Luke W; Harris, Stewart B; Retnakaran, Ravi; Giacca, Adria; Liu, Zhen; Bazinet, Richard P; Hanley, Anthony J

    2018-04-01

    Our aim was to determine the longitudinal associations of individual NEFA with the pathogenesis of diabetes, specifically with differences in insulin sensitivity and beta cell function over 6 years in a cohort of individuals who are at risk for diabetes. In the Prospective Metabolism and Islet Cell Evaluation (PROMISE) longitudinal cohort, 477 participants had serum NEFA measured at the baseline visit and completed an OGTT at three time points over 6 years. Outcome variables were calculated using the OGTT values. At each visit, insulin sensitivity was assessed using the HOMA2 of insulin sensitivity (HOMA2-%S) and the Matsuda index, while beta cell function was assessed using the insulinogenic index over HOMA-IR (IGI/IR) and the insulin secretion-sensitivity index-2 (ISSI-2). Generalised estimating equations were used, adjusting for time, waist, sex, ethnicity, baseline age, alanine aminotransferase (ALT) and physical activity. NEFA were analysed as both concentrations (nmol/ml) and proportions (mol%) of the total fraction. Participants' (73% female, 70% with European ancestry) insulin sensitivity and beta cell function declined by 14-21% over 6 years of follow-up. In unadjusted models, several NEFA (e.g. 18:1 n-7, 22:4 n-6) were associated with lower insulin sensitivity, however, nearly all of these associations were attenuated in fully adjusted models. In adjusted models, total NEFA, 16:0, 18:1 n-9 and 18:2 n-6 (as concentrations) were associated with 3.7-8.0% lower IGI/IR and ISSI-2, while only 20:5 n-3 (as mol%) was associated with 7.7% higher HOMA2-%S. Total NEFA concentration was a strong predictor of lower beta cell function over 6 years. Our results suggest that the association with beta cell function is due to the absolute size of the serum NEFA fraction, rather than the specific fatty acid composition.

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

    Science.gov (United States)

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

    2015-07-01

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

  20. Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlate with salt sensitivity in normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; ter Wee, PM; Gans, ROB

    1999-01-01

    Background. Insulin induces increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects

  1. Effect of vitamin K supplementation on insulin sensitivity: a meta-analysis

    OpenAIRE

    Suksomboon,Naeti; Poolsup,Nalinee; Darli Ko Ko,Htoo

    2017-01-01

    Naeti Suksomboon,1 Nalinee Poolsup,2 Htoo Darli Ko Ko1 1Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand; 2Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon-Pathom, Thailand Objective: To perform a systematic review and meta-analysis of randomized, placebo-controlled trials to assess the effect of vitamin K supplementation on insulin sensitivity.Data sources: MEDLINE, the Cochrane Library, CINAHL, Web of Science, Scopus, clinicaltrials...

  2. Constitutive insulin sensitivity and obesity my be caused by PTEN mutations

    Directory of Open Access Journals (Sweden)

    E A Pigarova

    2012-12-01

    Full Text Available Реферат по статье: Pal A, Barber TM, Van de Bunt M, Rudge SA, Zhang Q, Lachlan KL, Cooper NS, Linden H, Levy JC, Wakelam MJ, Walker L, Karpe F, Gloyn AL. PTEN mutations as a cause of constitutive insulin sensitivity and obesity. N Engl J Med. 2012 Sep 13;367(11:1002-11.

  3. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  4. Adaptive Detection and ISI Mitigation for Mobile Molecular Communication.

    Science.gov (United States)

    Chang, Ge; Lin, Lin; Yan, Hao

    2018-03-01

    Current studies on modulation and detection schemes in molecular communication mainly focus on the scenarios with static transmitters and receivers. However, mobile molecular communication is needed in many envisioned applications, such as target tracking and drug delivery. Until now, investigations about mobile molecular communication have been limited. In this paper, a static transmitter and a mobile bacterium-based receiver performing random walk are considered. In this mobile scenario, the channel impulse response changes due to the dynamic change of the distance between the transmitter and the receiver. Detection schemes based on fixed distance fail in signal detection in such a scenario. Furthermore, the intersymbol interference (ISI) effect becomes more complex due to the dynamic character of the signal which makes the estimation and mitigation of the ISI even more difficult. In this paper, an adaptive ISI mitigation method and two adaptive detection schemes are proposed for this mobile scenario. In the proposed scheme, adaptive ISI mitigation, estimation of dynamic distance, and the corresponding impulse response reconstruction are performed in each symbol interval. Based on the dynamic channel impulse response in each interval, two adaptive detection schemes, concentration-based adaptive threshold detection and peak-time-based adaptive detection, are proposed for signal detection. Simulations demonstrate that the ISI effect is significantly reduced and the adaptive detection schemes are reliable and robust for mobile molecular communication.

  5. Altered Fetal Skeletal Muscle Nutrient Metabolism Following an Adverse In Utero Environment and the Modulation of Later Life Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Kristyn Dunlop

    2015-02-01

    Full Text Available The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.

  6. Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

    Science.gov (United States)

    Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

    2015-02-12

    The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.

  7. Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jørgensen, Nils Bruun

    2014-01-01

    after RYGB. Participants were included after a preoperative diet induced total weight loss of -9.2±1.2%. Hepatic and peripheral insulin sensitivity were assessed using the hyperinsulinemic euglycemic clamp combined with glucose tracer technique and beta-cell function evaluated in response...... after surgery. Insulin mediated glucose disposal and suppression of fatty acids did not improve immediately after surgery but increased at 3 months and 1 year likely related to the reduction in body weight. Insulin secretion increased after RYGB, but only in patients with type 2 diabetes and only...

  8. The status of ISI in the UK nuclear industry

    Energy Technology Data Exchange (ETDEWEB)

    Bann, T.; Rogerson, A. [AEA Technology, Risley (United Kingdom). Nuclear NDE Services

    1999-08-01

    This paper reviews the status of in-service inspection (ISI) in UK nuclear power generation industry through the experience of its nuclear utilities. The paper is intended to be a summary of some of the most recent and relevant ISI issues facing the utilities and the solutions devised to address those issues. (orig.)

  9. Is serum zinc associated with pancreatic beta cell function and insulin sensitivity in pre-diabetic and normal individuals? Findings from the Hunter Community Study.

    Directory of Open Access Journals (Sweden)

    Khanrin P Vashum

    Full Text Available AIM: To determine if there is a difference in serum zinc concentration between normoglycaemic, pre-diabetic and type-2 diabetic groups and if this is associated with pancreatic beta cell function and insulin sensitivity in the former 2 groups. METHOD: Cross sectional study of a random sample of older community-dwelling men and women in Newcastle, New South Wales, Australia. Beta cell function, insulin sensitivity and insulin resistance were calculated for normoglycaemic and prediabetes participants using the Homeostasis Model Assessment (HOMA-2 calculator. RESULT: A total of 452 participants were recruited for this study. Approximately 33% (N = 149 had diabetes, 33% (N = 151 had prediabetes and 34% (N = 152 were normoglycaemic. Homeostasis Model Assessment (HOMA parameters were found to be significantly different between normoglycaemic and prediabetes groups (p<0.001. In adjusted linear regression, higher serum zinc concentration was associated with increased insulin sensitivity (p = 0.01 in the prediabetic group. There was also a significant association between smoking and worse insulin sensitivity. CONCLUSION: Higher serum zinc concentration is associated with increased insulin sensitivity. Longitudinal studies are required to determine if low serum zinc concentration plays a role in progression from pre-diabetes to diabetes.

  10. Stevioside from Stevia rebaudiana Bertoni Increases Insulin Sensitivity in 3T3-L1 Adipocytes

    Directory of Open Access Journals (Sweden)

    Nabilatul Hani Mohd-Radzman

    2013-01-01

    Full Text Available Stevioside from Stevia rebaudiana has been reported to exert antihyperglycemic effects in both rat and human subjects. There have been few studies on these effects in vitro. In this paper, radioactive glucose uptake assay was implemented in order to assess improvements in insulin sensitivity in 3T3-L1 cells by elevation of glucose uptake following treatment with stevioside. Oil Red-O staining and MTT assay were utilized to confirm adipocyte differentiation and cell viability, respectively. Findings from this research showed a significant increase in absorbance values in mature adipocytes following Oil Red-O staining, confirming the differentiation process. Stevioside was noncytotoxic to 3T3-L1 cells as cell viability was reduced by a maximum of 17%, making it impossible to determine its IC50. Stevioside increased glucose uptake activities by 2.1 times (p<0.001 in normal conditions and up to 4.4 times (p<0.001 in insulin-resistant states. At times, this increase was higher than that seen in positive control group treated with rosiglitazone maleate, an antidiabetic agent. Expressions of pY20 and p-IRS1 which were measured via Western blot were improved by stevioside treatment. In conclusion, stevioside has direct effects on 3T3-L1 insulin sensitivity via increase in glucose uptake and enhanced expression of proteins involved in insulin-signalling pathway.

  11. The Lemmatization of Loan Words in the isiNdebele–English ...

    African Journals Online (AJOL)

    user

    English Dictionary and the selection of words for lemmatization are ... The IsiNdebele–English Dictionary is a bilingual, bi-directional dictionary, which is divided ... In the above examples, lemmas are in isiNdebele and English and each lemma.

  12. Consumption of a diet low in advanced glycation end products for 4 weeks improves insulin sensitivity in overweight women

    DEFF Research Database (Denmark)

    Mark, Alicja Budek; Poulsen, Malene Wibe; Andersen, Stine

    2014-01-01

    of either fructose or glucose drinks. Glucose and insulin concentrations-after fasting and 2 h after an oral glucose tolerance test-were measured before and after the intervention. Homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index were calculated. Dietary and urinary...... AGE concentrations were measured (liquid chromatography tandem mass spectrometry) to estimate AGE intake and excretion. RESULTS When adjusted for changes in anthropometric measures during the intervention, the low-AGE diet decreased urinary AGEs, fasting insulin concentrations, and HOMA-IR, compared...

  13. Overall aspects of control of ISIS-type nuclear reactor

    International Nuclear Information System (INIS)

    Amato, S.; Santinelli, A.

    1996-01-01

    The paper describes the main aspects related to the definition of main controls required to operate an ISIS-type nuclear power reactors. ISIS is a PWR-type intrinsically safe nuclear reactor designed by ANSALDO, based on density lock concept; it presents, between the other safety functions, self-depressurization and core cooling capability for unlimited time. Due to its specific characteristics, the ISIS reactor required to development of new control philosophy (if compared with actual nuclear power reactor) with the implementation of new control functions, for instance the density locks hot/cold interface locations control. This paper describes the main control functions implemented, their rationale, as well as the dynamic simulation performed to verify the adequacy of controls definitions. The dynamic simulations here described refers to a step-wise power ramp of 100-90-100 (% of nominal power) and to a power ramp of 100-50-100 with a slope of 5%/min; the results obtained have shown the ISIS capability to perform such operational transients, despite its innovative design was mainly focused on intrinsically safe behaviour. (author)

  14. The sensitivity and specificity of one field non-mydriatic digital fundus photography for DR screening

    Directory of Open Access Journals (Sweden)

    Bin-Bin Li

    2013-07-01

    Full Text Available AIM:To evaluate the sensitivity and specificity of one-field non-mydriatic digital fundus photography and direct ophthalmoscopy for diabetic retinopathy(DRscreening, compared with fundus fluorescein angiography( FFA .METHODS:All 93 patients of type 1 or 2 diabetic who have underwent one-field non-mydriatic digital fundus photography, and direct ophthalmoscopy with dilation of their pupils, and FFA by ophthalmologists. The sensitivity and specificity of one-field non-mydriatic digital fundus photography and direct ophthalmoscopy were calculated respectively, compared with FFA.RESULTS: The sensitivity and specificity of one-field non-mydriatic digital fundus photography for detection of any DR were 80.4% and 94.7%; The sensitivity and specificity of direct ophthalmoscopy for detection of any DR were 64.2% and 84.2%; After the standard for referable DR being lowered down to the moderate non-proliferative diabetic retinopathy(M-NPDR, the sensitivity and specificity of non-mydriatic digital fundus photography for detection were 88.9% and 98.4%, the sensitivity and specificity of direct ophthalmoscopy for detection were 71.5% and 96.7%.CONCLUSION: One-field non-mydriatic digital fundus photography is an effective method for DR screening.

  15. Brain pericyte-derived soluble factors enhance insulin sensitivity in GT1-7 hypothalamic neurons.

    Science.gov (United States)

    Takahashi, Hiroyuki; Takata, Fuyuko; Matsumoto, Junichi; Machida, Takashi; Yamauchi, Atsushi; Dohgu, Shinya; Kataoka, Yasufumi

    2015-02-20

    Insulin signaling in the hypothalamus plays an important role in food intake and glucose homeostasis. Hypothalamic neuronal functions are modulated by glial cells; these form an extensive network connecting the neurons and cerebral vasculature, known as the neurovascular unit (NVU). Brain pericytes are periendothelial accessory structures of the blood-brain barrier and integral members of the NVU. However, the interaction between pericytes and neurons is largely unexplored. Here, we investigate whether brain pericytes could affect hypothalamic neuronal insulin signaling. Our immunohistochemical observations demonstrated the existence of pericytes in the mouse hypothalamus, exhibiting immunoreactivity of platelet-derived growth factor receptor β (a pericyte marker), and laminin, a basal lamina marker. We then exposed a murine hypothalamic neuronal cell line, GT1-7, to conditioned medium obtained from primary cultures of rat brain pericytes. Pericyte-conditioned medium (PCM), but not astrocyte- or aortic smooth muscle cell-conditioned medium, increased the insulin-stimulated phosphorylation of Akt in GT1-7 cells in a concentration-dependent manner. PCM also enhanced insulin-stimulated tyrosine phosphorylation of insulin receptor β without changing its expression or localization in cytosolic or plasma membrane fractions. These results suggest that pericytes, rather than astrocytes, increase insulin sensitivity in hypothalamic neurons by releasing soluble factors under physiological conditions in the NVU. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Mediterranean diet and insulin sensitivity, lipid profile and blood pressure levels, in overweight and obese people; The Attica study

    Directory of Open Access Journals (Sweden)

    Zampelas Antonis

    2007-09-01

    Full Text Available Abstract Background We aimed to investigate if overweight and obese adults "close" to Mediterranean diet present better insulin, lipids profile and better pressure levels, compared to individuals close to a more Westernized diet. Methods The ATTICA study is a population-based cohort that has randomly enrolled 3042 adult men and women, stratified by age – gender, from the greater area of Athens, during 2001–2002. Of them, in this work were have studied 1762 participants with excess body weight, meaning overweight (BMI: 25–29.9 kg/m2 and obese (BMI>30 kg/m2. 1064 were men and 698 women (20–89 years old. Adherence to Mediterranean diet was assessed through a diet-score that was based on a validated food-frequency questionnaire. Blood pressure was measured and also fasting glucose, insulin and blood lipids. Insulin sensitivity was also assessed by the homeostasis model assessment (HOMA approach (glucose × insulin/22.5. Results Individuals with excess bodyweight in the highest tertile of diet score, were more insulin sensitive than those in the lowest tertile (11.4% lower HOMA, p = 0.06, had 13% lower levels of total cholesterol (p = 0.001 and 3 mmHg decrease of systolic blood pressure levels (p Conclusion Adherence to Mediterranean diet is modeslty associated with a better insulin sensitivity, lower levels of total cholesterol and lower levels of systolic blood pressure in overweight and obese subjects. This may suggest that compared to general population, the beneficial effect of this diet in cardiovascular system of excess body weight people is limited.

  17. A molecular dynamics simulation code ISIS

    International Nuclear Information System (INIS)

    Kambayashi, Shaw

    1992-06-01

    Computer simulation based on the molecular dynamics (MD) method has become an important tool complementary to experiments and theoretical calculations in a wide range of scientific fields such as physics, chemistry, biology, and so on. In the MD method, the Newtonian equations-of-motion of classical particles are integrated numerically to reproduce a phase-space trajectory of the system. In the 1980's, several new techniques have been developed for simulation at constant-temperature and/or constant-pressure in convenient to compare result of computer simulation with experimental results. We first summarize the MD method for both microcanonical and canonical simulations. Then, we present and overview of a newly developed ISIS (Isokinetic Simulation of Soft-spheres) code and its performance on various computers including vector processors. The ISIS code has a capability to make a MD simulation under constant-temperature condition by using the isokinetic constraint method. The equations-of-motion is integrated by a very accurate fifth-order finite differential algorithm. The bookkeeping method is also utilized to reduce the computational time. Furthermore, the ISIS code is well adopted for vector processing: Speedup ratio ranged from 16 to 24 times is obtained on a VP2600/10 vector processor. (author)

  18. Distal gastrectomy in pancreaticoduodenectomy is associated with accelerated gastric emptying, enhanced postprandial release of GLP-1, and improved insulin sensitivity

    DEFF Research Database (Denmark)

    Harmuth, Stefan; Wewalka, Marlene; Holst, Jens Juul

    2014-01-01

    resistance (HOMA-IR) and oral glucose insulin sensitivity were calculated from glucose and insulin concentrations. RESULTS: Patients with Whipple procedure as compared to PPPD had accelerated gastric emptying (p = 0.01) which correlated with early (0-30 min) integrated GLP-1 (AUC30; r (2) = 0.61; p = 0.......02) and insulin sensitivity (r (2) = 0.41; p = 0.026) and inversely with HOMA-IR (r (2) = 0.17; p = 0.033). Two of 13 Whipple patients (15 %) as compared to seven of 13 after PPPD (54 %) had postload glucose concentrations (i.e. 120 min postmeal) ≥200 mg/dl (p 

  19. Discovery of a potent and selective GPR120 agonist

    DEFF Research Database (Denmark)

    Shimpukade, Bharat; Hudson, Brian D; Hovgaard, Christine Kiel

    2012-01-01

    GPR120 is a receptor of unsaturated long-chain fatty acids reported to mediate GLP-1 secretion, insulin sensitization, anti-inflammatory, and anti-obesity effects and is therefore emerging as a new potential target for treatment of type 2 diabetes and metabolic diseases. Further investigation...... is however hindered by the lack of suitable receptor modulators. Screening of FFA1 ligands provided a lead with moderate activity on GPR120 and moderate selectivity over FFA1. Optimization led to the discovery of the first potent and selective GPR120 agonist....

  20. The product of triglycerides and glucose, a simple measure of insulin sensitivity. Comparison with the euglycemic-hyperinsulinemic clamp.

    Science.gov (United States)

    Guerrero-Romero, Fernando; Simental-Mendía, Luis E; González-Ortiz, Manuel; Martínez-Abundis, Esperanza; Ramos-Zavala, María G; Hernández-González, Sandra O; Jacques-Camarena, Omar; Rodríguez-Morán, Martha

    2010-07-01

    To meet the worldwide challenge of emerging diabetes, accessible and inexpensive tests to identify insulin resistance are needed. To evaluate the sensitivity and specificity of the product of fasting, we compared the triglycerides and glucose (TyG) index, a simple measure of insulin resistance, with the euglycemic-hyperinsulinemic clamp test. We conducted a cross-sectional study of the general population and outpatients of the Internal Medicine Department at the Medical Unit of High Specialty of the Specialty Hospital at the West National Medical Center in Guadalajara, Mexico. Eleven nonobese healthy subjects, 34 obese normal glucose tolerance individuals, 22 subjects with prediabetes, and 32 diabetic patients participated in the study. We performed a euglycemic-hyperinsulinemic clamp test. Sensitivity and specificity of the TyG index [Ln(fasting triglycerides) (mg/dl) x fasting glucose (mg/dl)/2] were measured, as well as the area under the curve of the receiver operating characteristic scatter plot and the correlation between the TyG index and the total glucose metabolism (M) rates. Pearson's correlation coefficient between the TyG index and M rates was -0.681 (P index and M rates was similar between men (-0.740) and women (-0.730), nonobese (-0.705) and obese (-0.710), and nondiabetic (-0.670) and diabetic (-0.690) individuals. The best value of the TyG index for diagnosis of insulin resistance was 4.68, which showed the highest sensitivity (96.5%) and specificity (85.0%; area under the curve + 0.858). The TyG index has high sensitivity and specificity, suggesting that it could be useful for identification of subjects with decreased insulin sensitivity.

  1. Adsorption of Free Fatty Acid (FFA) in Low-Grade Cooking Oil Used Activated Natural Zeolite as Adsorbent

    Science.gov (United States)

    Larasati Tres Ayu Putranti, Monika; Kompiang Wirawan, Sang; Made Bendiyasa, I.

    2018-01-01

    Adsorption of free fatty acid (FFA) in low-grade cooking oil using active natural zeolite adsorbent was done as an effort to improve the quality of low-grade cooking oil so that it can fulfill the standard of fried oil which has been set on SNI 01-3741-2013. Adsorption was carried out with natural zeolite which activated with HCl and NaOH solution followed by the calcination process. The results showed that the NaOH activated zeolite decreased FFA content in low-grade cooking oil more than the HCl activated natural zeolite, with optimum NaOH concentration was 0.75 M. In the adsorption equilibrium analysis with temperature variation (25 °C, 40 °C, 80 °C ), obtained that adsorption of FFA with NaOH activated natural zeolite follows Adsorption Isotherm Freundlich Model with equilibrium constant value was 20,5873; 0,9629 dan 0,8053.

  2. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review.

    Science.gov (United States)

    Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Micronutrients are gaining acceptance as an important nutritional therapy for the prevention and/or management of diabetes and its associated health risks. Although a very small quantity of micronutrients are required for specific functions in our bodies, moderate deficiencies can lead to serious health issues. Impaired insulin sensitivity and glucose intolerance play a major role in the development of diabetic pathophysiology. Vitamin K is well known for its function in blood coagulation. Moreover, several human studies reported the beneficial role of vitamin K supplementation in improving insulin sensitivity and glucose tolerance, preventing insulin resistance, and reducing the risk of type 2 diabetes (T2 D). Both animal and human studies have suggested that vitamin K-dependent protein (osteocalcin [OC]), regulation of adipokine levels, antiinflammatory properties, and lipid-lowering effects may mediate the beneficial function of vitamin K in insulin sensitivity and glucose tolerance. This review for the first time provides an overview of the currently available preclinical and clinical evidences on the effect of vitamin K supplementation in the management of insulin sensitivity and glucose tolerance. The outcome of this review will increase understanding for the development of a novel adjuvant therapy to achieve better control of glycemia and improve the lives of diabetic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Adiponectin in mice with altered growth hormone action: links to insulin sensitivity and longevity?

    Science.gov (United States)

    Lubbers, Ellen R.; List, Edward O.; Jara, Adam; Sackman-Sala, Lucila; Cordoba-Chacon, Jose; Gahete, Manuel D.; Kineman, Rhonda D.; Boparai, Ravneet; Bartke, Andrzej; Kopchick, John J.; Berryman, Darlene E.

    2013-01-01

    Adiponectin is positively correlated with longevity and negatively correlated with many obesity-related diseases. While there are several circulating forms of adiponectin, the high molecular weight (HMW) version has been suggested to have the predominant bioactivity. Adiponectin gene expression and cognate serum protein levels are of particular interest in mice with altered growth hormone (GH) signaling as these mice exhibit extremes in obesity that are positively associated with insulin sensitivity and lifespan as opposed to the typical negative association of these factors. While a few studies have reported total adiponectin levels in young adult mice with altered GH signaling, much remains unresolved, including changes in adiponectin levels with advancing age, proportion of total adiponectin in the HMW form, adipose depot of origin, and differential effects of GH versus IGF1. Therefore, the purpose of this study was to address these issues using assorted mouse lines with altered GH signaling. Our results show that adiponectin is generally negatively associated with GH activity, regardless of age. Further, the amount of HMW adiponectin is consistently linked with the level of total adiponectin and not necessarily with previously reported lifespan or insulin sensitivity of these mice. Interestingly, circulating adiponectin levels correlated strongly with inguinal fat mass, implying the effects of GH on adiponectin are depot-specific. Interestingly rbGH, but not IGF1, decreased circulating total and HMW adiponectin levels. Taken together, these results fill important gaps in the literature related to GH and adiponectin and question the frequently reported associations of total and HMW adiponectin with insulin sensitivity and longevity. PMID:23261955

  4. Lack of relationship between 11 beta-hydroxysteroid dehydrogenase setpoint and insulin sensitivity in the basal state and after 24h of insulin infusion in healthy subjects and type 2 diabetic patients

    NARCIS (Netherlands)

    Kerstens, MN; Riemens, SC; Sluiter, WJ; Pratt, JJ; Wolthers, BG; Dullaart, RPF

    OBJECTIVES To test whether insulin resistance in type 2 diabetes mellitus is associated with an altered overall setpoint of the 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) mediated cortisol to cortisone interconversion towards cortisol, and to evaluate whether changes in insulin sensitivity

  5. Low fish oil intake improves insulin sensitivity, lipid profile and muscle metabolism on insulin resistant MSG-obese rats

    OpenAIRE

    Iagher Fabiola; Aikawa Julia; Rocha Ricelli ER; Machado Juliano; Kryczyk Marcelo; Schiessel Dalton; Borghetti Gina; Yamaguchi Adriana A; Pequitto Danielle CT; Coelho Isabela; Brito Gleisson AP; Yamazaki Ricardo K; Naliwaiko Katya; Tanhoffer Ricardo A; Nunes Everson A

    2011-01-01

    Abstract Background Obesity is commonly associated with diabetes, cardiovascular diseases and cancer. The purpose of this study was to determinate the effect of a lower dose of fish oil supplementation on insulin sensitivity, lipid profile, and muscle metabolism in obese rats. Methods Monosodium glutamate (MSG) (4 mg/g body weight) was injected in neonatal Wistar male rats. Three-month-old rats were divided in normal-weight control group (C), coconut fat-treated normal weight group (CO), fish...

  6. Hepatic Cholesterol-25-Hydroxylase Overexpression Improves Systemic Insulin Sensitivity in Mice

    Directory of Open Access Journals (Sweden)

    Britta Noebauer

    2017-01-01

    Full Text Available Obesity is a major risk factor for several diseases including diabetes, heart disease, and some forms of cancer and due to its rapidly increasing prevalence it has become one of the biggest problems medicine is facing today. All the more surprising, a substantial percentage of obese patients are metabolically healthy when classified based on insulin resistance and systemic inflammation. Oxysterols are naturally occurring molecules that play important role in various metabolic and inflammatory processes and their levels are elevated in patients suffering from obesity and diabetes. 25-Hydroxycholesterol (25-OHC is produced in cells from cholesterol by the enzyme cholesterol 25-hydroxylase (Ch25h and is involved in lipid metabolism, inflammatory processes, and cell proliferation. Here, we investigated the role of hepatic Ch25h in the transition from metabolically healthy obesity to insulin resistance and diabetes. Using several different experimental approaches, we demonstrated the significance of Ch25h on the border of “healthy” and “diseased” states of obesity. Adenovirus-mediated Ch25h overexpression in mice improved glucose tolerance and insulin sensitivity and lowered HOMA-IR. Our data suggest that low hepatic Ch25h levels could be considered a risk marker for unhealthy obesity.

  7. Drosophila Insulin receptor regulates the persistence of injury-induced nociceptive sensitization

    Science.gov (United States)

    Patel, Atit A.

    2018-01-01

    ABSTRACT Diabetes-associated nociceptive hypersensitivity affects diabetic patients with hard-to-treat chronic pain. Because multiple tissues are affected by systemic alterations in insulin signaling, the functional locus of insulin signaling in diabetes-associated hypersensitivity remains obscure. Here, we used Drosophila nociception/nociceptive sensitization assays to investigate the role of Insulin receptor (Insulin-like receptor, InR) in nociceptive hypersensitivity. InR mutant larvae exhibited mostly normal baseline thermal nociception (absence of injury) and normal acute thermal hypersensitivity following UV-induced injury. However, their acute thermal hypersensitivity persists and fails to return to baseline, unlike in controls. Remarkably, injury-induced persistent hypersensitivity is also observed in larvae that exhibit either type 1 or type 2 diabetes. Cell type-specific genetic analysis indicates that InR function is required in multidendritic sensory neurons including nociceptive class IV neurons. In these same nociceptive sensory neurons, only modest changes in dendritic morphology were observed in the InRRNAi-expressing and diabetic larvae. At the cellular level, InR-deficient nociceptive sensory neurons show elevated calcium responses after injury. Sensory neuron-specific expression of InR rescues the persistent thermal hypersensitivity of InR mutants and constitutive activation of InR in sensory neurons ameliorates the hypersensitivity observed with a type 2-like diabetic state. Our results suggest that a sensory neuron-specific function of InR regulates the persistence of injury-associated hypersensitivity. It is likely that this new system will be an informative genetically tractable model of diabetes-associated hypersensitivity. PMID:29752280

  8. Effects of febuxostat on insulin resistance and expression of high-sensitivity C-reactive protein in patients with primary gout.

    Science.gov (United States)

    Meng, Juan; Li, Yanchun; Yuan, Xiaoxu; Lu, Yuewu

    2017-02-01

    We aimed to investigate the effects of febuxostat on IR and the expression of high-sensitivity C-reactive protein (hs-CRP) in patients with primary gout. Forty-two cases of primary gout patients without uric acid-lowering therapy were included in this study. After a physical examination, 20 age- and sex-matched patients were included as normal controls. The levels of fasting insulin (INS), fasting blood glucose (FBG), and hs-CRP were determined. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Gout patients had higher levels of UA, INS, HOMA-IR, and hs-CRP than normal controls (P gout patients and implicate that febuxostat can effectively control the level of serum UA and increase insulin sensitivity in primary gout patients.

  9. Improved Insulin Sensitiv