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Sample records for whole-body insulin sensitivity

  1. Complement C3 Is the Strongest Predictor of Whole-Body Insulin Sensitivity in Psoriatic Arthritis.

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    Francesco Ursini

    Full Text Available To evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA patients.For the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT was performed. The insulin sensitivity index (ISI, insulinogenic index (IGI and oral disposition index (ODI were calculated from dynamic values of glucose and insulin obtained during OGTT.In our study population, mean ISI was 3.5 ± 2.5, median IGI was 1.2 (0.7-1.8, mean ODI 4.5 ± 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP (R = -0.52, p = 0.001, diastolic blood pressure (dBP (R = -0.45, p = 0.004 and complement C3 (R = -0.43, p = 0.006 and ODI correlated inversely with sBP (R = -0.38, p = 0.02, dBP (R = -0.35, p = 0.03 and complement C3 (R = -0.37, p = 0.02. No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients.In conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients.

  2. Subcutaneous adipose tissue zinc-α2-glycoprotein is associated with adipose tissue and whole-body insulin sensitivity.

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    Balaz, Miroslav; Vician, Marek; Janakova, Zuzana; Kurdiova, Timea; Surova, Martina; Imrich, Richard; Majercikova, Zuzana; Penesova, Adela; Vlcek, Miroslav; Kiss, Alexander; Belan, Vitazoslav; Klimes, Iwar; Olejnik, Juraj; Gasperikova, Daniela; Wolfrum, Christian; Ukropcova, Barbara; Ukropec, Jozef

    2014-08-01

    To examine the regulatory aspects of zinc-α2-glycoprotein (ZAG) association with obesity-related insulin resistance. ZAG mRNA and protein were analyzed in subcutaneous adipose tissue (AT) and circulation of lean, obese, prediabetic, and type 2 diabetic men; both subcutaneous and visceral AT were explored in lean and extremely obese. Clinical and ex vivo findings were corroborated by results of in vitro ZAG silencing experiment. Subcutaneous AT ZAG was reduced in obesity, with a trend to further decrease with prediabetes and type 2 diabetes. ZAG was 3.3-fold higher in subcutaneous than in visceral AT of lean individuals. All differences were lost in extreme obesity. Obesity-associated changes in AT were not paralleled by alterations of circulating ZAG. Subcutaneous AT ZAG correlated with adiposity, adipocyte hypertrophy, whole-body and AT insulin sensitivity, mitochondrial content, expression of GLUT4, PGC1α, and adiponectin. Subcutaneous AT ZAG and adipocyte size were the only predictors of insulin sensitivity, independent on age and BMI. Silencing ZAG resulted in reduced adiponectin, IRS1, GLUT4, and PGC1α gene expression in primary human adipocytes. ZAG in subcutaneous, but not in visceral AT, was markedly reduced in obesity. Clinical, cellular, and molecular evidence indicate that ZAG plays an important role in modulating whole-body and AT insulin sensitivity. Copyright © 2014 The Obesity Society.

  3. Repeated prolonged whole-body low-intensity exercise: effects on insulin sensitivity and limb muscle adaptations

    DEFF Research Database (Denmark)

    Helge, Jørn Mikael; Overgaard, Kristian; Damsgaard, Rasmus

    2006-01-01

    was performed to establish maximal oxygen uptake. During the crossing, subjects skied for 342 ± 41 min/d. Peak oxygen uptake (4.6 ± 0.2 L/min) was decreased (P body mass decreased (P body mass......This study investigates the effect of prolonged whole-body low-intensity exercise on insulin sensitivity and the limb muscle adaptive response. Seven male subjects (weight, 90.2 ± 3.2 kg; age, 35 ± 3 years) completed a 32-day unsupported crossing of the Greenland icecap on cross-country skies....... Glycosylated hemoglobin (5.6% ± 0.01%) was not affected by the crossing. The IVGTT data revealed that insulin sensitivity (7.3 ± 0.6 mU · L-1 · min-1) and glucose effectiveness (0.024 ± 0.002 min-1) were not changed after the crossing. Similarly, the IVGTT data, when expressed per kilogram of lean body mass...

  4. The heterozygous N291S mutation in the lipoprotein lipase gene impairs whole-body insulin sensitivity and affects a distinct set of plasma metabolites in humans.

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    Berg, Sofia Mikkelsen; Havelund, Jesper; Hasler-Sheetal, Harald; Kruse, Vibeke; Pedersen, Andreas James Thestrup; Hansen, Aleksander Bill; Nybo, Mads; Beck-Nielsen, Henning; Højlund, Kurt; Færgeman, Nils Joakim

    Mutations in the lipoprotein lipase gene causing decreased lipoprotein lipase activity are associated with surrogate markers of insulin resistance and the metabolic syndrome in humans. We investigated the hypothesis that a heterozygous lipoprotein lipase mutation (N291S) induces whole-body insulin resistance and alterations in the plasma metabolome. In 6 carriers of a heterozygous lipoprotein lipase mutation (N291S) and 11 age-matched and weight-matched healthy controls, we examined insulin sensitivity and substrate metabolism by euglycemic-hyperinsulinemic clamps combined with indirect calorimetry. Plasma samples were taken before and after the clamp (4 hours of physiological hyperinsulinemia), and metabolites were measured enzymatically or by gas chromatography-mass spectrometry. Compared with healthy controls, heterozygous carriers of a defective lipoprotein lipase allele had elevated fasting plasma levels triglycerides (P 1.5-fold change and P < .05). Heterozygous carriers with a defective lipoprotein lipase allele are less insulin sensitive and have increased plasma levels of nonesterified fatty acids and triglycerides. The heterozygous N291S carriers also have a distinct plasma metabolomic signature, which may serve as a diagnostic tool for deficient lipoprotein lipase activity and as a marker of lipid-induced insulin resistance. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

  5. 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

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    Stefan, Norbert; Vozarova, Barbora; Funahashi, Tohru

    2002-01-01

    with diabetes). Group 1 (19 subjects) underwent skeletal muscle biopsies for the measurement of basal and insulin-stimulated tyrosine phosphorylation of the IR (stimulated by 100 nmol/l insulin). The fold increase after insulin stimulation was calculated as the ratio between maximal and basal phosphorylation...

  6. The heterozygous N291S mutation in the lipoprotein lipase gene impairs whole-body insulin sensitivity and affects a distinct set of plasma metabolites in humans

    DEFF Research Database (Denmark)

    Berg, Sofia Mikkelsen; Havelund, Jesper Foged; Hasler-Sheetal, Harald

    2017-01-01

    Highlights • Insulin sensitivity is reduced in carriers with a defective lipoprotein lipase allele. • Heterozygous N291S carriers have a distinct plasma metabolomics signature. • Reduced α-tocopherol levels in heterozygous lipoprotein lipase carriers may contribute to the reduced insulin sensitiv...

  7. Role of Insulin-Stimulated Adipose Tissue Perfusion in the Development of Whole-Body Insulin Resistance.

    Science.gov (United States)

    Emanuel, Anna L; Meijer, Rick I; Muskiet, Marcel H A; van Raalte, Daniël H; Eringa, Etto C; Serné, Erik H

    2017-03-01

    After food ingestion, macronutrients are transported to and stored in the skeletal muscle and adipose tissue. They can be subsequently used as an energy source in times of energy deprivation. Uptake of these nutrients in myocytes and adipocytes depends largely on adequate tissue perfusion. Interestingly, insulin is able to dilate skeletal muscle arterioles, which facilitates the delivery of macronutrients and insulin itself to muscle tissue. Insulin-stimulated skeletal muscle perfusion is impaired in several insulin-resistant states and is believed to contribute to impaired skeletal muscle glucose uptake and consequently impaired whole-body glucose disposal. Insulin-resistant individuals also exhibit blunted postprandial adipose tissue perfusion. However, the relevance of this impairment to metabolic dysregulation is less clear. In this review, we provide an overview of adipose tissue perfusion in healthy and insulin-resistant individuals, its regulation among others by insulin, and the possible influences of impaired adipose tissue perfusion on whole-body insulin sensitivity. Finally, we propose a novel hypothesis that acute overfeeding impacts distribution of macronutrients by reducing skeletal muscle perfusion, while adipose tissue perfusion remains intact. An online visual overview is available for this article. © 2017 American Heart Association, Inc.

  8. Comparative Evaluation of Whole Body and Hepatic Insulin Resistance Using Indices from Oral Glucose Tolerance Test in Morbidly Obese Subjects with Nonalcoholic Fatty Liver Disease

    Directory of Open Access Journals (Sweden)

    Kamran Qureshi

    2010-01-01

    Full Text Available Nonalcoholic Fatty Liver Disease (NAFLD is the hepatic manifestation of metabolic syndrome and is a marker of Insulin Resistance (IR. Euglycemic-hyperinsulinemic clamp is the gold standard for measuring whole body IR (hepatic + peripheral IR. However, it is an invasive and expensive procedure. Homeostasis Model Assessment Index for Insulin Sensitivity (HOMA-IS, Quantitative Insulin Sensitivity Check Index (QUICKI for hepatic IR and Insulin Sensitivity Index (ISI0,120, and Whole Body Insulin Sensitivity Index (WBISI for whole body IR are the indices calculated after Oral Glucose Tolerance Test (OGTT. We used these indices as noninvasive methods of IR (inverse of insulin sensitivity estimation and compared hepatic/peripheral components of whole body IR in NAFLD. Methods. 113 morbidly obese, nondiabetic subjects who underwent gastric bypass surgery and intraoperative liver biopsy were included in the study. OGTT was performed preoperatively and the indices were calculated. Subjects were divided into closely matched groups as normal, fatty liver (FL and Non-Alcoholic Steatohepatitis (NASH based on histology. Results. Whole body IR was significantly higher in both FL and NASH groups (NAFLD as compared to Normal, while hepatic IR was higher only in NASH from Normal. Conclusions. FL is a manifestation of peripheral IR but not hepatic IR.

  9. Selective COX2 inhibition improves whole body and muscular insulin resistance in fructose-fed rats.

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    Hsieh, P-S; Tsai, H-C; Kuo, C-H; Chan, J Y-H; Shyu, J-F; Cheng, W-T; Liu, T-T

    2008-11-01

    The effects of cyclooxygenase-1 (COX1) and cyclooxygenase-2 (COX2) inhibition on insulin resistance in subjects with the metabolic syndrome remain elusive. Aims of this study were to examine the effects of COX1 and COX2 inhibitors on whole body and muscular insulin resistance in fructose-fed rats, an animal model of the metabolic syndrome. The rats on regular or 60% fructose-enriched diets for 6 weeks were further divided into rats combined with or without piroxicam (a selective COX1 inhibitor) or celecoxib (a selective COX2 inhibitor) treatment for an additional 2 weeks. Euglycaemic hyperinsulinaemic clamp (EHC) with a tracer dilution method was performed at the end of the study. The present result showed that fructose-induced increases in systolic blood pressure and fasting plasma insulin levels were significantly suppressed in rats treated with celecoxib but not piroxicam. In the EHC period, celecoxib significantly reversed fructose-induced decreases in whole body glucose uptake, mainly by glucose storage. Hepatic glucose production and whole body glycolysis were not significantly changed among groups. Celecoxib but not piroxicam significantly reversed fructose-induced decreases in glycogen synthase activities in red and white quadriceps muscles and insulin-stimulated membrane GLUT4 recruitment in soleus muscles. Celecoxib and piroxicam both significantly diminished fructose-induced increases in plasma thromboxane B2 and 6-keto prostaglandin (PG) F1alpha; but only celecoxib treatment significantly attenuated a fructose-induced increase in 8-isoprostane levels. Plasma PGE metabolites were not different among groups. This study demonstrates that a therapeutic dose of celecoxib, but not piroxicam, could significantly attenuate fructose-induced whole body and muscular insulin resistance in rats.

  10. Whole Body Vibration Improves Insulin Resistance in db/db Mice: Amelioration of Lipid Accumulation and Oxidative Stress.

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    Liu, Ying; Zhai, Mingming; Guo, Fan; Shi, Tengrui; Liu, Jiangzheng; Wang, Xin; Zhang, Xiaodi; Jing, Da; Hai, Chunxu

    2016-07-01

    Insulin resistance (IR) is the hallmark of type 2 diabetes mellitus (T2DM), which is one of the most important chronic noncommunicable diseases. Effective and feasible strategies to treat IR are still urgently needed. Previous research studies reported that whole body vibration (WBV) was beneficial for IR in clinical; however, its underlying mechanisms remains unknown. In the present study, db/db mice were treated with WBV administration 60 min/day for 12 weeks and the impaired insulin sensitivity was improved. Besides, liver steatosis was also ameliorated. Further explorations revealed that WBV could reduce the expression of SREBP1c and increase the expression of GSH-Px and consequently suppress oxidative stress. In conclusion, WBV attenuates oxidative stress to ameliorate liver steatosis and thus improves insulin resistance in db/db mice. Therefore, WBV administration is a promising treatment for individuals who suffered from central obesity and IR.

  11. Binge Drinking Induces Whole-Body Insulin Resistance by Impairing Hypothalamic Insulin Action

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    Lindtner, Claudia; Scherer, Thomas; Zielinski, Elizabeth; Filatova, Nika; Fasshauer, Martin; Tonks, Nicholas K.; Puchowicz, Michelle; Buettner, Christoph

    2013-01-01

    Individuals with a history of binge drinking have an increased risk of developing the metabolic syndrome and type 2 diabetes. Whether binge drinking impairs glucose homeostasis and insulin action is unknown. To test this, we treated Sprague-Dawley rats daily with alcohol (3 g/kg) for three consecutive days to simulate human binge drinking and found that these rats developed and exhibited insulin resistance even after blood alcohol concentrations had become undetectable. The animals were resistant to insulin for up to 54 hours after the last dose of ethanol, chiefly a result of impaired hepatic and adipose tissue insulin action. Because insulin regulates hepatic glucose production and white adipose tissue lipolysis, in part through signaling in the central nervous system, we tested whether binge drinking impaired brain control of nutrient partitioning. Rats that had consumed alcohol exhibited impaired hypothalamic insulin action, defined as the ability of insulin infused into the mediobasal hypothalamus to suppress hepatic glucose production and white adipose tissue lipolysis. Insulin signaling in the hypothalamus, as assessed by insulin receptor and AKT phosphorylation, decreased after binge drinking. Quantitative polymerase chain reaction showed increased hypothalamic inflammation and expression of protein tyrosine phosphatase 1B (PTP1B), a negative regulator of insulin signaling. Intracerebroventricular infusion of CPT-157633, a small-molecule inhibitor of PTP1B, prevented binge drinking–induced glucose intolerance. These results show that, in rats, binge drinking induces systemic insulin resistance by impairing hypothalamic insulin action and that this effect can be prevented by inhibition of brain PTP1B. PMID:23363978

  12. Periparturient insulin secretion and whole-body insulin responsiveness in dairy cows showing various forms of ketone pattern with or without puerperal metritis.

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    Kerestes, M; Faigl, V; Kulcsár, M; Balogh, O; Földi, J; Fébel, H; Chilliard, Y; Huszenicza, G

    2009-11-01

    To study the effect of time and different forms of hyperketonemia, with or without puerperal metritis, on insulin and glucose responses, 31 Holstein cows were subjected to glucose (GTT) and insulin tolerance tests (ITT) between 18 and 22 d before, and on days 7 and 60-70 after calving. Plasma concentrations of beta-hydroxybutyrate (BHB), nonesterified fatty acids, glucose, insulin, insulin-like growth factor I and leptin were measured from 18 d before until 70 d after calving. The revised quick insulin sensitivity index (RQUICKI) was calculated at each time point. First postpartum (PP) ovulation was monitored by milk progesterone. Based on BHB patterns and clinical findings, animals were classified as 1) Normoketonemic (NK, n=9); 2) Transiently hyperketonemic (tHK, n=7); 3) Continuously HK (cHK, n=7); and 4) Continuously HK, with signs of puerperal metritis (cHK+PM, n=6). Insulin area under the curve (AUC) and insulin response to glucose were significantly lower in the early PP period than in late-pregnancy (Pcows (group 1) ovulated earlier than all other groups (P=0.002). There was no correlation between GTT and ITT variables and the RQUICKI. Time had a significant effect on RQUICKI. Long-term hyperketonemia, especially combined with puerperal metritis, interacts with secretion of insulin and whole-body IR, and results in a significant delay in PP ovarian activity in dairy cows.

  13. Effects of whole body vibration plus diet on insulin-resistance in middle-aged obese subjects.

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    Bellia, A; Sallì, M; Lombardo, M; D'Adamo, M; Guglielmi, V; Tirabasso, C; Giordani, L; Federici, M; Lauro, D; Foti, C; Sbraccia, P

    2014-06-01

    We investigated the early effects of whole body vibration (WBV) added to hypocaloric diet on insulin-resistance and other parameters associated with glucose regulation in sedentary obese individuals. We randomly assigned 34 patients to WBV plus hypocaloric diet (WBV group) or diet alone (CON group) for 8 weeks. Fasting and post-load glucose, insulin, lipids, C-reactive protein, tumor necrosis factor-α, leptin, adiponectin were assessed. Insulin sensitivity index (ISI) was derived from oral-glucose-tolerance test. Body composition was evaluated with dual-energy X-ray absorptiometry. Both groups lost approximately 5% of weight, with greater reduction of body fat in WBV than in CON (-7.1±1.2 Kg vs. -5.3±1.0 Kg, p=0.003). Percent variation of ISI was more pronounced in WBV than in CON group (+35±4% vs. + 22±5%, p=0.002), accompanied by slight improvement in post-load glucose (-1.07±0.02 vs. - 0.12±0.01 mmol/l, p=0.031) but without changes in fasting levels. Adiponectin significantly increased in WBV group compared with CON (p=0.021 for comparison) whereas no differences in leptin and inflammatory markers were observed. In middle-aged sedentary obese subjects, WBV added to hypocaloric diet for 8 weeks improved body composition, insulin-resistance, glucose regulation and adiponectin levels to a greater extent compared with diet alone. Efficacy and feasibility of this approach in the long term need to be ascertained. © Georg Thieme Verlag KG Stuttgart · New York.

  14. Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese HIV-infected women123

    Science.gov (United States)

    Albu, Jeanine B; Kenya, Sonjia; He, Qing; Wainwright, Marsha; Berk, Evan S; Heshka, Stanley; Kotler, Donald P; Engelson, Ellen S

    2009-01-01

    Background Obesity and insulin resistance are growing problems in HIV-positive (HIV+) women receiving highly active antiretroviral therapy (HAART). Objective The objective was to determine the contribution of adipose tissue (AT) enlargement and distribution to the presence of insulin resistance in obese HIV+ women. Design Whole-body intermuscular AT (IMAT), visceral AT (VAT), subcutaneous AT (SAT), and SAT distribution (leg versus upper body) were measured by whole-body magnetic resonance imaging. Insulin sensitivity (SI) was measured with an intravenous glucose tolerance test in obese HIV+ women recruited because of their desire to lose weight (n = 17) and in obese healthy controls (n = 32). Results The HIV+ women had relatively less whole-body SAT and more VAT and IMAT than did the controls (P < 0.05 for all). A significant interaction by HIV status was observed for the relation of total SAT with SI (P < 0.001 for the regression’s slope interactions after adjustment for age, height, and weight). However, relations of IMAT, VAT, and SAT distribution (leg SAT as a percentage of total SAT; leg SAT%) with SI did not differ significantly between groups. For both groups combined, the best model predicting a low SI included significant contributions by both high IMAT and low leg SAT%, independent of age, height, and weight, and no interaction between groups was observed (overall r2 = 0.44, P = 0.0003). Conclusion In obese HIV+ women, high whole-body IMAT and low leg SAT% distribution are independently associated with insulin resistance. PMID:17616768

  15. Hepatic and Whole-Body Insulin Metabolism during Proestrus and Estrus in Mongrel Dogs.

    Science.gov (United States)

    Yu, Erin Nz; Winnick, Jason J; Edgerton, Dale S; Scott, Melanie F; Smith, Marta S; Farmer, Ben; Williams, Phillip E; Cherrington, Alan D; Moore, Mary Courtney

    2016-01-01

    Insulin resistance occurs during various stages of the estrus cycle in dogs. To quantify the effects of proestrus-estrus (PE) and determine whether PE affects liver insulin sensitivity, 11 female mongrel dogs were implanted with sampling and intraportal infusion catheters. Five of the dogs (PE group) entered proestrus after surgery; those remaining in anestrus were controls. The dogs were fasted overnight, [3-(3)H]glucose and somatostatin were infused through peripheral veins, and glucagon was infused intraportally. Insulin was infused intraportally, with the rate adjusted to maintain arterial plasma glucose at basal levels (PE, 294±25 μU/kg/min; control, 223±21 μU/kg/min). Subsequently the insulin infusion rate was increased by 0.2 mU/kg/min for 120 min (P1) and then to 1.5 mU/kg/min for the last 120 min (P2); glucose was infused peripherally as needed to maintain euglycemia. Insulin concentrations did not differ between groups at any time; they increased 3 μU/mL over baseline during P1 and to 3 times baseline during P2. The glucose infusion rate in PE dogs during P2 was 63% of that in control dogs. Net hepatic glucose output and the endogenous glucose production rate declined 40% to 50% from baseline in both groups during P1; during P2, both groups exhibited a low rate of net hepatic glucose uptake with full suppression of endogenous glucose production. The glucose disappearance rate during P1 and P2 was 35% greater in control than PE dogs. Therefore, PE in canines is associated with loss of nonhepatic (primarily muscle) but not hepatic insulin sensitivity.

  16. Increased skeletal muscle capillarization enhances insulin sensitivity

    DEFF Research Database (Denmark)

    Åkerström, Thorbjörn; Laub, Lasse; Vedel, Kenneth

    2014-01-01

    . 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-body...

  17. Comparison of the physiological relevance of systemic vs. portal insulin delivery to evaluate whole body glucose flux during an insulin clamp.

    Science.gov (United States)

    Farmer, Tiffany D; Jenkins, Erin C; O'Brien, Tracy P; McCoy, Gregory A; Havlik, Allison E; Nass, Erik R; Nicholson, Wendell E; Printz, Richard L; Shiota, Masakazu

    2015-02-01

    To understand the underlying pathology of metabolic diseases, such as diabetes, an accurate determination of whole body glucose flux needs to be made by a method that maintains key physiological features. One such feature is a positive differential in insulin concentration between the portal venous and systemic arterial circulation (P/S-IG). P/S-IG during the determination of the relative contribution of liver and extra-liver tissues/organs to whole body glucose flux during an insulin clamp with either systemic (SID) or portal (PID) insulin delivery was examined with insulin infusion rates of 1, 2, and 5 mU·kg(-1)·min(-1) under either euglycemic or hyperglycemic conditions in 6-h-fasted conscious normal rats. A P/S-IG was initially determined with endogenous insulin secretion to exist with a value of 2.07. During an insulin clamp, while inhibiting endogenous insulin secretion by somatostatin, P/S-IG remained at 2.2 with PID, whereas, P/S-IG disappeared completely with SID, which exhibited higher arterial and lower portal insulin levels compared with PID. Consequently, glucose disappearance rates and muscle glycogen synthetic rates were higher, but suppression of endogenous glucose production and liver glycogen synthetic rates were lower with SID compared with PID. When the insulin clamp was performed with SID at 2 and 5 mU·kg(-1)·min(-1) without managing endogenous insulin secretion under euglycemic but not hyperglycemic conditions, endogenous insulin secretion was completely suppressed with SID, and the P/S-IG disappeared. Thus, compared with PID, an insulin clamp with SID underestimates the contribution of liver in response to insulin to whole body glucose flux. Copyright © 2015 the American Physiological Society.

  18. Short communication: Maternal heat stress during the dry period alters postnatal whole-body insulin response of calves.

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    Tao, S; Monteiro, A P A; Hayen, M J; Dahl, G E

    2014-02-01

    Heat stress during the dry period not only negatively affects a cow's performance but also affects her offspring. Previous studies indicate that calves born to cows heat-stressed during late gestation have lower birth weight but similar overall weight gain during the prepubertal period compared with those cooled in utero. However, it is unclear if whole-body insulin response, and thus metabolism, of calves is altered in their postnatal life after in utero heat stress. The aim of the present study was to examine the effects of maternal heat stress during the dry period on whole-body insulin response of calves after weaning. Calves (10/treatment) were born to cows exposed to heat stress (HT) or cooling (CL) when dry. Calves were immediately separated from their dams and fed 3.8L of high-quality colostrum within 1h after birth and then 1.9L 12h later. All calves were fed 1.9 to 3.8L of pasteurized milk in the morning and afternoon from 2 to 42 d of age and then only in the morning until weaning at 49 d. Calf starter and water were offered ad libitum starting at 2 d of age. All calves were managed in the same manner throughout the study. All calves were subjected to a glucose tolerance test (GTT) and an insulin challenge (IC) at 55 d of age. Calves heat-stressed in utero were born lighter (40 ± 1.4 vs. 45 ± 1.4 kg) compared with CL calves. Both groups of calves had similar weaning weights (HT: 68 ± 3.2 kg; CL: 71 ± 3.3 kg) and body weight gain from birth to weaning (HT: 28 ± 2.2 kg; CL: 26 ± 2.3 kg). Compared with those cooled in utero, HT calves had a similar insulin response to GTT and insulin clearance during IC but faster glucose clearance during GTT and IC. In conclusion, in addition to impaired fetal growth, maternal heat stress during the dry period enhances the whole-body insulin response of calves after weaning, which suggests the possibility of accelerated lipogenesis and fat deposition in early life. Copyright © 2014 American Dairy Science Association

  19. Impact of weight loss-associated changes in detailed body composition as assessed by whole-body MRI on plasma insulin levels and homeostatis model assessment index.

    Science.gov (United States)

    Pourhassan, M; Glüer, C-C; Pick, P; Tigges, W; Müller, M J

    2017-02-01

    We assessed the effect of weight loss-associated changes in detailed body composition on plasma insulin levels and homeostatic model assessment (HOMA) index to calculate the magnitude of reduction in different adipose tissue depots required to improve insulin sensitivity. A total of 50 subjects aged 20-69 years were studied. The participants were compiled from low-calorie diet interventions and bariatric surgery and differed in their baseline body mass index (BMI; range 21.6-54.4 kg/m2) and degree of weight losses (range -3.3 to -56.9 kg). Detailed body composition and liver fat were measured using whole-body magnetic resonance imaging (MRI). Insulin resistance was assessed by HOMA. Mean body weight decreased by -16.0±13.6 kg. Significant changes were observed in total adipose tissue (TATMRI, range -0.5 to -36.0 kg), total subcutaneous adipose tissue (SATMRI), visceral adipose tissue (VATMRI), skeletal muscle, liver fat, plasma insulin levels and HOMA. Decreases in insulin and HOMA were correlated with reductions in TATMRI, SATMRI, VATMRI (just with HOMA) and liver fat. Losses of 2.9 and 6.5 kg body weight, 2.0 and 5.0 kg TATMRI as well as 1.6 and 6% liver fat were required to decrease plasma insulin levels by 1 μU/ml and HOMAadjusted for baseline HOMA by 1 point. Multiple regression analysis showed that baseline liver fat and changes in liver fat explained 49.7% and 55.1% of the variance in weight loss-associated changes in plasma insulin and HOMA, respectively. Decreases of adipose tissues and liver fat are the major determinants of reduction in plasma insulin levels and improvement in HOMA index.

  20. Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain.

    Science.gov (United States)

    Jensen, Benjamin A H; Nielsen, Thomas S; Fritzen, Andreas M; Holm, Jacob B; Fjære, Even; Serup, Annette K; Borkowski, Kamil; Risis, Steve; Pærregaard, Simone I; Søgaard, Ida; Poupeau, Audrey; Poulsen, Michelle; Ma, Tao; Sina, Christian; Kiens, Bente; Madsen, Lise; Kristiansen, Karsten; Treebak, Jonas T

    2016-12-01

    The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis and the gut microbiota. We fed C57BL6/J mice 3 different HFDs with decreasing protein:carbohydrate ratios for 8weeks and compared the results to a LFD reference group. We analyzed the gut microbiota composition by 16S rDNA amplicon sequencing and the intestinal gene expression by real-time PCR. Whole body glucose homeostasis was evaluated by insulin and glucose tolerance tests as well as by a hyperinsulinemic euglycemic clamp experiment. Compared with LFD-fed reference mice, HFD-fed mice, irrespective of protein:carbohydrate ratio, exhibited impaired glucose tolerance, whereas no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous glucose production under insulin-stimulated conditions. We observed no impairment of insulin-stimulated glucose uptake in skeletal muscles of different fiber type composition. HFD-feeding altered the gut microbiota composition paralleled by increased expression of pro-inflammatory cytokines and genes involved in gluconeogenesis in intestinal epithelial cells of the jejunum. Intake of a HFD profoundly affected glucose homeostasis, gut inflammatory responses, and gut microbiota composition in the absence of fat mass accretion. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Impact of 9 days of bed rest on hepatic and peripheral insulin action, insulin secretion, and whole-body lipolysis in healthy young male offspring of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Alibegovic, Amra C; Højbjerre, Lise; Sonne, Mette P

    2009-01-01

    deteriorates with 9 days of bed rest, converging toward similar degrees of whole-body insulin resistance. FDR subjects exhibit hepatic insulin resistance (HIR), which, in contrast to CON subjects, deteriorates in response to physical inactivity. FDR subjects exhibit reduced insulin secretion when seen...... in relation to their degree of HIR but not peripheral insulin resistance....

  2. Mathematical model of the glucose-insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    Science.gov (United States)

    Han, Kyungreem; Kang, Hyuk; Choi, M. Y.; Kim, Jinwoong; Lee, Myung-Shik

    2012-10-01

    A theoretical approach to the glucose-insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca2+ concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose-insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  3. PPARγ-mediated insulin sensitization: the importance of fat versus muscle

    National Research Council Canada - National Science Library

    Ulrich Kintscher; Ronald E. Law

    2005-01-01

    ...., through binding of the synthetic glitazones or thiazolidinediones (TZD), results in a marked improvement in type 2 diabetic patients of insulin and glucose parameters resulting from an improvement of whole body insulin sensitivity...

  4. Effect of acute and chronic whole-body vibration exercise on serum insulin-like growth factor-1 levels in women with fibromyalgia.

    Science.gov (United States)

    Alentorn-Geli, Eduard; Moras, Gerard; Padilla, Jaume; Fernández-Solà, Joaquim; Bennett, Robert M; Lázaro-Haro, Cristina; Pons, Sebastià

    2009-05-01

    The purpose of this study was to investigate the effect of acute and chronic whole-body vibration exercise on serum insulin-like growth factor-1 (IGF-1) levels in women with fibromyalgia. A randomized controlled two-factor mixed experimental design was used. Twenty-four women with fibromyalgia (age +/- standard error of the mean, 54.95 +/- 2.03) were randomized into the vibration group or the control group. The vibration group underwent a protocol of static and dynamic tasks with whole-body vibration exercise twice a week for a total of six weeks, whereas the control group performed the same protocol without vibratory stimulus. Both groups continued their usual pharmacological treatment. Serum IGF-1 levels were determined using enzyme-linked immunosorbent assay (ELISA). To test the effects of long-term whole-body vibration exercise, serum IGF-1 measurements were taken at baseline and at weeks 1, 3, and 6 of the intervention. To test the short-term effects, at week 1, serum IGF-1 measurements were taken before and immediately following a session of whole-body vibration exercise. Treatment adherence was 93% in the vibration group and 92% in the control group. None of the subjects dropped out of the study. There was an absence of change in IGF-1 at week 1 and week 6 of whole-body vibration exercise. Results show no change in serum IGF-1 levels in women with fibromyalgia undergoing whole-body vibration exercise. Although high-intensity exercise and whole-body vibration exercise have been shown to increase serum IGF-1 in healthy individuals, the effectiveness of whole-body vibration exercise as a strategy to produce improvements in serum IGF-1 levels in women with fibromyalgia could not be demonstrated.

  5. Mathematical model of the glucose–insulin regulatory system: From the bursting electrical activity in pancreatic β-cells to the glucose dynamics in the whole body

    Energy Technology Data Exchange (ETDEWEB)

    Han, Kyungreem [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Kang, Hyuk [National Institute for Mathematical Sciences, Daejeon 305-340 (Korea, Republic of); Choi, M.Y., E-mail: mychoi@snu.ac.kr [Department of Physics and Astronomy and Center for Theoretical Physics, Seoul National University, Seoul 151-747 (Korea, Republic of); Kim, Jinwoong, E-mail: jwkim@snu.ac.kr [College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742 (Korea, Republic of); Lee, Myung-Shik [Department of Medicine, Samsung Medical Center, and School of Medicine, Sungkyunkwan University, Seoul 135-710 (Korea, Republic of)

    2012-10-01

    A theoretical approach to the glucose–insulin regulatory system is presented. By means of integrated mathematical modeling and extensive numerical simulations, we probe the cell-level dynamics of the membrane potential, intracellular Ca{sup 2+} concentration, and insulin secretion in pancreatic β-cells, together with the whole-body level glucose–insulin dynamics in the liver, brain, muscle, and adipose tissues. In particular, the three oscillatory modes of insulin secretion are reproduced successfully. Such comprehensive mathematical modeling may provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination. -- Highlights: ► We present a mathematical model for the glucose–insulin regulatory system. ► This model combines the microscopic insulin secretion mechanism in a pancreatic β-cell and macroscopic glucose dynamics at the whole-body level. ► This work is expected to provide a theoretical basis for the simultaneous assessment of the β-cell function and insulin resistance in clinical examination.

  6. 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...... albuminuria. This finding suggests that reduced insulin sensitivity either is simply related to or might causally contribute to the initial pathogenesis of albuminuria....

  7. 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

    whole body (pinsulin stimulated leg glucose uptake (p=0.05) during an euglycemic-hyperinsulinemic ( approximately 70 uU/ml) clamp compared to matched male subjects. The higher insulin sensitivity in women could not be explained by higher expression of muscle GLUT4, insulin receptor (IR......Women have been shown to have higher muscle tricylglycerol (IMTG) levels than men and could therefore be expected to have lower insulin sensitivity than men, since previous studies have linked high IMTG to decreased insulin sensitivity. Thus, insulin sensitivity of whole body and leg glucose uptake......) or Akt expression or the ability of insulin to stimulate Akt (thr308) or Akt (ser473) phosphorylation. However, a 30% higher (p

  8. Parallax-sensitive remapping of visual space in occipito-parietal alpha-band activity during whole-body motion.

    Science.gov (United States)

    Gutteling, T P; Selen, L P J; Medendorp, W P

    2015-03-01

    Despite the constantly changing retinal image due to eye, head, and body movements, we are able to maintain a stable representation of the visual environment. Various studies on retinal image shifts caused by saccades have suggested that occipital and parietal areas correct for these perturbations by a gaze-centered remapping of the neural image. However, such a uniform, rotational, remapping mechanism cannot work during translations when objects shift on the retina in a more complex, depth-dependent fashion due to motion parallax. Here we tested whether the brain's activity patterns show parallax-sensitive remapping of remembered visual space during whole-body motion. Under continuous recording of electroencephalography (EEG), we passively translated human subjects while they had to remember the location of a world-fixed visual target, briefly presented in front of or behind the eyes' fixation point prior to the motion. Using a psychometric approach we assessed the quality of the memory update, which had to be made based on vestibular feedback and other extraretinal motion cues. All subjects showed a variable amount of parallax-sensitive updating errors, i.e., the direction of the errors depended on the depth of the target relative to fixation. The EEG recordings show a neural correlate of this parallax-sensitive remapping in the alpha-band power at occipito-parietal electrodes. At parietal electrodes, the strength of these alpha-band modulations correlated significantly with updating performance. These results suggest that alpha-band oscillatory activity reflects the time-varying updating of gaze-centered spatial information during parallax-sensitive remapping during whole-body motion. Copyright © 2015 the American Physiological Society.

  9. The inflammatory status score including IL-6, TNF-α, osteopontin, fractalkine, MCP-1 and adiponectin underlies whole-body insulin resistance and hyperglycemia in type 2 diabetes mellitus.

    Science.gov (United States)

    Daniele, G; Guardado Mendoza, R; Winnier, D; Fiorentino, T V; Pengou, Z; Cornell, J; Andreozzi, F; Jenkinson, C; Cersosimo, E; Federici, M; Tripathy, D; Folli, F

    2014-02-01

    A state of subclinical systemic inflammation is characteristically present in obesity/insulin resistance and type 2 diabetes mellitus (T2DM). The aim of the study was to develop an integrated measure of the circulating cytokines involved in the subclinical systemic inflammation and evaluate its relation with whole-body insulin sensitivity and glucose metabolism in T2DM. T2DM patients (n = 17, M/F 13/4, age = 55.0 ± 1.7 years, BMI = 33.5 ± 1.5 kg/m(2), HbA(1c) = 7.7 ± 0.3%) and normal glucose-tolerant (NGT) subjects (n = 15, M/F 7/8, age = 49.1 ± 2.5 years, BMI = 31.8 ± 1.2 kg/m(2), HbA(1c) = 5.6 ± 0.1%) were studied in a cross-sectional design. Whole-body insulin sensitivity was quantified by the euglycemic clamp. Beta-cell function [disposition index (DI)] was calculated using insulin and glucose values derived from an oral glucose tolerance test and the euglycemic clamp. Body fat mass was evaluated by dual-energy X-ray absorptiometry. Plasma cytokine [TNF-α, IL-6, MCP-1, osteopontin, fractalkine and adiponectin] values were divided into quintiles. A score ranging from 0 (lowest quintile) to 4 (highest quintile) was assigned. The inflammatory score (IS) was the sum of each cytokine score from which adiponectin score was subtracted in each study subject. Inflammatory cytokine levels were all higher in T2DM. IS was higher in T2DM as compared to NGT (10.0 ± 1.1 vs. 4.8 ± 0.8; p < 0.001). IS positively correlated with fasting plasma glucose (r = 0.638, p < 0.001), 1-h plasma glucose (r = 0.483, p = 0.005), 2-h plasma glucose (r = 0.611, p < 0.001) and HbA1c (r = 0.469, p = 0.007). IS was inversely correlated with insulin sensitivity (r = -0.478, p = 0.006) and DI (r = -0.523, p = 0.002). IS did not correlate with BMI and body fat mass. IS was an independent predictor of fasting plasma glucose and had a high sensibility and sensitivity to predict insulin resistance (M/I < 4). A state of subclinical inflammation defined and quantifiable by inflammatory score

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

    OpenAIRE

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

    2015-01-01

    Purpose: With the childhood obesity epidemic, efficient methods of exercise are sought to improve health. We tested whether whole body vibration (WBV) exercise can positively affect bone metabolism and improve insulin/glucose dynamics in sedentary overweight Latino boys. Methods: Twenty Latino boys 8-10 years of age were randomly assigned to either a control (CON) or 3 days/wk WBV exercise (VIB) for 10-wk. Results: Significant increases in BMC (4.5?3.2%; p=0.01) and BMD (1.3?1.3%; p

  11. Skeletal Muscle Angiogenesis and Its Relation to Insulin Sensitivity

    DEFF Research Database (Denmark)

    Lindqvist, Anna Maria Charlotte K

    to improved diffusion conditions for glucose in the muscle. The results of this PhD project show that treatment with an α1-adrenergic antagonist increases capillarization and whole-body insulin sensitivity in both rodents and humans. In addition, the combination of VEGF-A electrotransfer and training result...

  12. Whole Body Counters (rev.)

    Energy Technology Data Exchange (ETDEWEB)

    Woodburn, John H. [Walter Johnson High School, Rockville, MD; Lengemann, Frederick W. [Cornell University

    1967-01-01

    Whole body counters are radiation detecting and measuring instruments that provide information about the human body. This booklet describes different whole body counters, scientific principles that are applied to their design, and ways they are used.

  13. Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight

    DEFF Research Database (Denmark)

    Jensen, Christine B; Storgaard, Heidi; Madsbad, Sten

    2007-01-01

    CONTEXT: Low birth weight (LBW), a surrogate marker of an adverse fetal milieu, is linked to muscle insulin resistance, impaired insulin-stimulated glycolysis, and future risk of type 2 diabetes. Skeletal muscle mass, fiber composition, and capillary density are important determinants of muscle...

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

    Science.gov (United States)

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

    2017-03-01

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

  15. Dietary fat drives whole-body insulin resistance and promotes intestinal inflammation independent of body weight gain

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech; Nielsen, Thomas Svava; Fritzen, Andreas Mæchel

    2016-01-01

    BACKGROUND: The obesogenic potential of high-fat diets (HFD) in rodents is attenuated when the protein:carbohydrate ratio is increased. However, it is not known if intake of an HFD irrespective of the protein:carbohydrate ratio and in the absence of weight gain, affects glucose homeostasis...... no differences were observed during insulin tolerance tests. The hyperinsulinemic euglycemic clamp revealed tissue-specific effects on glucose homeostasis in all HFD-fed groups. HFD-fed mice exhibited decreased insulin-stimulated glucose uptake in white but not in brown adipose tissue, and sustained endogenous...

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

    DEFF Research Database (Denmark)

    Stallknecht, Bente; 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 [insu...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    metabolism by generating mice in which PKCδ was deleted specifically in muscle using Cre-lox recombination. Deletion of PKCδ in muscle improved insulin signaling in young mice, especially at low insulin doses; however, this did not change glucose tolerance or insulin tolerance tests done with pharmacological......-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......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...

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

    Science.gov (United States)

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

    2015-01-01

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

  19. Insulin sensitivity in clinically healthy individuals with microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, J S; Borch-Johnsen, K; Jensen, G

    1996-01-01

    glucose, tobacco and alcohol consumption, physical activity, and age and sex, fasting serum insulin concentration was the only variable independently associated with insulin sensitivity (r = -0.55; P = 0.0001). It is concluded that microalbuminuria is not associated with impaired insulin sensitivity...... excretion rate (UAER) of 6.6 to 150 micrograms/min) and 24 age- and sex-matched controls with normoalbuminuria (UAER rate on 2 mU/(kg body weight x min). Insulin sensitivity...... (whole body glucose disposal) was similar in the two groups ((mean (95% C.I.)) 351 (321-381) vs. 364 (339-388) mg/(m2 x min); P = 0.51). Among urinary albumin excretion rate, blood pressure, serum lipid concentrations, body mass index waist-hip ratio, fasting concentrations of serum insulin and blood...

  20. Insulin sensitivity in clinically healthy individuals with microalbuminuria

    DEFF Research Database (Denmark)

    Jensen, J S; Borch-Johnsen, K; Jensen, G

    1996-01-01

    excretion rate (UAER) of 6.6 to 150 micrograms/min) and 24 age- and sex-matched controls with normoalbuminuria (UAER body weight x min). Insulin sensitivity...... (whole body glucose disposal) was similar in the two groups ((mean (95% C.I.)) 351 (321-381) vs. 364 (339-388) mg/(m2 x min); P = 0.51). Among urinary albumin excretion rate, blood pressure, serum lipid concentrations, body mass index waist-hip ratio, fasting concentrations of serum insulin and blood...... glucose, tobacco and alcohol consumption, physical activity, and age and sex, fasting serum insulin concentration was the only variable independently associated with insulin sensitivity (r = -0.55; P = 0.0001). It is concluded that microalbuminuria is not associated with impaired insulin sensitivity...

  1. Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans

    Science.gov (United States)

    Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. T...

  2. Whole-body MRI screening

    Energy Technology Data Exchange (ETDEWEB)

    Puls, Ralf [HELIOS Klinikum Erfurt (Germany). Inst. of Diagnostic and Interventional Radiology and Neuroradiology; Hosten, Norbert (ed.) [Universitaetsklinikum Greifswald (Germany). Diagnostic Radiology and Neuroradiology

    2014-07-01

    The advent of dedicated whole-body MRI scanners has made it possible to image the human body from head to toe with excellent spatial resolution and with the sensitivity and specificity of conventional MR systems. A comprehensive screening examination by MRI relies on fast image acquisition, and this is now feasible owing to several very recent developments, including multichannel techniques, new surface coil systems, and automatic table movement. The daily analysis of whole-body MRI datasets uncovers many incidental findings, which are discussed by an interdisciplinary advisory board of physicians from all specialties. This book provides a systematic overview of these incidental findings with the aid of approximately 240 high-quality images. The radiologists involved in the project have written chapters on each organ system, presenting a structured compilation of the most common findings, their morphologic appearances on whole-body MRI, and guidance on their clinical management. Chapters on technical and ethical issues are also included. It is hoped that this book will assist other diagnosticians in deciding how to handle the most common incidental findings encountered when performing whole-body MRI.

  3. 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...... in both study I and II. Several indices of improved hepatic metabolism and function were observed after the highfat interventions. In contrast, the three-day hypercaloric carbohydrate-rich diet (study I) increased basal and insulin-stimulated glucose production, increased post-absorptive plasma TG...... metabolism in skeletal muscle and in the liver. A period of high fat (and low carbohydrate) intake may furthermore change hepatic glucoregulation and metabolism in a non-diabetic direction. Insulin´s action on glucose uptake in skeletal muscle seems, however, to be impaired when a high fat intake was coupled...

  4. Sensitivity of whole-body CT and MRI versus projection radiography in the detection of osteolyses in patients with monoclonal plasma cell disease

    Energy Technology Data Exchange (ETDEWEB)

    Wolf, Maya B., E-mail: m.mueller-wolf@dkfz.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Department of Radiology, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Murray, Fritz, E-mail: fritz.murray@hotmail.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Kilk, Kerstin, E-mail: k_fechtner@hotmail.com [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); Hillengass, Jens, E-mail: jens.hillengass@med.uni-heidelberg.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Delorme, Stefan, E-mail: s.delorme@dkfz-heidelberg.de [Department of Radiology, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Heiss, Christiane, E-mail: c.heiss@dkfz-heidelberg.de [Department of Biostatistics, German Cancer Research Center (Dkfz), Im Neuenheimer Feld 280, 69120 Heidelberg (Germany); Neben, Kai, E-mail: k.neben@klinikum-mittelbaden.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Goldschmidt, Hartmut, E-mail: hartmut.goldschmidt@med.uni-heidelberg.de [Department of Haematology, Oncology, Rheumatology, University Hospital Heidelberg and National Center for Tumour Diseases, Im Neuenheimer Feld 410, 69120 Heidelberg (Germany); Kauczor, Hans-Ulrich, E-mail: hu.kauczor@med.uni-heidelberg.de [Department of Diagnostic and Interventional Radiology, University Hospital Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg Germany (Germany); and others

    2014-07-15

    Purpose: To compare sensitivity of whole-body Computed Tomography (wb-CT) and whole-body Magnetic Resonance Imaging (wb-MRI) with Projection Radiography (PR) regarding each method's ability to detect osteolyses in patients with monoclonal plasma cell disease. Patients and methods: The bone status of 171 patients was evaluated. All patients presented with multiple myeloma (MM) of all stages, monoclonal gammopathy of unknown significance (MGUS) or solitary plasmacytoma. Two groups were formed. Group A consisted of 52 patients (26 females, 26 males) with an average age of 62 years (range, 45–89 years) who received, both, PR and wb-CT as part of their diagnostic work-up. Group B comprised 119 patients (58 females, 61 males) averaging 57 years of age (range, 20–80 years) who received, both, PR and wb-MRI. Two experienced radiologists were blinded regarding the disease status and assessed the number and location of osteolyses in consensus. A distinction was made between axial and extra-axial lesions. Results: In group A, wb-CT revealed osteolyses in 12 patients (23%) that were not detected in PR. CT was superior in detecting lesions in patients with osteopenia and osteoporosis. Compared with PR, wb-CT was significantly more sensitive in detecting osteolyses than PR (p < 0.001). This was particularly true for axial lesions. Additionally, CT revealed clinically relevant incidental findings in 33 patients (63%). In group B, wb-MRI revealed lesions in 19 patients (16%) that were not detected in PR. All lesions detected by PR were also detected by wb-MRI and wb-CT. Wb-MRI and wb-CT are each superior to PR in detecting axial lesions. Conclusion: Wb-CT can detect 23% more focal lesions than PR, especially in the axial skeleton. Therefore, this imaging method should be preferred over PR in the diagnostic work-up and staging of patients with monoclonal plasma cell disease.

  5. Simulation study of a D-shape PET scanner for improved sensitivity and reduced cost in whole-body imaging

    Science.gov (United States)

    Ahmed, Abdella M.; Tashima, Hideaki; Yamaya, Taiga

    2017-05-01

    Much research effort is being made to increase the sensitivity and improve the imaging performance of positron emission tomography (PET) scanners. Conventionally, sensitivity can be increased by increasing the number of detector rings in the axial direction (but at high cost) or reducing the diameter of the scanner (with the disadvantages of reducing the space for patients and degrading the spatial resolution due to the parallax error). In this study, we proposed a PET scanner with a truncated ring and an array of detectors that can be arranged in a straight line below the bed. We called this system ‘D-PET’ as it resembles the letter ‘D’ when it is rotated by 90° in the counterclockwise direction. The basic design idea was to cut the unused space under the patient’s bed; this area is usually not in use in clinical diagnosis. We conducted Monte Carlo simulations of the D-PET scanner and compared its performance with a cylindrical PET scanner. The scanners were constructed from 4-layer depth-of-interaction detectors which consisted of a 16  ×  16  ×  4 LYSO crystal array with dimensions of 2.85  ×  2.85  ×  5 mm3. The results showed that the D-PET had an increase in sensitivity and peak-NECR of 30% and 18%, respectively. The D-PET had low noise in the reconstructed images throughout the field-of-view compared to the cylindrical PET. These were achieved while keeping sufficient space for the patient, and also without a severe effect on the spatial resolution. Furthermore, the number of detectors (and hence the cost) of the D-PET scanner was reduced by 12% compared to the cylindrical PET scanner.

  6. Development, Evaluation, and Sensitivity Analysis of Parametric Finite Element Whole-Body Human Models in Side Impacts.

    Science.gov (United States)

    Hwang, Eunjoo; Hu, Jingwen; Chen, Cong; Klein, Katelyn F; Miller, Carl S; Reed, Matthew P; Rupp, Jonathan D; Hallman, Jason J

    2016-11-01

    Occupant stature and body shape may have significant effects on injury risks in motor vehicle crashes, but the current finite element (FE) human body models (HBMs) only represent occupants with a few sizes and shapes. Our recent studies have demonstrated that, by using a mesh morphing method, parametric FE HBMs can be rapidly developed for representing a diverse population. However, the biofidelity of those models across a wide range of human attributes has not been established. Therefore, the objectives of this study are 1) to evaluate the accuracy of HBMs considering subject-specific geometry information, and 2) to apply the parametric HBMs in a sensitivity analysis for identifying the specific parameters affecting body responses in side impact conditions. Four side-impact tests with two male post-mortem human subjects (PMHSs) were selected to evaluate the accuracy of the geometry and impact responses of the morphed HBMs. For each PMHS test, three HBMs were simulated to compare with the test results: the original Total Human Model for Safety (THUMS) v4.01 (O-THUMS), a parametric THUMS (P-THUMS), and a subject-specific THUMS (S-THUMS). The P-THUMS geometry was predicted from only age, sex, stature, and BMI using our statistical geometry models of skeleton and body shape, while the S-THUMS geometry was based on each PMHS's CT data. The simulation results showed a preliminary trend that the correlations between the PTHUMS- predicted impact responses and the four PMHS tests (mean-CORA: 0.84, 0.78, 0.69, 0.70) were better than those between the O-THUMS and the normalized PMHS responses (mean-CORA: 0.74, 0.72, 0.55, 0.63), while they are similar to the correlations between S-THUMS and the PMHS tests (mean-CORA: 0.85, 0.85, 0.67, 0.72). The sensitivity analysis using the PTHUMS showed that, in side impact conditions, the HBM skeleton and body shape geometries as well as the body posture were more important in modeling the occupant impact responses than the bone and soft

  7. Intermittent fasting does not affect whole-body glucose, lipid, or protein metabolism

    NARCIS (Netherlands)

    Soeters, Maarten R.; Lammers, Nicolette M.; Dubbelhuis, Peter F.; Ackermans, Mariëtte T.; Jonkers-Schuitema, Cora F.; Fliers, Eric; Sauerwein, Hans P.; Aerts, Johannes M.; Serlie, Mireille J.

    2009-01-01

    Background: Intermittent fasting (IF) was shown to increase whole-body insulin sensitivity, but it is uncertain whether IF selectively influences intermediary metabolism. Such selectivity might be advantageous when adapting to periods of food abundance and food shortage. Objective: The objective was

  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

    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...... insulin sensitivity in mouse skeletal muscle. Here we aimed to determine whether activation of AMPK is also a prerequisite for the ability of muscle contraction to increase insulin sensitivity. We found that prior in situ contraction of m. extensor digitorum longus (EDL) and treadmill exercise increased...... 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...

  9. Bioactives in Blueberries Improve Insulin Sensitivity in Obese, Insulin-Resistant Men and Women1234

    Science.gov (United States)

    Stull, April J.; Cash, Katherine C.; Johnson, William D.; Champagne, Catherine M.; Cefalu, William T.

    2010-01-01

    Dietary supplementation with whole blueberries in a preclinical study resulted in a reduction in glucose concentrations over time. We sought to evaluate the effect of daily dietary supplementation with bioactives from blueberries on whole-body insulin sensitivity in men and women. A double-blinded, randomized, and placebo-controlled clinical study design was used. After screening to resolve study eligibility, baseline (wk 0) insulin sensitivity was measured on 32 obese, nondiabetic, and insulin-resistant subjects using a high-dose hyperinsulinemic-euglycemic clamp (insulin infusion of 120 mU(861 pmol)⋅m−2⋅min−1). Serum inflammatory biomarkers and adiposity were measured at baseline. At the end of the study, insulin sensitivity, inflammatory biomarkers, and adiposity were reassessed. Participants were randomized to consume either a smoothie containing 22.5 g blueberry bioactives (blueberry group, n = 15) or a smoothie of equal nutritional value without added blueberry bioactives (placebo group, n = 17) twice daily for 6 wk. Both groups were instructed to maintain their body weight by reducing ad libitum intake by an amount equal to the energy intake of the smoothies. Participants’ body weights were evaluated weekly and 3-d food records were collected at baseline, the middle, and end of the study. The mean change in insulin sensitivity improved more in the blueberry group (1.7 ± 0.5 mg⋅kg FFM−1⋅min−1) than in the placebo group (0.4 ± 0.4 mg⋅kg FFM−1⋅min−1) (P = 0.04). Insulin sensitivity was enhanced in the blueberry group at the end of the study without significant changes in adiposity, energy intake, and inflammatory biomarkers. In conclusion, daily dietary supplementation with bioactives from whole blueberries improved insulin sensitivity in obese, nondiabetic, and insulin-resistant participants. PMID:20724487

  10. Virtual patients and sensitivity analysis of the Guyton model of blood pressure regulation: towards individualized models of whole-body physiology.

    Directory of Open Access Journals (Sweden)

    Robert Moss

    Full Text Available Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a "virtual population" from which "virtual individuals" can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the "virtual individuals" that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models.

  11. Virtual patients and sensitivity analysis of the Guyton model of blood pressure regulation: towards individualized models of whole-body physiology.

    Science.gov (United States)

    Moss, Robert; Grosse, Thibault; Marchant, Ivanny; Lassau, Nathalie; Gueyffier, François; Thomas, S Randall

    2012-01-01

    Mathematical models that integrate multi-scale physiological data can offer insight into physiological and pathophysiological function, and may eventually assist in individualized predictive medicine. We present a methodology for performing systematic analyses of multi-parameter interactions in such complex, multi-scale models. Human physiology models are often based on or inspired by Arthur Guyton's whole-body circulatory regulation model. Despite the significance of this model, it has not been the subject of a systematic and comprehensive sensitivity study. Therefore, we use this model as a case study for our methodology. Our analysis of the Guyton model reveals how the multitude of model parameters combine to affect the model dynamics, and how interesting combinations of parameters may be identified. It also includes a "virtual population" from which "virtual individuals" can be chosen, on the basis of exhibiting conditions similar to those of a real-world patient. This lays the groundwork for using the Guyton model for in silico exploration of pathophysiological states and treatment strategies. The results presented here illustrate several potential uses for the entire dataset of sensitivity results and the "virtual individuals" that we have generated, which are included in the supplementary material. More generally, the presented methodology is applicable to modern, more complex multi-scale physiological models.

  12. Insulin-Induced Microvascular Recruitment in Skin and Muscle are Related and Both are Associated with Whole-Body Glucose Uptake

    NARCIS (Netherlands)

    Meijer, R.I.; de Boer, M.P.; Groen, M.R.; Eringa, E.C.; Rattigan, S.; Barrett, E.J.; Smulders, Y.M.; Serné, E.H.

    2012-01-01

    Objective: Insulin-induced capillary recruitment is considered a determinant of insulin-mediated glucose uptake. Insulin action on the microvasculature has been assessed in skin; however, there is concern as to whether the vascular responses observed in skin reflect those in the muscle. We

  13. High levels of dietary stearate promote adiposity and deteriorate hepatic insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Havekes Louis M

    2010-03-01

    Full Text Available Abstract Background Relatively little is known about the role of specific saturated fatty acids in the development of high fat diet induced obesity and insulin resistance. Here, we have studied the effect of stearate in high fat diets (45% energy as fat on whole body energy metabolism and tissue specific insulin sensitivity. Methods C57Bl/6 mice were fed a low stearate diet based on palm oil or one of two stearate rich diets, one diet based on lard and one diet based on palm oil supplemented with tristearin (to the stearate level of the lard based diet, for a period of 5 weeks. Ad libitum fed Oxidative metabolism was assessed by indirect calorimetry at week 5. Changes in body mass and composition was assessed by DEXA scan analysis. Tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp analysis and Western blot at the end of week 5. Results Indirect calorimetry analysis revealed that high levels of dietary stearate resulted in lower caloric energy expenditure characterized by lower oxidation of fatty acids. In agreement with this metabolic phenotype, mice on the stearate rich diets gained more adipose tissue mass. Whole body and tissue specific insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and analysis of insulin induced PKBser473 phosphorylation. Whole body insulin sensitivity was decreased by all high fat diets. However, while insulin-stimulated glucose uptake by peripheral tissues was impaired by all high fat diets, hepatic insulin sensitivity was affected only by the stearate rich diets. This tissue-specific pattern of reduced insulin sensitivity was confirmed by similar impairment in insulin-induced phosphorylation of PKBser473 in both liver and skeletal muscle. Conclusion In C57Bl/6 mice, 5 weeks of a high fat diet rich in stearate induces a metabolic state favoring low oxidative metabolism, increased adiposity and whole body insulin resistance characterized by severe hepatic insulin

  14. Insulin does not stimulate muscle protein synthesis during increased plasma branched-chain amino acids alone but still decreases whole body proteolysis in humans.

    Science.gov (United States)

    Everman, Sarah; Meyer, Christian; Tran, Lee; Hoffman, Nyssa; Carroll, Chad C; Dedmon, William L; Katsanos, Christos S

    2016-10-01

    Insulin stimulates muscle protein synthesis when the levels of total amino acids, or at least the essential amino acids, are at or above their postabsorptive concentrations. Among the essential amino acids, branched-chain amino acids (BCAA) have the primary role in stimulating muscle protein synthesis and are commonly sought alone to stimulate muscle protein synthesis in humans. Fourteen healthy young subjects were studied before and after insulin infusion to examine whether insulin stimulates muscle protein synthesis in relation to the availability of BCAA alone. One half of the subjects were studied in the presence of postabsorptive BCAA concentrations (control) and the other half in the presence of increased plasma BCAA (BCAA). Compared with that prior to the initiation of the insulin infusion, fractional synthesis rate of muscle protein (%/h) did not change (P > 0.05) during insulin in either the control (0.04 ± 0.01 vs 0.05 ± 0.01) or the BCAA (0.05 ± 0.02 vs. 0.05 ± 0.01) experiments. Insulin decreased (P BCAA (0.89 ± 0.07 vs 0.61 ± 0.03) experiments, but the change was not different between the two experiments (P > 0.05). In conclusion, insulin does not stimulate muscle protein synthesis in the presence of increased circulating levels of plasma BCAA alone. Insulin's suppressive effect on proteolysis is observed independently of the levels of circulating plasma BCAA. Copyright © 2016 the American Physiological Society.

  15. Effects of adrenaline on whole-body glucose metabolism and insulin-mediated regulation of glycogen synthase and PKB phosphorylation in human skeletal muscle.

    Science.gov (United States)

    Jensen, Jørgen; Ruge, Toralph; Lai, Yu-Chiang; Svensson, Maria K; Eriksson, Jan W

    2011-02-01

    In the present study, we investigated the effect of adrenaline on insulin-mediated regulation of glucose and fat metabolism with focus on regulation of skeletal muscle PKB, GSK-3, and glycogen synthase (GS) phosphorylation. Ten healthy subjects (5 men and 5 women) received a 240-minute intravenous infusion of adrenaline (0.05 μg/[kg min]) or saline; after 120 minutes, a hyperinsulinemic-euglycemic clamp was added. Adrenaline infusion increased blood glucose concentration by approximately 50%, but the hyperinsulinemic clamp normalized blood glucose within 30 minutes. Glucose infusion rate during the last hour was approximately 60% lower during adrenaline infusion compared with saline (4.3 ± 0.5 vs 11.2 ± 0.6 mg/kg lean body mass per minute). Insulin increased PKB Ser⁴⁷³, PKB Thr³⁰⁸, and GSK-3β Ser⁹ phosphorylation in skeletal muscles; coinfusion of adrenaline did not influence insulin-stimulated PKB and GSK-3 phosphorylation. Adrenaline alone did not influence phosphorylation of PKB and GSK-3β. Insulin increased GS fractional activity and decreased GS Ser⁶⁴¹ and Ser⁶⁴⁵,⁶⁴⁹,⁶⁵³,⁶⁵⁷ phosphorylation. In the presence of adrenaline, insulin did neither activate GS nor dephosphorylate GS Ser⁶⁴¹. Surprisingly, GS Ser⁷ phosphorylation was not influenced by adrenaline. Adrenaline increased plasma lactate concentration; and muscle glycogen content was reduced in skeletal muscle the day after adrenaline infusion, supporting that insulin does not stimulate glycogen synthesis in skeletal muscles when adrenaline is present. In conclusion, adrenaline did not influence basal or insulin-stimulated PKB and GSK-3β phosphorylation in muscles, but completely blocked insulin-mediated GS activation and Ser⁶⁴¹ dephosphorylation. Still, insulin normalized adrenaline-mediated hyperglycemia. © 2011 Elsevier Inc. All rights reserved.

  16. Circulating Docosahexaenoic Acid Associates with Insulin-Dependent Skeletal Muscle and Whole Body Glucose Uptake in Older Women Born from Normal Weight Mothers

    Directory of Open Access Journals (Sweden)

    Robert M. Badeau

    2017-02-01

    Full Text Available Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. The circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women who were either female offspring from obese mothers (OOM or offspring of lean mothers (OLM. Metabolic changes were tested for associations with metrics for insulin resistance. Methods: Thirty-seven elderly women were separated into elderly offspring from obese mothers (OOM; n = 17 and elderly offspring from lean/normal weight mothers (OLM; n = 20 groups. We measured plasma metabolites using proton nuclear magnetic resonance (1H-NMR and insulin-dependent tissue-specific glucose uptake in skeletal muscle was assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the docosahexaenoic acid percentage of the total long-chain n-3 fatty acids (DHA/FA was significantly lower in OOM (p = 0.015. DHA/FA associated significantly with skeletal muscle glucose uptake (GU (p = 0.031 and the metabolizable glucose value derived from hyperinsulinemic-euglycemic clamp technique (M-value in the OLM group only (p = 0.050. Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and this association is significantly weakened in the offspring of obese mothers.

  17. Insulin-Like Growth Factor Binding Protein 1 Could Improve Glucose Regulation and Insulin Sensitivity Through Its RGD Domain.

    Science.gov (United States)

    Haywood, Natalie J; Cordell, Paul A; Tang, Kar Yeun; Makova, Natallia; Yuldasheva, Nadira Y; Imrie, Helen; Viswambharan, Hema; Bruns, Alexander F; Cubbon, Richard M; Kearney, Mark T; Wheatcroft, Stephen B

    2017-02-01

    Low circulating levels of insulin-like growth factor binding protein 1 (IGFBP-1) are associated with insulin resistance and predict the development of type 2 diabetes. IGFBP-1 can affect cellular functions independently of IGF binding through an Arg-Gly-Asp (RGD) integrin-binding motif. Whether causal mechanisms underlie the favorable association of high IGFBP-1 levels with insulin sensitivity and whether these could be exploited therapeutically remain unexplored. We used recombinant IGFBP-1 and a synthetic RGD-containing hexapeptide in complementary in vitro signaling assays and in vivo metabolic profiling in obese mice to investigate the effects of IGFBP-1 and its RGD domain on insulin sensitivity, insulin secretion, and whole-body glucose regulation. The RGD integrin-binding domain of IGFBP-1, through integrin engagement, focal adhesion kinase, and integrin-linked kinase, enhanced insulin sensitivity and insulin secretion in C2C12 myotubes and INS-1 832/13 pancreatic β-cells. Both acute administration and chronic infusion of an RGD synthetic peptide to obese C57BL/6 mice improved glucose clearance and insulin sensitivity. These favorable effects on metabolic homeostasis suggest that the RGD integrin-binding domain of IGFBP-1 may be a promising candidate for therapeutic development in the field of insulin resistance. © 2017 by the American Diabetes Association.

  18. Resistance training improves skeletal muscle insulin sensitivity in elderly offspring of overweight and obese mothers.

    Science.gov (United States)

    Bucci, Marco; Huovinen, Ville; Guzzardi, Maria Angela; Koskinen, Suvi; Raiko, Juho R; Lipponen, Heta; Ahsan, Shaila; Badeau, Robert M; Honka, Miikka-Juhani; Koffert, Jukka; Savisto, Nina; Salonen, Minna K; Andersson, Jonathan; Kullberg, Joel; Sandboge, Samuel; Iozzo, Patricia; Eriksson, Johan G; Nuutila, Pirjo

    2016-01-01

    Maternal obesity predisposes offspring to adulthood morbidities, including type 2 diabetes. Type 2 diabetes and insulin resistance have been associated with shortened telomere length. First, we aimed to investigate whether or not maternal obesity influences insulin sensitivity and its relationship with leucocyte telomere length (LTL) in elderly women. Second, we tested whether or not resistance exercise training improves insulin sensitivity in elderly frail women. Forty-six elderly women, of whom 20 were frail offspring of lean/normal weight mothers (OLM, BMI ≤26.3 kg/m2) and 17 were frail offspring of overweight/obese mothers (OOM,BMI ≥28.1 kg/m2), were studied before and after a 4 month resistance training (RT) intervention. Muscle insulin sensitivity of glucose uptake was measured using 18F-fluoro-2-deoxyglucose and positron emission tomography with computed tomography during a hyperinsulinaemic–euglycaemic clamp. Muscle mass and lipid content were measured using magnetic resonance and LTL was measured using real-time PCR. The OOM group had lower thigh muscle insulin sensitivity compared with the OLM group (p=0.048) but similar whole body insulin sensitivity. RT improved whole body and skeletal muscle insulin sensitivity in the OOM group only (p=0.004 and p=0.013, respectively), and increased muscle mass in both groups (p insulin sensitivity (ρ ≥ 0.53; p ≤ 0.05). Individuals with shorter LTL showed a higher increase in skeletal muscle insulin sensitivity after training (ρ ≥ −0.61; p ≤ 0.05). Maternal obesity and having telomere shortening were associated with insulin resistance in adult offspring. A resistance exercise training programme may reverse this disadvantage among offspring of obese mothers. Trial registration: ClinicalTrials.gov NCT01931540.

  19. Use of the hyperinsulinemic euglycemic clamp to assess insulin sensitivity in guinea pigs: dose response, partitioned glucose metabolism, and species comparisons.

    Science.gov (United States)

    Horton, Dane M; Saint, David A; Owens, Julie A; Gatford, Kathryn L; Kind, Karen L

    2017-07-01

    The guinea pig is an alternate small animal model for the study of metabolism, including insulin sensitivity. However, only one study to date has reported the use of the hyperinsulinemic euglycemic clamp in anesthetized animals in this species, and the dose response has not been reported. We therefore characterized the dose-response curve for whole body glucose uptake using recombinant human insulin in the adult guinea pig. Interspecies comparisons with published data showed species differences in maximal whole body responses (guinea pig ≈ human guinea pig > human ≈ rat > mouse). In subsequent studies, we used concomitant d-[3-3H]glucose infusion to characterize insulin sensitivities of whole body glucose uptake, utilization, production, storage, and glycolysis in young adult guinea pigs at human insulin doses that produced approximately half-maximal (7.5 mU·min-1·kg-1) and near-maximal whole body responses (30 mU·min-1·kg-1). Although human insulin infusion increased rates of glucose utilization (up to 68%) and storage and, at high concentrations, increased rates of glycolysis in females, glucose production was only partially suppressed (~23%), even at high insulin doses. Fasting glucose, metabolic clearance of insulin, and rates of glucose utilization, storage, and production during insulin stimulation were higher in female than in male guinea pigs (P guinea pigs, allowing studies of regulation of insulin sensitivity in this species. Copyright © 2017 the American Physiological Society.

  20. The ORNL whole body counter

    Energy Technology Data Exchange (ETDEWEB)

    1988-01-01

    This report is a non-technical document intended to provide an individual about to undergo a whole-body radiation count with a general understanding of the counting procedure and with the results obtained. 9 figs. (TEM)

  1. Human whole body cold adaptation.

    NARCIS (Netherlands)

    Daanen, Hein A.M.; Van Marken Lichtenbelt, Wouter D.

    2016-01-01

    Reviews on whole body human cold adaptation generally do not distinguish between population studies and dedicated acclimation studies, leading to confusing results. Population studies show that indigenous black Africans have reduced shivering thermogenesis in the cold and poor cold induced

  2. Deletion of hepatic carbohydrate response element binding protein (ChREBP impairs glucose homeostasis and hepatic insulin sensitivity in mice

    Directory of Open Access Journals (Sweden)

    Tara Jois

    2017-11-01

    Conclusions: Overall, hepatic ChREBP is protective in regards to hepatic insulin sensitivity and whole body glucose homeostasis. Hepatic ChREBP action can influence other peripheral tissues and is likely essential in coordinating the body's response to different feeding states.

  3. Exercise training reverses the negative effects of chronic L-arginine supplementation on insulin sensitivity.

    Science.gov (United States)

    Salgueiro, Rafael Barrera; Gerlinger-Romero, Frederico; Guimarães-Ferreira, Lucas; de Castro Barbosa, Thais; Nunes, Maria Tereza

    2017-12-15

    L-Arginine has emerged as an important supplement for athletes and non-athletes in order to improve performance. Arginine has been extensively used as substrate for nitric oxide synthesis, leading to increased vasodilatation and hormonal secretion. However, the chronic consumption of arginine has been shown to impair insulin sensitivity. In the present study, we aimed to evaluate whether chronic arginine supplementation associated with exercise training would have a beneficial impact on insulin sensitivity. We, therefore, treated Wistar rats for 4weeks with arginine, associated or not with exercise training (treadmill). We assessed the somatotropic activation, by evaluating growth hormone (GH) gene expression and protein content in the pituitary, as well is GH concentration in the serum. Additionally, we evaluate whole-body insulin sensitivity, by performing an insulin tolerance test. Skeletal muscle morpho-physiological parameters were also assessed. Insulin sensitivity was impaired in the arginine-treated rats. However, exercise training reversed the negative effects of arginine. Arginine and exercise training increased somatotropic axis function, muscle mass and body weight gain. The combination arginine and exercise training further decreased total fat mass. Our results confirm that chronic arginine supplementation leads to insulin resistance, which can be reversed in the association with exercise training. We provide further evidence that exercise training is an important tool to improve whole-body metabolism. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. PACAP stimulates insulin secretion but inhibits insulin sensitivity in mice

    NARCIS (Netherlands)

    Filipsson, K; Pacini, G; Scheurink, AJW; Ahren, B

    Although pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates insulin secretion, its net influence on glucose homeostasis in vivo has not been established. We therefore examined the action of PACAP-27 and PACAP-38 on insulin secretion, insulin sensitivity, and glucose disposal as

  5. The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-09-01

    Conclusions: Treatment of obese mice with R419 improved skeletal muscle insulin sensitivity through a mechanism that is independent of skeletal muscle AMPK. R419 also increases exercise capacity and improves mitochondrial function in obese WT mice; effects that are diminished in the absence of skeletal muscle AMPK. These findings suggest that R419 may be a promising therapy for improving whole-body glucose homeostasis and exercise capacity.

  6. Hanford whole body counting manual

    Energy Technology Data Exchange (ETDEWEB)

    Palmer, H.E.; Rieksts, G.A.; Lynch, T.P.

    1990-06-01

    This document describes the Hanford Whole Body Counting Program as it is administered by Pacific Northwest Laboratory (PNL) in support of the US Department of Energy--Richland Operations Office (DOE-RL) and its Hanford contractors. Program services include providing in vivo measurements of internally deposited radioactivity in Hanford employees (or visitors). Specific chapters of this manual deal with the following subjects: program operational charter, authority, administration, and practices, including interpreting applicable DOE Orders, regulations, and guidance into criteria for in vivo measurement frequency, etc., for the plant-wide whole body counting services; state-of-the-art facilities and equipment used to provide the best in vivo measurement results possible for the approximately 11,000 measurements made annually; procedures for performing the various in vivo measurements at the Whole Body Counter (WBC) and related facilities including whole body counts; operation and maintenance of counting equipment, quality assurance provisions of the program, WBC data processing functions, statistical aspects of in vivo measurements, and whole body counting records and associated guidance documents. 16 refs., 48 figs., 22 tabs.

  7. Comparison of regional fat mass measurement by whole body DXA scans and anthropometric measures to predict insulin resistance in women with polycystic ovary syndrome and controls

    DEFF Research Database (Denmark)

    Glintborg, Dorte; Houborg Petersen, Maria; Ravn, Pernille

    2016-01-01

    mass to predict insulin resistance in patients with PCOS MATERIAL AND METHODS: The study was cross-sectional in an academic tertiary-care medical center in 167 premenopausal women with PCOS and 110 controls matched for ethnicity, BMI and age. Total and regional fat and lean body mass were assessed......00451568, NCT00145340 RESULTS: Women with PCOS had higher central fat mass (waist, Waist-hip ratio, and upper/lower fat ratio) compared to controls. In bivariate associations, the strongest associations were found between HOMA-IR and the fat mass measures trunk fat (r=0.59), waist (r=0.57) and BMI (r= 0.......56), all pWomen with PCOS were characterized by central obesity. Trunk fat, waist and BMI were the best predictors of HOMA-IR in PCOS, but only...

  8. Periodontal disease decreases insulin sensitivity and insulin signaling.

    Science.gov (United States)

    Colombo, Natalia H; Shirakashi, Daisy J; Chiba, Fernando Y; Coutinho, Maria Sara de Lima; Ervolino, Edilson; Garbin, Cléa Adas Saliba; Machado, Ubiratan Fabres; Sumida, Doris H

    2012-07-01

    The purpose of this study is to investigate whether local inflammatory events, such as periodontal disease, are able to increase tumor necrosis factor-alpha (TNF-α) plasmatic concentration and decrease insulin sensitivity and insulin signaling in non-diabetic rats. Forty-eight male Wistar rats (2 months old) were divided into two groups, with either ligature-induced periodontal disease (LPD) or control conditions (CN). Experiments were performed in both groups 28 days after ligature placement. Plasmatic concentration of glycemia and TNF-α (n = 10) were analyzed by the glucose oxidase and enzyme-linked immunosorbent assay method, respectively. Insulin sensitivity (n = 7) was measured using the insulin tolerance test. Insulin signal transduction (n = 7) was measured by pp185 tyrosine phosphorylation status in insulin-sensitive tissues using the Western blotting method. The LPD group showed decreased insulin sensitivity (P 0.05). TNF-α plasmatic concentration was higher in LPD rats compared to CN rats. In addition, a decrease in the pp185 tyrosine phosphorylation status was observed after insulin stimulus in both white adipose and skeletal muscle tissues of the LPD group compared with the CN group. LPD is able to cause alterations to both insulin signaling and insulin sensitivity, probably because of the elevation of TNF-α plasmatic concentration. Thus, the present results emphasize the importance of the prevention of local inflammatory diseases, such as periodontitis, to prevent diabetes mellitus.

  9. 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

  10. Salt sensitivity correlates positively with insulin sensitivity in healthy volunteers

    NARCIS (Netherlands)

    ter Maaten, JC; Voordouw, JJ; Bakker, SJL; Gans, ROB

    Background The aim of the study was to assess the relationship between insulin sensitivity and salt sensitivity in healthy subjects who display a wide range of insulin sensitivity. As a secondary objective, we assessed the relationship between salt sensitivity and the other characteristics of the

  11. 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.

  12. 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

  13. 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......It has become increasingly apparent that substrate metabolism is subject to gender-specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have...... a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole-body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual...

  14. Euglycemic clamp insulin sensitivity and longitudinal systolic blood pressure

    DEFF Research Database (Denmark)

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

    2013-01-01

    Insulin resistance may be an independent risk factor for the development of hypertension, but change in blood pressure (BP) over time has not been adequately studied in healthy individuals fully characterized for insulin sensitivity. In the Relationship between Insulin Sensitivity...

  15. 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 weig...... 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)......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...

  16. Microbial Modulation of Insulin Sensitivity

    NARCIS (Netherlands)

    Khan, Muhammad Tanweer; Nieuwdorp, Max; Bäckhed, Fredrik

    2014-01-01

    The gut microbiota has emerged as an integral factor that impacts host metabolism and has been suggested to play a vital role in metabolic diseases such as obesity, insulin resistance, type 2 diabetes, and cardiovascular disease. In humans, cross-sectional studies have identified microbiota profiles

  17. The evolution of whole-body imaging.

    LENUS (Irish Health Repository)

    Moran, Deirdre E

    2012-02-01

    This article reviews the evolution of whole-body imaging, discussing the history and development of radiography, nuclear medicine, computed tomography (CT), positron emission tomography (PET), combined PET-CT, and magnetic resonance imaging. The obstacles hindering progress toward whole-body imaging using each of these modalities, and the technical advances that were developed to overcome them, are reviewed. The effectiveness and the limitations of whole-body imaging with each of these techniques are also briefly discussed.

  18. Feasibility of differential phase contrast CT for whole body imaging

    Science.gov (United States)

    Li, Ke; Bevins, Nicholas B.; Zambelli, Joseph N.; Chen, Guang-Hong

    2012-07-01

    Phase contrast based imaging techniques have shown improved contrast in certain biological materials. This has led to an increased interest for the potential of preclinical and clinical imaging systems that incorporate phase sensitive imaging techniques. However, the interplay between the phase contrast mechanism and the so-called small-angle scattering or dark-field mechanism is often not considered. In this work we explore the potential for phase-sensitive whole body imaging by imaging a freshly euthanized specimen. The results suggest that when extrapolating phantom and ex vivo results to whole body imaging, one must consider the complex anatomy of the entire body and its effect on each contrast mechanism.

  19. 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...

  20. Increased serum resistin in elite endurance athletes with high insulin sensitivity.

    Science.gov (United States)

    Perseghin, G; Burska, A; Lattuada, G; Alberti, G; Costantino, F; Ragogna, F; Oggionni, S; Scollo, A; Terruzzi, I; Luzi, L

    2006-08-01

    Resistin is an adipokine associated with obesity and type 2 diabetes in animal models, but in humans its role remains uncertain. This study was undertaken to test whether serum resistin is related to insulin resistance and markers of low-grade inflammation in elite athletes taken as a model of extreme insulin sensitivity. SUBJECTS MATERIALS AND METHODS: In 23 elite athletes (sprinters, middle-distance and marathon runners) and in 72 sedentary men including lean and obese individuals with NGT, and obese individuals with IGT or new-onset type 2 diabetes, we assessed insulin sensitivity using a whole-body insulin-sensitivity index (WBISI) derived from a 3-h OGTT; energy homeostasis was also assessed by means of indirect calorimetry, along with circulating adipokines and low-grade pro-inflammatory cyto-chemokines. Professional athletes had increased WBISIs (prunners, but not in the sprinters when compared with the lean, young, sedentary individuals. Serum resistin concentration is increased in elite athletes, providing evidence against the notion that resistin levels reflect insulin resistance in humans, as seen in animal studies. Increased resistin was observed in aerobic-endurance, but not sustained-power athletes and this feature appeared to be independently associated with parameters of fatty acid metabolism.

  1. 3D whole body scanners revisited

    NARCIS (Netherlands)

    Daanen, H.A.M.; Haar, F.B. ter

    2013-01-01

    An overview of whole body scanners in 1998 (H.A.M. Daanen, G.J. Van De Water. Whole body scanners, Displays 19 (1998) 111-120) shortly after they emerged to the market revealed that the systems were bulky, slow, expensive and low in resolution. This update shows that new developments in sensing and

  2. α-linolenic acid supplementation prevents exercise-induced improvements in white adipose tissue mitochondrial bioenergetics and whole-body glucose homeostasis in obese Zucker rats.

    Science.gov (United States)

    Monaco, Cynthia M F; Proudfoot, Ross; Miotto, Paula M; Herbst, Eric A F; MacPherson, Rebecca E K; Holloway, Graham P

    2018-02-01

    While the underlying mechanisms in the development of insulin resistance remain inconclusive, metabolic dysfunction in both white adipose tissue (WAT) and skeletal muscle have been implicated in the process. Therefore, we investigated the independent and combined effects of α-linolenic acid (ALA) supplementation and exercise training on whole-body glucose homeostasis and mitochondrial bioenergetics within the WAT and skeletal muscle of obese Zucker rats. We randomly assigned obese Zucker rats to receive a control diet alone or supplemented with ALA and to remain sedentary or undergo exercise training for 4 weeks (CON-Sed, ALA-Sed, CON-Ex and ALA-Ex groups). Whole-body glucose tolerance was determined in response to a glucose load. Mitochondrial content and bioenergetics were examined in skeletal muscle and epididymal WAT (eWAT). Insulin sensitivity and cellular stress were assessed by western blot. Exercise training independently improved whole-body glucose tolerance as well as insulin-induced signalling in muscle and WAT. However, the consumption of ALA during exercise training prevented exercise-mediated improvements in whole-body glucose tolerance. ALA consumption did not influence exercise-induced adaptations within skeletal muscle, insulin sensitivity and mitochondrial bioenergetics. In contrast, within eWAT, ALA supplementation attenuated insulin signalling, decreased mitochondrial respiration and increased the fraction of electron leak to reactive oxygen species (ROS). These findings indicate that, in an obese rodent model, consumption of ALA attenuates the favourable adaptive changes of exercise training within eWAT, which consequently impacts whole-body glucose homeostasis. The direct translation to humans, however, remains to be determined.

  3. Strawberry and cranberry polyphenols improve insulin sensitivity in insulin-resistant, non-diabetic adults: a parallel, double-blind, controlled and randomised clinical trial.

    Science.gov (United States)

    Paquette, Martine; Medina Larqué, Ana S; Weisnagel, S J; Desjardins, Yves; Marois, Julie; Pilon, Geneviève; Dudonné, Stéphanie; Marette, André; Jacques, Hélène

    2017-02-01

    Plant-derived foods rich in polyphenols are associated with several cardiometabolic health benefits, such as reduced postprandial hyperglycaemia. However, their impact on whole-body insulin sensitivity using the hyperinsulinaemic-euglycaemic clamp technique remains under-studied. We aimed to determine the effects of strawberry and cranberry polyphenols (SCP) on insulin sensitivity, glucose tolerance, insulin secretion, lipid profile, inflammation and oxidative stress markers in free-living insulin-resistant overweight or obese human subjects (n 41) in a parallel, double-blind, controlled and randomised clinical trial. The experimental group consumed an SCP beverage (333 mg SCP) daily for 6 weeks, whereas the Control group received a flavour-matched Control beverage that contained 0 mg SCP. At the beginning and at the end of the experimental period, insulin sensitivity was assessed by a hyperinsulinaemic-euglycaemic clamp, and glucose tolerance and insulin secretion by a 2-h oral glucose tolerance test (OGTT). Insulin sensitivity increased in the SCP group as compared with the Control group (+0·9 (sem 0·5)×10-3 v. -0·5 (sem 0·5)×10-3 mg/kg per min per pmol, respectively, P=0·03). Compared with the Control group, the SCP group had a lower first-phase insulin secretion response as measured by C-peptide levels during the first 30 min of the OGTT (P=0·002). No differences were detected between the two groups for lipids and markers of inflammation and oxidative stress. A 6-week dietary intervention with 333 mg of polyphenols from strawberries and cranberries improved insulin sensitivity in overweight and obese non-diabetic, insulin-resistant human subjects but was not effective in improving other cardiometabolic risk factors.

  4. Opposite Regulation of Insulin Sensitivity by Dietary Lipid Versus Carbohydrate Excess.

    Science.gov (United States)

    Lundsgaard, Anne-Marie; Sjøberg, Kim A; Høeg, Louise D; Jeppesen, Jacob; Jordy, Andreas B; Serup, Annette K; Fritzen, Andreas M; Pilegaard, Henriette; Myrmel, Lene S; Madsen, Lise; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2017-10-01

    To understand the mechanisms in lipid-induced insulin resistance, a more physiological approach is to enhance fatty acid (FA) availability through the diet. Nine healthy men ingested two hypercaloric diets (in 75% excess of habitual caloric intake) for 3 days, enriched in unsaturated FA (78 energy % [E%] fat) (UNSAT) or carbohydrates (80 E% carbohydrate) (CHO) as well as a eucaloric control diet (CON). Compared with CON, the UNSAT diet reduced whole-body and leg glucose disposal during a hyperinsulinemic-euglycemic clamp, while decreasing hepatic glucose production. In muscle, diacylglycerol (DAG) and intramyocellular triacylglycerol were increased. The accumulated DAG was sn-1,3 DAG, which is known not to activate PKC, and insulin signaling was intact. UNSAT decreased PDH-E1α protein content and increased inhibitory PDH-E1α Ser(300) phosphorylation and FA oxidation. CHO increased whole-body and leg insulin sensitivity, while increasing hepatic glucose production. After CHO, muscle PDH-E1α Ser(300) phosphorylation was decreased, and glucose oxidation increased. After UNSAT, but not CHO, muscle glucose-6-phosphate content was 103% higher compared with CON during the clamp. Thus, PDH-E1α expression and covalent regulation, and hence the tricarboxylic acid cycle influx of pyruvate-derived acetyl-CoA relative to β-oxidation-derived acetyl-CoA, are suggested to impact on insulin-stimulated glucose uptake. Taken together, the oxidative metabolic fluxes of glucose and FA are powerful and opposite regulators of insulin action in muscle. © 2017 by the American Diabetes Association.

  5. Disclosing caffeine action on insulin sensitivity: effects on rat skeletal muscle.

    Science.gov (United States)

    Sacramento, Joana F; Ribeiro, Maria J; Yubero, Sara; Melo, Bernardete F; Obeso, Ana; Guarino, Maria P; Gonzalez, Constancio; Conde, Silvia V

    2015-04-05

    Caffeine, a non-selective adenosine antagonist, has distinct effects on insulin sensitivity when applied acutely or chronically. Herein, we investigated the involvement of adenosine receptors on insulin resistance induced by single-dose caffeine administration. Additionally, the mechanism behind adenosine receptor-mediated caffeine effects in skeletal muscle was assessed. The effect of the administration of caffeine, 8-cycle-1,3-dipropylxanthine (DPCPX, A1 antagonist), 2-(2-Furanyl)-7-(2-phenylethyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine (SCH58261, A2A antagonist) and 8-(4-{[(4-cyanophenyl)carbamoylmethyl]-oxy}phenyl)-1,3-di(n-propyl)xanthine (MRS1754, A2B antagonist) on whole-body insulin sensitivity was tested. Skeletal muscle Glut4,5'-AMP activated protein kinase (AMPK) and adenosine receptor protein expression were also assessed. The effect of A1 and A2B adenosine agonists on skeletal muscle glucose uptake was evaluated in vitro. Sodium nitroprussiate (SNP, 10nM), a nitric oxide (NO) donor, was used to evaluate the effect of NO on insulin resistance induced by adenosine antagonists. Acute caffeine decreased insulin sensitivity in a concentration dependent manner (Emax=55.54±5.37%, IC50=11.61nM), an effect that was mediated by A1 and A2B adenosine receptors. Additionally, acute caffeine administration significantly decreased Glut4, but not AMPK expression, in skeletal muscle. We found that A1, but not A2B agonists increased glucose uptake in skeletal muscle. SNP partially reversed DPCPX and MRS1754 induced-insulin resistance. Our results suggest that insulin resistance induced by acute caffeine administration is mediated by A1 and A2B adenosine receptors. Both Glut4 and NO seem to be downstream effectors involved in insulin resistance induced by acute caffeine. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Estimates of insulin sensitivity from the intravenous-glucose-modified-clamp test depend on suppression of lipolysis in type 2 diabetes: a randomised controlled trial.

    Science.gov (United States)

    Kahl, Sabine; Nowotny, Bettina; Piepel, Simon; Nowotny, Peter J; Strassburger, Klaus; Herder, Christian; Pacini, Giovanni; Roden, Michael

    2014-10-01

    The combined IVGTT-hyperinsulinaemic-euglycaemic clamp (Botnia clamp) allows the assessment of insulin secretion and sensitivity in one experiment. It remains unclear whether this clamp yields results comparable with those of the standard hyperinsulinaemic-euglycaemic clamp (SHEC) in diabetes patients. We hypothesised that the IVGTT induces responses affecting insulin sensitivity assessment. Of 22 randomised diet- or metformin-treated patients with well-controlled type 2 diabetes, 19 randomly underwent a Botnia clamp and an SHEC, spaced by 2 weeks, in one clinical research centre in a crossover study. The main outcomes were whole-body and hepatic insulin sensitivity as measured by the clamp and [6,6-(2)H2]glucose. Substrate utilisation was assessed from indirect calorimetry and beta cell function from insulin dynamics during IVGTT. The values of whole-body insulin sensitivity obtained from Botnia clamp and SHEC were correlated (r = 0.87, p clamp, but differed after IVGTT. The contribution of glucose oxidation to glucose disposal increased by 2.2 ± 0.3 and 1.2 ± 0.4 mg kg fat-free mass (FFM)(-1) min(-1) (Botnia and SHEC, p clamps correlated with individual variations of insulin sensitivity. The Botnia clamp provides similar estimates of insulin sensitivity as SHEC in patients with type 2 diabetes, but changes in NEFA during IVGTT may affect insulin sensitivity and thereby the discrimination between insulin-sensitive and insulin-resistant individuals. ClinicalTrials.gov NCT01397279 FUNDING: The study was funded by the Ministry of Science and Research of the State of North Rhine-Westphalia and the German Federal Ministry of Health, and supported in part by grants from the Federal Ministry for Research to the Centers for Diabetes Research, Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases and the Schmutzler-Stiftung.

  7. 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

  8. Gender differences in skeletal muscle substrate metabolism - molecular mechanisms and insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Anne-Marie eLundsgaard

    2014-11-01

    Full Text Available It has become increasingly apparent that substrate metabolism is subject to gender specific regulation, and the aim of this review is to outline the available evidence of molecular gender differences in glucose and lipid metabolism of skeletal muscle. Female sex has been suggested to have a favorable effect on glucose homeostasis, and the available evidence from hyperinsulinemic-euglycemic clamp studies is summarized to delineate whether there is a gender difference in whole body insulin sensitivity and in particular insulin-stimulated glucose uptake of skeletal muscle. Whether an eventual 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 in men and women. In particular, the molecular machinery for glucose and fatty acid oxidative and storage capacities in skeletal muscle and its implications for substrate utilization during metabolic situations of daily living are discussed, emphasizing their relevance for substrate choice in the fed and fasted state, and during periods of physical activity and recovery. Together, handling of carbohydrate and lipids and regulation of their utilization in skeletal muscle have implications for whole body glucose homeostasis in men and women. 17-β estradiol is the most important female sex hormone, and the identification of estradiol receptors in skeletal muscle has opened for a role in regulation of substrate metabolism. Also, higher levels of circulating adipokines as adiponectin and leptin in women and their implications for muscle metabolism will be considered.

  9. Do whole-body vibrations affect spatial hearing?

    Science.gov (United States)

    Frissen, Ilja; Guastavino, Catherine

    2014-01-01

    To assist the human operator, modern auditory interfaces increasingly rely on sound spatialisation to display auditory information and warning signals. However, we often operate in environments that apply vibrations to the whole body, e.g. when driving a vehicle. Here, we report three experiments investigating the effect of sinusoidal vibrations along the vertical axis on spatial hearing. The first was a free-field, narrow-band noise localisation experiment with 5- Hz vibration at 0.88 ms(-2). The other experiments used headphone-based sound lateralisation tasks. Experiment 2 investigated the effect of vibration frequency (4 vs. 8 Hz) at two different magnitudes (0.83 vs. 1.65 ms(-2)) on a left-right discrimination one-interval forced-choice task. Experiment 3 assessed the effect on a two-interval forced-choice location discrimination task with respect to the central and two peripheral reference locations. In spite of the broad range of methods, none of the experiments show a reliable effect of whole-body vibrations on localisation performance. We report three experiments that used both free-field localisation and headphone lateralisation tasks to assess their sensitivity to whole-body vibrations at low frequencies. None of the experiments show a reliable effect of either frequency or magnitude of whole-body vibrations on localisation performance.

  10. Lipid in Skeletal Muscle Myotubes is associated to the Donors’ Insulin Sensitivity and Physical Activity Phenotypes

    Science.gov (United States)

    Bajpeyi, Sudip; Myrland, Cassandra K.; Covington, Jeffrey D.; Obanda, Diana; Cefalu, William T.; Smith, Steven R.; Rustan, Arild C.; Ravussin, Eric

    2013-01-01

    Objective This study investigated the relationship between in-vitro lipid content in myotubes and in-vivo whole body phenotypes of the donors such as insulin sensitivity, intramyocellular lipids (IMCL), physical activity and oxidative capacity. Design and Methods Six physically active donors were compared to 6 sedentary lean and 6 T2DM. Lipid content was measured in tissues and myotubes by immunohistochemistry. Ceramides, triacylglycerols (TAGs) and diacylglycerols (DAGs) were measured by LC-MS-MS and GC-FID. Insulin sensitivity was measured by hyperinsulinemic-euglycemic clamp (80mU/min/m2), maximal mitochondrial capacity (ATPmax) by 31P-MRS, physical fitness by VO2max and physical activity level (PAL) by accelerometers. Results Myotubes cultured from physically active donors had higher lipid content (0.047±0.003 vs. 0.032±0.001 and 0.033±0.001AU; p<0.001) than myotubes from lean and T2DM donors. Lipid content in myotubes was not associated with IMCL in muscle tissue but importantly, correlated with in-vivo measures of ATPmax (r=0.74; p<0.001), insulin sensitivity (r=0.54; p<0.05), type-I fibers (r=0.50; p<0.05) and PAL (r=0.92; p<0.0001). DAGs and ceramides in myotubes were inversely associated with insulin sensitivity (r=−0.55, r=−0.73; p<0.05) and ATPmax (r=−0.74, r=−0.85; p<0.01). Conclusions These results indicate that cultured human myotubes can be used in mechanistic studies to study the in vitro impact of interventions on phenotypes such as mitochondrial capacity, insulin sensitivity, and physical activity. PMID:23818429

  11. Insulin sensitivity from preschool to school age in patients with severe obesity.

    Directory of Open Access Journals (Sweden)

    Melania Manco

    Full Text Available BACKGROUND: Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age. RESEARCH DESIGN AND METHODS: Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI, Insulinogenic Index (IGI; β-cell demand index (BCDI and Insulin Secretion-Sensitivity Index 2 (ISSI-2 were longitudinally estimated during the oral glucose tolerance test. RESULTS: After a median follow-up of 2.23 (1-4.52 y, obese patients showed significant decrease in WBISI (p<0.0001, and increase in fasting (p = 0.005 and 2 h glucose (2HG, p = 0.001. One child in preschool age and 4 school age children presented with 2HG between 7.8-11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R(2 = 0.309; p = 0.002; β = -0.556, ISSI-2 (R(2 = 0.465; p<0.0001; β = -0.682, and BMI z-score (R(2 = 0.246; p = 0.008; 0.496, respectively. CONCLUSIONS: In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation.

  12. Insulin resistance vs. hyperinsulinemia in hypertension: insulin regulation of Ca2+ transport and Ca(2+)-regulation of insulin sensitivity.

    Science.gov (United States)

    Zemel, M B

    1995-06-01

    Hypertension in obesity and insulin resistance has been attributed to insulin stimulation of sympathetic neural output and renal sodium retention. However, recent data demonstrates a significant vasodilatory effect of insulin and suggests that vascular smooth muscle resistance to this action may instead be the cause of hypertension in insulin resistance. This concept is supported by the observation that pharmacological amplification of peripheral insulin sensitivity results in reduced arterial pressure. Insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle relaxation, while these effects are blunted in obesity and insulin resistance. Insulin regulation of vasoconstriction and vascular relaxation appears to be secondary to regulation of intracellular Ca2+ ([Ca2+]i), as insulin attenuates both voltage- and receptor-mediated Ca2+ influx and stimulates both the transcription and activity of Ca(2+)-ATPase in vascular smooth muscle cells. Further, these effects are also blunted in insulin resistance. Although [Ca2+]i plays a poorly understood role in insulin signalling, increases beyond an optimal range results in impaired insulin sensitivity, possibly by Ca(2+)-inhibition of insulin-induced dephosphorylation of insulin-sensitive substrates. Consistent with this concept, ectopic overexpression of the agouti gene in the viable yellow (Avy) mouse results in increased skeletal myocyte [Ca2+]i. Accordingly, increased [Ca2+]i in primary insulin target tissues appears to result in peripheral insulin resistance which then results in aberrant regulation of vascular smooth muscle [Ca2+]i and increases in arterial pressure.

  13. 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 thei......-IR (homeostasis model assessment-insulin resistance) when calculated with M-values. CONCLUSIONS: The SPISE seems well suited to surrogate whole-body insulin sensitivity from inexpensive fasting single-point blood draw and BMI in white adolescents and adults....... 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......), 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...

  14. Insulin sensitizer prevents and ameliorates experimental type 1 diabetes.

    Science.gov (United States)

    Valitsky, Michael; Hoffman, Amnon; Unterman, Terry; Bar-Tana, Jacob

    2017-12-01

    Insulin-dependent type-1 diabetes (T1D) is driven by autoimmune β-cell failure, whereas systemic resistance to insulin is considered the hallmark of insulin-independent type-2 diabetes (T2D). In contrast to this canonical dichotomy, insulin resistance appears to precede the overt diabetic stage of T1D and predict its progression, implying that insulin sensitizers may change the course of T1D. However, previous attempts to ameliorate T1D in animal models or patients by insulin sensitizers have largely failed. Sensitization to insulin by MEthyl-substituted long-chain DICArboxylic acid (MEDICA) analogs in T2D animal models surpasses that of current insulin sensitizers, thus prompting our interest in probing MEDICA in the T1D context. MEDICA efficacy in modulating the course of T1D was verified in streptozotocin (STZ) diabetic rats and autoimmune nonobese diabetic (NOD) mice. MEDICA treatment normalizes overt diabetes in STZ diabetic rats when added on to subtherapeutic insulin, and prevents/delays autoimmune T1D in NOD mice. MEDICA treatment does not improve β-cell insulin content or insulitis score, but its efficacy is accounted for by pronounced total body sensitization to insulin. In conclusion, potent insulin sensitizers may counteract genetic predisposition to autoimmune T1D and amplify subtherapeutic insulin into an effective therapeutic measure for the treatment of overt T1D. Copyright © 2017 the American Physiological Society.

  15. 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...

  16. Substantial replacement of lactose with fat in a high-lactose milk replacer diet increases liver fat accumulation but does not affect insulin sensitivity in veal calves.

    Science.gov (United States)

    Pantophlet, A J; Gerrits, W J J; Vonk, R J; van den Borne, J J G C

    2016-12-01

    In veal calves, the major portion of digestible energy intake originates from milk replacer (MR), with lactose and fat contributing approximately 45 and 35%, respectively. In veal calves older than 4 mo, prolonged high intakes of MR may lead to problems with glucose homeostasis and insulin sensitivity, ultimately resulting in sustained insulin resistance, hepatic steatosis, and impaired animal performance. The contribution of each of the dietary energy sources (lactose and fat) to deteriorated glucose homeostasis and insulin resistance is currently unknown. Therefore, an experiment was designed to compare the effects of a high-lactose and a high-fat MR on glucose homeostasis and insulin sensitivity in veal calves. Sixteen male Holstein-Friesian calves (120±2.8kg of BW) were assigned to either a high-lactose (HL) or a high-fat (HF) MR for 13 consecutive weeks. After at least 7 wk of adaptation, whole-body insulin sensitivity and insulin secretion were assessed by euglycemic-hyperinsulinemic and hyperglycemic clamps, respectively. Postprandial blood samples were collected to assess glucose, insulin, and triglyceride responses to feeding, and 24-h urine was collected to quantify urinary glucose excretion. At the end of the trial, liver and muscle biopsies were taken to assess triglyceride contents in these tissues. Long-term exposure of calves to HF or HL MR did not affect whole-body insulin sensitivity (averaging 4.2±0.5×10(-2) [(mg/kg∙min)/(μU/mL)]) and insulin secretion. Responses to feeding were greater for plasma glucose and tended to be greater for plasma insulin in HL calves than in HF calves. Urinary glucose excretion was substantially higher in HL calves (75±13g/d) than in HF calves (21±6g/d). Muscle triglyceride content was not affected by treatment and averaged 4.5±0.6g/kg, but liver triglyceride content was higher in HF calves (16.4±0.9g/kg) than in HL calves (11.2±0.7g/kg), indicating increased hepatic fat accumulation. We conclude that

  17. 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.

  18. Rac1 in muscle is dispensable for improved insulin action after exercise in mice

    DEFF Research Database (Denmark)

    Sylow, Lykke; Møller, Lisbeth Liliendal Valbjørn; D'Hulst, Gommaar

    2016-01-01

    . However, whether Rac1 is involved in mediating enhanced insulin sensitivity after an acute bout of exercise is unresolved. To address this question we investigated post exercise whole body (insulin tolerance test) as well as muscle (insulin-stimulated 2DG transport in isolated soleus muscle) insulin...

  19. 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

  20. 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

  1. Towards whole-body fluorescence imaging in humans.

    Directory of Open Access Journals (Sweden)

    Sophie K Piper

    Full Text Available Dynamic near-infrared fluorescence (DNIF whole-body imaging of small animals has become a popular tool in experimental biomedical research. In humans, however, the field of view has been limited to body parts, such as rheumatoid hands, diabetic feet or sentinel lymph nodes. Here we present a new whole-body DNIF-system suitable for adult subjects. We explored whether this system (i allows dynamic whole-body fluorescence imaging and (ii can detect modulations in skin perfusion. The non-specific fluorescent probe indocyanine green (ICG was injected intravenously into two subjects, and fluorescence images were obtained at 5 Hz. The in- and out-flow kinetics of ICG have been shown to correlate with tissue perfusion. To validate the system, skin perfusion was modulated by warming and cooling distinct areas on the chest and the abdomen. Movies of fluorescence images show a bolus passage first in the face, then in the chest, abdomen and finally in the periphery (~10, 15, 20 and 30 seconds, respectively. When skin perfusion is augmented by warming, bolus arrives about 5 seconds earlier than when the skin is cooled and perfusion decreased. Calculating bolus arrival times and spatial fitting of basis time courses extracted from different regions of interest allowed a mapping of local differences in subcutaneous skin perfusion. This experiment is the first to demonstrate the feasibility of whole-body dynamic fluorescence imaging in humans. Since the whole-body approach demonstrates sensitivity to circumscribed alterations in skinperfusion, it may be used to target autonomous changes in polyneuropathy and to screen for peripheral vascular diseases.

  2. Diuretics prevent thiazolidinedione-induced cardiac hypertrophy without compromising insulin-sensitizing effects in mice.

    Science.gov (United States)

    Chang, Cherng-Shyang; Tsai, Pei-Jane; Sung, Junne-Ming; Chen, Ju-Yi; Ho, Li-Chun; Pandya, Kumar; Maeda, Nobuyo; Tsai, Yau-Sheng

    2014-02-01

    Much concern has arisen regarding critical adverse effects of thiazolidinediones (TZDs), including rosiglitazone and pioglitazone, on cardiac tissue. Although TZD-induced cardiac hypertrophy (CH) has been attributed to an increase in plasma volume or a change in cardiac nutrient preference, causative roles have not been established. To test the hypothesis that volume expansion directly mediates rosiglitazone-induced CH, mice were fed a high-fat diet with rosiglitazone, and cardiac and metabolic consequences were examined. Rosiglitazone treatment induced volume expansion and CH in wild-type and PPARγ heterozygous knockout (Pparg(+/-)) mice, but not in mice defective for ligand binding (Pparg(P465L/+)). Cotreatment with the diuretic furosemide in wild-type mice attenuated rosiglitazone-induced CH, hypertrophic gene reprogramming, cardiomyocyte apoptosis, hypertrophy-related signal activation, and left ventricular dysfunction. Similar changes were observed in mice treated with pioglitazone. The diuretics spironolactone and trichlormethiazide, but not amiloride, attenuated rosiglitazone effects on volume expansion and CH. Interestingly, expression of glucose and lipid metabolism genes in the heart was altered by rosiglitazone, but these changes were not attenuated by furosemide cotreatment. Importantly, rosiglitazone-mediated whole-body metabolic improvements were not affected by furosemide cotreatment. We conclude that releasing plasma volume reduces adverse effects of TZD-induced volume expansion and cardiac events without compromising TZD actions in metabolic switch in the heart and whole-body insulin sensitivity. Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. 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...... = 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....... Training increased lean body mass (estimate [95% confidence interval] 0.5 [0.2-0.9] kg, P ...

  4. week whole-body vibration training

    African Journals Online (AJOL)

    The results in this study therefore indicate that WBVT could be used as an ffective training modality to improve cardiovascular function in adult males. As such, WBVT is recommended for use in sedentary adults given its benefits. Keywords: Whole-body vibration training, heart rate, blood pressure, cardiovascular responses.

  5. 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.

  6. Murine High Specificity/Sensitivity Competitive Europium Insulin Autoantibody Assay

    Science.gov (United States)

    Babaya, Naru; Liu, Edwin; Miao, DongMei; Li, Marcella; Yu, Liping

    2009-01-01

    Abstract Background Most insulin autoantibody assays for both human and animal models are in a radioassay format utilizing 125I-insulin, but despite the radioassay format international workshops have documented difficulty in standardization between laboratories. There is thus a need for simpler assay formats that do not utilize radioactivity, yet retain the high specificity and sensitivity of radioassays. Methods To establish an easier enzyme-linked immunosorbent assay (ELISA) for insulin autoantibodies of non-obese diabetic (NOD) mice, we used an ELISA format, competition with unlabeled insulin, europium-avidin, and time-resolved fluorescence detection (competitive europium insulin autoantibody assay). Results The competitive europium assay of insulin autoantibodies when applied to sera from NOD mice had high sensitivity and specificity (92% sensitivity, 100% specificity) compared to our standard insulin autoantibody radioassay (72% sensitivity, 100% specificity) in analyzing blind workshop sera. It is noteworthy that though the assay has extremely high sensitivity for murine insulin autoantibodies and utilizes human insulin as target autoantigen, human sera with high levels of insulin autoantibodies are not detected. Conclusions Our results clearly indicate that low levels of insulin autoantibodies can be detected in an ELISA-like format. Combining a europium-based ELISA with competition with fluid-phase autoantigen can be applicable to many autoantigens to achieve high specificity and sensitivity in an ELISA format. PMID:19344197

  7. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity.

    Science.gov (United States)

    Carrasco-Benso, Maria P; Rivero-Gutierrez, Belen; Lopez-Minguez, Jesus; Anzola, Andrea; Diez-Noguera, Antoni; Madrid, Juan A; Lujan, Juan A; Martínez-Augustin, Olga; Scheer, Frank A J L; Garaulet, Marta

    2016-09-01

    In humans, insulin sensitivity varies according to time of day, with decreased values in the evening and at night. Mechanisms responsible for the diurnal variation in insulin sensitivity are unclear. We investigated whether human adipose tissue (AT) expresses intrinsic circadian rhythms in insulin sensitivity that could contribute to this phenomenon. Subcutaneous and visceral AT biopsies were obtained from extremely obese participants (body mass index, 41.8 ± 6.3 kg/m(2); 46 ± 11 y) during gastric-bypass surgery. To assess the rhythm in insulin signaling, AKT phosphorylation was determined every 4 h over 24 h in vitro in response to different insulin concentrations (0, 1, 10, and 100 nM). Data revealed that subcutaneous AT exhibited robust circadian rhythms in insulin signaling (P circadian rhythms were detected in visceral AT (P = 0.643). Here, we demonstrate the relevance of the time of the day for how sensitive AT is to the effects of insulin. Subcutaneous AT shows an endogenous circadian rhythm in insulin sensitivity that could provide an underlying mechanism for the daily rhythm in systemic insulin sensitivity.-Carrasco-Benso, M. P., Rivero-Gutierrez, B., Lopez-Minguez, J., Anzola, A., Diez-Noguera, A., Madrid, J. A., Lujan, J. A., Martínez-Augustin, O., Scheer, F. A. J. L., Garaulet, M. Human adipose tissue expresses intrinsic circadian rhythm in insulin sensitivity. © FASEB.

  8. Artemisia extracts activate PPARγ, promote adipogenesis, and enhance insulin sensitivity in adipose tissue of obese mice.

    Science.gov (United States)

    Richard, Allison J; Burris, Thomas P; Sanchez-Infantes, David; Wang, Yongjun; Ribnicky, David M; Stephens, Jacqueline M

    2014-01-01

    Studies have shown that the inability of adipose tissue to properly expand during the obese state or respond to insulin can lead to metabolic dysfunction. Artemisia is a diverse group of plants that has a history of medicinal use. The aim of this study was to examine the ability of ethanolic extracts of Artemisia scoparia (SCO) and Artemisia santolinifolia (SAN) to modulate adipocyte development in cultured adipocytes and white adipose tissue (WAT) function in vivo using a mouse model of diet-induced obesity. Adipogenesis was assessed using Oil Red O staining and immunoblotting. A nuclear receptor specificity assay was used to examine the specificity of SCO- and SAN-induced PPARγ activation. C57BL/6J mice, fed a high-fat diet, were gavaged with saline, SCO, or SAN for 2 wk. Whole-body insulin sensitivity was examined using insulin tolerance tests. WAT depots were assessed via immunoblotting for markers of insulin action and adipokine production. We established that SCO and SAN were highly specific activators of PPARγ and did not activate other nuclear receptors. After a 1-wk daily gavage, SCO- and SAN-treated mice had lower insulin-induced glucose disposal rates than control mice. At the end of the 2-wk treatment period, SCO- and SAN-treated mice had enhanced insulin-responsive Akt serine-473 phosphorylation and significantly decreased monocyte chemotactic protein-1 levels in visceral WAT compared with control mice; these differences were depot specific. Moreover, plasma adiponectin levels were increased following SCO treatment. Overall, these studies demonstrate that extracts from two Artemisia species can have metabolically favorable effects on adipocytes and WAT. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. 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.

  10. PPAR-α agonism improves whole body and muscle mitochondrial fat oxidation, but does not alter intracellular fat concentrations in burn trauma children in a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Dohm G Lynis

    2007-04-01

    Full Text Available Abstract Background Insulin resistance is often associated with increased levels of intracellular triglycerides, diacylglycerol and decreased fat β-oxidation. It was unknown if this relationship was present in patients with acute insulin resistance induced by trauma. Methods A double blind placebo controlled trial was conducted in 18 children with severe burn injury. Metabolic studies to assess whole body palmitate oxidation and insulin sensitivity, muscle biopsies for mitochondrial palmitate oxidation, diacylglycerol, fatty acyl Co-A and fatty acyl carnitine concentrations, and magnetic resonance spectroscopy for muscle and liver triglycerides were compared before and after two weeks of placebo or PPAR-α agonist treatment. Results Insulin sensitivity and basal whole body palmitate oxidation as measured with an isotope tracer increased significantly (P = 0.003 and P = 0.004, respectively after PPAR-α agonist treatment compared to placebo. Mitochondrial palmitate oxidation rates in muscle samples increased significantly after PPAR-α treatment (P = 0.002. However, the concentrations of muscle triglyceride, diacylglycerol, fatty acyl CoA, fatty acyl carnitine, and liver triglycerides did not change with either treatment. PKC-θ activation during hyper-insulinemia decreased significantly following PPAR-α treatment. Conclusion PPAR-α agonist treatment increases palmitate oxidation and decreases PKC activity along with reduced insulin sensitivity in acute trauma, However, a direct link between these responses cannot be attributed to alterations in intracellular lipid concentrations.

  11. Radiation exposure in whole body CT screening.

    Science.gov (United States)

    Suresh, Pamidighantam; Ratnam, S V; Rao, K V J

    2011-04-01

    Using a technology that "takes a look" at people's insides and promises early warnings of cancer, cardiac disease, and other abnormalities, clinics and medical imaging facilities nationwide are touting a new service for health conscious people: "Whole body CT screening" this typically involves scanning the body from the chin to below the hips with a form of x-ray imaging that produces cross-sectional images. In USA direct-to-consumer marketing of whole body CT is occurring today in many metropolitan areas. Free standing CT screening centres are being sited in shopping malls and other high density public areas, and these centres are being advertised in the electronic and print media. In this context the present article discussed the pros and cons of having such centres in India with the advent of multislice CT leading to fast scan times.

  12. Cardiovascular control during whole body exercise

    DEFF Research Database (Denmark)

    Volianitis, Stefanos; Secher, Niels H.

    2016-01-01

    It has been considered whether during whole body exercise the increase in cardiac output is large enough to support skeletal muscle blood flow. This review addresses four lines of evidence for a flow limitation to skeletal muscles during whole body exercise. First, even though during exercise...... the blood flow achieved by the arms is lower than that achieved by the legs (=160 vs. 385 mlmin1100 g1), the muscle mass that can be perfused with such flow is limited by the capacity to increase cardiac output (42 l/min, highest recorded value). Secondly, activation of the exercise pressor reflex during...... fatiguing work with one muscle group limits flow to other muscle groups. Another line of evidence comes from evaluation of regional blood flow during exercise where there is a discrepancy between flow to a muscle group when it is working exclusively and when it works together with other muscles. Finally...

  13. Cerebral blood flow links insulin resistance and baroreflex sensitivity.

    Directory of Open Access Journals (Sweden)

    John P Ryan

    Full Text Available Insulin resistance confers risk for diabetes mellitus and associates with a reduced capacity of the arterial baroreflex to regulate blood pressure. Importantly, several brain regions that comprise the central autonomic network, which controls the baroreflex, are also sensitive to the neuromodulatory effects of insulin. However, it is unknown whether peripheral insulin resistance relates to activity within central autonomic network regions, which may in turn relate to reduced baroreflex regulation. Accordingly, we tested whether resting cerebral blood flow within central autonomic regions statistically mediated the relationship between insulin resistance and an indirect indicator of baroreflex regulation; namely, baroreflex sensitivity. Subjects were 92 community-dwelling adults free of confounding medical illnesses (48 men, 30-50 years old who completed protocols to assess fasting insulin and glucose levels, resting baroreflex sensitivity, and resting cerebral blood flow. Baroreflex sensitivity was quantified by measuring the magnitude of spontaneous and sequential associations between beat-by-beat systolic blood pressure and heart rate changes. Individuals with greater insulin resistance, as measured by the homeostatic model assessment, exhibited reduced baroreflex sensitivity (b = -0.16, p < .05. Moreover, the relationship between insulin resistance and baroreflex sensitivity was statistically mediated by cerebral blood flow in central autonomic regions, including the insula and cingulate cortex (mediation coefficients < -0.06, p-values < .01. Activity within the central autonomic network may link insulin resistance to reduced baroreflex sensitivity. Our observations may help to characterize the neural pathways by which insulin resistance, and possibly diabetes mellitus, relates to adverse cardiovascular outcomes.

  14. Insulin sensitivity and secretory status of a healthy malay population.

    Science.gov (United States)

    Al-Mahmood, Abu Kholdun; Ismail, Aziz Al-Safi; Rashid, Faridah Abdul; Wan Bebakar, Wan Mohamad

    2006-07-01

    Insulin insensitivity is a common finding in several metabolic disorders including glucose intolerance, dyslipidemia, hyperuricemia and hypertension. Most of the previous studies on insulin sensitivity were performed on diabetic or obese population. So our knowledge about insulin sensitivity of healthy population remains limited. Rising prevalence of obesity, diabetes and metabolic syndrome is a serious issue in Malaysia and some other rapidly developing countries. So it is important to look at the insulin sensitivity status of healthy Malaysian subjects and to compare it in future with those of diabetic, obese or metabolic syndrome patients. In this study we sampled subjects who were independent of confounding factors such as obesity (including abdominal obesity), hypertension and glucose intolerance (diabetes, IGT or IFG) which may influence insulin sensitivity. Fasting plasma glucose, fasting insulin and lipid profile were determined. Insulin sensitivity and secretory status were calculated using the homeostasis model assessment (HOMA) software (HOMA%S, HOMA%B and HOMA-IR). The insulin sensitivity (HOMA%S) of healthy Malay subjects aged between 30-60 years was 155.17%, HOMA-IR was 1.05 and HOMA%B was 116.65% (values adjusted for age, sex, BMI and waist circumference). It was seen that non-obese Malaysians can prevent age related lowering of insulin sensitivity if they can retain their BMI within limit.

  15. 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 determine if bone turnover markers predict changes in insulin secretion and sensitivity. The study population encompassed 576 non-diabetic adult men with normal glucose tolerance (NGT; n=503) or impaired glucose regulation (IGR; n=73). Baseline markers of bone resorption (CTX) and formation (P1NP) were......, baseline bone turnover markers were neither associated with insulin sensitivity (assessed using hyperinsulinaemic euglycaemic clamp and OGTT) nor with insulin secretion capacity (based on IVGTT and OGTT) at baseline or at follow-up. Although inverse associations between fasting glucose and markers of bone...

  16. Reducing whole body vibration in forklift drivers.

    Science.gov (United States)

    Motmans, R

    2012-01-01

    Forklift drivers in warehouses are often exposed to whole body vibration (WBV) during the total day. There is however an association between working as a forklift operator and the development of low back pain. In this study the exposure to WBV was measured in five forklift drivers who performed a standardised order picking task during 10 minutes. The effect of driving surface (uneven concrete vs. new flat concrete), driving speed (15 km/h vs. 8 km/h) and seat suspension (mechanical suspension vs. air suspension) was investigated. Improving the driving surface was the most effective preventive measure by reducing the whole body vibration with 39%, from 1.14 to 0.69 m/s2. Lowering the speed limit resulted in a reduction of WBV with 26% (1.05 vs. 0.78 m/s2). An air suspension seat was 22% more effective compared to mechanical suspension (1.02 vs. 0.80 m/s2). On uneven concrete an air suspension seat performed even better by reducing the WBV by 29% (1.33 vs. 0.95 m/s2). A combination of a new driving surface, limiting the maximum speed and the introduction of an air suspension seat reduced the whole body vibrations below the action limit of 0.5 m/s2 as mentioned in the European directive. None of the interventions were effective enough on their own.

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

    Science.gov (United States)

    Bird, Stephen R; Hawley, John A

    2016-01-01

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

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

    Science.gov (United States)

    Bird, Stephen R; Hawley, John A

    2016-01-01

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

  19. Indanylacetic acids as PPAR-delta activator insulin sensitizers.

    Science.gov (United States)

    Wickens, Philip; Zhang, Chengzhi; Ma, Xin; Zhao, Qian; Amatruda, John; Bullock, William; Burns, Michael; Cantin, Louis-David; Chuang, Chih-Yuan; Claus, Thomas; Dai, Miao; Dela Cruz, Fernando; Dickson, David; Ehrgott, Frederick J; Fan, Dongping; Heald, Sarah; Hentemann, Martin; Iwuagwu, Christiana I; Johnson, Jeffrey S; Kumarasinghe, Ellalahewage; Ladner, David; Lavoie, Rico; Liang, Sidney; Livingston, James N; Lowe, Derek; Magnuson, Steve; Mannelly, Gretchen; Mugge, Ingo; Ogutu, Herbert; Pleasic-Williams, Susan; Schoenleber, Robert W; Shapiro, Jeff; Shelekhin, Tatiana; Sweet, Laurel; Town, Christopher; Tsutsumi, Manami

    2007-08-01

    A series of indane acetic acid derivatives were prepared which show a spectrum of activity as insulin sensitizers and PPAR-alpha and PPAR-delta ligands. In vivo data are presented for insulin sensitizers with selectivity for PPAR-delta over PPAR-alpha.

  20. 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

  1. Effects of acute exercise and training on insulin binding to monocytes and insulin sensitivity in vivo.

    Science.gov (United States)

    Koivisto, V A; Soman, V R; Defronzo, R; Felig, P

    1980-01-01

    Insulin binding to monocytes was studied in well-trained long distance runners and in sedentary control subjects in the resting state and after 3 h cycle ergometer exercise at 40% of maximal aerobic power. In addition, in previously untrained subjects we examined the effect of 6 weeks of training on insulin binding to monocytes and insulin sensitivity in vivo. In the athletes at rest, insulin binding to monocytes was 69% higher than in controls (p less than 0.01), and correlated with maximal aerobic power (r = 9.63, p less than 0.05). The rise in insulin binding in the athletes was due to an increase in binding capacity rather than a change in binding affinity. During exercise, insulin binding fell in athletes by 31% (p less than 0.025) in contrast to a 35% rise observed in control subjects (p less than 0.01). As compared to controls, the athletes had a lower respiratory exchange ratio and a smaller decline in plasma glucose during exercise. In previously untrained subjects, physical training resulted in a 35% rise in insulin binding to monocytes (p less than 0.02). The rise in binding was due mainly to an increase in binding capacity. Insulin mediated glucose uptake (as measured by insulin clamp technique) also rose by 30% after physical training (p less than 0.01). The rise in insulin sensitivity was proportional to the improvement in physical fitness (r = 0.81, p less than 0.05). These findings indicate that (a) elevated insulin binding may contribute to the enhanced insulin sensitivity observed after physical training, (b) a fall in insulin binding in athletes during acute exercise may contribute to a greater shift from carbohydrate to fat utilization during exercise in athletes as compared to sedentary controls. These data suggest that physical training may provide a means of reversing or ameliorating abnormalities in insulin binding and sensitivity in insulin resistant states, such as obesity or maturity onset diabetes.

  2. Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion

    Directory of Open Access Journals (Sweden)

    Vishal A. Salunkhe

    2016-08-01

    Full Text Available Statins are beneficial in the treatment of cardiovascular disease (CVD, but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND and high fat diet (HFD with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca2+ signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.

  3. 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.

  4. Low ethanol consumption increases insulin sensitivity in Wistar rats

    Directory of Open Access Journals (Sweden)

    D.T. Furuya

    2003-01-01

    Full Text Available Several human studies suggest that light-to-moderate alcohol consumption is associated with enhanced insulin sensitivity, but these studies are not free of conflicting results. To determine if ethanol-enhanced insulin sensitivity could be demonstrated in an animal model, male Wistar rats were fed a standard chow diet and received drinking water without (control or with different ethanol concentrations (0.5, 1.5, 3, 4.5 and 7%, v/v for 4 weeks ad libitum. Then, an intravenous insulin tolerance test (IVITT was performed to determine insulin sensitivity. Among the ethanol groups, only the 3% ethanol group showed an increase in insulin sensitivity based on the increase of the plasma glucose disappearance rate in the IVITT (30%, P<0.05. In addition, an intravenous glucose tolerance test (IVGTT was performed in control and 3% ethanol animals. Insulin sensitivity was confirmed in 3% ethanol rats based on the reduction of insulin secretion in the IVGTT (35%, P<0.05, despite the same glucose profile. Additionally, the 3% ethanol treatment did not impair body weight gain or plasma aspartate aminotransferase and alanine aminotransferase activities. Thus, the present study established that 3% ethanol in the drinking water for 4 weeks in normal rats is a model of increased insulin sensitivity, which can be used for further investigations of the mechanisms involved.

  5. Whole-body intravoxel incoherent motion imaging

    Energy Technology Data Exchange (ETDEWEB)

    Filli, Lukas; Wurnig, Moritz C.; Eberhardt, Christian; Guggenberger, Roman; Boss, Andreas [University Hospital Zurich, Department of Radiology, Zurich (Switzerland); Luechinger, Roger [University and ETH Zurich, Institute of Biomedical Technology, Zurich (Switzerland)

    2015-07-15

    To investigate the technical feasibility of whole-body intravoxel incoherent motion (IVIM) imaging. Whole-body MR images of eight healthy volunteers were acquired at 3T using a spin-echo echo-planar imaging sequence with eight b-values. Coronal parametrical whole-body maps of diffusion (D), pseudodiffusion (D*), and the perfusion fraction (F{sub p}) were calculated. Image quality was rated qualitatively by two independent radiologists, and inter-reader reliability was tested with intra-class correlation coefficients (ICCs). Region of interest (ROI) analysis was performed in the brain, liver, kidney, and erector spinae muscle. Depiction of anatomic structures was rated as good on D maps and good to fair on D* and F{sub p} maps. Exemplary mean D (10{sup -3} mm{sup 2}/s), D* (10{sup -3} mm{sup 2}/s) and F{sub p} (%) values (± standard deviation) of the renal cortex were as follows: 1.7 ± 0.2; 15.6 ± 6.5; 20.9 ± 4.4. Inter-observer agreement was ''substantial'' to ''almost perfect'' (ICC = 0.80 - 0.92). The coefficient of variation of D* was significantly lower with the proposed algorithm compared to the conventional algorithm (p < 0.001), indicating higher stability. The proposed IVIM protocol allows computation of parametrical maps with good to fair image quality. Potential future clinical applications may include characterization of widespread disease such as metastatic tumours or inflammatory myopathies. (orig.)

  6. Role of AMPK in Regulating Muscle Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kjøbsted, Rasmus

    in response to exercise and contraction. It is considered an important sensor of cellular energy-fuel status and fulfills the purpose of regulating energy-fuel homeostasis. Based on this, the aim of the present PhD was to investigate the involvement of AMPK in regulating insulin sensitivity following acute...... signaling in skeletal muscle of type 2 diabetic patients in response to exercise. Interestingly, we observe that AMPK activity and phosphorylation of TBC1D4 Ser318, Ser341 and Ser704 are increased 3 hours into exercise recovery - a time point when post-exercise improvements in muscle insulin sensitivity...... that induces a half-maximal biological response (e.g., glucose uptake). Accordingly, the concentration of insulin that induces half-maximal glucose uptake is reduced with increased insulin sensitivity. Skeletal muscle from both healthy and type 2 diabetic individuals display enhanced muscle insulin sensitivity...

  7. 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

    significant depressive symptoms was not related to either OGIS [standardized beta (β) -0.033; P=0.24] or beta-cell glucose sensitivity (β -0.007; P=0.82). Significant depressive symptoms were related to decreased beta-cell rate sensitivity (odds ratio for significant depressive symptoms of the lowest vs...... 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...... 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...

  8. Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes

    DEFF Research Database (Denmark)

    Xie, Weijia; Wood, Andrew R; Lyssenko, Valeriya

    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....

  9. 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...... 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....

  10. 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.

  11. Adipokines and Hepatic Insulin Resistance

    Science.gov (United States)

    Hassan, Waseem

    2013-01-01

    Obesity is a major risk factor for insulin resistance and type 2 diabetes. Adipose tissue is now considered to be an active endocrine organ that secretes various adipokines such as adiponectin, leptin, resistin, tumour necrosis factor-α, and interleukin-6. Recent studies have shown that these factors might provide a molecular link between increased adiposity and impaired insulin sensitivity. Since hepatic insulin resistance plays the key role in the whole body insulin resistance, clarification of the regulatory processes about hepatic insulin resistance by adipokines in rodents and human would seem essential in order to understand the mechanism of type 2 diabetes and for developing novel therapeutic strategies to treat it. PMID:23762871

  12. 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 utilization......) and were instructed to maintain a eucaloric diet. A euglycemic-hyperinsulinemic clamp (40 mU/m(2)/min) with [6,6-(2)H]-glucose was used to determine peripheral and hepatic insulin sensitivity. Non-oxidative glucose disposal and metabolic flexibility (insulin-stimulated respiratory quotient [RQ] minus...... fasting RQ) were also assessed. Glucose incremental area under the curve was calculated from the OGTT (iAUCOGTT). Exercise increased clamp-derived peripheral and hepatic insulin sensitivity more in adults with IFG or IGT alone than IFG+IGT (P...

  13. Effect of training intensity on insulin sensitivity evaluated by insulin tolerance test

    NARCIS (Netherlands)

    H.A. Keizer; K. Backx; M.F. Mensink; dr. Lars B. Borghouts

    1999-01-01

    This research article shows that a high intensity exercise program compared to a low intensity exercise program of the same session duration and frequency, increases insulin sensitivity to a larger extend in healthy subjects. It also shows that the short insulin tolerance test can be used to detect

  14. Short communication: Supplementation of fructo-oligosaccharides does not improve insulin sensitivity in heavy veal calves fed different sources of carbohydrates.

    Science.gov (United States)

    Pantophlet, A J; Gilbert, M S; Gerrits, W J J; Vonk, R J

    2017-11-01

    Heavy veal calves (4-6 mo old) often develop problems with insulin sensitivity. This could lead to metabolic disorders and impaired animal growth performance. Studies in various animal species have shown that the supplementation of short-chain fructo-oligosaccharides (scFOS) can improve insulin sensitivity. We therefore studied the effects of scFOS supplementation on insulin sensitivity in heavy veal calves. Forty male Holstein-Friesian calves (BW = 190 ± 2.9 kg; age = 162 ± 1.4 d at the start of the trial) were fed either a control milk replacer (MR) diet or a diet in which one-third of the lactose was replaced by glucose, fructose, or glycerol for 10 wk prior to the start of the trial. At the start of the trial, calves were subjected to a frequently sampled intravenous glucose tolerance test to assess whole-body insulin sensitivity (muscle and hepatic insulin sensitivity). Calves within each dietary treatment group were ranked based on their insulin sensitivity value. Half of the calves received scFOS (12 mg/kg of BW) with the MR for 6 wk (supplementation was equally distributed over the insulin sensitivity range). Subsequently, a second frequently sampled intravenous glucose tolerance test was conducted to assess the effect of scFOS. In addition, fasting plasma levels of glucose, insulin, triglycerides, and cholesterol were determined to calculate the quantitative insulin sensitivity check index and triglyceride:high-density lipoprotein cholesterol ratio (fasting indicators of insulin sensitivity). Whole-body insulin sensitivity was low at the start of the trial and remained low in all groups [1.0 ± 0.1 and 0.8 ± 0.1 (mU/L)-1 · min-1 on average, respectively]. Supplementation of scFOS did not improve insulin sensitivity in any of the treatment groups. The quantitative insulin sensitivity check index and the triglyceride:high-density lipoprotein cholesterol ratio also did not differ between scFOS and non-scFOS calves and averaged 0.326 ± 0.003 and 0.088

  15. 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.

  16. 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...

  17. Insulin resistance in type 1 diabetes mellitus.

    Science.gov (United States)

    Kaul, Kirti; Apostolopoulou, Maria; Roden, Michael

    2015-12-01

    For long the presence of insulin resistance in type 1 diabetes has been questioned. Detailed metabolic analyses revealed 12%-61% and up to 20% lower whole-body (skeletal muscle) and hepatic insulin sensitivity in type 1 diabetes, depending on the population studied. Type 1 diabetes patients feature impaired muscle adenosine triphosphate (ATP) synthesis and enhanced oxidative stress, predominantly relating to hyperglycemia. They may also exhibit abnormal fasting and postprandial glycogen metabolism in liver, while the role of hepatic energy metabolism for insulin resistance remains uncertain. Recent rodent studies point to tissue-specific differences in the mechanisms underlying insulin resistance. In non-obese diabetic mice, increased lipid availability contributes to muscle insulin resistance via diacylglycerol/protein kinase C isoforms. Furthermore, humans with type 1 diabetes respond to lifestyle modifications or metformin by 20%-60% increased whole-body insulin sensitivity, likely through improvement in both glycemic control and oxidative phosphorylation. Intensive insulin treatment and islet transplantation also increase but fail to completely restore whole-body and hepatic insulin sensitivity. In conclusion, insulin resistance is a feature of type 1 diabetes, but more controlled trials are needed to address its contribution to disease progression, which might help to optimize treatment and reduce comorbidities. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 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.

  19. Insulin sensitivity predicts brain network connectivity following a meal.

    Science.gov (United States)

    Ryan, John P; Karim, Helmet T; Aizenstein, Howard J; Helbling, Nicole L; Toledo, Frederico G S

    2018-01-12

    There is converging evidence that insulin plays a role in food-reward signaling in the brain and has effects on enhancing cognition. Little is known about how these effects are altered in individuals with insulin resistance. The present study was designed to identify the relationships between insulin resistance and functional brain connectivity following a meal. Eighteen healthy adults (7 male, 11 female, age: 41-57 years-old) completed a frequently-sampled intravenous glucose tolerance test to quantify insulin resistance. On separate days at least one week apart, a resting state functional magnetic resonance imaging scan was performed: once after a mixed-meal and once after a 12-h fast. Seed-based resting state connectivity of the caudate nucleus and eigenvector centrality were used to identify relationships between insulin resistance and functional brain connectivity. Individuals with greater insulin resistance displayed stronger connectivity within reward networks following a meal suggesting insulin was less able to suppress reward. Insulin resistance was negatively associated with eigenvector centrality in the dorsal anterior cingulate cortex following a meal. These data suggest that individuals with less sensitivity to insulin may fail to shift brain networks away from reward and toward cognitive control following a meal. This altered feedback loop could promote overeating and obesity. Copyright © 2018. Published by Elsevier Inc.

  20. 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

    Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption of t....... 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.......Lipid metabolism plays an important role in glucose homeostasis under normal and pathological conditions. In adipocytes, skeletal muscle, and pancreatic beta-cells, lipids are mobilized from acylglycerides by the hormone-sensitive lipase (HSL). Here, the consequences of a targeted disruption...... 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...

  1. Decreased acylcarnitine content improves insulin sensitivity in experimental mice models of insulin resistance.

    Science.gov (United States)

    Liepinsh, Edgars; Makrecka-Kuka, Marina; Makarova, Elina; Volska, Kristine; Svalbe, Baiba; Sevostjanovs, Eduards; Grinberga, Solveiga; Kuka, Janis; Dambrova, Maija

    2016-11-01

    The important pathological consequences of insulin resistance arise from the detrimental effects of accumulated long-chain fatty acids and their respective acylcarnitines. The aim of this study was to test whether exercise combined with decreasing the content of long-chain acylcarnitines represents an effective strategy to improve insulin sensitivity in diabetes. We used a novel compound, 4-[ethyl(dimethyl)ammonio]butanoate (methyl-GBB), treatment and exercise to decrease acylcarnitine contents in the plasma and muscles in the insulin resistance models of high fat diet (HFD) fed C57BL/6 mice and db/db mice. The methyl-GBB treatment induced a substantial decrease in all acylcarnitine concentrations in both fed and fasted states as well as when it was combined with exercise. In the HFD fed mice methyl-GBB treatment improved both glucose and insulin tolerance. Methyl-GBB administration, exercise and the combination of both improved insulin sensitivity and reduced blood glucose levels in db/db mice. Methyl-GBB administration and the combination of the drug and exercise activated the PPARα/PGC1α signaling pathway and stimulated the corresponding target gene expression. Insulin insensitivity in db/db mice was not induced by significantly increased fatty acid metabolism, while increased insulin sensitivity by both treatments was not related to decreased fatty acid metabolism in muscles. The pharmacologically reduced long-chain acylcarnitine content represents an effective strategy to improve insulin sensitivity. The methyl-GBB treatment and lifestyle changes via increased physical activity for one hour a day have additive insulin sensitizing effects in db/db mice. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Effect of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy men.

    Science.gov (United States)

    González-Ortiz, Manuel; Pascoe-González, Sara; Kam-Ramos, Angélica M; Martínez-Abundis, Esperanza

    2005-01-01

    The purpose of this study is to identify the effect of a low dose of tequila on homocysteine, insulin secretion, insulin sensitivity, and metabolic profile in healthy young men. An open clinical trial was carried out in eight healthy nonobese, young male volunteers. The study was divided in two phases. The first one evaluated metabolic changes, including insulin secretion and sensitivity due to acute administration of 30 ml of straight tequila. The second phase of the study evaluated metabolic effects due to the daily administration of 30 ml of tequila during 30 days. There were no significant metabolic changes after the single oral administration of 30 ml of straight tequila. After the administration of tequila during 30 days, a significant increase in homocysteine levels and a tendency to increase the glucose concentration and to decrease the insulin sensitivity were found. Detrimental metabolic changes were observed with the daily administration of 30 ml of tequila during 30 days.

  3. 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

    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...... 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 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...

  4. 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.

  5. 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 periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

  6. Whole body interaction with public displays

    CERN Document Server

    Walter, Robert

    2017-01-01

    This book develops valuable new approaches to digital out-of-home media and digital signage in urban environments. It offers solutions for communicating interactive features of digital signage to passers-by. Digital out-of-home media and digital signage screens are becoming increasingly interactive thanks to touch input technology and gesture recognition. To optimize their conversion rate, interactive public displays must 1) attract attention, 2) communicate to passers-by that they are interactive, 3) explain the interaction, and 4) provide a motivation for passers-by to interact. This book highlights solutions to problems 2 and 3 above. The focus is on whole-body interaction, where the positions and orientations of users and their individual body parts are captured by specialized sensors (e.g., depth cameras). The book presents revealing findings from a field study on communicating interactivity, a laboratory on analysing visual attention, a field study on mid-air gestures, and a field study on using mid-air...

  7. Morning Circadian Misalignment during Short Sleep Duration Impacts Insulin Sensitivity.

    Science.gov (United States)

    Eckel, Robert H; Depner, Christopher M; Perreault, Leigh; Markwald, Rachel R; Smith, Mark R; McHill, Andrew W; Higgins, Janine; Melanson, Edward L; Wright, Kenneth P

    2015-11-16

    Short sleep duration and circadian misalignment are hypothesized to causally contribute to health problems including obesity, diabetes, metabolic syndrome, heart disease, mood disorders, cognitive impairment, and accidents. Here, we investigated the influence of morning circadian misalignment induced by an imposed short nighttime sleep schedule on impaired insulin sensitivity, a precursor to diabetes. Imposed short sleep duration resulted in morning wakefulness occurring during the biological night (i.e., circadian misalignment)-a time when endogenous melatonin levels were still high indicating the internal circadian clock was still promoting sleep and related functions. We show the longer melatonin levels remained high after wake time, insulin sensitivity worsened. Overall, we find a simulated 5-day work week of 5-hr-per-night sleep opportunities and ad libitum food intake resulted in ∼20% reduced oral and intravenous insulin sensitivity in otherwise healthy men and women. Reduced insulin sensitivity was compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels during sleep loss. Furthermore, we find that transitioning from the imposed short sleep schedule to 9-hr sleep opportunities for 3 days restored oral insulin sensitivity to baseline, but 5 days with 9-hr sleep opportunities was insufficient to restore intravenous insulin sensitivity to baseline. These findings indicate morning wakefulness and eating during the biological night is a novel mechanism by which short sleep duration contributes to metabolic dysregulation and suggests food intake during the biological night may contribute to other health problems associated with short sleep duration. Copyright © 2015 Elsevier Ltd. All rights reserved.

  8. Role of rapid sequence whole-body MRI screening in SDH-associated hereditary paraganglioma families.

    Science.gov (United States)

    Jasperson, Kory W; Kohlmann, Wendy; Gammon, Amanda; Slack, Heidi; Buchmann, Luke; Hunt, Jason; Kirchhoff, Anne C; Baskin, Henry; Shaaban, Akram; Schiffman, Joshua D

    2014-06-01

    Patients with germline mutations in one of the SDH genes are at substantially increased risk of developing paragangliomas, pheochromocytomas (pheos), and other tumors (all combined referred to as SDH-related tumors). However, limited data exist on screening in SDH mutation carriers and no studies have evaluated whole-body MRI as a screening tool in asymptomatic patients. This was a single-center observational study. We evaluated the results of screening in 37 SDH carriers who underwent 45 whole-body MRIs and 47 biochemical tests. Screening included annual biochemical testing (catecholamines, metanephrines and chromogranin A) and biennial or annual rapid sequence whole-body MRI from the base of the skull to the pelvis beginning at age 10 years old. Six tumors (paragangliomas of the organ of Zuckerkandl, the aortocaval/vas deferens, of the carotid body times three, and a renal cell carcinoma) were diagnosed in five patients. In total, 13.5 % of all patients screened were diagnosed with SDH-related tumors. Whole-body MRI missed one tumor, while biochemical testing was normal in five patients with SDH-related tumors. The sensitivity of whole-body MRI was 87.5 % and the specificity was 94.7 %, while the sensitivity of biochemical testing was 37.5 % and the specificity was 94.9 %. Whole-body MRI had a higher sensitivity for SDH-related tumors than biochemical testing in patients undergoing screening due to their SDHB or SDHC mutation status. Whole-body MRI reduces radiation exposure compared to computed tomography scan and time compared to dedicated MRI of the head/neck, thorax, and abdomen/pelvis.

  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. Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy.

    Science.gov (United States)

    Magnussen, Line V; Glintborg, Dorte; Hermann, Pernille; Hougaard, David M; Højlund, Kurt; Andersen, Marianne

    2016-10-01

    To evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy. We conducted a randomized, double-blind, placebo-controlled study in 39 men aged 50-70 years with BioT levels testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole-body dual-energy X-ray absorptiometry scans. Whole-body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic-hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (β) represent the placebo-controlled mean effect of intervention. LBM (β = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (β = -1.3 kg, p = 0.009), fat mass trunk (β = -0.7 kg, p = 0.043), fat mass legs (β = -0.7 kg, p = 0.025), fat mass arms (β = -0.3 kg, p = 0.001), and HDL cholesterol (β = -0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin-stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin-stimulated rates of EGP, lipid- and glucose-oxidation were unaltered after TRT. TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged. © 2016 John Wiley & Sons Ltd.

  11. THE NEUROPHYSIOLOGICAL EFFECTS OF WHOLE BODY VIBRATION TRAINING

    OpenAIRE

    KOÇ, Gözde; K. Alparslan ERMAN

    2012-01-01

    Whole body vibration training, the person’s entire body on a platform, creates a vibration that may affect the muscles and bones. Despite the vibration used of massage and treatment since ancient times, it was used as a training method in recent years and became very popular and has attracted the attention of researchers. Whole body vibration training used both sport science with the aim to improve performance and in the fields of medicine for sports therapy. Whole body vibration training bri...

  12. Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion.

    Science.gov (United States)

    Salunkhe, Vishal A; Mollet, Inês G; Ofori, Jones K; Malm, Helena A; Esguerra, Jonathan L S; Reinbothe, Thomas M; Stenkula, Karin G; Wendt, Anna; Eliasson, Lena; Vikman, Jenny

    2016-08-01

    Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca(2+) signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  13. Insulin sensitivity in Chinese ovo-lactovegetarians compared with omnivores.

    Science.gov (United States)

    Kuo, C-S; Lai, N-S; Ho, L-T; Lin, C-L

    2004-02-01

    To compare the insulin sensitivity indices between Chinese vegetarians and omnivores. The study included 36 healthy volunteers (vegetarian, n=19; omnivore, n=17) who had normal fasting plasma glucose levels. Each participant completed an insulin suppression test. We compared steady-state plasma glucose (SSPG), fasting insulin, the homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and beta-cell function (HOMA %beta) between the groups. We also tested the correlation of SSPG with years on a vegetarian diet. The omnivore subjects were younger than the vegetarians (55.7+/-3.7 vs 58.6+/-3.6 year of age, P=0.022). There was no difference between the two groups in sex, blood pressure, renal function tests and lipid profiles. The omnivores had higher serum uric acid levels than vegetarians (5.25+/-0.84 vs 4.54+/-0.75 mg/dl, P=0.011). The results of the indices were different between omnivores and vegetarians (SSPG (mean+/-s.d.) 105.4+/-10.2 vs 80.3+/-11.3 mg/dl, Pvs 3.02+/-1.19 microU/ml, P=0.004; HOMA-IR, 6.75+/-1.31 vs 4.78+/-2.07, P=0.002; HOMA %S, 159.2+/-31.7 vs 264.3+/-171.7%, P=0.018) except insulin secretion index, HOMA %beta (65.6+/-18.0 vs 58.6+/-14.8%, P=0.208). We found a clear linear relation between years on a vegetarian diet and SSPG (r=-0.541, P=0.017). The vegetarians were more insulin sensitive than the omnivore counterparts. The degree of insulin sensitivity appeared to be correlated with years on a vegetarian diet.

  14. Quantification of interstitial fluid on whole body CT: comparison with whole body autopsy.

    Science.gov (United States)

    Lo Gullo, Roberto; Mishra, Shelly; Lira, Diego A; Padole, Atul; Otrakji, Alexi; Khawaja, Ranish Deedar Ali; Pourjabbar, Sarvenaz; Singh, Sarabjeet; Shepard, Jo-Anne O; Digumarthy, Subba R; Kalra, Mannudeep K; Stone, James R

    2015-12-01

    Interstitial fluid accumulation can occur in pleural, pericardial, and peritoneal spaces, and subcutaneous tissue planes. The purpose of the study was to assess if whole body CT examination in a postmortem setting could help determine the presence and severity of third space fluid accumulation in the body. Our study included 41 human cadavers (mean age 61 years, 25 males and 16 females) who had whole-body postmortem CT prior to autopsy. All bodies were maintained in the morgue in the time interval between death and autopsy. Two radiologists reviewed the whole-body CT examinations independently to grade third space fluid in the pleura, pericardium, peritoneum, and subcutaneous space using a 5-point grading system. Qualitative CT grading for third space fluid was correlated with the amount of fluid found on autopsy and the quantitative CT fluid volume, estimated using a dedicated software program (Volume, Syngo Explorer, Siemens Healthcare). Moderate and severe peripheral edema was seen in 16/41 and 7/41 cadavers respectively. It is not possible to quantify anasarca at autopsy. Correlation between imaging data for third space fluid and the quantity of fluid found during autopsy was 0.83 for pleural effusion, 0.4 for pericardial effusion and 0.9 for ascites. The degree of anasarca was significantly correlated with the severity of ascites (p < 0.0001) but not with pleural or pericardial effusion. There was strong correlation between volumetric estimation and qualitative grading for anasarca (p < 0.0001) and pleural effusion (p < 0.0001). Postmortem CT can help in accurate detection and quantification of third space fluid accumulation. The quantity of ascitic fluid on postmortem CT can predict the extent of anasarca.

  15. [How to measure insulin sensitivity in clinical practice?].

    Science.gov (United States)

    Rabasa-Lhoret, R; Laville, M

    2001-04-01

    Insulin resistance is common and cluster with glucose intolerance, dyslipidaemia and high blood pressure,. in type 2 diabetes mellitus it play a key role in the occurence of hyperglycemia. The importance of the insulin-resistant phenotype for the assessment of cardiovascular risk and response to intervention is increasingly being recognized. Therefore there is a need for accurate, reproducible and simple methods for measuring insulin resistance in vivo. The euglycemic hyperinsulinemic clamp is currently the best available standard technique but is not suitable for clinical practice. Thus, numerous index for insulin resistance estimation from fasting or post-load OGTT glycemia and insulinemia have been proposed. Although their simplicity is an obvious advantage, their application is subject to numerous limitations. The choice of the method to evaluate insulin sensitivity thus depend on objectives and available means. For clinical research, euglycemic clamp is the gold standard. In the case of epidemiologic studies, validated models like HOMA model are suitable. Finally in clinical practice, for type 2 diabetic patients, evaluation of insulin resistance should be made from clinical and biological context eventually associated with an estimation of respectives roles of insulinopenia and insulin resistance with a validated index like the HOMA model.

  16. Spectroscopic study of the interaction of insulin and its aptamer – sensitive optical detection of insulin

    Energy Technology Data Exchange (ETDEWEB)

    Verdian-Doghaei, A.; Housaindokht, M.R., E-mail: housain@um.ac.ir

    2015-03-15

    The binding of insulin to the insulin binding aptamer (IBA) was investigated with different spectroscopy techniques (UV/vis absorption, fluorescence, resonance light-scattering spectra (RLS), synchronous fluorescence, and three-dimensional fluorescence). The thermodynamic parameters (K{sub b}, ΔH, ΔG, and ΔS) of the insulin–IBA complex were further investigated by temperature-dependent fluorescence measurement over the range of 25–37 °C. The results of synchronous fluorescence, resonance light scattering (RLS) and three-dimensional fluorescence spectra showed that IBA would alter the structure of insulin. Folding of the dual-labeled insulin binding aptamer, FL-IBA, carrying 6-carboxyfluorescein (FAM) and 6-carboxytetramethylrhodamine (TAMRA) labels at termini of the insulin binding aptamer (IBA), into G-quadruplex leading to the contact quenching occurs as a result of the formation of a nonfluorescent complex between donor and acceptor. Significant fluorescent signal change when FL-IBA was bound to insulin is attributed to a conformational change in FL-IBA from a loose random coil to a compact G-quadruplex. Based on fluorescence quenching of IBA folding, a simple and sensitive insulin aptamer-based biosensor in the range of 2–70 nM was proposed. - Highlights: • The binding parameters were gotten from contact quenching data. • The binding of IBA induced some microenvironment and conformational changes in insulin. • The van der Waals interactions or hydrogen bonds play a major role on this binding. • A simple and sensitive insulin aptamer-based biosensor was proposed.

  17. Improvements in insulin sensitivity are blunted by subclinical hypothyroidism.

    Science.gov (United States)

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

    2009-02-01

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

  18. Whole body vibration improves body mass, flexibility and strength in ...

    African Journals Online (AJOL)

    Whole body vibration improves body mass, flexibility and strength in previously sedentary adults. Abstract. Objectives. This study aimed to determine the effectiveness of whole body vibration (WBV) training for promoting health- related physical fitness in sedentary adults. Design. A non-randomised sampling technique was ...

  19. Multi-Party, Whole-Body Interactions in Mathematical Activity

    Science.gov (United States)

    Ma, Jasmine Y.

    2017-01-01

    This study interrogates the contributions of multi-party, whole-body interactions to students' collaboration and negotiation of mathematics ideas in a task setting called walking scale geometry, where bodies in interaction became complex resources for students' emerging goals in problem solving. Whole bodies took up overlapping roles representing…

  20. High-dose metformin (420mg/kg daily p.o.) increases insulin sensitivity but does not affect neointimal thickness in the rat carotid balloon injury model of restenosis.

    Science.gov (United States)

    Guo, June; Pereira, Troy J; Dalvi, Prasad; Yeung, Lucy Shu Nga; Swain, Nathan; Breen, Danna M; Lam, Loretta; Dolinsky, Vernon W; Giacca, Adria

    2017-03-01

    Our laboratory has shown that insulin's effect to decrease neointimal thickness after arterial injury is greatly diminished in insulin resistant conditions. Thus, in these conditions, a better alternative to insulin could be to use an insulin sensitizing agent. Metformin, the most commonly prescribed insulin sensitizer, has a cardiovascular protective role. Therefore, the objective of this study was to investigate the potential benefit of metformin on neointimal area after arterial injury in a rat model of restenosis. Rats fed with either normal or high fat diet and treated with or without oral metformin (420mg/kg daily) underwent carotid balloon injury. Effects of metformin on clamp-determined insulin sensitivity, vessel AMPK (AMP-activated protein kinase) phosphorylation (activation marker) and neointimal area were evaluated. Metformin increased insulin sensitivity, but did not affect neointimal thickness in either the normal fat or high fat diet-fed rats. Furthermore, metformin activated AMPK in uninjured but not in injured vessels. Similarly, 10mmol/L metformin inhibited proliferation and activated AMPK in smooth muscle cells of uninjured but not injured vessels, whereas 2mmol/L metformin did not have any effect. In rats, metformin does not decrease neointimal growth after arterial injury, despite increasing whole body insulin sensitivity. Copyright © 2016. Published by Elsevier Inc.

  1. Gα13 ablation reprograms myofibers to oxidative phenotype and enhances whole-body metabolism.

    Science.gov (United States)

    Koo, Ja Hyun; Kim, Tae Hyun; Park, Shi-Young; Joo, Min Sung; Han, Chang Yeob; Choi, Cheol Soo; Kim, Sang Geon

    2017-10-02

    Skeletal muscle is a key organ in energy homeostasis owing to its high requirement for nutrients. Heterotrimeric G proteins converge signals from cell-surface receptors to potentiate or blunt responses against environmental changes. Here, we show that muscle-specific ablation of Gα13 in mice promotes reprogramming of myofibers to the oxidative type, with resultant increases in mitochondrial biogenesis and cellular respiration. Mechanistically, Gα13 and its downstream effector RhoA suppressed nuclear factor of activated T cells 1 (NFATc1), a chief regulator of myofiber conversion, by increasing Rho-associated kinase 2-mediated (Rock2-mediated) phosphorylation at Ser243. Ser243 phosphorylation of NFATc1 was reduced after exercise, but was higher in obese animals. Consequently, Gα13 ablation in muscles enhanced whole-body energy metabolism and increased insulin sensitivity, thus affording protection from diet-induced obesity and hepatic steatosis. Our results define Gα13 as a switch regulator of myofiber reprogramming, implying that modulations of Gα13 and its downstream effectors in skeletal muscle are a potential therapeutic approach to treating metabolic diseases.

  2. Zataria multiflora increases insulin sensitivity and PPARγ gene expression in high fructose fed insulin resistant rats

    Directory of Open Access Journals (Sweden)

    Abbas Mohammadi

    2014-04-01

    Full Text Available   Objective(s:In insulin resistance, the insulin action in liver, muscles and adipocytes decreases and result in hyperglycemia, dyslipidemia and hyperinsulinemia. In this study we evaluate the effect of Zataria multiflora extract on insulin sensitivity in high fructose fed insulin resistant rats, since this extract was shown antihyperglycemic effect in streptozotocin induced diabetes in rats.   Materials and Methods:Experimental rats were fed with high fructose diet for 6 weeks and then were treated with Z. multiflora extractor a pioglitazone solution for 2 weeks. Blood and tissue samples were collected for analysis at the end of two weeks. Blood glucose, serum level of triglyceride and cholesterol were measured by auto analyzer. Insulin and adiponectin levels were assayed by enzyme-linked immunosorbent assay (ELISA method. Plasma free fatty acids profile was studied by gas chromatography.  Peroxisome proliferator activated receptor (PPAR.γ and Glucose transporter type 4 (GLUT.4 gene expressions were assessed by real time polymerase chain reaction (PCR and western blotting. Results: Animals were treated by Z. multiflora extractshowed insulin (43±11pmol/l, adiponectin (5.3±0.5 μg/ml, glucose (144±9.8 mg/dl, and triglyceride (120±10 mg/dl levels significantly improved as compare with the control group [insulin (137±34 pmol/l, adiponectin (3.9±0.15 μg/ml, glucose (187±15mg/dl, and triglycerides (217±18 mg/dl]. PPARγ protein level, also significantly increased in Zataria multiflora treated group. Conclusion: This study demonstrates the beneficial effects of Zataria multiflora extract on insulin resistance in rats fed with a high-fructose diet through at least three mechanisms including direct insulin like effect, increasing in adiponectin and of PPARγ protein expression.   

  3. Insulin Sensitivity and Mortality Risk Estimation in Patients with Type ...

    African Journals Online (AJOL)

    2016-07-15

    Jul 15, 2016 ... Akinlade et al.: Insulin sensitivity and mortality risk estimation in diabetics. 772. Nigerian Journal of Clinical Practice ¦ Volume 20 ¦ Issue 6 ¦ June 2017 albuminuria.[16] It is, however, known that albuminuria is an important biomarker to predict micro and macrovascular complications and mortality in patients.

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

    Directory of Open Access Journals (Sweden)

    Rosa Lauretta

    2016-01-01

    Full Text Available 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.

  5. 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

  6. The impact of kidney transplantation on insulin sensitivity

    DEFF Research Database (Denmark)

    Jørgensen, Morten Buhl; Hornum, Mads; van Hall, Gerrit

    2017-01-01

    To investigate the impact of kidney transplantation (KTx) on insulin sensitivity affecting glucose metabolism. 9 nondiabetic patients awaiting living donor KTx were examined prior to transplantation with an oral glucose tolerance test and a 3-h hyperinsulinaemic-euglycaemic clamp. The clamp...

  7. Whole-body imaging of the musculoskeletal system: the value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Schmidt, Gerwin P.; Reiser, Maximilian F.; Baur-Melnyk, Andrea [University Hospitals Munich/Grosshadern, LMU, Institute of Clinical Radiology, Munich (Germany)

    2007-12-15

    In clinical practice various modalities are used for whole-body imaging of the musculoskeletal system, including radiography, bone scintigraphy, computed tomography, magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT). Multislice CT is far more sensitive than radiographs in the assessment of trabecular and cortical bone destruction and allows for evaluation of fracture risk. The introduction of combined PET-CT scanners has markedly increased diagnostic accuracy for the detection of skeletal metastases compared with PET alone. The unique soft-tissue contrast of MRI enables for precise assessment of bone marrow infiltration and adjacent soft tissue structures so that alterations within the bone marrow may be detected before osseous destruction becomes apparent in CT or metabolic changes occur on bone scintigraphy or PET scan. Improvements in hard- and software, including parallel image acquisition acceleration, have made high resolution whole-body MRI clinically feasible. Whole-body MRI has successfully been applied for bone marrow screening of metastasis and systemic primary bone malignancies, like multiple myeloma. Furthermore, it has recently been proposed for the assessment of systemic bone diseases predisposing for malignancy (e.g., multiple cartilaginous exostoses) and muscle disease (e.g., muscle dystrophy). The following article gives an overview on state-of-the-art whole-body imaging of the musculoskeletal system and highlights present and potential future applications, especially in the field of whole-body MRI. (orig.)

  8. c-Abl inhibition mitigates diet-induced obesity through improving insulin sensitivity of subcutaneous fat in mice.

    Science.gov (United States)

    Wu, Rong; Sun, Jian-Guang; Wang, Ji-Qiu; Li, Binhua; Liu, Qingsong; Ning, Guang; Jin, Wanzhu; Yuan, Zengqiang

    2017-05-01

    High-energy diets are among the main causes of the global epidemic of metabolic disorders, including obesity and type 2 diabetes. The mechanisms of high-energy-diet-induced metabolic disorders are complex and largely unknown. The non-receptor tyrosine kinase c-Abl plays an important role in adipogenesis in vitro but its role in vivo in the regulation of metabolism is still elusive. Hence, we sought to address the role of c-Abl in diet-induced obesity and obesity-associated insulin resistance. The expression of c-Abl in different fat tissues from obese humans or mice fed a high-fat diet (HFD) were first analysed by western blotting and quantitative PCR. We employed conditional deletion of the c-Abl gene (also known as Abl1) in adipose tissue using Fabp4-Cre and 6-week-old mice were fed with either a chow diet (CD) or an HFD. Age-matched wild-type mice were treated with the c-Abl inhibitor nilotinib or with vehicle and exposed to either CD or HFD, followed by analysis of body mass, fat mass, glucose and insulin tolerance. Histological staining, ELISA and biochemical analysis were used to clarify details of changes in physiology and molecular signalling. c-Abl was highly expressed in subcutaneous fat from obese humans and HFD-induced obese mice. Conditional knockout of c-Abl in adipose tissue improved insulin sensitivity and mitigated HFD-induced body mass gain, hyperglycaemia and hyperinsulinaemia. Consistently, treatment with nilotinib significantly reduced fat mass and improved insulin sensitivity in HFD-fed mice. Further biochemical analyses suggested that c-Abl inhibition improved whole-body insulin sensitivity by reducing HFD-triggered insulin resistance and increasing adiponectin in subcutaneous fat. Our findings define a new biological role for c-Abl in the regulation of diet-induced obesity through improving insulin sensitivity of subcutaneous fat. This suggests it may become a novel therapeutic target in the treatment of metabolic disorders.

  9. Chromium and polyphenols from cinnamon improve insulin sensitivity.

    Science.gov (United States)

    Anderson, Richard A

    2008-02-01

    Naturally-occurring compounds that have been shown to improve insulin sensitivity include Cr and polyphenols found in cinnamon (Cinnamomon cassia). These compounds also have similar effects on insulin signalling and glucose control. The signs of Cr deficiency are similar to those for the metabolic syndrome and supplemental Cr has been shown to improve all these signs in human subjects. In a double-blind placebo-controlled study it has been demonstrated that glucose, insulin, cholesterol and HbA1c are all improved in patients with type 2 diabetes following Cr supplementation. It has also been shown that cinnamon polyphenols improve insulin sensitivity in in vitro, animal and human studies. Cinnamon reduces mean fasting serum glucose (18-29%), TAG (23-30%), total cholesterol (12-26%) and LDL-cholesterol (7-27%) in subjects with type 2 diabetes after 40 d of daily consumption of 1-6 g cinnamon. Subjects with the metabolic syndrome who consume an aqueous extract of cinnamon have been shown to have improved fasting blood glucose, systolic blood pressure, percentage body fat and increased lean body mass compared with the placebo group. Studies utilizing an aqueous extract of cinnamon, high in type A polyphenols, have also demonstrated improvements in fasting glucose, glucose tolerance and insulin sensitivity in women with insulin resistance associated with the polycystic ovary syndrome. For both supplemental Cr and cinnamon not all studies have reported beneficial effects and the responses are related to the duration of the study, form of Cr or cinnamon used and the extent of obesity and glucose intolerance of the subjects.

  10. Effect of Gymnema sylvestre Administration on Metabolic Syndrome, Insulin Sensitivity, and Insulin Secretion.

    Science.gov (United States)

    Zuñiga, Laura Y; González-Ortiz, Manuel; Martínez-Abundis, Esperanza

    2017-08-01

    Gymnema sylvestre is a medicinal plant whose consumption has demonstrated benefits on lipid and glucose levels, blood pressure, and body weight (BWt). The aim of this study was to evaluate the effect of G. sylvestre administration on metabolic syndrome (MetS), insulin secretion, and insulin sensitivity. A randomized, double-blind, placebo-controlled clinical trial was carried out in 24 patients (without pharmacological treatment), 30-60 years old, with diagnosis of MetS in accordance with the modified International Diabetes Federation criteria. Patients were randomly assigned to receive G. sylvestre or placebo twice daily before breakfast and dinner in 300 mg capsules for a total of 600 mg per day for 12 weeks. Before and after the intervention, the components of MetS were evaluated as well as BWt, body mass index (BMI), total cholesterol, low-density lipoprotein cholesterol, and very low-density lipoprotein (VLDL). Area under the curve of glucose and insulin, phases of insulin secretion, and insulin sensitivity were calculated. Statistical analysis was performed using Wilcoxon signed-rank, Mann-Whitney U, and chi-square tests; P ≤ .05 was considered statistically significant. After G. sylvestre administration, significant decreases in BWt (81.3 ± 10.6 kg vs. 77.9 ± 8.4 kg, P = .02), BMI (31.2 ± 2.5 kg/m 2 vs. 30.4 ± 2.2 kg/m 2 , P = .02), and VLDL levels (0.45 ± 0.15 mmol/dL vs. 0.35 ± 0.15 mmol/dL, P = .05) were observed, without modifying the components of MetS, insulin secretion, and insulin sensitivity. In conclusion, G. sylvestre administration decreased BWt, BMI, and VLDL levels in subjects with MetS, without changes in insulin secretion and insulin sensitivity.

  11. Whole-body computed tomography versus conventional skeletal survey in patients with multiple myeloma

    DEFF Research Database (Denmark)

    Hillengass, J; Moulopoulos, L A; Delorme, S

    2017-01-01

    For decades, conventional skeletal survey (CSS) has been the standard imaging technique for multiple myeloma (MM). However, recently whole-body computed tomography (WBCT) has been implemented into the diagnostic criteria of MM. This analysis compares sensitivity and prognostic significance of WBC...

  12. Effect of metformin on peripheral insulin sensitivity in non insulin dependent diabetes mellitus.

    Science.gov (United States)

    Prager, R; Schernthaner, G; Graf, H

    1986-12-01

    To test whether metformin treatment might improve peripheral insulin sensitivity in non insulin dependent diabetes, we measured peripheral glucose uptake in 12 non insulin dependent diabetics before (A) and after 4 weeks (B) of metformin therapy (2 X 850 mg/day) by the hyperinsulinemic clamp technique (80 mU/m2/min). In addition, insulin binding to monocytes was compared between A and B. Diabetic control, evaluated by measurement of fasting blood glucose and glycosylated hemoglobin, was significantly improved by metformin treatment (P less than 0.01). Insulin binding to monocytes was not significantly influenced by metformin (A-4.53% vs. B-5.12%, n.s. at insulin tracer concentration). Peripheral glucose utilisation improved slightly, but significantly after 4 weeks of metformin therapy (A: 4.4 +/- 0.6 mg/kg/min, B: 5.4 +/- 0.8 mg/kg/min, p less than 0.01). Improvement in peripheral glucose utilisation correlated significantly with improved metabolic control, estimated by fasting blood glucose measurements (p less than 0.01).

  13. Glycyrrhizic acid improved lipoprotein lipase expression, insulin sensitivity, serum lipid and lipid deposition in high-fat diet-induced obese rats

    Directory of Open Access Journals (Sweden)

    Eu Chia

    2010-07-01

    Full Text Available Abstract Background The metabolic syndrome, known also as the insulin resistance syndrome, refers to the clustering of several risk factors for atherosclerotic cardiovascular disease. Dyslipidaemia is a hallmark of the syndrome and is associated with a whole body reduction in the activity of lipoprotein lipase (LPL, an enzyme under the regulation of the class of nuclear receptors known as peroxisome proliferator-activated receptor (PPAR. Glycyrrhizic acid (GA, a triterpenoid saponin, is the primary bioactive constituent of the roots of the shrub Glycyrrhiza glabra. Studies have indicated that triterpenoids could act as PPAR agonists and GA is therefore postulated to restore LPL expression in the insulin resistant state. Results Oral administration of 100 mg/kg of GA to high-fat diet-induced obese rats for 28 days led to significant reduction in blood glucose concentration and improvement in insulin sensitivity as indicated by the homeostasis model assessment of insulin resistance (HOMA-IR (p Conclusion In conclusion, GA may be a potential compound in improving dyslipidaemia by selectively inducing LPL expression in non-hepatic tissues. Such up-regulation was accompanied by a GA-mediated improvement in insulin sensitivity, which may be associated with a decrease in tissue lipid deposition. The HDL-raising effect of GA suggests the antiatherosclerotic properties of GA.

  14. Short-term interval training alters brain glucose metabolism in subjects with insulin resistance.

    Science.gov (United States)

    Honkala, Sanna M; Johansson, Jarkko; Motiani, Kumail K; Eskelinen, Jari-Joonas; Virtanen, Kirsi A; Löyttyniemi, Eliisa; Knuuti, Juhani; Nuutila, Pirjo; Kalliokoski, Kari K; Hannukainen, Jarna C

    2017-01-01

    Brain insulin-stimulated glucose uptake (GU) is increased in obese and insulin resistant subjects but normalizes after weight loss along with improved whole-body insulin sensitivity. Our aim was to study whether short-term exercise training (moderate intensity continuous training (MICT) or sprint interval training (SIT)) alters substrates for brain energy metabolism in insulin resistance. Sedentary subjects ( n = 21, BMI 23.7-34.3 kg/m2, age 43-55 y) with insulin resistance were randomized into MICT ( n = 11, intensity≥60% of VO2peak) or SIT ( n = 10, all-out) groups for a two-week training intervention. Brain GU during insulin stimulation and fasting brain free fatty acid uptake (FAU) was measured using PET. At baseline, brain GU was positively associated with the fasting insulin level and negatively with the whole-body insulin sensitivity. The whole-body insulin sensitivity improved with both training modes (20%, p = 0.007), while only SIT led to an increase in aerobic capacity (5%, p = 0.03). SIT also reduced insulin-stimulated brain GU both in global cortical grey matter uptake (12%, p = 0.03) and in specific regions ( p Brain FAU remained unchanged after the training in both groups. These findings show that short-term SIT effectively decreases insulin-stimulated brain GU in sedentary subjects with insulin resistance.

  15. Whole-body MRI in the pediatric patient.

    Science.gov (United States)

    Ley, Sebastian; Ley-Zaporozhan, Julia; Schenk, Jens-Peter

    2009-06-01

    Whole-body MRI is a fast and accurate modality for detection and monitoring of disease throughout the entire body. For pediatric use the technique is of special interest twofold: first it is a radiological method without radiation exposure and second it allows for whole-body staging as well as for detailed local evaluation for surgical treatment thus reducing the number of examinations to be performed in sedation. In the pediatric population the technique is used for oncological, non-oncological (i.e. fever of unknown origin, osteonecrosis) staging and for disease severity assessment of syndromes affecting the whole body. These applications will be reviewed and imaging protocols will be presented.

  16. Whole-body MRI in the pediatric patient

    Energy Technology Data Exchange (ETDEWEB)

    Ley, Sebastian [Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Ruprecht-Karls-University Heidelberg (Germany)], E-mail: ley@gmx.de; Ley-Zaporozhan, Julia; Schenk, Jens-Peter [Department of Diagnostic and Interventional Radiology, Section of Pediatric Radiology, Ruprecht-Karls-University Heidelberg (Germany)

    2009-06-15

    Whole-body MRI is a fast and accurate modality for detection and monitoring of disease throughout the entire body. For pediatric use the technique is of special interest twofold: first it is a radiological method without radiation exposure and second it allows for whole-body staging as well as for detailed local evaluation for surgical treatment thus reducing the number of examinations to be performed in sedation. In the pediatric population the technique is used for oncological, non-oncological (i.e. fever of unknown origin, osteonecrosis) staging and for disease severity assessment of syndromes affecting the whole body. These applications will be reviewed and imaging protocols will be presented.

  17. Whole body vibration exercise training for fibromyalgia.

    Science.gov (United States)

    Bidonde, Julia; Busch, Angela J; van der Spuy, Ina; Tupper, Susan; Kim, Soo Y; Boden, Catherine

    2017-09-26

    Exercise training is commonly recommended for adults with fibromyalgia. We defined whole body vibration (WBV) exercise as use of a vertical or rotary oscillating platform as an exercise stimulus while the individual engages in sustained static positioning or dynamic movements. The individual stands on the platform, and oscillations result in vibrations transmitted to the subject through the legs. This review is one of a series of reviews that replaces the first review published in 2002. To evaluate benefits and harms of WBV exercise training in adults with fibromyalgia. We searched the Cochrane Library, MEDLINE, Embase, CINAHL, PEDro, Thesis and Dissertation Abstracts, AMED, WHO ICTRP, and ClinicalTrials.gov up to December 2016, unrestricted by language, to identify potentially relevant trials. We included randomized controlled trials (RCTs) in adults with the diagnosis of fibromyalgia based on published criteria including a WBV intervention versus control or another intervention. Major outcomes were health-related quality of life (HRQL), pain intensity, stiffness, fatigue, physical function, withdrawals, and adverse events. Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessments, and assessed the quality of evidence for major outcomes using the GRADE approach. We used a 15% threshold for calculation of clinically relevant differences. We included four studies involving 150 middle-aged female participants from one country. Two studies had two treatment arms (71 participants) that compared WBV plus mixed exercise plus relaxation versus mixed exercise plus relaxation and placebo WBV versus control, and WBV plus mixed exercise versus mixed exercise and control; two studies had three treatment arms (79 participants) that compared WBV plus mixed exercise versus control and mixed relaxation placebo WBV. We judged the overall risk of bias as low for selection (random sequence generation), detection (objectively

  18. Associations of Physical Activity Intensities with Markers of Insulin Sensitivity.

    Science.gov (United States)

    Jelleyman, Charlotte; Edwardson, Charlotte L; Henson, Joseph; Gray, Laura J; Rowlands, Alex V; Khunti, Kamlesh; Davies, Melanie J; Yates, Thomas

    2017-12-01

    Objectively measured physical activity (PA) intensity has traditionally been categorized as light, moderate, and vigorous using laboratory calibrated cut points. The relative contribution of time spent across a spectrum of accelerometer-determined intensities on health outcomes is less clear. This study aimed to assess the relationship between objectively measured PA intensity on a continuous scale and markers of insulin sensitivity (IS). Participants at high risk of type 2 diabetes mellitus were recruited from primary care (Leicestershire, UK). PA was measured using an ActiGraph accelerometer. Fasting and postchallenge glucose and insulin levels were assessed using an oral glucose tolerance test. IS was calculated using the Matsuda-IS and the HOMA-IS indices. Log-linear regression modeling was used to assess the relationship between PA intensity, in increments of 500 counts per minute, with markers of IS. Models were controlled for known confounders. Complete data were available for 569 participants. PA intensity was favorably associated with fasting and 2 h of insulin and IS, with the association increasing in magnitude with each increment of 500 counts per minute. Differences in HOMA-IS per 10 min of PA ranged from 12.4% (95% confidence interval = 3.7%-21.8%) to 26.8% (11.0%-44.7%) within the moderate-intensity PA category (from 2000-2499 to 3500-3999 counts per minute). For Matsuda-IS, these differences were 22.0% (10.3%-34.9%) and 34.7% (13.9%-59.3%), respectively. Significant associations for fasting insulin were no longer observed after controlling for body mass index, whereas differences associated with 2-h insulin and IS were attenuated but still significant. PA of any intensity may positively influence glucose regulation and insulin sensitivity in individuals at high risk of type 2 diabetes mellitus in a dose-response manner. Further research is required to identify the intensity thresholds at which clinically relevant benefits occur in this population.

  19. 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...

  20. Fasting insulin sensitivity indices are not better than routine clinical variables at predicting insulin sensitivity among Black Africans: a clamp study in sub-Saharan Africans

    Science.gov (United States)

    2014-01-01

    Background We aimed to evaluate the predictive utility of common fasting insulin sensitivity indices, and non-laboratory surrogates [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)] in sub-Saharan Africans without diabetes. Methods We measured fasting glucose and insulin, and glucose uptake during 80/mU/m2/min euglycemic clamp in 87 Cameroonians (51 men) aged (SD) 34.6 (11.4) years. We derived insulin sensitivity indices including HOMA-IR, quantitative insulin sensitivity check index (QUICKI), fasting insulin resistance index (FIRI) and glucose-to-insulin ratio (GIR). Indices and clinical predictors were compared to clamp using correlation tests, robust linear regressions and agreement of classification by sex-specific thirds. Results The mean insulin sensitivity was M = 10.5 ± 3.2 mg/kg/min. Classification across thirds of insulin sensitivity by clamp matched with non-laboratory surrogates in 30-48% of participants, and with fasting indices in 27-51%, with kappa statistics ranging from −0.10 to 0.26. Fasting indices correlated significantly with clamp (/r/=0.23-0.30), with GIR performing less well than fasting insulin and HOMA-IR (both p insulin sensitivity indices are modest predictors of insulin sensitivity measured by euglycemic clamp, and do not perform better than clinical surrogates in this population. PMID:25106496

  1. Glucose- and temperature-sensitive nanoparticles for insulin delivery.

    Science.gov (United States)

    Wu, Jun-Zi; Williams, Gareth R; Li, He-Yu; Wang, Dongxiu; Wu, Huanling; Li, Shu-De; Zhu, Li-Min

    2017-01-01

    Glucose- and temperature-sensitive polymers of a phenylboronic acid derivative and diethylene glycol dimethacrylate (poly(3-acrylamidophenyl boronic acid-b-diethylene glycol methyl ether methacrylate); p(AAPBA-b-DEGMA)) were prepared by reversible addition-fragmentation chain transfer polymerization. Successful polymerization was evidenced by 1H nuclear magnetic resonance and infrared spectroscopy, and the polymers were further explored in terms of their glass transition temperatures and by gel permeation chromatography (GPC). The materials were found to be temperature sensitive, with lower critical solution temperatures in the region of 12°C-47°C depending on the monomer ratio used for reaction. The polymers could be self-assembled into nanoparticles (NPs), and the zeta potential and size of these particles were determined as a function of temperature and glucose concentration. Subsequently, the optimum NP formulation was loaded with insulin, and the drug release was studied. We found that insulin was easily encapsulated into the p(AAPBA-b-DEGMA) NPs, with a loading capacity of ~15% and encapsulation efficiency of ~70%. Insulin release could be regulated by changes in temperature and glucose concentration. Furthermore, the NPs were non-toxic both in vitro and in vivo. Finally, the efficacy of the formulations at managing blood glucose levels in a murine hyperglycemic diabetes model was studied. The insulin-loaded NPs could reduce blood glucose levels over an extended period of 48 h. Since they are both temperature and glucose sensitive and offer a sustained-release profile, these systems may comprise potent new formulations for insulin delivery.

  2. Dietary patterns, insulin sensitivity and inflammation in older adults.

    Science.gov (United States)

    Anderson, A L; Harris, T B; Tylavsky, F A; Perry, S E; Houston, D K; Lee, J S; Kanaya, A M; Sahyoun, N R

    2012-01-01

    Several studies have linked dietary patterns to insulin sensitivity and systemic inflammation, which affect risk of multiple chronic diseases. The purpose of this study was to investigate the dietary patterns of a cohort of older adults, and to examine relationships of dietary patterns with markers of insulin sensitivity and systemic inflammation. The Health, Aging and Body Composition (Health ABC) Study is a prospective cohort study of 3075 older adults. In Health ABC, multiple indicators of glucose metabolism and systemic inflammation were assessed. Food intake was estimated with a modified Block food frequency questionnaire. In this study, dietary patterns of 1751 participants with complete data were derived by cluster analysis. Six clusters were identified, including a 'healthy foods' cluster, characterized by higher intake of low-fat dairy products, fruit, whole grains, poultry, fish and vegetables. In the main analysis, the 'healthy foods' cluster had significantly lower fasting insulin and homeostasis model assessment of insulin resistance values than the 'breakfast cereal' and 'high-fat dairy products' clusters, and lower fasting glucose than the 'high-fat dairy products' cluster (P≤0.05). No differences were found in 2-h glucose. With respect to inflammation, the 'healthy foods' cluster had lower interleukin-6 than the 'sweets and desserts' and 'high-fat dairy products' clusters, and no differences were seen in C-reactive protein or tumor necrosis factor-α. A dietary pattern high in low-fat dairy products, fruit, whole grains, poultry, fish and vegetables may be associated with greater insulin sensitivity and lower systemic inflammation in older adults.

  3. Transient global amnesia following a whole-body cryotherapy session

    National Research Council Canada - National Science Library

    Justin Carrard; Anne Chantal Lambert; Daniel Genné

    2017-01-01

    Whole-body cryotherapy (WBC), which consists of a short exposure to very cold and dry air in special 'cryo-chambers', is believed to reduce inflammation and musculoskeletal pain as well as improve athletes' recovery...

  4. Whole body vibration improves body mass, flexibility and strength in ...

    African Journals Online (AJOL)

    related fitness benefits; not only those associated with obesity, but also the reduction ... The use of whole body vibration (WBV) as an exercise intervention for health ..... muscular strength, muscular endurance and aerobic capacity. In addition ...

  5. Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study

    NARCIS (Netherlands)

    Kozakova, M.; Natali, A.; Dekker, J.M.; Beck-Nielsen, H.; Laakso, M.; Nilsson, P.; Balkau, B.; Ferrannini, E.

    2013-01-01

    Objective-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

  6. Whole-body MRI for the staging and follow-up of patients with metastasis.

    Science.gov (United States)

    Schmidt, Gerwin P; Reiser, Maximilian F; Baur-Melnyk, Andrea

    2009-06-01

    The advent of whole-body MRI (WB-MRI) has introduced tumor imaging with a systemic approach compared to established sequential, multi-modal diagnostic algorithms. Hardware innovations, such as the introduction of multi-receiver channel whole-body scanners at 1.5 T and recently 3T, combined with acquisition acceleration techniques, have made high resolution WB-MRI clinically feasible. Now, a dedicated assessment of individual organs with various soft tissue contrast, spatial resolution and contrast media dynamics can be combined with whole-body anatomic coverage in a multi-planar imaging approach. More flexible protocols, e.g. including T1-weighted TSE- and STIR-imaging, dedicated lung imaging or dynamic contrast-enhanced studies of the abdomen can be performed within less than 45 min. For initial tumor staging PET-CT as a competing whole-body modality in oncologic imaging has proved more accurate for the definition of T-stage and lymph node assessment, using the additional metabolic information of PET for the assessment of tumor viability and therapy response. However, new applications, such as MR-whole-body diffusion imaging, may significantly increase sensitivity in near future. WB-MRI has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and it is especially useful as a radiation-free alternative for the surveillance of tumor patients with multiple follow-up exams. Furthermore, it has been introduced as a whole-body bone marrow screening application. Within this context WB-MRI is highly accurate for the detection of skeletal metastases and staging of hematologic diseases, such as multiple myeloma or lymphoma. This article summarizes recent developments and applications of WB-MRI and highlights its performance within the scope of systemic oncologic staging and surveillance.

  7. Environmental factors and dam characteristics associated with insulin sensitivity and insulin secretion in newborn Holstein calves.

    Science.gov (United States)

    Kamal, M M; Van Eetvelde, M; Bogaert, H; Hostens, M; Vandaele, L; Shamsuddin, M; Opsomer, G

    2015-09-01

    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), length 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 gender and season of birth when data of all calves were analyzed. In addition, the insulin traits in calves born to cows were significantly associated with MGEST, DP and LL. The Insb was estimated to be higher in calves born to the cows having passed a higher MGEST (P=0.076) and longer DP (P=0.034). The

  8. Ethnic Differences in Insulin Sensitivity, β-Cell Function, and Hepatic Extraction Between Japanese and Caucasians

    DEFF Research Database (Denmark)

    Møller, Jonas B; Dalla Man, Chiara; Overgaard, Rune V

    2014-01-01

    : This was a cross-sectional study with oral glucose tolerance tests to assess β-cell function, hepatic insulin extraction, and insulin sensitivity. PARTICIPANTS: PARTICIPANTS included 120 Japanese and 150 Caucasian subjects. MAIN OUTCOMES: Measures of β-cell function, hepatic extraction, and insulin sensitivity...... were assessed using C-peptide, glucose, and insulin minimal models. RESULTS: Basal β-cell function (Φ(b)) was lower in Japanese compared with Caucasians (P ... compared with Caucasians (P insulin action showed higher sensitivity in the Japanese IGT subjects. Hepatic extraction was similar in NGT and IGT groups but higher in Japanese type 2 diabetic subjects (P insulin sensitivity, β-cell function...

  9. Prediction of the insulin sensitivity index using Bayesian networks

    DEFF Research Database (Denmark)

    Bøttcher, Susanne Gammelgaard; Dethlefsen, Claus

    The insulin sensitivity index () can be used in assessing the risk of developing type 2 diabetes. An intravenous study is used to determine using Bergmans minimal model. However, an intravenous study is time consuming and expensive and therefore not suitable for large scale epidemiological studie...... test instead of an intravenous study. The methodology is applied to a dataset with 187 patients. We find that the values from this study are highly correlated to the values determined from the intravenous study. S_I S_I S_I S_I S_I......The insulin sensitivity index () can be used in assessing the risk of developing type 2 diabetes. An intravenous study is used to determine using Bergmans minimal model. However, an intravenous study is time consuming and expensive and therefore not suitable for large scale epidemiological studies...

  10. Effect of arotinolol on insulin sensitivity in obese hypertensive patients.

    Science.gov (United States)

    Kageyama, S; Yamamoto, J; Mimura, A; Sakurai, T; Ishibashi, K; Isogai, Y

    1994-01-01

    Insulin sensitivity in terms of glucose disposal rate was determined by using the hyperinsulinemic euglycemic clamp technique in seven obese hypertensive patients and nine normotensive control subjects. The technique was used on all study subjects at baseline and on the hypertensive patients after 12 weeks of arotinolol treatment. Mean supine systolic blood pressure decreased from 155 +/- 3 mm Hg before treatment to 133 +/- 6 mm Hg after treatment (P arotinolol was 10 mg/d, except for one patient who received 20 mg/d. The glucose disposal rate during the last 30 minutes of the glucose clamp procedure was not significantly affected by treatment with arotinolol. Compared with the hypertensive patients, the glucose disposal rate in the normotensive subjects was significantly increased, both before and after treatment (P arotinolol did not significantly affect insulin sensitivity.

  11. Fish consumption, insulin sensitivity and beta-cell function in the Insulin Resistance Atherosclerosis Study (IRAS).

    Science.gov (United States)

    Lee, C; Liese, A; Wagenknecht, L; Lorenzo, C; Haffner, S; Hanley, A

    2013-09-01

    Previous research on the association between fish consumption and incident type 2 diabetes has been inconclusive. In addition, few studies have investigated how fish consumption may be related to the metabolic abnormalities underlying diabetes. Therefore, we examined the association of fish consumption with measures of insulin sensitivity and beta-cell function in a multi-ethnic population. We examined the cross-sectional association between fish consumption and measures of insulin sensitivity and secretion in 951 non-diabetic participants in the Insulin Resistance Atherosclerosis Study (IRAS). Fish consumption, categorized as consumption was independently associated with lower S(I)-adjusted AIR (β = -0.13 [-0.25, -0.016], p = 0.03, comparing ≥2 vs. consumption was positively associated with intact and split proinsulin/C-peptide ratios, however, these associations were confounded by ethnicity (multivariable-adjusted β = 0.073 [-0.014, 0.16] for intact proinsulin/C-peptide ratio, β = 0.031 [-0.065, 0.13] for split proinsulin/C-peptide ratio). We also observed a significant positive association between fish consumption and fasting blood glucose (multivariable-adjusted β = 2.27 [0.68, 3.86], p = 0.005). We found no association between fish consumption and S(I) (multivariable-adjusted β = -0.015 [-0.083, 0.053]) or fasting insulin (multivariable-adjusted β = 0.016 [-0.066, 0.10]). Fish consumption was not associated with measures of insulin sensitivity in the multi-ethnic IRAS cohort. However, higher fish consumption may be associated with pancreatic beta-cell dysfunction. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. 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.

  13. Effect of IL-6 on the insulin sensitivity in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Harder-Lauridsen, N M; Krogh-Madsen, R; Holst, Jens Juul

    2014-01-01

    Elevated interleukin-6 (IL-6) levels are associated with type 2 diabetes, but its role in glucose metabolism is controversial. We investigated the effect of IL-6 on insulin-stimulated glucose metabolism in type 2 diabetes patients and hypothesized that an acute, moderate IL-6 elevation would...... increase the insulin-mediated glucose uptake. Men with type 2 diabetes not treated with insulin [n = 9, age 54.9 ± 9.7 (mean ± SD) yr, body mass index 34.8 ± 6.1 kg/m(2), HbA1c 7.0 ± 1.0%] received continuous intravenous infusion with either recombinant human IL-6 (rhIL-6) or placebo. After 1 h...... in muscle biopsies. Whole body energy expenditure was measured using indirect calorimetry. In response to the infusion of rhIL-6, circulating levels of IL-6 (P

  14. Whole-body magnetic resonance imaging and positron emission tomography-computed tomography in oncology.

    Science.gov (United States)

    Schmidt, Gerwin P; Kramer, Harald; Reiser, Maximilian F; Glaser, Christian

    2007-06-01

    agents, may significantly increase sensitivity in near future. Whole-body magnetic resonance imaging has shown advantages for the detection of distant metastatic disease, especially from tumors frequently spreading to the liver or brain and as a whole-body bone marrow screening application. Within this context, WB-MRI is highly accurate for the detection of skeletal metastases and staging of multiple myeloma. This article summarizes recent developments of CT/PET-CT and WB-MRI and highlights their performance within the scope of systemic oncological imaging.

  15. 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.

  16. The Effects of Telmisartan and Losartan on Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Okan Bakıner

    2013-12-01

    Full Text Available Purpose: Telmisartan has been reported to increase insulin sensitivity by acting as a partial PPAR-gamma agonist, regardless of its renin-angiotensin system inhibition, but losartan has no such activity. In this study, we compared the effects of telmisartan and losartan on insulin sensitivity among type 2 diabetic patients. Material and Method: Age-, sex- and weight-matched patients, who had been on telmisartan or losartan treatment for at least 3 months, were included. Their anthropometric measurements were performed, blood pressures were recorded. Fasting venous blood samples were obtained for analyzing the levels of glucose, HbA1C, insulin and adiponectin. HOMA-IR was calculated. An euglycemic hyperinsulinemic clamp procedure was performed in each subject and M index was calculated. Thereafter, telmisartan and losartan were withdrawn in both groups. A cross-over design was planned; following a wash-out period of 15 days, losartan group (Group 1 was given telmisartan 80 mg/day, telmisartan group (Group 2 was administered losartan 50 mg/day. After 12 weeks of therapy, all measurements, calculations and the euglycemic hyperinsulinemic clamp test were re-performed. Results: General characteristics of the patients at inclusion were similar. Nine cases in group 1 and 8 cases in Group 2 concluded the follow-up. In Group 1, among all follow-up parameters, only weight exhibited a significant decrease at final evaluation (p=0,034. In Group 2, only M value was found to increase (p=0,028. Discussion: Our findings indicated that losartan improved insulin sensitivity in patients with concomitant hypertension and type 2 diabetes, and telmisartan use resulted in more weight loss. Turk Jem 2013; 17: 92-7

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

    Directory of Open Access Journals (Sweden)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Mutual stabilization of rhythmic vocalization and whole-body movement.

    Science.gov (United States)

    Miyata, Kohei; Kudo, Kazutoshi

    2014-01-01

    The current study investigated the rhythmic coordination between vocalization and whole-body movement. Previous studies have reported that spatiotemporal stability in rhythmic movement increases when coordinated with a rhythmic auditory stimulus or other effector in a stable coordination pattern. Therefore, the present study conducted two experiments to investigate (1) whether there is a stable coordination pattern between vocalization and whole-body movement and (2) whether a stable coordination pattern reduces variability in whole-body movement and vocalization. In Experiment 1, two coordination patterns between vocalizations and whole-body movement (hip, knee, and ankle joint flexion-on-the-voice vs. joint extension-on-the-voice) in a standing posture were explored at movement frequencies of 80, 130, and 180 beats per minute. At higher movement frequencies, the phase angle in the extension-on-the-voice condition deviated from the intended phase angle. However, the angle of the flexion-on-the-voice was maintained even when movement frequency increased. These results suggest that there was a stable coordination pattern in the flexion-on-the-voice condition. In Experiment 2, variability in whole-body movement and voice-onset intervals was compared between two conditions: one related to tasks performed in the flexion-on-the-voice coordination (coordination condition) that was a stable coordination pattern, and the other related to tasks performed independently (control condition). The results showed that variability in whole-body movement and voice-onset intervals was smaller in the coordination condition than in the control condition. Overall, the present study revealed mutual stabilization between rhythmic vocalization and whole-body movement via coordination within a stable pattern, suggesting that coupled action systems can act as a single functional unit or coordinative structure.

  20. Mutual stabilization of rhythmic vocalization and whole-body movement.

    Directory of Open Access Journals (Sweden)

    Kohei Miyata

    Full Text Available The current study investigated the rhythmic coordination between vocalization and whole-body movement. Previous studies have reported that spatiotemporal stability in rhythmic movement increases when coordinated with a rhythmic auditory stimulus or other effector in a stable coordination pattern. Therefore, the present study conducted two experiments to investigate (1 whether there is a stable coordination pattern between vocalization and whole-body movement and (2 whether a stable coordination pattern reduces variability in whole-body movement and vocalization. In Experiment 1, two coordination patterns between vocalizations and whole-body movement (hip, knee, and ankle joint flexion-on-the-voice vs. joint extension-on-the-voice in a standing posture were explored at movement frequencies of 80, 130, and 180 beats per minute. At higher movement frequencies, the phase angle in the extension-on-the-voice condition deviated from the intended phase angle. However, the angle of the flexion-on-the-voice was maintained even when movement frequency increased. These results suggest that there was a stable coordination pattern in the flexion-on-the-voice condition. In Experiment 2, variability in whole-body movement and voice-onset intervals was compared between two conditions: one related to tasks performed in the flexion-on-the-voice coordination (coordination condition that was a stable coordination pattern, and the other related to tasks performed independently (control condition. The results showed that variability in whole-body movement and voice-onset intervals was smaller in the coordination condition than in the control condition. Overall, the present study revealed mutual stabilization between rhythmic vocalization and whole-body movement via coordination within a stable pattern, suggesting that coupled action systems can act as a single functional unit or coordinative structure.

  1. Pre-pubertal children born post-term have reduced insulin sensitivity and other markers of the metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Ahila Ayyavoo

    Full Text Available BACKGROUND: There are no data on the metabolic consequences of post-term birth (≥42 weeks gestation. We hypothesized that post-term birth would adversely affect insulin sensitivity, as well as other metabolic parameters and body composition in childhood. METHODS: 77 healthy pre-pubertal children, born appropriate-for-gestational-age were studied in Auckland, New Zealand: 36 born post-term (18 boys and 41 (27 boys born at term (38-40 weeks gestation. Primary outcome was insulin sensitivity measured using intravenous glucose tolerance tests and Bergman's minimal model. Other assessments included fasting hormone concentrations and lipid profiles, body composition from whole-body dual-energy X-ray absorptiometry, 24-hour ambulatory blood pressure monitoring, and inflammatory markers. RESULTS: Insulin sensitivity was 34% lower in post-term than in term children (7.7 vs. 11.6 x10⁻⁴·min⁻¹·(mU/l; p<0.0001. There was a compensatory increase in acute insulin response among post-term children (418 vs 304 mU/l; p=0.037, who also displayed lower glucose effectiveness than those born at term (2.25 vs 3.11 x10⁻²·min⁻¹; p=0.047. Post-term children not only had more body fat (p=0.014 and less fat-free mass (p=0.014, but also had increased central adiposity with more truncal fat (p=0.017 and greater android to gynoid fat ratio (p=0.007 compared to term controls. Further, post-term children displayed other markers of the metabolic syndrome: lower normal nocturnal systolic blood pressure dipping (p=0.027, lower adiponectin concentrations (p=0.005, as well as higher leptin (p=0.008 and uric acid (p=0.033 concentrations. Post-term boys (but not girls also displayed a less favourable lipid profile, with higher total cholesterol (p=0.018 and LDL-C (p=0.006 concentrations, and total cholesterol to HDL-C ratio (p=0.048. CONCLUSIONS: Post-term children have reduced insulin sensitivity and display a number of early markers of the metabolic syndrome. These

  2. Elevated GH/IGF-I, due to somatotrope-specific loss of both IGF-I and insulin receptors, alters glucose homeostasis and insulin sensitivity in a diet-dependent manner.

    Science.gov (United States)

    Gahete, Manuel D; Córdoba-Chacón, José; Anadumaka, Chike V; Lin, Qing; Brüning, Jens C; Kahn, C Ronald; Luque, Raúl M; Kineman, Rhonda D

    2011-12-01

    A unique mouse model was developed with elevated endogenous GH (2- to 3-fold) and IGF-I (1.2- to 1.4-fold), due to somatotrope-specific Cre-mediated inactivation of IGF-I receptor (IgfIr) and insulin receptor (Insr) genes (IgfIr,Insr(rGHpCre), referred to as HiGH mice). We demonstrate that the metabolic phenotype of HiGH mice is diet dependent and differs from that observed in other mouse models of GH excess due to ectopic heterologous transgene expression or pituitary tumor formation. Elevated endogenous GH promotes lean mass and whole-body lipid oxidation but has minimal effects on adiposity, even in response to diet-induced obesity. When caloric intake is moderated, elevated GH improves glucose clearance, despite low/normal insulin sensitivity, which may be explained in part by enhanced IGF-I and insulin output. However, when caloric intake is in excess, elevated GH promotes hepatic lipid accumulation, insulin resistance, hyperglycemia, and ketosis. The HiGH mouse model represents a useful tool to study the role endogenous circulating GH levels play in regulating health and disease.

  3. Detecting the relevance to performance of whole-body movements.

    Science.gov (United States)

    Furuki, Daisuke; Takiyama, Ken

    2017-11-15

    Goal-directed whole-body movements are fundamental in our daily life, sports, music, art, and other activities. Goal-directed movements have been intensively investigated by focusing on simplified movements (e.g., arm-reaching movements or eye movements); however, the nature of goal-directed whole-body movements has not been sufficiently investigated because of the high-dimensional nonlinear dynamics and redundancy inherent in whole-body motion. One open question is how to overcome high-dimensional nonlinear dynamics and redundancy to achieve the desired performance. It is possible to approach the question by quantifying how the motions of each body part at each time point contribute to movement performance. Nevertheless, it is difficult to identify an explicit relation between each motion element (the motion of each body part at each time point) and performance as a result of the high-dimensional nonlinear dynamics and redundancy inherent in whole-body motion. The current study proposes a data-driven approach to quantify the relevance of each motion element to the performance. The current findings indicate that linear regression may be used to quantify this relevance without considering the high-dimensional nonlinear dynamics of whole-body motion.

  4. Insulin requirement in non-insulin-dependent diabetes mellitus: relation to simple tests of islet B-cell function and insulin sensitivity

    DEFF Research Database (Denmark)

    Gjessing, H J; Matzen, L E; Pedersen, P C

    1988-01-01

    Evaluation of simple tests of islet B-cell function and insulin sensitivity as predictors of metabolic control was performed during 3 months of insulin withdrawal in 25 insulin-treated diabetic subjects. All patients had a glucagon stimulated plasma C-peptide concentration above 0.33 nmol....../l and a fasting plasma C-peptide concentration above 0.20 nmol/l a few days before insulin withdrawal. Insulin sensitivity was measured as the glucose disappearance rate (k) during an intravenous insulin tolerance test. Two patients were considered insulin-requiring due to high fasting blood glucose levels......-peptide levels the predictive value of a positive test was 100% while the predictive value of a negative test was as low as 33% or 27% depending on whether fasting or stimulated C-peptide concentration was used. Including the k value in the prediction only increased the predictive values of negative tests to 40...

  5. Measuring beta-cell function relative to insulin sensitivity in youth: Does the hyperglycemic clamp suffice?

    Science.gov (United States)

    To compare beta-cell function relative to insulin sensitivity, disposition index (DI), calculated from two clamps (2cDI, insulin sensitivity from the hyperinsulinemic-euglycemic clamp and first-phase insulin from the hyperglycemic clamp) with the DI calculated from the hyperglycemic clamp alone (hcD...

  6. Sustained Self-Regulation of Energy Intake: Initial Hunger Improves Insulin Sensitivity

    Directory of Open Access Journals (Sweden)

    Mario Ciampolini

    2010-01-01

    Results. In trained subjects, significant decreases were found in insulin sensitivity index, insulin and BG peaks, glycated haemoglobin, mean pre-meal BG, standard deviation of diary BG (BG as recorded by subjects' 7-day diary, energy intake, BMI, and body weight when compared to control subjects. Conclusion. The IHMP improved insulin sensitivity and other cardiovascular risk factors over a 5-month period.

  7. Whole-body impedance control of wheeled humanoid robots

    CERN Document Server

    Dietrich, Alexander

    2016-01-01

    Introducing mobile humanoid robots into human environments requires the systems to physically interact and execute multiple concurrent tasks. The monograph at hand presents a whole-body torque controller for dexterous and safe robotic manipulation. This control approach enables a mobile humanoid robot to simultaneously meet several control objectives with different pre-defined levels of priority, while providing the skills for compliant physical contacts with humans and the environment. After a general introduction into the topic of whole-body control, several essential reactive tasks are developed to extend the repertoire of robotic control objectives. Additionally, the classical Cartesian impedance is extended to the case of mobile robots. All of these tasks are then combined and integrated into an overall, priority-based control law. Besides the experimental validation of the approach, the formal proof of asymptotic stability for this hierarchical controller is presented. By interconnecting the whole-body ...

  8. DHA at nutritional doses restores insulin sensitivity in skeletal muscle by preventing lipotoxicity and inflammation.

    Science.gov (United States)

    Capel, Frédéric; Acquaviva, Cécile; Pitois, Elodie; Laillet, Brigitte; Rigaudière, Jean-Paul; Jouve, Chrystèle; Pouyet, Corinne; Gladine, Cècile; Comte, Blandine; Vianey Saban, Christine; Morio, Bèatrice

    2015-09-01

    Skeletal muscle plays a major role in the control of whole body glucose disposal in response to insulin stimulus. Excessive supply of fatty acids to this tissue triggers cellular and molecular disturbances leading to lipotoxicity, inflammation, mitochondrial dysfunctions, impaired insulin response and decreased glucose uptake. This study was conducted to analyze the preventive effect of docosahexaenoic acid (DHA), a long-chain polyunsaturated n-3 fatty acid, against insulin resistance, lipotoxicity and inflammation in skeletal muscle at doses compatible with nutritional supplementation. DHA (30 μM) prevented insulin resistance in C2C12 myotubes exposed to palmitate (500 μM) by decreasing protein kinase C (PKC)-θ activation and restoring cellular acylcarnitine profile, insulin-dependent AKT phosphorylation and glucose uptake. Furthermore, DHA protected C2C12 myotubes from palmitate- or lipopolysaccharide-induced increase in Ptgs2, interleukin 6 and tumor necrosis factor-α mRNA level, probably through the inhibition of p38 MAP kinase and c-Jun amino-terminal kinase. In LDLR -/- mice fed a high-cholesterol-high-sucrose diet, supplementation with DHA reaching up to 2% of daily energy intake enhanced the insulin-dependent AKT phosphorylation and reduced the PKC-θ activation in skeletal muscle. Therefore, DHA used at physiological doses participates in the regulation of muscle lipid and glucose metabolisms by preventing lipotoxicity and inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Insulin-mediated FFA suppression is associated with triglyceridemia and insulin sensitivity independent of adiposity.

    Science.gov (United States)

    Bush, Nikki C; Basu, Rita; Rizza, Robert A; Nair, K Sreekumaran; Khosla, Sundeep; Jensen, Michael D

    2012-11-01

    A central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear. The aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia. We measured systemic palmitate turnover using an iv infusion of [9,10-(3)H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SI(IVGTT)) and mixed meal tolerance test (SI(Meal)). The study was conducted at a General Clinical Research Center. Baseline data were obtained from 140 elderly adults (age, 60-88 yr; 83 males) and 60 young adults (age, 18-31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density. There were no interventions. We measured fasting plasma triglyceride (TG) concentrations, SI(IVGTT), and SI(Meal). Using multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SI(IVGTT) were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SI(Meal) were meal nadir palmitate concentration, UBSQ fat, fitness, and sex. FFA suppression is associated with both fasting TG concentrations and insulin sensitivity, independent of measures of adiposity.

  10. 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...... used to determine oral glucose-stimulated insulin secretion (GSISOGTT), and DIOGTT was calculated as the product of SI OGTT and GSISOGTT. Our novel SI OGTT showed high agreement with clamp-derived insulin sensitivity (typical error = +3.6%; r = 0.69, P ... (DIOGTT) that is a measure of pancreatic β-cell insulin secretory compensation for changing insulin sensitivity. We conducted an observational study of n = 187 subjects, representing the entire glucose tolerance continuum from normal glucose tolerance to type 2 diabetes. OGTT-derived insulin sensitivity...

  11. L-Citrulline increases hepatic sensitivity to insulin by reducing the phosphorylation of serine 1101 in insulin receptor substrate-1.

    Science.gov (United States)

    Yoshitomi, Hisae; Momoo, Maki; Ma, Xiao; Huang, Yewei; Suguro, Shiori; Yamagishi, Yoshie; Gao, Ming

    2015-06-18

    Insulin resistance is characterized by deficient responses to insulin in its target tissues. In the present study, we examined the effects of L-Citrulline (L-Cit) on insulin sensitivity and signaling cascades in rat hepatoma H4IIE cells and SHRSP.Z-Leprfa/IzmDmcr rats. H4IIE cells were pretreated in the presence or absence of 250 μM L-Cit in serum-free medium and then incubated in the presence or absence of 0.1 nM insulin. Rats were allocated into 2 groups; a control group (not treated) and L-Cit group (2 g/kg/day, L-Cit) and treated for 8 weeks. L-Cit enhanced the insulin-induced phosphorylation of Akt in H4IIE cells. Moreover, the inhibited expression of Dex/cAMP-induced PEPCK mRNA by insulin was enhanced by the L-Cit treatment. The phosphorylation of tyrosine, which is upstream of Akt, in insulin receptor substrate-1 (IRS-1) was increased by the L-Cit treatment. The L-Cit-induced enhancement in insulin signaling was not related to the binding affinity of insulin to the insulin receptor or to the expression of the insulin receptor, but to a decrease in the phosphorylation of serine 1101 in IRS-1. These results were also confirmed in animal experiments. In the livers of L-Cit-treated rats, PI3K/Akt signaling was improved by decreases in the phosphorylation of serine 1101. We herein demonstrated for the first time the beneficial effects of L-Cit on improved insulin resistance associated with enhanced insulin sensitivity. These results may have clinical applications for insulin resistance and the treatment of type-2 diabetes.

  12. Anesthesia and monitoring during whole body radiation in children

    DEFF Research Database (Denmark)

    Henneberg, S; Nilsson, A; Hök, B

    1991-01-01

    During whole body radiation therapy of children, treatment may be done in places not equipped with acceptable scavenging systems for anesthetic gases and where clinical observation of the patient may be impossible. In order to solve this problem, the authors have used a total intravenous (IV) ane....... This anesthetic technique and the stethoscope have been used in seven children. The total IV anesthesia proved to be a useful method for children during whole body radiation. The modified stethoscope functioned very well and was a useful complement to the monitoring equipment....

  13. Anesthesia and monitoring during whole body radiation in children

    DEFF Research Database (Denmark)

    Henneberg, S; Nilsson, A; Hök, B

    1990-01-01

    During whole body radiation therapy of children, treatment may be done in places not equipped with acceptable scavenging systems for anesthetic gases and where clinical observation of the patient may be impossible. In order to solve this problem, the authors have used a total intravenous (IV) ane....... This anesthetic technique and the stethoscope have been used in seven children. The total IV anesthesia proved to be a useful method for children during whole body radiation. The modified stethoscope functioned very well and was a useful complement to the monitoring equipment....

  14. 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.

  15. Higher insulin sensitivity in vegans is not associated with higher mitochondrial density.

    Science.gov (United States)

    Gojda, J; Patková, J; Jaček, M; Potočková, J; Trnka, J; Kraml, P; Anděl, M

    2013-12-01

    Vegans have a lower incidence of insulin resistance (IR)-associated diseases and a higher insulin sensitivity (IS) compared with omnivores. The aim of this study was to examine whether the higher IS in vegans relates to markers of mitochondrial biogenesis and to intramyocellular lipid (IMCL) content. Eleven vegans and 10 matched (race, age, sex, body mass index, physical activity and energy intake) omnivorous controls were enrolled in a case-control study. Anthropometry, bioimpedance (BIA), ultrasound measurement of visceral and subcutaneous fat layer, parameters of glucose and lipid homeostasis, hyperinsulinemic euglycemic clamp and muscle biopsies were performed. Citrate synthase (CS) activity, mitochondrial DNA (mtDNA) and IMCL content were assessed in skeletal muscle samples. Both groups were comparable in anthropometric and BIA parameters, physical activity and protein-energy intake. Vegans had significantly higher glucose disposal (M-value, vegans 8.11±1.51 vs controls 6.31±1.57 mg/kg/min, 95% confidence interval: 0.402 to 3.212, P=0.014), slightly lower IMCL content (vegans 13.91 (7.8 to 44.0) vs controls 17.36 (12.4 to 78.5) mg/g of muscle, 95% confidence interval: -7.594 to 24.550, P=0.193) and slightly higher relative muscle mtDNA amount (vegans 1.36±0.31 vs controls 1.13±0.36, 95% confidence interval:-0.078 to 0.537, P=0.135). No significant differences were found in CS activity (vegans 18.43±5.05 vs controls 18.16±5.41 μmol/g/min, 95% confidence interval: -4.503 to 5.050, P=0.906). Vegans have a higher IS, but comparable mitochondrial density and IMCL content with omnivores. This suggests that a decrease in whole-body glucose disposal may precede muscle lipid accumulation and mitochondrial dysfunction in IR development.

  16. Vestibular-somatosensory interactions: effects of passive whole-body rotation on somatosensory detection.

    Directory of Open Access Journals (Sweden)

    Elisa Raffaella Ferrè

    Full Text Available Vestibular signals are strongly integrated with information from several other sensory modalities. For example, vestibular stimulation was reported to improve tactile detection. However, this improvement could reflect either a multimodal interaction or an indirect interaction driven by vestibular effects on spatial attention and orienting. Here we investigate whether natural vestibular activation induced by passive whole-body rotation influences tactile detection. In particular, we assessed the ability to detect faint tactile stimuli to the fingertips of the left and right hand during spatially congruent or incongruent rotations. We found that passive whole-body rotations significantly enhanced sensitivity to faint shocks, without affecting response bias. Critically, this enhancement of somatosensory sensitivity did not depend on the spatial congruency between the direction of rotation and the hand stimulated. Thus, our results support a multimodal interaction, likely in brain areas receiving both vestibular and somatosensory signals.

  17. Low-energy diets differing in fibre, red meat and coffee intake equally improve insulin sensitivity in type 2 diabetes: a randomised feasibility trial.

    Science.gov (United States)

    Nowotny, Bettina; Zahiragic, Lejla; Bierwagen, Alessandra; Kabisch, Stefan; Groener, Jan B; Nowotny, Peter J; Fleitmann, Ann Kristin; Herder, Christian; Pacini, Giovanni; Erlund, Iris; Landberg, Rikard; Haering, Hans-Ulrich; Pfeiffer, Andreas F H; Nawroth, Peter P; Roden, Michael

    2015-02-01

    Epidemiological studies have found that a diet high in fibre and coffee, but low in red meat, reduces the risk for type 2 diabetes. We tested the hypothesis that these nutritional modifications differentially improve whole-body insulin sensitivity (primary outcome) and secretion. Inclusion criteria were: age 18-69 years, BMI ≥ 30 kg/m(2), type 2 diabetes treated with diet, metformin or acarbose and known disease duration of ≤ 5 years. Exclusion criteria were: HbA1c >75 mmol/mol (9.0%), type 1 or secondary diabetes types and acute or chronic diseases including cancer. Patients taking any medication affecting the immune system or insulin sensitivity, other than metformin, were also excluded. Of 59 patients (randomised using randomisation blocks [four or six patients] with consecutive numbers), 37 (54% female) obese type 2 diabetic patients completed this controlled parallel-group 8-week low-energy dietary intervention. The participants consumed either a diet high in cereal fibre (whole grain wheat/rye: 30-50 g/day) and coffee (≥ 5 cups/day), and free of red meat (L-RISK, n = 17) or a diet low in fibre (≤ 10 g/day), coffee-free and high in red meat (≥ 150 g/day) diet (H-RISK, n = 20). Insulin sensitivity and secretion were assessed by hyperinsulinaemic-euglycaemic clamp and intravenous glucose tolerance tests with isotope dilution. Whole-body and organ fat contents were measured by magnetic resonance imaging and spectroscopy. Whole-body insulin sensitivity increased in both groups (mean [95% CI]) (H-RISK vs L-RISK: 0.8 [0.2, 1.4] vs 1.0 [0.4, 1.7]mg kg(-1) min(-1), p = 0.59), while body weight decreased (-4.8% [-6.1%, -3.5%] vs -4.6% [-6.0%, -3.3%], respectively). Hepatic insulin sensitivity remained unchanged, whereas hepatocellular lipid content fell in both groups (-7.0% [-9.6%, -4.5%] vs -6.7% [-9.5%, -3.9%]). Subcutaneous fat mass (-1,553 [-2,767, -340] cm(3) vs -751 [-2,047; 546] cm(3), respectively) visceral fat mass (-206 [-783, 371] cm(3) vs -241

  18. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    Science.gov (United States)

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  19. Enhanced skeletal muscle lipid oxidative efficiency in insulin-resistant vs insulin-sensitive nondiabetic, nonobese humans.

    Science.gov (United States)

    Galgani, Jose E; Vasquez, Karla; Watkins, Guillermo; Dupuy, Aude; Bertrand-Michel, Justine; Levade, Thierry; Moro, Cedric

    2013-04-01

    Skeletal muscle insulin resistance is proposed to result from impaired skeletal muscle lipid oxidative capacity. However, there is no evidence indicating that muscle lipid oxidative capacity is impaired in healthy otherwise insulin-resistant individuals. The objective of the study was to assess muscle lipid oxidative capacity in young, nonobese, glucose-tolerant, insulin-resistant vs insulin-sensitive individuals. In 13 insulin-sensitive [by Matsuda index (MI) (22.6 ± 0.6 [SE] kg/m(2)); 23 ± 1 years; MI 5.9 ± 0.1] and 13 insulin-resistant (23.2 ± 0.6 kg/m(2); 23 ± 3 years; MI 2.2 ± 0.1) volunteers, skeletal muscle biopsy, blood extraction before and after an oral glucose load, and dual-energy x-ray absorptiometry were performed. Skeletal muscle mitochondrial to nuclear DNA ratio, oxidative phosphorylation protein content, and citrate synthase and β-hydroxyacyl-CoA dehydrogenase activities were assessed. Muscle lipids and palmitate oxidation ((14)CO2 and (14)C-acid soluble metabolites production) at 4 [1-(14)C]palmitate concentrations (45-520 μM) were also measured. None of the muscle mitochondrial measures showed differences between groups, except for a higher complex V protein content in insulin-resistant vs insulin-sensitive volunteers (3.5 ± 0.4 vs 2.2 ± 0.4; P = .05). Muscle ceramide content was significantly increased in insulin-resistant vs insulin-sensitive individuals (P = .04). Total palmitate oxidation showed a similar concentration-dependent response in both groups (P = .69). However, lipid oxidative efficiency (CO2 to (14)C-acid soluble metabolites ratio) was enhanced in insulin-resistant vs insulin-sensitive individuals, particularly at the highest palmitate concentration (0.24 ± 0.04 vs 0.12 ± 0.02; P = .02). We found no evidence of impaired muscle mitochondrial oxidative capacity in young, nonobese, glucose-tolerant, otherwise insulin-resistant vs insulin-sensitive individuals. Enhanced muscle lipid oxidative efficiency in insulin

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

    DEFF Research Database (Denmark)

    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 Sou...

  1. Decreased insulin sensitivity during dietary sodium restriction is not mediated by effects of angiotensin II on insulin action.

    Science.gov (United States)

    Perry, Colin G; Palmer, Tim; Cleland, Steven J; Morton, Ian J; Salt, Ian P; Petrie, John R; Gould, Gwyn W; Connell, John M C

    2003-08-01

    We have previously reported that modest dietary sodium restriction, as advocated in management guidelines for diabetes, may reduce insulin sensitivity. It has since been suggested that this effect may be mediated via cross-talk between insulin and angiotensin II (AII)-stimulated intracellular second messengers. In order to assess the effect of 5 days of modest sodium restriction (to sodium intake) on insulin sensitivity, 15 healthy males underwent a double-blind, placebo-controlled, randomized, cross-over euglycaemic hyperinsulinaemic clamp study. One phase was supplemented with sodium tablets and the other with matched placebo. Insulin sensitivity (M) was reduced during dietary sodium restriction [median M value, 10.2 mg/kg per min (interquartile range 9.50-13.85) versus 12.8 mg/kg per min (interquartile range 9.60-14.30), P potential mechanisms that may explain this observation, we investigated the effect of AII on insulin action in isolated adipocytes obtained from healthy females. No effect of AII on insulin-mediated glucose transport or suppression of lipolysis was observed. In conclusion, despite the observation that dietary sodium restriction was associated with a median 15% reduction in insulin sensitivity, we found no evidence of a direct effect of AII on insulin action in human adipocytes.

  2. Fasting insulin sensitivity indices are not better than routine clinical variables at predicting insulin sensitivity among Black Africans: a clamp study in sub-Saharan Africans.

    Science.gov (United States)

    Sobngwi, Eugene; Kengne, Andre-Pascal; Echouffo-Tcheugui, Justin B; Choukem, Simeon; Sobngwi-Tambekou, Joelle; Balti, Eric V; Pearce, Mark S; Siaha, Valentin; Mamdjokam, Aissa S; Effoe, Valery; Lontchi-Yimagou, Eric; Donfack, Oliver T; Atogho-Tiedeu, Barbara; Boudou, Philippe; Gautier, Jean-Francois; Mbanya, Jean-Claude

    2014-08-09

    We aimed to evaluate the predictive utility of common fasting insulin sensitivity indices, and non-laboratory surrogates [BMI, waist circumference (WC) and waist-to-height ratio (WHtR)] in sub-Saharan Africans without diabetes. We measured fasting glucose and insulin, and glucose uptake during 80/mU/m2/min euglycemic clamp in 87 Cameroonians (51 men) aged (SD) 34.6 (11.4) years. We derived insulin sensitivity indices including HOMA-IR, quantitative insulin sensitivity check index (QUICKI), fasting insulin resistance index (FIRI) and glucose-to-insulin ratio (GIR). Indices and clinical predictors were compared to clamp using correlation tests, robust linear regressions and agreement of classification by sex-specific thirds. The mean insulin sensitivity was M = 10.5 ± 3.2 mg/kg/min. Classification across thirds of insulin sensitivity by clamp matched with non-laboratory surrogates in 30-48% of participants, and with fasting indices in 27-51%, with kappa statistics ranging from -0.10 to 0.26. Fasting indices correlated significantly with clamp (/r/=0.23-0.30), with GIR performing less well than fasting insulin and HOMA-IR (both p fasting indices (/r/=0.38-0.43). Combinations of fasting indices and clinical predictors explained 25-27% of variation in clamp values. Fasting insulin sensitivity indices are modest predictors of insulin sensitivity measured by euglycemic clamp, and do not perform better than clinical surrogates in this population.

  3. Exercise Enhances Whole-Body Cholesterol Turnover in Mice

    NARCIS (Netherlands)

    Meissner, Maxi; Havinga, Rick; Boverhof, Renze; Kema, Ido; Groen, Albert K.; Kuipers, Folkert

    MEISSNER, M., R. HAVINGA, R. BOVERHOF, I. KEMA, A. K. GROEN, and F. KUIPERS. Exercise Enhances Whole-Body Cholesterol Turnover in Mice. Med. Sci. Sports Exerc., Vol. 42, No. 8, pp. 1460-1468, 2010. Purpose: Regular exercise reduces cardiovascular risk in humans by reducing cholesterol levels, but

  4. Accuracy of whole-body plethysmography requires biological calibration

    DEFF Research Database (Denmark)

    Poorisrisak, Porntiva; Vrang, Carsten; Henriksen, Jorn Molgaard

    2009-01-01

    BACKGROUND: Specific airway resistance (sRaw) measured by whole-body plethysmography in young children is increasingly used in research and clinical practice. The method is precise and feasible. However, there is no available method for calibration of the resistance measure, which raises concern...

  5. Interventions for chronic low back pain: whole body vibration and ...

    African Journals Online (AJOL)

    Objectives. This study explored, described and compared the effects of whole body vibration (WBV) therapy and conventional spinal stabilisation exercises in persons with chronic low back pain (CLBP). Design. A non-randomised sampling technique was used to delineate the base of volunteers gathered by a combination ...

  6. Effects of whole body vibration intervention on handgrip strength of ...

    African Journals Online (AJOL)

    Effects of whole body vibration intervention on handgrip strength of Brazilian healthy soldiers. Danielle Soares Morel, Eloá Moreira-Marconi, Samuel Brandão Sobrinho Neto, Laisa Liane Paineiras Domingos, Patrícia Lopes de Souza, Danúbia da Cunha de Sá Caputo, Glenda Dias Costa, Cláudia Ferreira de Figueiredo, ...

  7. Whole-body vibration dosage alters leg blood flow

    NARCIS (Netherlands)

    Lythgo, Noel; Eser, Prisca; de Groot, Patricia; Galea, Mary

    The effect of whole-body vibration dosage on leg blood flow was investigated. Nine healthy young adult males completed a set of 14 random vibration and non-vibration exercise bouts whilst squatting on a Galileo 900 plate. Six vibration frequencies ranging from 5 to 30 Hz (5 Hz increments) were used

  8. The effect of whole-body vibration training on selected ...

    African Journals Online (AJOL)

    The information on the use of whole-body vibration training (WBVT) on some health-related risk factors such as body composition and biochemical parameters is limited. The purpose of the study was therefore, to assess the effect of progressive WBVT on selected anthropometric and biochemical parameters in healthy ...

  9. Whole body vibration improves attention and motor performance in ...

    African Journals Online (AJOL)

    Background: Whole body vibration (WBV) is a form of physical stimulation via mechanical vibrations transmitted to a subject. It is assumed that WBV induces sensory stimulation in cortical brain regions through the activation of skin and muscle receptors responding to the vibration. The effects of WBV on muscle strength are ...

  10. Whole body vibration improves body mass, flexibility and strength in ...

    African Journals Online (AJOL)

    Objectives. This study aimed to determine the effectiveness of whole body vibration (WBV) training for promoting healthrelated physical fitness in sedentary adults. Design. A non-randomised sampling technique was used with an equivalent match-pair comparison group, pre- and posttest design. Volunteers were gathered ...

  11. The effect of whole body vibration exercise on muscle activation ...

    African Journals Online (AJOL)

    The effect of whole body vibration exercise (WBV) on muscle activation has recently been a topic for discussion amongst some researchers. Researchers are divided on the safety and effectiveness of WBV. The aim of this study was to investigate the effect of WBV on muscle activation. Healthy university students (N = 11; ...

  12. Acute effects of varying whole body vibration exposure on jump ...

    African Journals Online (AJOL)

    Whole body vibration (WBV) has been shown to result in rapid improvement in muscle strength and power. However, WBV studies have utilised sedentary individuals as participants and research is limited on athletes for whom strength and power are their primary assets in sport. Utilising WBV as part of a training ...

  13. Back disorders and whole-body vibration at work

    NARCIS (Netherlands)

    Bongers, P.M.; Boshuizen, H.C.

    1990-01-01

    This thesis describes the relation between occupational exposure to whole body vibration and the incidence and prevalence of disorders of the spine and the back. It focuses on sickness absence and permanente work disability of crane operators, tractor drivers, helicopter pilots, forklift

  14. Visuospatial memory computations during whole-body rotations in roll

    NARCIS (Netherlands)

    Pelt, S. van; Gisbergen, J.A.M. van; Medendorp, W.P.

    2005-01-01

    We used a memory-saccade task to test whether the location of a target, briefly presented before a whole-body rotation in roll, is stored in egocentric or in allocentric coordinates. To make this distinction, we exploited the fact that subjects, when tilted sideways in darkness, make systematic

  15. Kappa Delta Award. Low back pain and whole body vibration.

    Science.gov (United States)

    Pope, M H; Magnusson, M; Wilder, D G

    1998-09-01

    The investigators describe their multifaceted approach to the study of the relationship between whole body vibration and low back pain. The epidemiologic study was a two center study of drivers and sedentary workers in the United States and Sweden. The vibration exposure was measured in the vehicles. It was found that the career vibration exposure was related to low back, neck, and shoulder pain. However, disability was related to job satisfaction. In vivo experiments, using percutaneous pin mounted accelerometers have shown that the natural frequency is at 4.5 Hz. The frequency response is affected by posture, seating, and seat back inclination. The response appears to be determined largely by the rocking of the pelvis. Electromyographic studies have shown that muscle fatigue occurs under whole body vibration. After whole body vibration exposure the muscle response to a sudden load has greater latency. Vehicle driving may be a reason for low back pain or herniated nucleus pulposus. Prolonged seating exposure, coupled with the whole body vibration, should be reduced for those recovering from these problems. Vibration attenuating seats and correct ergonomic layout of the cabs may reduce the risks of recurrence.

  16. BABYSCAN - a whole body counter for small children in Fukushima

    CERN Document Server

    Hayano, Ryugo S; Bronson, Frazier L; Oginni, Babatunde; Muramatsu, Isamu

    2014-01-01

    BABYSCAN, a whole body counter for small children with a detection limit for $^{137}$Cs of better than 50 Bq/body, was developed, and the first unit has been installed at a hospital in Fukushima, to help families with small children who are very much concerned about internal exposures. The design principles, implementation details and the initial operating experience are described.

  17. Effects of aerobic exercise and whole body vibration on glycaemia control in type 2 diabetic males.

    Science.gov (United States)

    Behboudi, Lale; Azarbayjani, Mohammad-Ali; Aghaalinejad, Hamid; Salavati, Mahyar

    2011-06-01

    Aerobic exercise has been identified as the main treatment for type 2 diabetic patients. Such an exercise, however, is usually repined by some of patients who suffer from lack of stamina. Therefore, whole body vibration has recently been introduced as a passive intervention. The present study aimed at comparing how aerobic exercise and whole body vibration affect glycaemia control in type 2 diabetic males. Thirty diabetic males were divided into three groups, namely aerobic exercise (AE), whole body vibration (WBV), and control. Aerobic exercise schedule consisted of three walking sessions a week, each for 30-60 minutes and in 60-70% of maximum stock heartbeat. Vibration exercise was composed of 8-12-min stand-up and semi-squat positioning in frequency of 30 Hz and amplitude of 2 mm. Concentrations of fasting glycosylated hemoglobin, fasting glucose, and insulin were measured in the beginning of the trial, after the fourth week, and after the eighth week. After 8 weeks of exercise, no significant difference was detected in concentrations of fasting glycosylated hemoglobin and insulin between the groups (P=0.83, P=0.12). There were no significant differences in any of the variables between AE and WBV (P>0.05). But a more significant decrease in fasting glucose was observed in exercise groups (AE and WBV) compared with control group (P=0.02). The present study showed that AE and WBV identically stimulate metabolic system. Thus, it can be concluded that type 2 diabetic patients lacking stamina for aerobic exercise can opt for vibration exercise as an effective substitute.

  18. 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.

  19. Longitudinal relationship of physical activity with insulin sensitivity in overweight and obese pregnant women.

    Science.gov (United States)

    van Poppel, Mireille N M; Oostdam, Nicolette; Eekhoff, Marelise E W; Wouters, Maurice G A J; van Mechelen, Willem; Catalano, Patrick M

    2013-07-01

    Physical activity (PA) initiated in the second half of pregnancy does not affect (or modify) insulin sensitivity in normal weight women. However, this might be different in obese women with lower insulin sensitivity. To test the hypothesis that in overweight and obese women at risk for gestational diabetes, PA is related to improved maternal glucose and insulin metabolism in pregnancy. A longitudinal study, with measurements at 15, 24, and 32 weeks of gestation, was conducted. Time spent in moderate-to-vigorous PA (MVPA) was measured objectively. In regression models, the relationship between time spent in MVPA at week 15 and changes in MVPA from 15 weeks to 24 or 32 weeks with fasting glucose, glycosylated hemoglobin, fasting insulin, insulin sensitivity, and insulin response at week 24 or 32 was assessed. In a group of 24 women, MVPA in early pregnancy was significantly associated with a reduced first- and second-phase insulin response at week 32. Women with larger decreases in MVPA throughout pregnancy had significantly higher fasting insulin levels, worse insulin sensitivity, increased first- and second-phase insulin response, and higher triglyceride levels in late pregnancy compared to women with smaller decreases in MVPA. Time spent in MVPA was not related to glucose or glycosylated hemoglobin levels. In our group of overweight and obese pregnant women, MVPA was associated with improved insulin sensitivity, insulin response, and decreased triglycerides at 32 weeks of pregnancy. This supports efforts for counseling obese women at risk for gestational diabetes in pregnancy to maintain their MVPA levels.

  20. 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.

  1. Intestinal SIRT3 overexpression in mice improves whole body glucose homeostasis independent of body weight.

    Science.gov (United States)

    Ramachandran, Deepti; Clara, Rosmarie; Fedele, Shahana; Hu, Junmin; Lackzo, Endre; Huang, Jing-Yi; Verdin, Eric; Langhans, Wolfgang; Mansouri, Abdelhak

    2017-10-01

    Intestinal metabolism might play a greater role in regulating whole body metabolism than previously believed. We aimed to enhance enterocyte metabolism in mice and investigate if it plays a role in diet-induced obesity (DIO) and its comorbidities. Using the cre-loxP system, we overexpressed the mitochondrial NAD+ dependent protein deacetylase SIRT3 in enterocytes of mice (iSIRT3 mice). We chronically fed iSIRT3 mice and floxed-SIRT3 control (S3fl) mice a low-fat, control diet (CD) or a high-fat diet (HFD) and then phenotyped the mice. There were no genotype differences in any of the parameters tested when the mice were fed CD. Also, iSIRT3 mice were equally susceptible to the development of DIO as S3fl mice when fed HFD. They were, however, better able than S3fl mice to regulate their blood glucose levels in response to exogenous insulin and glucose, indicating that they were protected from developing insulin resistance. This improved glucose homeostasis was accompanied by an increase in enterocyte metabolic activity and an upregulation of ketogenic gene expression in the small intestine. Enhancing enterocyte oxidative metabolism can improve whole body glucose homeostasis. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

  2. Effect of Low Salt Diet on Insulin Resistance in Salt Sensitive versus Salt Resistant Hypertension

    OpenAIRE

    Garg, Rajesh; Sun, Bei; Williams, Jonathan

    2014-01-01

    Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt sensitive versus salt resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after one week of high salt (200 mmol/day Na) and one week of low salt (10 mmol/day Na) diet. Salt sensitivit...

  3. Specificity of insulin signalling in human skeletal muscle as revealed by small interfering RNA.

    Science.gov (United States)

    Krook, A; Zierath, J R

    2009-07-01

    Insulin action on metabolically active tissues is a complex process involving positive and negative feedback regulation to control whole body glucose homeostasis. At the cellular level, glucose and lipid metabolism, as well as protein synthesis, are controlled through canonical insulin signalling cascades. The discovery of small interfering RNA (siRNA) allows for the molecular dissection of critical components of the regulation of metabolic and gene regulatory events in insulin-sensitive tissues. The application of siRNA to tissues of human origin allows for the molecular dissection of the mechanism(s) regulating glucose and lipid metabolism. Penetration of the pathways controlling insulin action in human tissue may aid in discovery efforts to develop diabetes prevention and treatment strategies. This review will focus on the use of siRNA to validate critical regulators controlling insulin action in human skeletal muscle, a key organ important for the control of whole body insulin-mediated glucose uptake and metabolism.

  4. Molecular Imaging in Breast Cancer: From Whole-Body PET/CT to Dedicated Breast PET

    Directory of Open Access Journals (Sweden)

    B. B. Koolen

    2012-01-01

    Full Text Available Positron emission tomography (PET, with or without integrated computed tomography (CT, using 18F-fluorodeoxyglucose (FDG is based on the principle of elevated glucose metabolism in malignant tumors, and its use in breast cancer patients is frequently being investigated. It has been shown useful for classification, staging, and response monitoring, both in primary and recurrent disease. However, because of the partial volume effect and limited resolution of most whole-body PET scanners, sensitivity for the visualization of small tumors is generally low. To improve the detection and quantification of primary breast tumors with FDG PET, several dedicated breast PET devices have been developed. In this nonsystematic review, we shortly summarize the value of whole-body PET/CT in breast cancer and provide an overview of currently available dedicated breast PETs.

  5. Enhanced insulin secretion and insulin sensitivity in young lambs with placental insufficiency-induced intrauterine growth restriction.

    Science.gov (United States)

    Camacho, Leticia E; Chen, Xiaochuan; Hay, William W; Limesand, Sean W

    2017-08-01

    Intrauterine growth restriction (IUGR) is associated with persistent metabolic complications, but information is limited for IUGR infants. We determined glucose-stimulated insulin secretion (GSIS) and insulin sensitivity in young lambs with placental insufficiency-induced IUGR. Lambs with hyperthermia-induced IUGR ( n = 7) were compared with control lambs ( n = 8). GSIS was measured at 8 ± 1 days of age, and at 15 ± 1 days, body weight-specific glucose utilization rates were measured with radiolabeled d-glucose during a hyperinsulinemic-euglycemic clamp (HEC). IUGR lambs weighed 23% less ( P insulin concentrations were not different between IUGR and controls for either study. First-phase insulin secretion was enhanced 2.3-fold in IUGR lambs compared with controls. However, second-phase insulin concentrations, glucose-potentiated arginine-stimulated insulin secretion, and β-cell mass were not different, indicating that IUGR β-cells have an intrinsic enhancement in acute GSIS. Compared with controls, IUGR lambs had higher body weight-specific glucose utilization rates and greater insulin sensitivity at fasting (1.6-fold) and hyperinsulinemic periods (2.4-fold). Improved insulin sensitivity for glucose utilization was not due to differences in skeletal muscle insulin receptor and glucose transporters 1 and 4 concentrations. Plasma lactate concentrations during HEC were elevated in IUGR lambs compared with controls, but no differences were found for glycogen content or citrate synthase activity in liver and muscle. Greater insulin sensitivity for glucose utilization and enhanced acute GSIS in young lambs are predicted from fetal studies but may promote conditions that exaggerate glucose disposal and lead to episodes of hypoglycemia in IUGR infants. Copyright © 2017 the American Physiological Society.

  6. 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....

  7. 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

    Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS of the...... novel loci and replicated known variants associated with insulin sensitivity. Further studies are needed to clarify the causal variant and function at the BCL2 and FAM19A2 loci.......Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed GWAS...... 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...

  8. Whole-body MRI for initial staging of paediatric lymphoma: prospective comparison to an FDG-PET/CT-based reference standard

    Energy Technology Data Exchange (ETDEWEB)

    Littooij, Annemieke S. [University Medical Centre Utrecht/Wilhelmina Children' s Hospital, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); KK Women' s and Children' s Hospital, Department of Diagnostic and Interventional Imaging, Singapore (Singapore); Kwee, Thomas C.; Vermoolen, Malou A.; Keizer, Bart de; Beek, Frederik J.A.; Hobbelink, Monique G.; Nievelstein, Rutger A.J. [University Medical Centre Utrecht/Wilhelmina Children' s Hospital, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Barber, Ignasi; Enriquez, Goya [Hospital Materno-Infantil Vall d' Hebron, Department of Paediatric Radiology, Barcelona (Spain); Granata, Claudio [IRCCS Giannina Gaslini Hospital, Department of Radiology, Genoa (Italy); Zsiros, Jozsef [University of Amsterdam, Department of Paediatric Oncology, Emma Children' s Hospital, Academic Medical Centre, Amsterdam (Netherlands); Soh, Shui Yen [KK Women' s and Children' s Hospital, Haematology and Oncology service, Department of Paediatric Subspecialities, Singapore (Singapore); Bierings, Marc B. [University Medical Centre Utrecht/Wilhelmina Children' s Hospital, Department of Paediatric Haematology-Oncology, Utrecht (Netherlands); Stoker, Jaap [University of Amsterdam, Department of Radiology, Academic Medical Centre, Amsterdam (Netherlands)

    2014-05-15

    To compare whole-body MRI, including diffusion-weighted imaging (whole-body MRI-DWI), with FDG-PET/CT for staging newly diagnosed paediatric lymphoma. A total of 36 children with newly diagnosed lymphoma prospectively underwent both whole-body MRI-DWI and FDG-PET/CT. Whole-body MRI-DWI was successfully performed in 33 patients (mean age 13.9 years). Whole-body MRI-DWI was independently evaluated by two blinded observers. After consensus reading, an unblinded expert panel evaluated the discrepant findings between whole-body MRI-DWI and FDG-PET/CT and used bone marrow biopsy, other imaging data and clinical information to derive an FDG-PET/CT-based reference standard. Interobserver agreement of whole-body MRI-DWI was good [all nodal sites together (κ = 0.79); all extranodal sites together (κ = 0.69)]. There was very good agreement between the consensus whole-body MRI-DWI- and FDG-PET/CT-based reference standard for nodal (κ = 0.91) and extranodal (κ = 0.94) staging. The sensitivity and specificity of consensus whole-body MRI-DWI were 93 % and 98 % for nodal staging and 89 % and 100 % for extranodal staging, respectively. Following removal of MRI reader errors, the disease stage according to whole-body MRI-DWI agreed with the reference standard in 28 of 33 patients. Our results indicate that whole-body MRI-DWI is feasible for staging paediatric lymphoma and could potentially serve as a good radiation-free alternative to FDG-PET/CT. (orig.)

  9. [Whole-body MRI and FDG-PET/CT imaging diagnostics in oncology].

    Science.gov (United States)

    Schmidt, G P; Haug, A; Reiser, M F; Rist, C

    2010-04-01

    The advent of whole-body MRI (WB-MRI) has introduced a systemic approach to oncologic imaging compared to established sequential, multi-modal diagnostic algorithms. Hardware innovations, such as whole-body scanners at 1.5 Tesla and also recently 3 Tesla, combined with acquisition acceleration techniques, have made WB-MRI clinically feasible. With this method dedicated assessment of individual organs with various soft tissue contrast, high spatial resolution and contrast media dynamics can be combined with whole-body anatomic coverage.PET/CT has established itself as a powerful modality in the staging of patients suffering from malignant tumors. In addition to the morphologic information provided by the CT component of this hybrid modality, the PET component contributes invaluable metabolic information, which greatly enhances accuracy in the assessment of lymphatic spread and viability of tumor tissue. Whole-body MR diffusion imaging is a novel and promising technique which may contribute to superior sensitivity in the detection of tumor manifestations. In the assessment of distant metastatic spread WB-MRI is highly sensitive and has advantages over PET/CT, especially in those tumors frequently spreading to the liver, bone or brain. WB-MRI is also very attractive as a radiation-free alternative for imaging of pediatric tumor patients in whom multiple follow-up examinations may be required.WB-MRI allows for precise assessment of the bone marrow and has been proven to be highly accurate for the staging of hematologic diseases, such as multiple myeloma. In this article recent developments and applications of WB-MRI in oncologic imaging are addressed and compared to the results of PET/CT.

  10. Gsα deficiency in adipose tissue improves glucose metabolism and insulin sensitivity without an effect on body weight.

    Science.gov (United States)

    Li, Yong-Qi; Shrestha, Yogendra B; Chen, Min; Chanturiya, Tatyana; Gavrilova, Oksana; Weinstein, Lee S

    2016-01-12

    Gsα, the G protein that transduces receptor-stimulated cAMP generation, mediates sympathetic nervous system stimulation of brown adipose tissue (BAT) thermogenesis and browning of white adipose tissue (WAT), which are both potential targets for treating obesity, as well as lipolysis. We generated a mouse line with Gsα deficiency in mature BAT and WAT adipocytes (Ad-GsKO). Ad-GsKO mice had impaired BAT function, absent browning of WAT, and reduced lipolysis, and were therefore cold-intolerant. Despite the presence of these abnormalities, Ad-GsKO mice maintained normal energy balance on both standard and high-fat diets, associated with decreases in both lipolysis and lipid synthesis. In addition, Ad-GsKO mice maintained at thermoneutrality on a standard diet also had normal energy balance. Ad-GsKO mice had improved insulin sensitivity and glucose metabolism, possibly secondary to the effects of reduced lipolysis and lower circulating fatty acid binding protein 4 levels. Gsα signaling in adipose tissues may therefore affect whole-body glucose metabolism in the absence of an effect on body weight.

  11. Increased insulin secretory capacity but decreased insulin sensitivity after correction of iron overload by phlebotomy in hereditary haemochromatosis.

    Science.gov (United States)

    Abraham, D; Rogers, J; Gault, P; Kushner, J P; McClain, D A

    2006-11-01

    We recently demonstrated that humans with hereditary haemochromatosis have decreased insulin secretory capacity with a compensatory increase in insulin sensitivity. We therefore determined how these measures change after correction of tissue iron overload. Five non-diabetic subjects who had been studied previously at the time of initial diagnosis by means of the OGTT and frequently sampled intravenous glucose tolerance tests (FSIVGTT) underwent phlebotomy to normalise their serum ferritin. After normalisation of ferritin they were studied again (33+/-4 months after the initial studies) by OGTT and FSIVGTT. Normalisation of tissue iron stores resulted in an average 1.8-fold increase in the integrated area under the insulin curve during OGTT (pdisposition index (AIRgxSi) was unchanged (5% increase, p=0.90). BMI and fasting glucose were unchanged. At the time of diagnosis of haemochromatosis, four of the subjects had IGT. After normalisation of ferritin, two achieved NGT and two remained with IGT, despite 2.5- and 3.7-fold increases in insulin secretory capacity. Insulin secretory capacity improves after normalisation of iron stores in subjects with hereditary haemochromatosis. Glucose tolerance status improves incompletely because of decreased insulin sensitivity after phlebotomy. We conclude that tissue iron levels are an important determinant of insulin secretion and insulin action.

  12. Human gut microbes impact host serum metabolome and insulin sensitivity

    DEFF Research Database (Denmark)

    Pedersen, Helle Krogh; Gudmundsdottir, Valborg; Nielsen, Henrik Bjørn

    2016-01-01

    Insulin resistance is a forerunner state of ischaemic cardiovascular disease and type 2 diabetes. Here we show how the human gut microbiome impacts the serum metabolome and associates with insulin resistance in 277 non-diabetic Danish individuals. The serum metabolome of insulin-resistant...... are identified as the main species driving the association between biosynthesis of BCAAs and insulin resistance, and in mice we demonstrate that P. copri can induce insulin resistance, aggravate glucose intolerance and augment circulating levels of BCAAs. Our findings suggest that microbial targets may have...... the potential to diminish insulin resistance and reduce the incidence of common metabolic and cardiovascular disorders....

  13. pH sensitive insulin-loaded nanohydrogel increases the effect of oral insulin in diabetic rats.

    Science.gov (United States)

    Karnoosh-Yamchi, Jalil; Rahmati-Yamchi, Mohammad; Akbarzadeh, Abolfazl; Davaran, Soodabeh; Ostad Rahimi, Ali Reza; Garnoosh, Khalil; Bahmani, Zahra; Ashoori, Mohammad; Mobasseri, Majid

    2017-09-01

    There are different methods for insulin administration in diabetic patient. Nano-hydrogel is one of the most talented drug carrier for its sensitivity to environmental stimulus. NIPAAm-MAA-HEM copolymers were synthesized by radical chain reaction. The copolymers were characterized with Scanning electron microscopy (SEM) and Transient electron microscopy (TEM). Copolymers were loaded with regular insulin by modified double emulsion method. Diabetic rats are used for feeding insulin-loaded nanohydrogel. Analysis of the results from the measurement of the amount of blood insulin from the rats blood that received insulin in nanohydrogel loaded form compared with rats that received pure insulin is significantly high, which confirm that insulin has been able to pass from the stomach acid barrier by nanohydrogel and is absorbed from the intestine. Blood sugar levels from tested rats indicate that with increasing amount of insulin, blood sugar levels fall down. Our study confirms that insulin has been able to pass from the stomach acid barrier by nanohydrogel and be absorbed from the intestine.

  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. Whole body vibration in sport: a critical review.

    Science.gov (United States)

    Costantino, C; Gimigliano, R; Olvirri, S; Gimigliano, F

    2014-12-01

    Whole body vibration training is a recent area of study in athletic conditioning, health and rehabilitation. This paper provides a review of the effectiveness of this type of training in sport. A search was conducted across several electronic databases and studies on effects of whole body vibration training on sport performance were reviewed. Thirteen articles were included in the final analysis. The following variables were considered: participants investigated (sex and age), characteristics of the vibration (frequency and amplitude), training (type of sport, exposure time and intensity, tests used, type of study, effects examined and results obtained). This review considers proposed neural mechanisms and identifies studies that have demonstrated the effectiveness of WBV in sports. It considers where WBV might act and suggests that vibration can be an effective training stimulus. Future studies should focus on evaluating the long-term effects of vibration training and identify optimum frequency and amplitude, improve strength and muscular performance.

  16. Whole-body MRI evaluation of facioscapulohumeral muscular dystrophy

    Science.gov (United States)

    Leung, Doris G.; Carrino, John A.; Wagner, Kathryn R.; Jacobs, Michael A.

    2015-01-01

    Introduction Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. Increasing knowledge of the pathophysiology of FSHD has stimulated interest in developing biomarkers of disease severity. Methods Two groups of MRI scans were analyzed: whole-body scans from 13 subjects with FSHD, and upper and lower extremity scans from 34 subjects with FSHD who participated in the MYO-029 clinical trial. Muscles were scored for fat infiltration and edema-like changes. Fat infiltration scores were compared to muscle strength and function. Results Our analysis reveals a distinctive pattern of both frequent muscle involvement and frequent sparing in FSHD. Averaged fat infiltration scores for muscle groups in the legs correlated with quantitative muscle strength and 10-meter walk times. Discussion Advances in MRI technology allow for the acquisition of rapid, high-quality whole-body imaging in diffuse muscle disease. This technique offers a promising disease biomarker in FSHD and other muscle diseases. PMID:25641525

  17. A Portable Stereo Vision System for Whole Body Surface Imaging.

    Science.gov (United States)

    Yu, Wurong; Xu, Bugao

    2010-04-01

    This paper presents a whole body surface imaging system based on stereo vision technology. We have adopted a compact and economical configuration which involves only four stereo units to image the frontal and rear sides of the body. The success of the system depends on a stereo matching process that can effectively segment the body from the background in addition to recovering sufficient geometric details. For this purpose, we have developed a novel sub-pixel, dense stereo matching algorithm which includes two major phases. In the first phase, the foreground is accurately segmented with the help of a predefined virtual interface in the disparity space image, and a coarse disparity map is generated with block matching. In the second phase, local least squares matching is performed in combination with global optimization within a regularization framework, so as to ensure both accuracy and reliability. Our experimental results show that the system can realistically capture smooth and natural whole body shapes with high accuracy.

  18. Thermal, circulatory, and neuromuscular responses to whole-body cryotherapy

    OpenAIRE

    Westerlund, T. (Tarja)

    2009-01-01

    Abstract The purpose of this study was to examine thermal (body temperature, thermal sensation and comfort ratings), circulatory (blood pressure, heart rate variability) and neuromuscular performance responses to whole-body cryotherapy (WBC, -110 °C). Altogether 66 healthy subjects were exposed to WBC for two minutes. The acute and long-term changes were examined, when the subjects were exposed to WBC three times a week during three months. Skin temperatures decreased very rapidl...

  19. A whole body statistical shape model for radio frequency simulation.

    Science.gov (United States)

    Lee, Su-Lin; Ali, Khaleda; Brizzi, Alessio; Keegan, Jennifer; Hao, Yang; Yang, Guang-Zhong

    2011-01-01

    The development of ultra low power wireless sensors for customized wearable and implantable medical devices requires patient specific models for radio frequency simulation to understand wave propagation in the body. In practice, the creation of a patient specific whole-body model is difficult and time consuming to create. It is therefore necessary to establish a method for studying a population in a statistical manner. In this paper, we present a statistical shape model for the whole body for RF simulation. It is built from 10 male and 10 female subjects of varying size and height. This model has the ability to instantiate a new surface mesh with the parameters allowed by the training set. This model would provide shapes of varying sizes for studies, without the requirement of obtaining subject specific whole body models. Results from finite-differences time-domain simulation are presented on the extreme shapes from the model and demonstrate the need for a full understanding of the range in body shapes.

  20. Whole-body magnetic resonance imaging in children: state of the art

    Directory of Open Access Journals (Sweden)

    Sara Reis Teixeira

    2015-04-01

    Full Text Available Whole-body imaging in children was classically performed with radiography, positron-emission tomography, either combined or not with computed tomography, the latter with the disadvantage of exposure to ionizing radiation. Whole-body magnetic resonance imaging (MRI, in association with the recently developed metabolic and functional techniques such as diffusion-weighted imaging, has brought the advantage of a comprehensive evaluation of pediatric patients without the risks inherent to ionizing radiation usually present in other conventional imaging methods. It is a rapid and sensitive method, particularly in pediatrics, for detecting and monitoring multifocal lesions in the body as a whole. In pediatrics, it is utilized for both oncologic and non-oncologic indications such as screening and diagnosis of tumors in patients with genetic syndromes, evaluation of disease extent and staging, evaluation of therapeutic response and post-therapy follow-up, evaluation of non neoplastic diseases such as multifocal osteomyelitis, vascular malformations and syndromes affecting multiple regions of the body. The present review was aimed at describing the major indications of whole-body MRI in pediatrics added of technical considerations.

  1. 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.

  2. 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.

  3. Melanoma screening with serial whole body photographic change detection using Melanoscan technology.

    Science.gov (United States)

    Drugge, Rhett J; Nguyen, Chi; Drugge, Elizabeth D; Gliga, Luciana; Broderick, Patrick A; McClain, Steve A; Brown, Christopher C

    2009-06-15

    The use of an automated, whole-body, diffusely lit digital imaging enclosure to produce serial images, which were then compared, using an astrophysics image display method, enabled a private practice dermatologist to detect melanoma at significantly thinner Breslow depths compared to all other clinical detection paradigms examined in this study. The patients were triaged to scanning using a melanoma risk survey system. The system employed a 24 camera semicircular imaging wall, with front and back views. 10,000 whole body photographic scans were obtained. Privacy was maintained with 128-bit image encryption and off-line storage. Image to image comparison of whole body digital photography was combined with a whole body skin exam in order to sensitize a clinical dermatologist to skin changes in individuals at risk for melanoma. Mean depths (Breslow scores) were compiled from six distinct melanoma biopsy cohorts segregated and based on different clinical screening paradigms. The Breslow depth of invasive lesions of the serial screening cohort was significantly less (by at least 0.050 mm) compared to three other clinical screening groups (patient self-detection 0.55 mm, p=0.007; referred by outside non-dermatologist physician 0.73 mm, p=0.03; and serial dermatologic evaluation 0.23 mm, p=0.03) as well as two pathology laboratory cohorts (community hospital laboratory 1.45 mm, p=0.003; dermatopathology laboratory 0.18, p=0.0003). This approach provides a quick and effective method for detection of early melanomas with a significant reduction in the skin area required for lesion examination.

  4. AMP-activated Protein Kinase (AMPK): Does This Master Regulator of Cellular Energy State Distinguish Insulin Sensitive from Insulin Resistant Obesity?

    Science.gov (United States)

    Xu, X Julia; Valentine, Rudy J; Ruderman, Neil B

    2014-06-01

    Although a correlation exists between obesity and insulin resistance, roughly 25 % of obese individuals are insulin sensitive. AMP-activated protein kinase (AMPK) is a cellular energy sensor that among its many actions, integrates diverse physiological signals to restore energy balance. In addition, in many situations it also increases insulin sensitivity. In this context, AMPK activity is decreased in very obese individuals undergoing bariatric surgery who are insulin resistant compared to equally obese patients who are insulin sensitive. In this review, we will both explore what distinguishes these individuals, and evaluate the evidence that diminished AMPK is associated with insulin resistance and metabolic syndrome-associated disorders in other circumstances.

  5. 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

    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...... 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...... [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...

  6. Longitudinal Relationship of Physical Activity With Insulin Sensitivity in Overweight and Obese Pregnant Women

    NARCIS (Netherlands)

    van Poppel, M.N.M.; Oostdam, E.W.M.; Eekhoff, E.M.W.; Wouters, M.G.A.J.; van Mechelen, W.; Catalano, P.M.

    2013-01-01

    Background: Physical activity (PA) initiated in the second half of pregnancy does not affect (or modify) insulin sensitivity in normal weight women. However, this might be different in obese women with lower insulin sensitivity. Objective: To test the hypothesis that in overweight and obese women at

  7. 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.

  8. Apple polyphenol extract improves insulin sensitivity in vitro and in vivo in animal models of insulin resistance

    OpenAIRE

    Manzano, Manuel; Giron, Mar?a D; Vilchez, Jos? D.; Sevillano, Natalia; El-Azem, Nuri; Rueda, Ricardo; Salto, Rafael; Lopez-Pedrosa, Jose M.

    2016-01-01

    Background Apple polyphenols could represent a novel nutritional approach in the management and control of blood glucose, especially in type 2 diabetics. The aim of this study was to test the therapeutic potential of an apple polyphenol extract (APE) in an insulin-resistant rat model and to determine the molecular basis of insulin sensitivity action in skeletal muscle cells. Methods Acute effect of APE on the postprandial hyperglycemic response was assayed in 15?week old obese Zucker rats (OZ...

  9. Improved insulin sensitivity and resistance to weight gain in mice null for the Ahsg gene.

    Science.gov (United States)

    Mathews, Suresh T; Singh, Gurmant P; Ranalletta, Mollie; Cintron, Vivian J; Qiang, Xiaoling; Goustin, Anton Scott; Jen, Kai-Lin Catherine; Charron, Maureen J; Jahnen-Dechent, Willi; Grunberger, George

    2002-08-01

    Fetuin inhibits insulin-induced insulin receptor (IR) autophosphorylation and tyrosine kinase activity in vitro, in intact cells, and in vivo. The fetuin gene (AHSG) is located on human chromosome 3q27, recently identified as a susceptibility locus for type 2 diabetes and the metabolic syndrome. Here, we explore insulin signaling, glucose homeostasis, and the effect of a high-fat diet on weight gain, body fat composition, and glucose disposal in mice carrying two null alleles for the gene encoding fetuin, Ahsg (B6, 129-Ahsg(tm1Mbl)). Fetuin knockout (KO) mice demonstrate increased basal and insulin-stimulated phosphorylation of IR and the downstream signaling molecules mitogen-activated protein kinase (MAPK) and Akt in liver and skeletal muscle. Glucose and insulin tolerance tests in fetuin KO mice indicate significantly enhanced glucose clearance and insulin sensitivity. Fetuin KO mice subjected to euglycemic-hyperinsulinemic clamp show augmented sensitivity to insulin, evidenced by increased glucose infusion rate (P = 0.077) and significantly increased skeletal muscle glycogen content (P < 0.05). When fed a high-fat diet, fetuin KO mice are resistant to weight gain, demonstrate significantly decreased body fat, and remain insulin sensitive. These data suggest that fetuin may play a significant role in regulating postprandial glucose disposal, insulin sensitivity, weight gain, and fat accumulation and may be a novel therapeutic target in the treatment of type 2 diabetes, obesity, and other insulin-resistant conditions.

  10. Whole-body MRI for the detection of bone marrow involvement in lymphoma: prospective study in 116 patients and comparison with FDG-PET

    Energy Technology Data Exchange (ETDEWEB)

    Adams, Hugo J.A.; Kwee, Thomas C.; Vermoolen, Malou A.; Keizer, Bart de; Nievelstein, Rutger A.J. [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Adam, Judit A. [Academic Medical Center, Department of Nuclear Medicine, Amsterdam (Netherlands); Fijnheer, Rob [Meander Medical Center, Department of Hematology, Amersfoort (Netherlands); Kersten, Marie Jose [Academic Medical Center, Department of Hematology, Amsterdam (Netherlands); Stoker, Jaap [Academic Medical Center, Department of Radiology, Amsterdam (Netherlands)

    2013-08-15

    To assess and compare the value of whole-body MRI with FDG-PET for detecting bone marrow involvement in lymphoma. A total of 116 patients with newly diagnosed lymphoma prospectively underwent whole-body MRI and blind bone marrow biopsy (BMB) of the posterior iliac crest. Of 116 patients, 80 also underwent FDG-PET. Patient-based sensitivities of whole-body MRI for detecting bone marrow involvement were calculated using BMB as reference standard and compared with FDG-PET in aggressive and indolent lymphomas separately. Sensitivity of whole-body MRI in all lymphomas was 45.5 % [95 % confidence interval (CI): 29.8-62.0 %]. Sensitivity of whole-body MRI in aggressive lymphoma [88.9 % (95 % CI: 54.3-100 %)] was significantly higher (P = 0.0029) than that in indolent lymphoma [23.5 % (95 % CI: 9.1-47.8 %)]. Sensitivity of FDG-PET in aggressive lymphoma [83.3 % (95 % CI: 41.8-98.9 %)] was also significantly higher (P = 0.026) than that in indolent lymphoma [12.5 % (95 % CI: 0-49.2 %)]. There were no significant differences in sensitivity between whole-body MRI and FDG-PET (P = 1.00) Sensitivity of whole-body MRI for detecting lymphomatous bone marrow involvement is too low to (partially) replace BMB. Sensitivity of whole-body MRI is significantly higher in aggressive lymphoma than in indolent lymphoma and is equal to FDG-PET in both entities. (orig.)

  11. Early responses of insulin signaling to high-carbohydrate and high-fat overfeeding

    Directory of Open Access Journals (Sweden)

    Gray Karen

    2009-09-01

    Full Text Available Abstract Background Early molecular changes of nutritionally-induced insulin resistance are still enigmatic. It is also unclear if acute overnutrition alone can alter insulin signaling in humans or if the macronutrient composition of the diet can modulate such effects. Methods To investigate the molecular correlates of metabolic adaptation to either high-carbohydrate (HC or high-fat (HF overfeeding, we conducted overfeeding studies in 21 healthy lean (BMI in vivo insulin sensitivity was assessed using the hyperinsulinemic-euglycemic clamp technique. Ex vivo insulin action was measured from skeletal muscle tissue samples obtained 15 minutes after insulin infusion was initiated. Results Overall there was no change in whole-body insulin sensitivity as measured by glucose disposal rate (GDR, EC: 12.1 ± 4.7; HC: 10.9 ± 2.7; HF: 10.8 ± 3.4. Assessment of skeletal muscle insulin signaling demonstrated increased tyrosine phosphorylation of IRS-1 (p Conclusion We conclude that acute bouts of overnutrition lead to changes at the cellular level before whole-body insulin sensitivity is altered. On a signaling level, HC overfeeding resulted in changes compatible with increased insulin sensitivity. In contrast, molecular changes in HF overfeeding were compatible with a reduced insulin sensitivity.

  12. Effects of whole-body vibration exercise on the endocrine system of healthy men.

    Science.gov (United States)

    Di Loreto, C; Ranchelli, A; Lucidi, P; Murdolo, G; Parlanti, N; De Cicco, A; Tsarpela, O; Annino, G; Bosco, C; Santeusanio, F; Bolli, G B; De Feo, P

    2004-04-01

    Whole-body vibration is reported to increase muscle performance, bone mineral density and stimulate the secretion of lipolytic and protein anabolic hormones, such as GH and testosterone, that might be used for the treatment of obesity. To date, as no controlled trial has examined the effects of vibration exercise on the human endocrine system, we performed a randomized controlled study, to establish whether the circulating concentrations of glucose and hormones (insulin, glucagon, cortisol, epinephrine, norepinephrine, GH, IGF-1, free and total testosterone) are affected by vibration in 10 healthy men [age 39 +/- 3, body mass index (BMI) of 23.5 +/- 0.5 kg/m2, mean +/- SEM]. Volunteers were studied on two occasions before and after standing for 25 min on a ground plate in the absence (control) or in the presence (vibration) of 30 Hz whole body vibration. Vibration slightly reduced plasma glucose (30 min: vibration 4.59 +/- 0.21, control 4.74 +/- 0.22 mM, p=0.049) and increased plasma norepinephrine concentrations (60 min: vibration 1.29 +/- 0.18, control 1.01 +/- 0.07 nM, p=0.038), but did not change the circulating concentrations of other hormones. These results demonstrate that vibration exercise transiently reduces plasma glucose, possibly by increasing glucose utilization by contracting muscles. Since hormonal responses, with the exception of norepinephrine, are not affected by acute vibration exposure, this type of exercise is not expected to reduce fat mass in obese subjects.

  13. Mechanism by which arylamine N-acetyltransferase 1 ablation causes insulin resistance in mice

    DEFF Research Database (Denmark)

    Camporez, João Paulo; Wang, Yongliang; Faarkrog, Kasper

    2017-01-01

    A single-nucleotide polymorphism in the human arylamine N-acetyltransferase 2 (Nat2) gene has recently been identified as associated with insulin resistance in humans. To understand the cellular and molecular mechanisms by which alterations in Nat2 activity might cause insulin resistance, we...... examined murine ortholog Nat1 knockout (KO) mice. Nat1 KO mice manifested whole-body insulin resistance, which could be attributed to reduced muscle, liver, and adipose tissue insulin sensitivity. Hepatic and muscle insulin resistance were associated with marked increases in both liver and muscle...... triglyceride (TAG) and diacylglycerol (DAG) content, which was associated with increased PKCϵ activation in liver and increased PKCθ activation in skeletal muscle. Nat1 KO mice also displayed reduced whole-body energy expenditure and reduced mitochondrial oxygen consumption in white adipose tissue, brown...

  14. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage.

    Science.gov (United States)

    Muniyappa, Ranganath; Lee, Sihoon; Chen, Hui; Quon, Michael J

    2008-01-01

    Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance.

  15. 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, P<0.001). Antepartum maternal and neonatal omentin levels did not differ significantly (fetal: 62.2, 44.3-74.2 ng/mL, P=0.77) and did not correlate (P=0.6). Circulating maternal omentin levels are correlated with insulin 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.

  16. 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.

  17. Association of obesity and insulin resistance with asthma and aeroallergen sensitization

    DEFF Research Database (Denmark)

    Husemoen, L L N; Glümer, C; Lau, C

    2008-01-01

    BACKGROUND: It has been hypothesized that obesity and insulin resistance may play a role in the development of asthma and allergy. The aim of the study was to examine the association of obesity and insulin resistance with asthma and aeroallergen sensitization. METHODS: Cross-sectional population...... and aeroallergen sensitization. The homeostasis model assessment of insulin resistance was used to estimate the degree of insulin resistance. Body mass index, waist-to-hip ratio, and waist circumference were used as measures of obesity. Data were analyzed by multiple logistic regression analyses. RESULTS: Obesity...

  18. Whole body vibration in cystic fibrosis--a pilot study.

    Science.gov (United States)

    Roth, J; Wust, M; Rawer, R; Schnabel, D; Armbrecht, G; Beller, G; Rembitzki, I; Wahn, U; Felsenberg, D; Staab, D

    2008-01-01

    In cystic fibrosis (CF), bone mass deficits as well as a lack of muscle mass and force have been described. The bone mass deficits are thought to be at least in part secondary to the reduced muscle mass. Whole body vibration has recently been suggested as an effective technique to increase muscle force and power. The aim of this pilot study was to evaluate the compliance and safety of a side-alternating, whole body vibration platform in patients with CF and to assess its effects on muscle force, muscle power, bone mass and lung function. Eleven adult CF patients participated in a six-months home-based training programme on a whole body vibration platform. Muscle force and power were assessed with three standard manoeuvres on a ground reaction force plate at regular intervals. Bone densitometry was performed at the spine, the radius and the tibia using quantitative computerized tomography. Regular cardiovascular monitoring did not show any critical drop in oxygen saturation or blood pressure. Lung function remained relatively constant with a median FEV1 change [% of norm] of -3.1% (range -7-20). Trabecular density at the spine and parameters of bone density and geometry at the radius and tibia did not show consistent changes. A median decrease of -0.3% (-31.0-17.9) for muscle force and a median increase of 4.7% (-16.4-74.5) for muscle power and 6.6% (-0.9-48.3) for velocity was noted in the two-leg jump. In the one-leg jump, a median increase of 6.7% (-8.5-24.3) for muscle force was measured. Whole body vibration was well tolerated in the majority of the study participants. Most patients were able to increase peak force in the one-leg jump. In the two-leg jump, velocity and muscle power increased with equal or decreased muscle force. This may indicate an improvement in neuromuscular and intramuscular co-ordination (and therefore efficiency) with less muscle force necessary to generate the same power.

  19. Electromyographic activity of back muscles during stochastic whole body vibration

    OpenAIRE

    Blasimann, A.; Fleuti, U.; Rufener, M.; Elfering, A.; Radlinger, L.

    2014-01-01

    OBJECTIVES: Stochastic resonance whole body vibrations (SR-WBV) may reduce and prevent musculoskeletal problems (MSP). The aim of this study was to evaluate how activities of the lumbar erector spinae (ES) and of the ascending and descending trapezius (TA, TD) change in upright standing position during SR-WBV. METHODS: Nineteen female subjects completed 12 series of 10 seconds of SR-WBV at six different frequencies (2, 4, 6, 8, 10, 12Hz) and two types of "noise"-applications. An asse...

  20. Whole-body microvascular permeability of small molecules in man

    DEFF Research Database (Denmark)

    Henriksen, J H

    1985-01-01

    In order to estimate whole-body permeability-surface area (PS) product, the initial slope of the plasma disappearance curve was determined after simultaneous i.v. injection of 24Na+ (mol.wt 24) and 51Cr-EDTA (mol.wt 342). Twelve subjects were studied. Plasma volume (PV) was measured by the indica...... of the plasma disappearance curve of a tracer, but mixing problems and flow-limited transport, as indicated by a PS ratio below that of the free diffusion coefficients, may be difficult to overcome, especially when using tracers of a low molecular weight....

  1. 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

  2. Changes in subcutaneous fat cell volume and insulin sensitivity after weight loss.

    Science.gov (United States)

    Andersson, Daniel P; Eriksson Hogling, Daniel; Thorell, Anders; Toft, Eva; Qvisth, Veronica; Näslund, Erik; Thörne, Anders; Wirén, Mikael; Löfgren, Patrik; Hoffstedt, Johan; Dahlman, Ingrid; Mejhert, Niklas; Rydén, Mikael; Arner, Erik; Arner, Peter

    2014-07-01

    Large subcutaneous fat cells associate with insulin resistance and high risk of developing type 2 diabetes. We investigated if changes in fat cell volume and fat mass correlate with improvements in the metabolic risk profile after bariatric surgery in obese patients. Fat cell volume and number were measured in abdominal subcutaneous adipose tissue in 62 obese women before and 2 years after Roux-en-Y gastric bypass (RYGB). Regional body fat mass by dual-energy X-ray absorptiometry; insulin sensitivity by hyperinsulinemic-euglycemic clamp; and plasma glucose, insulin, and lipid profile were assessed. RYGB decreased body weight by 33%, which was accompanied by decreased adipocyte volume but not number. Fat mass in the measured regions decreased and all metabolic parameters were improved after RYGB (P fat cell size correlated strongly with improved insulin sensitivity (P = 0.0057), regional changes in fat mass did not, except for a weak correlation between changes in visceral fat mass and insulin sensitivity and triglycerides. The curve-linear relationship between fat cell size and fat mass was altered after weight loss (P = 0.03). After bariatric surgery in obese women, a reduction in subcutaneous fat cell volume associates more strongly with improvement of insulin sensitivity than fat mass reduction per se. An altered relationship between adipocyte size and fat mass may be important for improving insulin sensitivity after weight loss. Fat cell size reduction could constitute a target to improve insulin sensitivity. © 2014 by the American Diabetes Association.

  3. Abdominal obesity in BTBR male mice is associated with peripheral but not hepatic insulin resistance.

    Science.gov (United States)

    Flowers, Jessica B; Oler, Angie T; Nadler, Samuel T; Choi, YounJeong; Schueler, Kathryn L; Yandell, Brian S; Kendziorski, Christina M; Attie, Alan D

    2007-03-01

    Insulin resistance is a common feature of obesity. BTBR mice have more fat mass than most other inbred mouse strains. On a chow diet, BTBR mice have elevated insulin levels relative to the C57BL/6J (B6) strain. Male F1 progeny of a B6 x BTBR cross are insulin resistant. Previously, we reported insulin resistance in isolated muscle and in isolated adipocytes in this strain. Whereas the muscle insulin resistance was observed only in male F1 mice, adipocyte insulin resistance was also present in male BTBR mice. We examined in vivo mechanisms of insulin resistance with the hyperinsulinemic euglycemic clamp technique. At 10 wk of age, BTBR and F1 mice had a >30% reduction in whole body glucose disposal primarily due to insulin resistance in heart, soleus muscle, and adipose tissue. The increased adipose tissue mass and decreased muscle mass in BTBR and F1 mice were negatively and positively correlated with whole body glucose disposal, respectively. Genes involved in focal adhesion, actin cytoskeleton, and inflammation were more highly expressed in BTBR and F1 than in B6 adipose tissue. The BTBR and F1 mice have higher levels of testosterone, which may be related to the pathological changes in adipose tissue that lead to systemic insulin resistance. Despite profound peripheral insulin resistance, BTBR and F1 mice retained hepatic insulin sensitivity. These studies reveal a genetic difference in body composition that correlates with large differences in peripheral insulin sensitivity.

  4. MG53-IRS-1 (Mitsugumin 53-Insulin Receptor Substrate-1) Interaction Disruptor Sensitizes Insulin Signaling in Skeletal Muscle.

    Science.gov (United States)

    Lee, Hyun; Park, Jung-Jin; Nguyen, Nga; Park, Jun Sub; Hong, Jin; Kim, Seung-Hyeob; Song, Woon Young; Kim, Hak Joong; Choi, Kwangman; Cho, Sungchan; Lee, Jae-Seon; Kim, Bong-Woo; Ko, Young-Gyu

    2016-12-23

    Mitsugumin 53 (MG53) is an E3 ligase that interacts with and ubiquitinates insulin receptor substrate-1 (IRS-1) in skeletal muscle; thus, an MG53-IRS-1 interaction disruptor (MID), which potentially sensitizes insulin signaling with an elevated level of IRS-1 in skeletal muscle, is an excellent candidate for treating insulin resistance. To screen for an MID, we developed a bimolecular luminescence complementation system using an N-terminal luciferase fragment fused with IRS-1 and a C-terminal luciferase fragment fused with an MG53 C14A mutant that binds to IRS-1 but does not have E3 ligase activity. An MID, which was discovered using the bimolecular luminescence complementation system, disrupted the molecular association of MG53 with IRS-1, thus abolishing MG53-mediated IRS-1 ubiquitination and degradation. Thus, the MID sensitized insulin signaling and increased insulin-elicited glucose uptake with an elevated level of IRS-1 in C2C12 myotubes. These data indicate that this MID holds promise as a drug candidate for treating insulin resistance. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  5. Insulin and Insulin Resistance

    Science.gov (United States)

    2005-01-01

    As obesity and diabetes reach epidemic proportions in the developed world, the role of insulin resistance and its consequences are gaining prominence. Understanding the role of insulin in wide-ranging physiological processes and the influences on its synthesis and secretion, alongside its actions from the molecular to the whole body level, has significant implications for much chronic disease seen in Westernised populations today. This review provides an overview of insulin, its history, structure, synthesis, secretion, actions and interactions followed by a discussion of insulin resistance and its associated clinical manifestations. Specific areas of focus include the actions of insulin and manifestations of insulin resistance in specific organs and tissues, physiological, environmental and pharmacological influences on insulin action and insulin resistance as well as clinical syndromes associated with insulin resistance. Clinical and functional measures of insulin resistance are also covered. Despite our incomplete understanding of the complex biological mechanisms of insulin action and insulin resistance, we need to consider the dramatic social changes of the past century with respect to physical activity, diet, work, socialisation and sleep patterns. Rapid globalisation, urbanisation and industrialisation have spawned epidemics of obesity, diabetes and their attendant co-morbidities, as physical inactivity and dietary imbalance unmask latent predisposing genetic traits. PMID:16278749

  6. Insulin Sensitivity and Mortality Risk Estimation in Patients with Type ...

    African Journals Online (AJOL)

    2017-06-28

    Jun 28, 2017 ... contribution of insulin resistance to scores obtained from mortality risk estimation in patients with type 2 diabetes mellitus (T2DM). Aim: This study determined the mortality risk scores in patients with T2DM and its relationship with insulin resistance. Methods: Fasting plasma glucose, total cholesterol, high‑ ...

  7. Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice

    NARCIS (Netherlands)

    Heijboer, A. C.; van den Hoek, A. M.; Parlevliet, E. T.; Havekes, L. M.; Romijn, J. A.; Pijl, H.; Corssmit, E. P. M.

    2006-01-01

    This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin,

  8. Metabolic characteristics of patients with myocardial visualization in fasting whole body F-18 FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, S. N. [College of Medicine, Ajou Univ., Suwon (Korea, Republic of); Lee, D. S.; Kang, W. Z.; Jeong, J. M.; Jeong, Z. K.; Lee, M. C.; Ko, C. S. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    1997-07-01

    When we would like to find a lesion in the chest malignant or benign, increased myocardial metabolic rate of glucose is so disturbing that bright myocardium obscures nearby lesions in F-18-FDG PET. This study aimed at finding metabolic characteristics of myocardial visualization when we tried not to make myocardium shining by fasting our patients. Plasma insulin, free fatty acid (FFA) and glucose were measured before injection of F-18-FDG in 36 cancer patients who had performed F-18-FDG PET in fasting state. F-18-FDG PET images were grouped in two according to the presence (group I) or absence (group II) of myocardial visualization. When the myocardium was visualized, we measured myocardium to backgroud (lung) count ratio using regions of interest on the segmented attenuation-corrected whole body PET coronal images. We examined the characteristics of metabolic mileu of group I and II. We correlated myocardium to background (M/B) ratio and metabolic indices in group I. Myocardium was visualized in 21 cases (58%) and not in 15 (42%) during fasting. Plasma glucose concentration was 98.5{+-}13.3 and 91.4{+-}9.1 mg/dl in group I and II, respectively (P <0.05). Plasma insulin concentration was 10.5{+-}5.0 and 8.1{+-}3.2mIU/L in group I and II(P >0.05). Plasma FFA concentration was 0.62{+-}0.23 and 0.92{+-}0.17 mEq/L in group I and II (P<0.05). Among the correlation between M/B ratios and metabolic factors, FFA concentration was negatively correlated with M/B ratio (r=0.3, p<0.05). In conclusion, free fatty acid concentration could be a determining factor to let myocardium show up and shine in fasting state. Artificial increase of free fatty acid could help myocardium not to appear in fasting whole body F-18-FDG PET.

  9. Whole-body vibration exercise in postmenopausal osteoporosis

    Directory of Open Access Journals (Sweden)

    Magdalena Weber-Rajek

    2015-01-01

    Full Text Available The report of the World Health Organization (WHO of 2008 defines osteoporosis as a disease characterized by low bone mass and an increased risk of fracture. Postmenopausal osteoporosis is connected to the decrease in estrogens concentration as a result of malfunction of endocrine ovarian function. Low estrogens concentration causes increase in bone demineralization and results in osteoporosis. Physical activity, as a component of therapy of patients with osteoporosis, has been used for a long time now. One of the forms of safe physical activity is the vibration training. Training is to maintain a static position or execution of specific exercises involving the appropriate muscles on a vibrating platform, the mechanical vibrations are transmitted to the body of the patient. According to the piezoelectric theory, pressure induces bone formation in the electrical potential difference, which acts as a stimulant of the process of bone formation. Whole body vibration increases the level of growth hormone and testosterone in serum, preventing sarcopenia and osteoporosis. The aim of this study was to review the literature on vibration exercise in patients with postmenopausal osteoporosis based on the PubMed and Medline database. While searching the database, the following key words were used ‘postmenopausal osteoporosis’ and ‘whole-body vibration exercise’.

  10. Safety aspects of whole-body cryochamber and cryosauna operation

    Science.gov (United States)

    Agnieszka, Piotrowska

    2017-12-01

    Interest in low temperature treatment is constantly increasing. Whole-body cryotherapy (WBC) devices are becoming available not only in medical centers but also in local gyms and spa centers. A new group of users are professional sport clubs where 3-minutes session of whole-body cryotherapy is post-training procedure to improve and speed up the recovery process. There are four different types of WBC devices available on the market and offered to commercial (non-medical) users. The American and European market is dominated by two of them: classic cryochambers and cryosaunas. Both constructions are supplied with liquid nitrogen. Low temperature inside classic cryochamber is produced by evaporating of liquid nitrogen in two or more heat exchangers. There is never a direct contact between user and cryogenic medium in any of system operation mode (closed supply system). Cryosauna is cooled down by filling with cold vapor of liquid nitrogen. Supply system is considered open because it allows for direct contact between user and cryogenic medium. Open supply system of cryosauna is primary and most questionable issue of its operational safety, particularly after tragic accident in October 2015. This paper presents the comparative analysis of classic cryochamber and cryosauna from safety point of view. Both devices have been analyzes and tested on existing systems in operation. Paper gives detailed analysis of constructions, supply systems and working parameters. Special attention has been focused to problem of oxygen deficiency hazard. Different failure or accident scenarios have been analyzed and discussed.

  11. Neural systemic impairment from whole-body vibration.

    Science.gov (United States)

    Yan, Ji-Geng; Zhang, Lin-ling; Agresti, Michael; LoGiudice, John; Sanger, James R; Matloub, Hani S; Havlik, Robert

    2015-05-01

    Insidious brain microinjury from motor vehicle-induced whole-body vibration (WBV) has not yet been investigated. For a long time we have believed that WBV would cause cumulative brain microinjury and impair cerebral function, which suggests an important risk factor for motor vehicle accidents and secondary cerebral vascular diseases. Fifty-six Sprague-Dawley rats were divided into seven groups (n = 8): 1) 2-week normal control group, 2) 2-week sham control group (restrained in the tube without vibration), 3) 2-week vibration group (exposed to whole-body vibration at 30 Hz and 0.5g acceleration for 4 hr/day, 5 days/week, for 2 weeks), 4) 4-week sham control group, 5) 4-week vibration group, 6) 8-week sham control group, and 7) 8-week vibration group. At the end point, all rats were evaluated in behavior, physiological, and brain histopathological studies. The cerebral injury from WBV is a cumulative process starting with vasospasm squeezing of the endothelial cells, followed by constriction of the cerebral arteries. After the 4-week vibration, brain neuron apoptosis started. After the 8-week vibration, vacuoles increased further in the brain arteries. Brain capillary walls thickened, mean neuron size was obviously reduced, neuron necrosis became prominent, and wide-ranging chronic cerebral edema was seen. These pathological findings are strongly correlated with neural functional impairments. © 2014 Wiley Periodicals, Inc.

  12. Integrating cellular metabolism into a multiscale whole-body model.

    Directory of Open Access Journals (Sweden)

    Markus Krauss

    Full Text Available Cellular metabolism continuously processes an enormous range of external compounds into endogenous metabolites and is as such a key element in human physiology. The multifaceted physiological role of the metabolic network fulfilling the catalytic conversions can only be fully understood from a whole-body perspective where the causal interplay of the metabolic states of individual cells, the surrounding tissue and the whole organism are simultaneously considered. We here present an approach relying on dynamic flux balance analysis that allows the integration of metabolic networks at the cellular scale into standardized physiologically-based pharmacokinetic models at the whole-body level. To evaluate our approach we integrated a genome-scale network reconstruction of a human hepatocyte into the liver tissue of a physiologically-based pharmacokinetic model of a human adult. The resulting multiscale model was used to investigate hyperuricemia therapy, ammonia detoxification and paracetamol-induced toxication at a systems level. The specific models simultaneously integrate multiple layers of biological organization and offer mechanistic insights into pathology and medication. The approach presented may in future support a mechanistic understanding in diagnostics and drug development.

  13. Whole-Body CT Screening--Should I or Shouldn't I Get One?

    Science.gov (United States)

    ... Procedures Medical Imaging Medical X-ray Imaging Whole-Body CT Screening--Should I or shouldn't I ... What are the risks and benefits of whole-body CT screening? Many people believe incorrectly that a ...

  14. Correction of hyperglycemia with phlorizin normalizes tissue sensitivity to insulin in diabetic rats.

    OpenAIRE

    Rossetti, L; Smith, D; Shulman, G I; Papachristou, D; DeFronzo, R A

    1987-01-01

    Insulin resistance is characteristic of the diabetic state. To define the role of hyperglycemia in generation of the insulin resistance, we examined the effect of phlorizin treatment on tissue sensitivity to insulin in partially pancreatectomized rats. Five groups were studied: group I, sham-operated controls; group II, partially pancreatectomized diabetic rats with moderate glucose intolerance; group III, diabetic rats treated with phlorizin to normalize glucose tolerance; group IV, phlorizi...

  15. 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......) and could be explained by BMI alone in a multivariate analysis. Neither insulin pulsatility, incretin secretion nor insulin sensitivity differed among the groups. CONCLUSIONS: We found no evidence that LADA and Type 2 diabetes were distinct disease entities beyond the differences explained by BMI....... 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...

  16. Insulin Sensitivity and Inflammation Mediate the Impact of Fitness on Cerebrovascular Health in Adolescents.

    Science.gov (United States)

    Yau, Po Lai; Ross, Naima; Tirsi, Andrew; Arif, Arslan; Ozinci, Zeynep; Convit, Antonio

    2017-06-01

    To investigate in adolescents the relationships between retinal vessel diameter, physical fitness, insulin sensitivity, and systemic inflammation. We evaluated 157 adolescents, 112 with excessive weight and 45 lean, all without type 2 diabetes mellitus. All received detailed evaluations, including measurements of retinal vessel diameter, insulin sensitivity, levels of inflammation, and physical fitness. Overweight/obese adolescents had significantly narrower retinal arteriolar and wider venular diameters, significantly lower insulin sensitivity, and physical fitness. They also had decreased levels of anti-inflammatory and increased levels of proinflammatory markers as well as an overall higher inflammation balance score. Fitness was associated with larger retinal arteriolar and narrower venular diameters and these relationships were mediated by insulin sensitivity. We demonstrate that inflammation also mediates the relationship between fitness and retinal venular, but not arterial diameter; insulin sensitivity and inflammation balance score jointly mediate this relationship with little overlap in their effects. Increasing fitness and insulin sensitivity and reducing inflammation among adolescents carrying excess weight may improve microvascular integrity. Interventions to improve physical fitness and insulin function and reduce inflammation in adolescents, a group likely to benefit from such interventions, may reduce not only cardiovascular disease in middle age, but also improve cerebrovascular function later in life.

  17. Comparison of atlas-based techniques for whole-body bone segmentation

    NARCIS (Netherlands)

    Arabi, Hossein; Zaidi, Habib

    We evaluate the accuracy of whole-body bone extraction from whole-body MR images using a number of atlas-based segmentation methods. The motivation behind this work is to find the most promising approach for the purpose of MRI-guided derivation of PET attenuation maps in whole-body PET/MRI. To this

  18. Insulin sensitivity derived from oral glucose tolerance testing in athletes: disagreement between available indices.

    Science.gov (United States)

    Niakaris, Konstantinos; Magkos, Faidon; Geladas, Nikos; Sidossis, Labros S

    2005-10-01

    The aims of the present study were to determine whether available "fasting" and oral glucose tolerance test-derived insulin sensitivity indices could effectively discriminate between individuals with higher than normal insulin sensitivity, and whether they would all provide similar information in clinical practice. Sprint runners (n = 8), endurance runners (n = 8) and sedentary controls (n = 7) received a 75-g oral glucose tolerance test. All participants were healthy lean males, aged 21-29 years. Besides glucose and insulin responses, a total of nine such indices were computed. Fasting as well as post-load glucose concentrations were similar in the three groups, while basal plasma insulin and the insulinaemic response to glucose were both higher in untrained individuals (at P runners. The results for insulin sensitivity, however, were quite variable: three indices showed that both groups of athletes were more insulin-sensitive than controls; three indicated that this was the case for endurance runners only; one indicated that this was the case for sprint runners only; and two showed that sprint runners were more insulin-sensitive than either sedentary individuals or endurance runners (all differences were significant at P < 0.05). Controlling for total body weight or lean mass did not effectively resolve this disagreement. Apparently, the various insulin sensitivity indices examined provided different quantitative and qualitative information, despite insulin action being greater in both groups of athletes relative to controls, as reflected by their similar glucose tolerance with lower insulin concentrations. We suggest, therefore, that the use and interpretation of such indices among physically active individuals be made with caution.

  19. 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

    Insulin resistance is a major health risk and although exercise clearly improves skeletal muscle insulin sensitivity, the mechanisms are unclear. Here we show that initiation of a euglycemic hyperinsulinemic clamp four hours after single-legged exercise in humans increased microvascular perfusion...

  20. 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

    sensitivity (Si) was estimated as the rate of glucose disappearance divided by the area under the insulin curve during an intravenous glucose tolerance test. RESULTS: Insulin and C-peptide levels were not correlated with BMD, but Si was a significant predictor of femur (log, r = 0.35) and WB BMD (log r = 0...

  1. 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 ...

  2. 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...

  3. 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

  4. Effect of exercise on insulin sensitivity in healthy postmenopausal women : The SHAPE study

    NARCIS (Netherlands)

    Van Gemert, Willemijn A.; Monninkhof, Evelyn M.; May, Anne M.; Peeters, Petra H.; Schuit, Albertine J.

    2015-01-01

    Background: An inactive lifestyle is a risk factor for several types of cancer. A proposed pathway through which exercise influences cancer risk is via insulin. We aim to investigate the effect of a oneyear exercise intervention on insulin sensitivity, and the role of body fat in this association,

  5. Whole body MR imaging in neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Meerbeeck, S.F.L. van [Department of Radiology and Medical Imaging, Ghent University, De Pintelaan 185, B-9000 Gent (Belgium)], E-mail: stephen.vm@rad-vanmeerbeeck.be; Verstraete, K.L. [Department of Radiology and Medical Imaging, Ghent University, De Pintelaan 185, B-9000 Gent (Belgium)], E-mail: koenraad.verstraete@ugent.be; Janssens, S.; Mortier, G. [Department of Medical Genetics, Ghent University Hospital, De Pintelaan 185, B-9000 Gent (Belgium)

    2009-02-15

    Objective: To assess the value of whole body MR imaging in patients with neurofibromatosis type 1 (NF1). Materials and methods: 24 patients (15-59 years; mean and median 36 years; 7 males; 17 females) with genetically proven neurofibromatosis type 1 were examined with whole body MR imaging. Axial and coronal T1- and fat-suppressed T2-weighted images (slice thickness 6-12 mm) were acquired on a 1.5 T MR unit (Symphony; Siemens, Erlangen, Germany). The images were reviewed by 2 radiologists: 1 senior, 1 junior. The criterion for a neurofibroma was a mass lesion with low signal intensity on T1 and high signal intensity on T2, along the course of a nerve. The location, size, general morphology and course along plexuses and nerves were evaluated. Cutaneous and subcutaneous neurofibromas were defined as 'superficial' neurofibromas. The other neurofibromas were regarded as 'deep' neurofibromas. Results: There were no major problems to differentiate neurofibromas from lymph nodes, vessels or cysts. The latter three were easily recognised by their typical shape and location, whereas neurofibromas occurred in regions where no mass lesion was anatomically expected. There was no relation between age and total number of neurofibromas throughout the body. Classification according to location and number of neurofibromas: 8 patients had only superficial neurofibromas, 1 only deep and 15 both superficial and deep lesions. Twelve patients had less than 15 neurofibromas and 12 had more. Classification according to course: in 8 patients the neurofibromas occurred along plexuses or proximal part of the intercostal nerves; in 16 patients the lesions were more peripheral. Classification according to morphology: 4 patients had plexiform neurofibromas and 20 patients had multiple solitary lesions. Twelve of these 20 patients had less than 15 lesions, and 8 had more. In 2 patients multiple solitary neurofibromas occurred along the nerve in a chain configuration. In one

  6. Insulin

    Science.gov (United States)

    ... Information by Audience For Women Women's Health Topics Insulin Share Tweet Linkedin Pin it More sharing options ... medicines. You can do it. Back to Top Insulin Safety Tips Never drink insulin. Do not share ...

  7. Whole-body magnetic resonance imaging in inflammatory arthritis

    DEFF Research Database (Denmark)

    Østergaard, Mikkel; Eshed, Iris; Althoff, Christian E.

    2017-01-01

    Objective: Whole-body magnetic resonance imaging (WB-MRI) is a relatively new technique that can enable assessment of the overall inflammatory status of people with arthritis, but standards for image acquisition, definitions of key pathologies, and a quantification system are required. Our aim...... was to perform a systematic literature review (SLR) and to develop consensus definitions of key pathologies, anatomical locations for assessment, a set of MRI sequences and imaging planes for the different body regions, and a preliminary scoring system for WB-MRI in inflammatory arthritis. Methods: An SLR...... was initially performed, searching for WB-MRI studies in arthritis, osteoarthritis, spondyloarthritis, or enthesitis. These results were presented to a meeting of the MRI in Arthritis Working Group together with an MR image review. Following this, preliminary standards for WB-MRI in inflammatory arthritides...

  8. Computational Fluid Dynamics of Whole-Body Aircraft

    Science.gov (United States)

    Agarwal, Ramesh

    1999-01-01

    The current state of the art in computational aerodynamics for whole-body aircraft flowfield simulations is described. Recent advances in geometry modeling, surface and volume grid generation, and flow simulation algorithms have led to accurate flowfield predictions for increasingly complex and realistic configurations. As a result, computational aerodynamics has emerged as a crucial enabling technology for the design and development of flight vehicles. Examples illustrating the current capability for the prediction of transport and fighter aircraft flowfields are presented. Unfortunately, accurate modeling of turbulence remains a major difficulty in the analysis of viscosity-dominated flows. In the future, inverse design methods, multidisciplinary design optimization methods, artificial intelligence technology, and massively parallel computer technology will be incorporated into computational aerodynamics, opening up greater opportunities for improved product design at substantially reduced costs.

  9. Whole-body magnetic resonance angiography; Ganzkoerper-MR-Angiografie

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, Harald; Nikolaou, Konstantin [Klinikum der Univ. Muenchen, Grosshadern (Germany). Inst. fuer Klinische Radiologie; Reiser, Maximilian F. [Klinikum der Univ. Muenchen, Grosshadern (Germany). Inst. fuer Radiologische Diagnostik

    2009-09-15

    Cardiovascular diseases still rank number one in terms of morbidity and mortality statistics in the western industrialized world. The majority of these diseases are due to atherosclerotic vessel wall changes. Atherosclerosis gets symptomatic in an advanced stage where vessel wall changes are apparent. Thus an early diagnosis of this disease is desirable. Especially atherosclerosis but also most of the inflammatory vessel diseases are known as systemic in nature. Magnetic resonance angiography offers an excellent and ethically justifiable method for non invasive imaging of the entire arterial vasculature without ionizing radiation. DSA comparable imaging results can be achieved nowadays. Possibilities to perform a whole body MR angiography and concerning imaging protocols are very dependent on the configuration of the available MR scanner. (orig.)

  10. Analysis and Modelling of Muscles Motion during Whole Body Vibration

    Directory of Open Access Journals (Sweden)

    La Gatta A

    2010-01-01

    Full Text Available The aim of the study is to characterize the local muscles motion in individuals undergoing whole body mechanical stimulation. In this study we aim also to evaluate how subject positioning modifies vibration dumping, altering local mechanical stimulus. Vibrations were delivered to subjects by the use of a vibrating platform, while stimulation frequency was increased linearly from 15 to 60 Hz. Two different subject postures were here analysed. Platform and muscles motion were monitored using tiny MEMS accelerometers; a contra lateral analysis was also presented. Muscle motion analysis revealed typical displacement trajectories: motion components were found not to be purely sinusoidal neither in phase to each other. Results also revealed a mechanical resonant-like behaviour at some muscles, similar to a second-order system response. Resonance frequencies and dumping factors depended on subject and his positioning. Proper mechanical stimulation can maximize muscle spindle solicitation, which may produce a more effective muscle activation.

  11. Neuromuscular fatigue induced by whole-body vibration exercise.

    Science.gov (United States)

    Maffiuletti, Nicola A; Saugy, Jonas; Cardinale, Marco; Micallef, Jean-Paul; Place, Nicolas

    2013-06-01

    The aim of this study was to examine the magnitude and the origin of neuromuscular fatigue induced by half-squat static whole-body vibration (WBV) exercise, and to compare it to a non-WBV condition. Nine healthy volunteers completed two fatiguing protocols (WBV and non-WBV, randomly presented) consisting of five 1-min bouts of static half-squat exercise with a load corresponding to 50 % of their individual body mass. Neuromuscular fatigue of knee and ankle muscles was investigated before and immediately after each fatiguing protocol. The main outcomes were maximal voluntary contraction (MVC) torque, voluntary activation, and doublet peak torque. Knee extensor MVC torque decreased significantly (P fatiguing protocols. Doublet peak torque decreased significantly and to a similar extent following WBV and non-WBV exercise, for both knee extensors (-25 %; P fatigue and did not change its causative factors compared to non-WBV half-squat resistive exercise in recreationally active subjects.

  12. Whole-body MRI in adult inflammatory myopathies: Do we need imaging of the trunk?

    Energy Technology Data Exchange (ETDEWEB)

    Filli, Lukas; Manoliu, Andrei; Andreisek, Gustav; Guggenberger, Roman [University Hospital Zurich, University of Zurich, Institute of Diagnostic and Interventional Radiology, Zurich (Switzerland); Maurer, Britta [University Hospital Zurich, University of Zurich, Division of Rheumatology, Zurich (Switzerland)

    2015-12-15

    To evaluate whether imaging of the trunk could be omitted in patients with inflammatory myopathies without losing diagnostic accuracy using a restricted whole-body magnetic resonance imaging (rWB-MRI) protocol. After approval by the institutional review board, this study was performed in 63 patients (male/female, 13/50; median age, 52 years; range, 20-81 years) with new-onset myopathic symptoms (group 1, n = 41) or previously diagnosed inflammatory myopathy (group 2, n = 22). After performing whole-body MRI (WB-MRI) at 3.0 Tesla, myositis and fatty atrophy were evaluated in different muscles by two independent radiologists. The intra-class correlation coefficient (ICC) was calculated to evaluate inter-observer reliability. Acquisition time was 56:01 minutes for WB-MRI and 37:37 minutes (32.8 % shorter) for rWB-MRI. In group 1, 14 patients were diagnosed with inflammatory myopathy based on muscle biopsy. rWB-MRI and WB-MRI showed equal sensitivity (42.9 %) and specificity (100 %) for myositis, and showed equal sensitivity (71.4 %) and similar specificity (63.0 % and 48.1 %, respectively) for fatty atrophy. No myositis was found in the body trunk in any patient. Inter-observer reliability was between substantial and perfect (ICC, 0.77-1.00). rWB-MRI showed diagnostic accuracy similar to WB-MRI for inflammatory myopathy at markedly reduced overall acquisition time. (orig.)

  13. Whole-body cryotherapy: empirical evidence and theoretical perspectives

    Directory of Open Access Journals (Sweden)

    Bleakley CM

    2014-03-01

    Full Text Available Chris M Bleakley,1 François Bieuzen,2 Gareth W Davison,1 Joseph T Costello3 1Sport and Exercise Science Research Institute, Faculty of Life and Health Sciences, University of Ulster, Newtownabbey, Northern Ireland; 2Research Department, Laboratory of Sport, Expertise and Performance, French National Institute of Sport (INSEP, Paris, France; 3School of Exercise and Nutrition Sciences and Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Australia Abstract: Whole-body cryotherapy (WBC involves short exposures to air temperatures below –100°C. WBC is increasingly accessible to athletes, and is purported to enhance recovery after exercise and facilitate rehabilitation postinjury. Our objective was to review the efficacy and effectiveness of WBC using empirical evidence from controlled trials. We found ten relevant reports; the majority were based on small numbers of active athletes aged less than 35 years. Although WBC produces a large temperature gradient for tissue cooling, the relatively poor thermal conductivity of air prevents significant subcutaneous and core body cooling. There is weak evidence from controlled studies that WBC enhances antioxidant capacity and parasympathetic reactivation, and alters inflammatory pathways relevant to sports recovery. A series of small randomized studies found WBC offers improvements in subjective recovery and muscle soreness following metabolic or mechanical overload, but little benefit towards functional recovery. There is evidence from one study only that WBC may assist rehabilitation for adhesive capsulitis of the shoulder. There were no adverse events associated with WBC; however, studies did not seem to undertake active surveillance of predefined adverse events. Until further research is available, athletes should remain cognizant that less expensive modes of cryotherapy, such as local ice-pack application or cold-water immersion, offer comparable

  14. Weight loss reduces liver fat and improves hepatic and skeletal muscle insulin sensitivity in obese adolescents.

    Science.gov (United States)

    Vitola, Bernadette E; Deivanayagam, Sheela; Stein, Richard I; Mohammed, Balsamanirina S; Magkos, Faidon; Kirk, Erik P; Klein, Samuel

    2009-09-01

    Obesity in adolescents is associated with metabolic risk factors for type 2 diabetes, particularly insulin resistance and excessive accumulation of intrahepatic triglyceride (IHTG). The purpose of this study was to evaluate the effect of moderate weight loss on IHTG content and insulin sensitivity in obese adolescents who had normal oral glucose tolerance. Insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp technique in conjunction with stable isotopically labeled tracer infusion, and IHTG content, assessed by using magnetic resonance spectroscopy, were evaluated in eight obese adolescents (BMI >or=95th percentile for age and sex; age 15.3 +/- 0.6 years) before and after moderate diet-induced weight loss (8.2 +/- 2.0% of initial body weight). Weight loss caused a 61.6 +/- 8.5% decrease in IHTG content (P = 0.01), and improved both hepatic (56 +/- 18% increase in hepatic insulin sensitivity index, P = 0.01) and skeletal muscle (97 +/- 45% increase in insulin-mediated glucose disposal, P = 0.01) insulin sensitivity. Moderate diet-induced weight loss decreases IHTG content and improves insulin sensitivity in the liver and skeletal muscle in obese adolescents who have normal glucose tolerance. These results support the benefits of weight loss therapy in obese adolescents who do not have evidence of obesity-related metabolic complications during a standard medical evaluation.

  15. 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

  16. Contralateral subtraction technique for detection of asymmetric abnormalities on whole-body bone scintigrams

    Science.gov (United States)

    Shiraishi, Junji; Li, Qiang; Appelbaum, Daniel; Pu, Yonglin; Doi, Kunio

    2007-03-01

    We developed a computer-aided diagnostic (CAD) scheme for assisting radiologists in the detection of asymmetric abnormalities on a single whole-body bone scintigram by applying a contralateral subtraction (CS) technique. Twenty whole-body bone scans including 107 abnormal lesions in anterior and/or posterior images (the number of lesions per case ranged from 1 to 16, mean 5.4) were used in this study. In our scheme, the original bone scan image was flipped horizontally to provide a mirror image. The mirror image was first rotated and shifted globally to match the original image approximately, and then was nonlinearly warped by use of an elastic matching technique in order to match the original image accurately. We applied a nonlinear lookup table to convert the difference in pixel values between the original and the warped images to new pixel values for a CS image, in order to enhance dark shadows at the locations of abnormal lesions where uptake of radioisotope was asymmetrically high, and to suppress light shadows of the lesions on the contralateral side. In addition, we applied a CAD scheme for the detection of asymmetric abnormalities by use of rule-based tests and sequential application of artificial neural networks with 25 image features extracted from the original and CS images. The performance of the CAD scheme, which was evaluated by a leave-one-case-out method, indicated an average sensitivity of 80.4 % with 3.8 false positives per case. This CAD scheme with the contralateral subtraction technique has the potential to improve radiologists' diagnostic accuracy and could be used for computerized identification of asymmetric abnormalities on whole-body bone scans.

  17. Thyroid function tests in obese prepubertal children: correlations with insulin sensitivity and body fat distribution.

    Science.gov (United States)

    Brufani, Claudia; Manco, Melania; Nobili, Valerio; Fintini, Danilo; Barbetti, Fabrizio; Cappa, Marco

    2012-01-01

    Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly elevated free triiodothyronine (fT(3)) and/or free thyroxine (fT(4)) have been consistently found in obese children. To examine relationships between adiposity, insulin sensitivity, and TSH, fT(3) and fT(4). 240 overweight/obese prepubertal children were studied. Fasting TSH, fT(3), fT(4), glucose, insulin, C-peptide, lipids, leptin and adiponectin were evaluated. Insulin sensitivity and resistance were estimated [quantitative insulin check index (QUICKI), insulin sensitivity index (ISI), and hepatic insulin resistance index]. Body fat was measured by dual-energy X-ray absorptiometry. The central obesity index was calculated as the ratio of fat tissue in the trunk region to fat tissue in the leg region. The multiple regression analysis with age, gender and measures of fatness as covariates showed that QUICKI was the only significant negative predictor of TSH and central obesity index the strongest positive predictor of fT(3), in association with either age or hepatic insulin resistance index, and that the only positive determinant of fT(4) was hepatic insulin resistance index. Reduced insulin sensitivity is associated with augmented TSH and fT(4), while progressive central fat accumulation is strictly related to a parallel increase in fT(3) levels, independently from total body fat. Further studies are needed to understand mechanisms linking thyroid function to insulin sensitivity and body composition in obese children. Copyright © 2012 S. Karger AG, Basel.

  18. Association Of Sleep Deprivation With Reduction In Insulin Sensitivity As Assessed By The Hyperglycemic Clamp Technique In Adolescents

    OpenAIRE

    Rodrigues; AMD; da Silva; CD; Vasques; ACJ; Camilo; DF; Barreiro; Cassani, F; RSL; Zambon; MP; Antonio; MARDM; Geloneze; B.,

    2016-01-01

    IMPORTANCE The association between short sleep duration and decreased insulin sensitivity in adolescents has been described. However, to our knowledge, no studies have investigated this association measuring insulin sensitivity by the hyperglycemic clamp technique. OBJECTIVES To compare the distributions of parameters of insulin resistance in adolescents with sleep deprivation vs adequate sleep, and to investigate the association between sleep deprivation and insulin sensitivity. DESIGN, SETT...

  19. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  20. 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 (insulin action, cellular insulin signaling, and intrahepatic triglyceride (IHTG) content before, after 48 hours, and after approximately 11 weeks (7% weight loss) of diet therapy. At 48 hours, IHTG content decreased more in the LC than the HC diet group (29.6% +/- 4.8% vs 8.9% +/- 1.4%; P 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 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 insulin sensitivity, and glucose production), whereas moderate weight loss affects muscle (insulin-mediated glucose uptake and insulin signaling).

  1. 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

  2. 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.

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

    NARCIS (Netherlands)

    Coomans, C.P.; Biermasz, N.R.; Geerling, J.J.; Guigas, B.; Rensen, P.C.N.; Havekes, L.M.; Romijn, J.A.

    2011-01-01

    OBJECTIVE - 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

  4. 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

  5. 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....

  6. Adding to the spectrum of insulin sensitive populations for mixed meal tolerance test glucose reliability assessment.

    Science.gov (United States)

    Paglialunga, Sabina; Guerrero, Angelica; Roessig, Julie M; Rubin, Paul; Dehn, Clayton A

    2016-01-01

    As a measure of insulin sensitivity, the mixed meal tolerance test (MMTT) is a simple technique that can provide robust results. The assay consists of examining plasma glucose, insulin and C-peptide prior to and following the consumption of a test meal. While this procedure has been used in clinical research for several years, there is no set standard protocol, and only until recently has the reliability of this assay been thoroughly evaluated in prediabetes and type 2 diabetes subjects. Interestingly, the results from this recent study demonstrated stronger MMTT reliability for the prediabetes and diabetes cohorts compared to obese controls. This finding suggests that the obese control group may have more inherent variability in glucose response during a meal challenge likely due to compensatory influences typically observed in non-diabetic insulin-resistant subjects. Furthermore, this study raises the question whether the MMTT assay is reliable in a non-obese cohort. Therefore, to promote the standardization of this technique and contribute to the band of insulin sensitive populations, we employed the same methodology and test meal as the reference study to evaluate the MMTT reliability in healthy and overweight men. Indeed, the interclass coefficient revealed high glucose response repeatability during the MMTT in insulin-sensitive men. Overall, the MMTT is a reliable test across a range of insulin sensitivity including healthy men. However, we propose further investigation may be required to fully define the utility of this methodology in obese non-diabetic insulin-resistant populations.

  7. Resistance training, insulin sensitivity and muscle function in the elderly

    DEFF Research Database (Denmark)

    Dela, Flemming; Kjaer, Michael

    2006-01-01

    Ageing is associated with a loss in both muscle mass and in the metabolic quality of skeletal muscle. This leads to sarcopenia and reduced daily function, as well as to an increased risk for development of insulin resistance and type 2 diabetes. A major part, but not all, of these changes...... are associated with an age-related decrease in the physical activity level and can be counteracted by increased physical activity of a resistive nature. Strength training has been shown to improve insulin-stimulated glucose uptake in both healthy elderly individuals and patients with manifest diabetes...

  8. High glycemic index starch promotes hypersecretion of insulin and higher body fat in rats without affecting insulin sensitivity.

    Science.gov (United States)

    Pawlak, D B; Bryson, J M; Denyer, G S; Brand-Miller, J C

    2001-01-01

    In rats, prolonged feeding of high glycemic index (GI) starch results in basal hyperinsulinemia and an elevated insulin response to an intravenous glucose tolerance test (IVGTT). The aim of this study was to assess hepatic and peripheral insulin resistance (IR) using euglycemic hyperinsulinemic clamps. Insulin sensitivity, epididymal fat deposition and fasting leptin concentrations were compared in rats fed isocalorically a low or high GI diet for 7 wk (45% carbohydrate, 35% fat and 20% protein as energy) or a high fat diet (20% carbohydrate, 59% fat and 21% protein as energy) for 4 wk so that final body weights were similar. At the end of the study, high GI rats had higher basal leptin concentration and epididymal fat mass than the low GI group, despite comparable body weights. High GI and high fat feeding both resulted in the higher insulin response during IVGTT, but impaired glucose tolerance was seen only in rats fed high fat. The GI of the diet did not affect basal and clamp glucose uptake or hepatic glucose output, but high fat feeding induced both peripheral and hepatic IR. The findings suggest that hypersecretion of insulin without IR may be one mechanism for increased fat deposition in rats fed high GI diets.

  9. Factors affecting gastric uptake in whole body FDG-PET imaging

    Energy Technology Data Exchange (ETDEWEB)

    Tomemori, Takashi; Kitagawa, Mami; Nakahara, Tadaki; Wu, Jin; Nakagawa, Keiichi; Uno, Kimiichi; Abe, Kinji; Tomiyoshi, Katsumi [Nishidai Clinic Diagnostic Imaging Center, Tokyo (Japan)

    2001-06-01

    Positron emission tomography (PET) using 2-deoxy-2-[{sup 18}F]-fluoro-D-glucose (FDG) is very useful for the detection and staging of tumors. However, FDG is also accumulated in the normal tissues in various degrees. This physiological FDG uptake is often seen in intestine, making confusion with malignant tumor. The aim of this study was to identify factors influencing physiological FDG uptake in the stomach. A total of 136 people who underwent cancer screening or staging of tumors except for gastric cancer using FDG whole-body PET was examined (mean age: 55.6 yrs). All subjects fasted for at least 4 hours before the PET study and were administrated with FDG intravenously (mean FDG dose: 308.9 MBq). Emission images were acquired on a whole-body PET scanner and images were reconstructed without attenuation correction. The intensity of gastric uptake of FDG whole-body PET image was visually classified into 3 grades; grade 2 = the intensity of gastric uptake more than pulmonary uptake, grade 1 = the intensity of gastric uptake equal to or less than pulmonary uptake, grade 0 = no contrast between gastric uptake and background. Twenty-eight subjects (20.6%) were classified into grade 2, 42 subjects (30.9%) were grade 1 and 66 subjects (48.5%) were grade 0. Subjects' age, fasting time, FDG dose, serum glucose level, free fatty acid level and insulin level were not significantly correlated with the intensity of gastric uptake. But the subjects with higher gastric uptake tended to have anti-Helicobactor pylori (H. pylori) antibodies. The rate of having anti-H.pylori antibodies in the grade 2 group is significantly higher than the grade 1 group (85.7% vs. 72.5%, p<0.05), and that of the grade 1 group is significantly higher than the grade 0 group (72.5% vs. 42.2%, p<0.01). Gastric uptake was observed in about half of subjects. Especially, approximately 20% of all showed high gastric uptake, which was associated with H.pylori infection. Therefore, most of the subjects

  10. Genetic Markers of Insulin Sensitivity and Insulin Secretion Are Associated With Spontaneous Postnatal Growth and Response to Growth Hormone Treatment in Short SGA Children

    DEFF Research Database (Denmark)

    Jensen, Rikke Beck; Thankamony, Ajay; Day, Felix

    2015-01-01

    PURPOSE: The wide heterogeneity in the early growth and metabolism of children born small for gestational age (SGA), both before and during GH therapy, may reflect common genetic variations related to insulin secretion or sensitivity. METHOD: Combined multiallele single nucleotide polymorphism...... scores with known associations with insulin sensitivity or insulin secretion were analyzed for their relationships with spontaneous postnatal growth and first-year responses to GH therapy in 96 short SGA children. RESULTS: The insulin sensitivity allele score (GS-InSens) was positively associated...... scores indicative of insulin sensitivity and insulin secretion were associated with spontaneous postnatal growth and responses to GH therapy in short SGA children. Further pharmacogenetic studies may support the rationale for adjuvant therapies by informing the mechanisms of treatment response....

  11. Insulin-sensitive adiposity is associated with a relatively lower risk of diabetes than insulin-resistant adiposity: the Bogalusa Heart Study.

    Science.gov (United States)

    Zhang, Tao; Li, Ying; Zhang, Huijie; Sun, Dianjianyi; Li, Shengxu; Fernandez, Camilo; Harville, Emily; Bazzano, Lydia; He, Jiang; Chen, Wei

    2016-10-01

    Obesity and insulin resistance are both closely associated with type 2 diabetes mellitus (T2DM). It is, however, not clear whether the role of obesity in the development of T2DM is dependent on insulin resistance. This study aims to assess the hypothesis that insulin-sensitive adiposity is associated with a relatively lower risk of T2DM than insulin-resistant adiposity, and the adiposity-T2DM association is modified by insulin resistance in middle-aged black and white adults. The longitudinal study cohort consisted of 1588 middle-aged normoglycemic black and white adults aged 18-44 years at baseline who were followed for 16 years on average. Overweight/obesity at baseline was defined as BMI ≥25, and insulin resistance was measured using the homeostasis model assessment of insulin resistance (HOMA). The prevalence of incident pre-diabetes and T2DM was compared between the insulin-sensitive and insulin-resistant adiposity groups. The prevalence of both incident pre-diabetes and T2DM was higher in the insulin-resistant adiposity than in the insulin-sensitive adiposity group (11.5 vs. 7.5 %, p = 0.023 for pre-diabetes; 16.7 vs. 2.7 %, p BMI with pre-diabetes and T2DM significantly increased across increasing quartiles of baseline HOMA (p for trend = 0.032 for pre-diabetes and BMI, measured as regression coefficients (β), were significantly greater in insulin-resistant than in insulin-sensitive individuals (β = 0.86 vs. 0.38, p = 0.009 for difference in slopes). These findings suggest that insulin resistance amplifies the obesity-diabetes association and underscore the importance of preventing both adiposity and insulin resistance in young adults.

  12. Low-Dose Adefovir-Induced Hypophosphatemic Osteomalacia on Whole-Body Bone Scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Hoon; Won, Kyoung Sook; Song, Bongil; Jo, Il; Zeon, Seok Kil [Keimyung Univ., Daegu (Korea, Republic of)

    2013-12-15

    While adefovir dipivoxil (ADV) effectively suppresses the hepatitis B virus, it can cause proximal renal tubular dysfunction leading to phosphate wasting. The safety of low-dose ADV (a dose of 10 mg/day), which does not induce clinically significant nephrotoxicity, is well recognized, but a few cases of hypophosphatemic osteomalacia (HO) caused by low-dose ADV therapy have recently been reported. Although HO induced by low-dose ADV therapy is rare, the presence of bone pain in patients treated with ADV should be monitored. Bone scintigraphy can be performed to confirm the occurrence of osteomalacia and to determine the disease extent. Bone scintigraphic and radiological image findings with a brief review of the literature are presented in this article. We report two cases of HO induced by low-dose ADV therapy that showed multifocal increased radiotracer uptakes in the bilateral bony ribs, spines, pelvic bones and lower extremities on whole-body bone scintigraphy. Bone pain gradually improved after phosphate supplementation and by changing the antiviral agent. Whole-body bone scintigraphy is a highly sensitive imaging tool and can show disease extent at once in the setting of the wide range of the clinical spectrum with nonspecific radiological findings. Furthermore, frequent involvement of the lower extremities, as a result of maximum weight bearing, could be an additional scintigraphic clue for the diagnosis of HO. These cases could be helpful for both clinicians prescribing ADV and nuclear physicians to prevent delayed diagnosis and plan further appropriate treatment.

  13. Combined epigallocatechin-3-gallate and resveratrol supplementation for 12 wk increases mitochondrial capacity and fat oxidation, but not insulin sensitivity, in obese humans: a randomized controlled trial.

    Science.gov (United States)

    Most, Jasper; Timmers, Silvie; Warnke, Ines; Jocken, Johan We; van Boekschoten, Mark; de Groot, Philip; Bendik, Igor; Schrauwen, Patrick; Goossens, Gijs H; Blaak, Ellen E

    2016-07-01

    The obese insulin-resistant state is characterized by impairments in lipid metabolism. We previously showed that 3-d supplementation of combined epigallocatechin-3-gallate and resveratrol (EGCG+RES) increased energy expenditure and improved the capacity to switch from fat toward carbohydrate oxidation with a high-fat mixed meal (HFMM) test in men. The present study aimed to investigate the longer-term effect of EGCG+RES supplementation on metabolic profile, mitochondrial capacity, fat oxidation, lipolysis, and tissue-specific insulin sensitivity. In this randomized double-blind study, 38 overweight and obese subjects [18 men; aged 38 ± 2 y; body mass index (kg/m(2)): 29.7 ± 0.5] received either EGCG+RES (282 and 80 mg/d, respectively) or placebo for 12 wk. Before and after the intervention, oxidative capacity and gene expression were assessed in skeletal muscle. Fasting and postprandial (HFMM) lipid metabolism was assessed by using indirect calorimetry, blood sampling, and microdialysis. Tissue-specific insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp with [6,6-(2)H2]-glucose infusion. EGCG+RES supplementation did not affect the fasting plasma metabolic profile. Although whole-body fat mass was not affected, visceral adipose tissue mass tended to decrease after the intervention compared with placebo (P-time × treatment = 0.09). EGCG+RES supplementation significantly increased oxidative capacity in permeabilized muscle fibers (P-time × treatment fat oxidation was not significantly affected by EGCG+RES (P-EGCG+RES = 0.46 and 0.38, respectively) but declined after placebo (P-placebo = 0.05 and 0.03, respectively). Energy expenditure was not altered (P-time × treatment = 0.96). Furthermore, EGCG+RES supplementation attenuated the increase in plasma triacylglycerol concentrations during the HFMM test that was observed after placebo (P-time × treatment = 0.04, P-placebo = 0.01). Finally, EGCG+RES had no effect on insulin-stimulated glucose

  14. Influence of vitamin D treatment on transcriptional regulation of insulin-sensitive genes.

    Science.gov (United States)

    Alkharfy, Khalid M; Al-Daghri, Nasser M; Yakout, Sobhy M; Hussain, Tajamul; Mohammed, Abdul Khader; Krishnaswamy, Soundararajan

    2013-08-01

    Obesity is a risk factor for diabetes and metabolic syndrome, which are characterized by insulin resistance. Inflammation is a co-morbid condition associated with obesity. Vitamin D, besides being a transcriptional regulator, is an inflammation suppressor. However, the role of vitamin D in alleviating obesity-induced insulin resistance is still not well understood. The influence of vitamin D treatment on the transcriptional level of insulin receptor (IR), insulin receptor substrate (IRS-1), glucose transporter type 4 (GLUT-4), and vitamin D receptor (VDR) in insulin target tissues of liver, adipose, and muscle of mice fed on a high-fat diet (HFD) or low-fat diet (LFD) was studied by quantitative RT-PCR. A gradual weight reduction was observed in HFD-fed mice treated with vitamin D compared to a steady weight increase in control animals (Pinfluence tissue expression of IR in either LFD- or HFD-fed mice. Muscle IRS-1 transcription level was upregulated to 2.4-fold (P=0.005) in HFD mice, whereas it was reduced to 0.15-fold in liver tissue (Pinfluenced the expression of insulin-sensitive genes in a tissue-specific fashion. On the basis of the present findings, vitamin D does not aid glucose transport across cells of liver and adipose tissues, the major insulin-sensitive tissues, in HFD-fed mice; however, it appears to enhance the intracellular mechanisms of insulin action mediated by IRS-1 and VDR in muscle tissue.

  15. Fitness, insulin sensitivity, and frontal lobe integrity in adults with overweight and obesity.

    Science.gov (United States)

    Castro, Mary Grace; Venutolo, Christopher; Yau, Po Lai; Convit, Antonio

    2016-06-01

    To formally test whether insulin sensitivity mediates the relationship between fitness and brain integrity. Eighty-four middle-aged participants without diabetes received a 6-min walk test from which maximal oxygen uptake (VO2 max) was derived, a structural magnetic resonance scan, and a medical evaluation including fasting glucose and insulin levels. This study showed significant associations between fitness, abdominal obesity, and insulin sensitivity and anterior cingulate cortex (ACC) volume as well as between ACC thickness and quantitative insulin-sensitivity check index (QUICKI). The relationship between ACC volume and VO2 max was completely mediated through QUICKI. Further, this strong association was confirmed by a single and very significant cluster on the ACC linking gray matter volume and QUICKI in a voxel-based morphometry analysis. As expected, increased abdominal obesity was associated with reductions in fitness, ACC volumes, and insulin sensitivity. Importantly, this study demonstrated a significant mediation of the relationship between VO2 max and ACC volume by QUICKI. This suggests that the links between impaired insulin sensitivity and brain abnormalities in adults carrying excess weight could be alleviated through increased physical activity and fitness. © 2016 The Obesity Society.

  16. Fitness, Insulin Sensitivity and Frontal Lobe Integrity in Overweight and Obese Adults

    Science.gov (United States)

    Castro, Mary Grace; Venutolo, Christopher; Yau, Po Lai; Convit, Antonio

    2016-01-01

    Objective To formally test whether insulin sensitivity mediates the relationship between fitness and brain integrity. Methods Eighty-four non-diabetic, middle-aged participants received a 6-minute walk test from which maximal oxygen uptake (VO2 max) was derived, a structural MR scan, and a medical evaluation including fasting glucose and insulin levels. Results We showed significant associations between fitness, abdominal obesity, and insulin sensitivity and anterior cingulate cortex (ACC) volume as well as between ACC thickness and quantitative insulin-sensitivity check index (QUICKI). We showed that the relationship between ACC volume and VO2 max was completely mediated through QUICKI, see Figure 3. Further, this strong association was confirmed by a single and very significant cluster on the ACC linking gray matter volume and QUICKI in a voxel-based morphometry analysis. Conclusions As expected, increased abdominal obesity was associated with reductions in fitness, ACC volumes, and insulin sensitivity. Importantly, we demonstrate a significant mediation of the relationship between VO2 max and ACC volume by QUICKI. This suggests that the links between impaired insulin sensitivity and brain abnormalities in adults carrying excess weight could be alleviated through increased physical activity and fitness. PMID:27123868

  17. Whole Body Awareness for Controlling a Robotic Transfemoral Prosthesis

    Directory of Open Access Journals (Sweden)

    Andrea Parri

    2017-05-01

    Full Text Available Restoring locomotion functionality of transfemoral amputees is essential for early rehabilitation treatment and for preserving mobility and independence in daily life. Research in wearable robotics fostered the development of innovative active mechatronic lower-limb prostheses designed with the goal to reduce the cognitive and physical effort of lower-limb amputees in rehabilitation and daily life activities. To ensure benefits to the users, active mechatronic prostheses are expected to be aware of the user intention and properly interact in a closed human-in-the-loop paradigm. In the state of the art various cognitive interfaces have been proposed to online decode the user's intention. Electromyography in combination with mechanical sensing such as inertial or pressure sensors is a widely adopted solution for driving active mechatronic prostheses. In this framework, researchers also explored targeted muscles re-innervation for an objective-oriented surgical amputation promoting wider usability of active prostheses. However, information kept by the neural component of the cognitive interface deteriorates in a prolonged use scenario due to electrodes-related issues, thereby undermining the correct functionality of the active prosthesis. The objective of this work is to present a novel controller for an active transfemoral prosthesis based on whole body awareness relying on a wireless distributed non-invasive sensory apparatus acting as cognitive interface. A finite-state machine controller based on signals monitored from the wearable interface performs subject-independent intention detection of functional tasks such as ground level walking, stair ascent, and sit-to-stand maneuvres and their main sub-phases. Experimental activities carried out with four transfemoral amputees (among them one dysvascular demonstrated high reliability of the controller capable of providing 100% accuracy rate in treadmill walking even for weak subjects and low walking

  18. Insulin sensitivity : modulation by the gut-brain axis

    NARCIS (Netherlands)

    Heijboer, Annemieke Corine

    2006-01-01

    Er zijn steeds meer aanwijzingen dat neuropeptiden in de hypothalamus en maagdarmhormonen die hun werking hebben op de hypothalamus en betrokken zijn bij de regulatie van voedselinname, ook betrokken zouden kunnen zijn bij de regulatie van insuline gevoeligheid. Daarom hebben we eerst de effecten

  19. 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 know...

  20. Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice

    NARCIS (Netherlands)

    Heijboer, A.C.; Hoek, A.M. van den; Parlevliet, E.T.; Havekes, L.M.; Romijn, J.A.; Pijl, H.; Corssmit, E.P.M.

    2006-01-01

    Aims/hypothesis: This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the

  1. Responses of primate caudal parabrachial nucleus and Kolliker-fuse nucleus neurons to whole body rotation

    Science.gov (United States)

    Balaban, Carey D.; McGee, David M.; Zhou, Jianxun; Scudder, Charles A.

    2002-01-01

    The caudal aspect of the parabrachial (PBN) and Kolliker-Fuse (KF) nuclei receive vestibular nuclear and visceral afferent information and are connected reciprocally with the spinal cord, hypothalamus, amygdala, and limbic cortex. Hence, they may be important sites of vestibulo-visceral integration, particularly for the development of affective responses to gravitoinertial challenges. Extracellular recordings were made from caudal PBN cells in three alert, adult female Macaca nemestrina through an implanted chamber. Sinusoidal and position trapezoid angular whole body rotation was delivered in yaw, roll, pitch, and vertical semicircular canal planes. Sites were confirmed histologically. Units that responded during rotation were located in lateral and medial PBN and KF caudal to the trochlear nerve at sites that were confirmed anatomically to receive superior vestibular nucleus afferents. Responses to whole-body angular rotation were modeled as a sum of three signals: angular velocity, a leaky integration of angular velocity, and vertical position. All neurons displayed angular velocity and integrated angular velocity sensitivity, but only 60% of the neurons were position-sensitive. These responses to vertical rotation could display symmetric, asymmetric, or fully rectified cosinusoidal spatial tuning about a best orientation in different cells. The spatial properties of velocity and integrated velocity and position responses were independent for all position-sensitive neurons; the angular velocity and integrated angular velocity signals showed independent spatial tuning in the position-insensitive neurons. Individual units showed one of three different orientations of their excitatory axis of velocity rotation sensitivity: vertical-plane-only responses, positive elevation responses (vertical plane plus ipsilateral yaw), and negative elevation axis responses (vertical plane plus negative yaw). The interactions between the velocity and integrated velocity components

  2. Preserved insulin sensitivity predicts metabolically healthy obese phenotype in children and adolescents.

    Science.gov (United States)

    Vukovic, Rade; Milenkovic, Tatjana; Mitrovic, Katarina; Todorovic, Sladjana; Plavsic, Ljiljana; Vukovic, Ana; Zdravkovic, Dragan

    2015-12-01

    Available data on metabolically healthy obese (MHO) phenotype in children suggest that gender, puberty, waist circumference, insulin sensitivity, and other laboratory predictors have a role in distinguishing these children from metabolically unhealthy obese (MUO) youth. The goal of this study was to identify predictors of MHO phenotype and to analyze glucose and insulin metabolism during oral glucose tolerance test (OGTT) in MHO children. OGTT was performed in 244 obese children and adolescents aged 4.6-18.9 years. Subjects were classified as MHO in case of no fulfilled criterion of metabolic syndrome except anthropometry or as MUO (≥2 fulfilled criteria). Among the subjects, 21.7 % had MHO phenotype, and they were more likely to be female, younger, and in earlier stages of pubertal development, with lower degree of abdominal obesity. Insulin resistance was the only independent laboratory predictor of MUO phenotype (OR 1.59, CI 1.13-2.25), with 82 % sensitivity and 60 % specificity for diagnosing MUO using HOMA-IR cutoff point of ≥2.85. Although no significant differences were observed in glucose regulation, MUO children had higher insulin demand throughout OGTT, with 1.53 times higher total insulin secretion. Further research is needed to investigate the possibility of targeted treatment of insulin resistance to minimize pubertal cross-over to MUO in obese children. • Substantial proportion of the obese youth (21-68 %) displays a metabolically healthy (MHO) phenotype. • Gender, puberty, waist circumference, insulin sensitivity, and lower levels of uric acid and transaminases have a possible role in distinguishing MHO from metabolically unhealthy obese (MUO) children. • Insulin resistance was found to be the only significant laboratory predictor of MUO when adjusted for gender, puberty, and the degree of abdominal obesity. • Besides basal insulin resistance, MUO children were found to have a significantly higher insulin secretion throughout OGTT in

  3. 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.

  4. Fish oil supplementation for two generations increases insulin sensitivity in rats.

    Science.gov (United States)

    Hirabara, Sandro M; Folador, Alessandra; Fiamoncini, Jarlei; Lambertucci, Rafael H; Rodrigues, Carlos F; Rocha, Marlene S; Aikawa, Julia; Yamazaki, Ricardo K; Martins, Amanda R; Rodrigues, Alice C; Carpinelli, Angelo R; Pithon-Curi, Tania C; Fernandes, Luiz C; Gorjão, Renata; Curi, Rui

    2013-06-01

    We investigated the effect of fish oil supplementation for two consecutive generations on insulin sensitivity in rats. After the nursing period (21 days), female rats from the same prole were divided into two groups: (a) control group and (b) fish oil group. Female rats were supplemented with water (control) or fish oil at 1 g/kg body weight as a single bolus for 3 months. After this period, female rats were mated with male Wistar rats fed on a balanced chow diet (not supplemented). Female rats continued to receive supplementation throughout gestation and lactation periods. The same treatment was performed for the next two generations (G1 and G2). At 75 days of age, male offspring from G1 and G2 generations from both groups were used in the experiments. G1 rats did not present any difference with control rats. However, G2 rats presented reduction in glycemia and lipidemia and improvement in in vivo insulin sensitivity (model assessment of insulin resistance, insulin tolerance test) as well as in vitro insulin sensitivity in soleus muscle (glucose uptake and metabolism). This effect was associated with increased insulin-stimulated p38 MAP kinase phosphorylation and lower n-6/n-3 fatty acid ratio, but not with activation of proteins from insulin signaling (IR, IRS-1 and Akt). Global DNA methylation was decreased in liver but not in soleus muscle. These results suggest that long-term fish oil supplementation improves insulin sensitivity in association with increased insulin-stimulated p38 activation and decreased n-6:n-3 ratio in skeletal muscle and decreased global DNA methylation in liver. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Effect of 10 days of bedrest on metabolic and vascular insulin action: a study in individuals at risk for type 2 diabetes

    DEFF Research Database (Denmark)

    Sonne, Mette P; Alibegovic, Amra C; Højbjerre, Lise

    2010-01-01

    ) was measured by venous occlusion plethysmography. All groups responded with a decrease in whole body insulin sensitivity in response to bedrest [CON group: 6.8 +/- 0.5 to 4.3 +/- 0.3 mg x min(-1) x kg(-1) (P

  6. Electromyographic activity of back muscles during stochastic whole body vibration.

    Science.gov (United States)

    Blasimann, A; Fleuti, U; Rufener, M; Elfering, A; Radlinger, L

    2014-09-01

    Stochastic resonance whole body vibrations (SR-WBV) may reduce and prevent musculoskeletal problems (MSP). The aim of this study was to evaluate how activities of the lumbar erector spinae (ES) and of the ascending and descending trapezius (TA, TD) change in upright standing position during SR-WBV. Nineteen female subjects completed 12 series of 10 seconds of SR-WBV at six different frequencies (2, 4, 6, 8, 10, 12Hz) and two types of "noise"-applications. An assessment at rest had been executed beforehand. Muscle activities were measured with EMG and normalized to the maximum voluntary contraction (MVC%). For statistical testing a three-factorial analysis of variation (ANOVA) was applied. The maximum activity of the respective muscles was 14.5 MVC% for the ES, 4.6 MVC% for the TA (12Hz with "noise" both), and 7.4 MVC% for the TD (10Hz without "noise"). Furthermore, all muscles varied significantly at 6Hz and above (p⋜0.047) compared to the situation at rest. No significant differences were found at SR-WBV with or without "noise". In general, muscle activity during SR-WBV is reasonably low and comparable to core strength stability exercises, sensorimotor training and "abdominal hollowing" in water. SR-WBV may be a therapeutic option for the relief of MSP.

  7. Whole body vibration improves cognition in healthy young adults.

    Directory of Open Access Journals (Sweden)

    G Ruben H Regterschot

    Full Text Available This study investigated the acute effects of passive whole body vibration (WBV on executive functions in healthy young adults. Participants (112 females, 21 males; age: 20.5±2.2 years underwent six passive WBV sessions (frequency 30 Hz, amplitude approximately 0.5 mm and six non-vibration control sessions of two minutes each while sitting on a chair mounted on a vibrating platform. A passive WBV session was alternated with a control session. Directly after each session, performance on the Stroop Color-Block Test (CBT, Stroop Color-Word Interference Test (CWIT, Stroop Difference Score (SDS and Digit Span Backward task (DSBT was measured. In half of the passive WBV and control sessions the test order was CBT-CWIT-DSBT, and DSBT-CBT-CWIT in the other half. Passive WBV improved CWIT (p = 0.009; effect size r = 0.20 and SDS (p = 0.034; r = 0.16 performance, but only when the CBT and CWIT preceded the DSBT. CBT and DSBT performance did not change. This study shows that two minutes passive WBV has positive acute effects on attention and inhibition in young adults, notwithstanding their high cognitive functioning which could have hampered improvement. This finding indicates the potential of passive WBV as a cognition-enhancing therapy worth further evaluation, especially in persons unable to perform active forms of exercise.

  8. Cryotherapy: local - whole-body; Kryotherapie Lokal - Ganzkoerper

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, R. [Klinik fuer Rheumatologie, St. Josef-Stift Sendenhorst (Germany)

    1994-12-31

    Cryotherapy, whether administered through ice, cold air, nitrogen or cold pack has an effect that can even reach the point of pain elimination. It also acts antiinflammatorily, eases swelling, and improves the function of inflamed joints. Further effects are alleviation of excess muscle tone and maintenance of blood irrigation in inflamed tissue. The fields of indication for cryotherapy can be summarised as follows: inflammation, pain, swelling, functional inhibition, excess muscle tone. Whole-body therapy at -110 C effects significantly enhanced function as compared with a control groups. Blood oxygen rises. Stenocarias have not been reported, whereas extrasystoles are said to decrease. Helper T lymphocytes in the circulating blood drop significantly in rheumatoid arthritis and Bechterev`s disease. This suggests autoimmune disease as a further field of indication. (orig.) [Deutsch] Kryotherapie mit Eis, Kaltluft, Stickstoff, Kaltluft oder Kaeltepackungen wirkt schmerzlindernd bis hin zu Schmerzaufhebung, wirkt entzuendungshemmend, abschwellend und bei Entzuendung funktionsverbessernd in betroffenen Gelenken, Muskeltonuserhoehungen werden abgebaut. Die Durchblutung, wird unter Ryotherapie im Entzuendungsbereich aufrechterhalten. Somit ergeben sich folgende Indikationen: Entzuendung, Schmerz, Schwellung, Funktionseinschraenkung, Muskeltonuserhoehung. Eine Ganzkoerperkaeltetherapie bei -110 C bewirkt eine signifikante Funktionsverbesserung gegenueber einer Kontrollgruppe. Die Sauerstoffkonzentration steigt im Blut. Stenokardien wurden nicht beobachtet. Extrasystolien nahmen ab. T-Helferlymphozyten sinken im zirkulierenden Blut bei Rheumatoider Arthritis und Morbus Bechterew signifikant ab. Daraus erbit sich als weitere Indikation die Behandlung von Autoimmunerkrankungen. (orig.)

  9. Cryotherapy: local - whole-body; Kryotherapie: Lokal - Ganzkoerper

    Energy Technology Data Exchange (ETDEWEB)

    Fricke, R. [Klinik fuer Rheumatologie, St. Josef-Stift, Sendenhorst (Germany)

    1994-12-31

    Cryotherapy, whether administered through ice, cold air, nitrogen, or cold packs has an analgetic effect that can even reach the point of pain elimination. It also inhibits inflammation, relieves swelling, and improves the function of inflamed joints. Further effects are alleviation of excess muscle tone and maintenance of blood irrigation in inflamed tissue. The fields of indication for cryotherapy can be summarised as follows: inflammation, pain, swelling, functional inhibition, excess muscle tone. Whole-body therapy at -110 C effects significantly enhanced function as compared with a control group. Blood oxygen rises. Stenocardias have not been reported, whereas extrasystoles are said to decrease. Helper T lymphocytes in the circulating blood drop significantly in rheumatoid arthritis and Bechterev`s disease. This suggests autoimmune disease as a further field of indication. (orig.) [Deutsch] Kryotherapie mit Eis, Kaltluft, Stickstoff, Kaltluft oder Kaeltepackungen wirkt schmerzlindernd bis hin zur Schmerzaufhebung, wirkt entzuendungshemmend, abschwellend und bei Entzuendung funktionsverbessernd in betroffenen Gelenken. Muskeltonuserhoehungen werden abgebaut. Die Durchblutung wird unter Kryotherapie im Entzuendungsbereich aufrechterhalten. Somit ergeben sich folgende Indikationen: Entzuendung, Schmerz, Schwellung, Funktionseinschraenkung, Muskeltonuserhoehung. Eine Ganzkoerperkaeltetherapie bei -110 C bewirkt eine signifikante Funktionsverbesserung gegenueber einer Kontrollgruppe. Die Sauerstoffkonzentration steigt im Blut. Stenokardien wurden nicht beobachtet. Extrasystolien nahmen ab. T-Helferlymphozyten sinken im zirkulierenden Blut bei Rheumatoider Arthritis und Morbus Bechterew signifikant ab. Daraus ergibt sich als weitere Indikation die Behandlung von Autoimmunerkrankungen. (orig.)

  10. Whole body vibration as an adjunct to static stretching.

    Science.gov (United States)

    Feland, J B; Hawks, M; Hopkins, J T; Hunter, I; Johnson, A W; Eggett, D L

    2010-08-01

    This study was a randomized control trial. The purpose of this study was twofold: 1) to determine if stretching the hamstrings during whole-body-vibration (WBV) is more effective than static stretching alone; and 2) to monitor retention of flexibility changes. The main outcome measure was hamstring flexibility as measured in degrees using a passive knee extension test. Thirty-four recreationally active college-age subjects (23.4+/-1.7 yrs) completed this study (22 males, 12 females, avg. ht.=175.6+/-6.4 cm, avg. wt.=74.9+/-11.8 kg). Subjects were assigned to a control group (C), a static stretch group (SS), or a vibration + static stretch group (V). Subjects stretched 5 days/wk for 4-weeks and were followed for 3-weeks after cessation to monitor retention. Analysis showed a significant difference between treatment groups (pstretching for the SS and V groups respectively. Three-week follow-up showed SS returning to baseline with V group still 6.4 degrees (11%+/-3.88% (SEM)) more flexible than at baseline. Stretching concurrently with vibration on a WBV platform appears to be a good adjunct to static stretching with the potential to enhance retention of flexibility gains. (c) Georg Thieme Verlag KG Stuttgart . New York.

  11. Acoustical method of whole-body hydration status monitoring

    Science.gov (United States)

    Sarvazyan, A. P.; Tsyuryupa, S. N.; Calhoun, M.; Utter, A.

    2016-07-01

    An acoustical handheld hydration monitor (HM) for assessing the water balance of the human body was developed. Dehydration is a critical public health problem. Many elderly over age of 65 are particularly vulnerable as are infants and young children. Given that dehydration is both preventable and reversible, the need for an easy-to-perform method for the detection of water imbalance is of the utmost clinical importance. The HM is based on an experimental fact that ultrasound velocity in muscle is a linear function of water content and can be referenced to the hydration status of the body. Studies on the validity of HM for the assessment of whole-body hydration status were conducted in the Appalachian State University, USA, on healthy young adults and on elderly subjects residing at an assisted living facility. The HM was able to track changes in total body water during periods of acute dehydration and rehydration in athletes and day-to-day and diurnal variability of hydration in elderly. Results of human studies indicate that HM has a potential to become an efficient tool for detecting abnormal changes in the body hydration status.

  12. Increase of insulin sensitivity by stevioside in fructose-rich chow-fed rats.

    Science.gov (United States)

    Chang, J-C; Wu, M C; Liu, I-M; Cheng, J-T

    2005-10-01

    The intake of dietary fructose has undergone a marked increase around the world, especially the developed countries, in recent times. Stevioside, a glycoside contained in the leaves of Stevia rebaudiana Bertoni (Compositae), was used to screen the effect induced by a diet containing 60% fructose on insulin resistance in rats. Single oral administration of stevioside for 90 min decreased plasma glucose concentrations in a dose-dependent manner in rats receiving fructose-rich chow for four weeks. In addition, insulin action on glucose disposal rate was measured using the glucose-insulin index, the product of the areas under the curve of glucose, and insulin during the intraperitoneal glucose tolerance test. Oral administration of stevioside (5.0 mg/kg) in rats given four weeks of fructose-rich chow for 90 min reversed the value of glucose-insulin index, indicating that stevioside has the ability to improve insulin sensitivity in this insulin-resistant animal model. Time for the loss of plasma glucose lowering response to tolbutamide (10.0 mg/kg, i. p.) in fructose-rich chow fed rats was also markedly delayed by repeated stevioside treatment three times daily compared to the vehicle-treated group. The plasma glucose-lowering activity of tolbutamide was introduced to account for varying levels of endogenous insulin secretion, and is widely used as the indicator of insulin resistance development. Thus, it provided the supportive data that repeated oral administration of stevioside delayed the development of insulin resistance in rats on a high-fructose diet. Increased insulin sensitivity by stevioside administration was further identified using the plasma glucose-lowering action of exogenous insulin in streptozotocin-induced diabetic rats (STZ-diabetic rats). Oral administration of stevioside at 0.2 mg/kg three times daily into STZ-diabetic rats for ten days increased the response to exogenous insulin. Taken together, this demonstrated that oral administration of

  13. mTORC2 Regulation of Muscle Metabolism and Insulin Sensitivity

    DEFF Research Database (Denmark)

    Kleinert, Maximilian

    by defects in the insulin signaling chain necessary for glucose uptake. To better understand the underlying molecular mechanisms of how mTORC2 regulates metabolism in skeletal muscle, we performed unbiased, global quantitative phospho- and total proteomic analyses of mouse Ric mKO muscles. This revealed......Type 2 diabetes (T2D) is a pandemic that continues to grow at alarming rates. In healthy individuals, blood glucose levels are tightly controlled. After eating a meal blood glucose levels rise. This triggers insulin release from the pancreas, which in turn signals organs like the liver, fat...... 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...

  14. 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

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

    Science.gov (United States)

    Van Der Heijden, Gert-Jan; Wang, Zhiyue J; Chu, Zili; Toffolo, Gianna; Manesso, Erica; Sauer, Pieter J J; Sunehag, Agneta L

    2010-11-01

    Data on the metabolic effects of resistance exercise (strength training) in adolescents are limited. The objective of this study was to determine whether a controlled resistance exercise program without dietary intervention or weight loss reduces body fat accumulation, increases lean body mass, and improves insulin sensitivity and glucose metabolism in sedentary obese Hispanic adolescents. Twelve obese adolescents (age = 15.5 ± 0.5 yr, body mass index = 35.3 ± 0.8 kg·m; 40.8% ± 1.5% body fat) completed a 12-wk resistance exercise program (two times 1 h·wk, exercising all major muscle groups). At baseline and on completion of the program, body composition was measured by dual-energy x-ray absorptiometry, abdominal fat distribution was measured by magnetic resonance imaging, hepatic and intramyocellular fat was measured by magnetic resonance spectroscopy, peripheral insulin sensitivity was measured by the stable-label intravenous glucose tolerance test, and hepatic insulin sensitivity was measured by the hepatic insulin sensitivity index = 1000/(GPR × fasting insulin). Glucose production rate (GPR), gluconeogenesis, and glycogenolysis were quantified using stable isotope gas chromatography/mass spectrometry techniques. All participants were normoglycemic. The exercise program resulted in significant strength gain in both upper and lower body muscle groups. Body weight increased from 97.0 ± 3.8 to 99.6 ± 4.2 kg (P mass (55.7 ± 2.8 to 57.9 ± 3.0 kg, P ≤ 0.01). Total, visceral, hepatic, and intramyocellular fat contents remained unchanged. Hepatic insulin sensitivity increased by 24% ± 9% (P mass, improves hepatic insulin sensitivity, and decreases GPR without affecting total fat mass or visceral, hepatic, and intramyocellular fat contents.

  16. Ecscr regulates insulin sensitivity and predisposition to obesity by modulating endothelial cell functions.

    Science.gov (United States)

    Akakabe, Yoshiki; Koide, Masahiro; Kitamura, Youhei; Matsuo, Kiyonari; Ueyama, Tomomi; Matoba, Satoaki; Yamada, Hiroyuki; Miyata, Keishi; Oike, Yuichi; Ikeda, Koji

    2013-01-01

    Insulin resistance is closely associated with obesity and is one of the earliest symptoms of type-2 diabetes. Endothelial cells are involved in the pathogenesis of insulin resistance through their role in insulin delivery and adipose tissue angiogenesis. Here we show that Ecscr (endothelial cell surface expressed chemotaxis and apoptosis regulator; also known as ARIA), the transmembrane protein that regulates endothelial cell signalling, is highly expressed in white and brown adipose tissues, and regulates energy metabolism and glucose homeostasis by modulating endothelial cell functions. Ecscr-deficient mice fed a normal chow show improved glucose tolerance and enhanced insulin sensitivity. We demonstrate that Ecscr deletion enhances the insulin-mediated Akt/endothelial nitric oxide synthase activation in endothelial cells, which increases insulin delivery into the skeletal muscle. Ecscr deletion also protects mice on a high-fat diet from obesity and obesity-related metabolic disorders by enhancing adipose tissue angiogenesis. Conversely, targeted activation of Ecscr in endothelial cells impairs glucose tolerance and predisposes mice to diet-induced obesity. Our results suggest that the inactivation of Ecscr enhances insulin sensitivity and may represent a new therapeutic strategy for treating metabolic syndrome.

  17. 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

    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...... 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...... of vigorous exercise training can induce significant improvements in insulin action in type 2 diabetes. These improvements include increased peripheral insulin sensitivity and responsiveness as well as enhanced suppression of hepatic glucose production....

  18. Estimated insulin sensitivity predicts regression of albuminuria in Type 1 diabetes.

    Science.gov (United States)

    Bjornstad, P; Maahs, D M; Johnson, R J; Rewers, M; Snell-Bergeon, J K

    2015-02-01

    To test the hypothesis that greater baseline insulin sensitivity would predict regression of albuminuria over 6 years in adults with Type 1 diabetes. We enrolled 81 people aged 30-48 years with albuminuria at baseline in the present study and re-examined them 6 years later. Urinary albumin excretion rate was measured and albuminuria was defined as urinary albumin excretion rate ≥ 20 μg/min. Regression of albuminuria was defined as normoalbuminuria (urinary albumin excretion rate albuminuria were examined in stepwise logistic regression. The variables age, diabetes duration, sex, serum uric acid, HbA1c , systolic blood pressure, LDL cholesterol, HDL cholesterol, BMI, baseline albumin excretion rate, estimated insulin sensitivity at baseline, change in estimated insulin sensitivity from baseline to follow-up and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were considered for inclusion in the model. Estimated insulin sensitivity was significantly higher at both baseline (4.6 ± 1.2 vs 3.4 ± 1.7; P = 0.002) and follow-up (5.2 ± 1.9 vs. 3.5 ± 1.7; P albuminuria vs those who did not. HbA1c (odds ratio 0.4, 95% CI 0.2-0.8; P = 0.006), estimated insulin sensitivity (odds ratio 2.5, 95% CI 1.3-4.9; P = 0.006) at baseline and change in estimated insulin sensitivity from baseline to follow-up (odds ratio 2.7, 95% CI 1.4-5.3; P = 0.003) were independently associated with regression of albuminuria in a multivariable stepwise model. In conclusion, over 6 years, higher baseline estimated insulin sensitivity and change in estimated insulin sensitivity independently predicted regression of albuminuria. Improving insulin sensitivity in people with Type 1 diabetes is a potential therapeutic target to increase rates of regression of albuminuria. © 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.

  19. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1

    OpenAIRE

    Chen, Hubert C.; Smith, Steven J.; Ladha, Zuleika; Jensen, Dalan R.; Ferreira, Luis D.; Pulawa, Leslie K.; McGuire, James G.; Pitas, Robert E.; Robert H Eckel; Farese, Robert V.

    2002-01-01

    Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti...

  20. Circulating free testosterone in obese men after bariatric surgery increases in parallel with insulin sensitivity.

    Science.gov (United States)

    Botella-Carretero, J I; Balsa, J A; Gómez-Martin, J M; Peromingo, R; Huerta, L; Carrasco, M; Arrieta, F; Zamarron, I; Martin-Hidalgo, A; Vazquez, C

    2013-04-01

    Male hypogonadism has been linked to obesity and diabetes. We aimed to study the association of changes in insulin sensitivity and testosterone levels in severe obese patients submitted to bariatric surgery. Prospective intervention study with twenty consecutive patients who underwent bariatric surgery studied before and after significant weight loss. Serum testosterone, SHBG, fasting glucose, and insulin were measured among others. Free testosterone was calculated with the Vermeulen formula and insulin sensitivity with the homeostatic model assessment (HOMA). At baseline, thirteen patients had low total testosterone levels, whereas eight of these patients also had free testosterone levels below the reference range obtained from the control group. After bariatric surgery total testosterone, SHBG, and free testosterone significantly increased and achieved normal values in all evaluated patients. Insulin sensitivity improved in all of them. Multivariate linear regression showed that changes in fasting glucose (β=-1.868, p=0.001), insulin (β=-3.782, p=0.001), weight (β=-0.622, p=0.002), and SHBG (β=-0.635, p=0.022) were associated with changes in free testosterone (adjusted R2=0.936, F=26.613, p=0.001). When insulin resistance calculated by HOMA was in the model instead of insulin and glucose, it also was associated (β=-3.488, p=0.008) with free testosterone (adjusted R2=0.821, F=11.111, p=0.005). Circulating tes tos terone in obese men increases after bariatric surgery in parallel with an improvement in insulin sensitivity.

  1. DLK1 Regulates Whole-Body Glucose Metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem M; Ditzel, Nicholas; Laborda, Jorge

    2015-01-01

    due to impaired insulin signaling in OB and lowered Glu-OCN serum levels. Furthermore, Dlk1(-/-) mice treated with Glu-OC experienced significantly lower blood glucose levels than Glu-OCN-treated wild-type mice. The data suggest that Glu-OCN-controlled production of DLK1 by pancreatic β-cells acts...

  2. Accuracy of whole-body plethysmography requires biological calibration.

    Science.gov (United States)

    Poorisrisak, Porntiva; Vrang, Carsten; Henriksen, Jorn Molgaard; Klug, Bent; Hanel, Birgitte; Bisgaard, Hans

    2009-06-01

    Specific airway resistance (sRaw) measured by whole-body plethysmography in young children is increasingly used in research and clinical practice. The method is precise and feasible. However, there is no available method for calibration of the resistance measure, which raises concern of accuracy. Our aim was to determine the agreement of sRaw measurements in six centers and expand normative sRaw values for nonasthmatic children including these centers. Identical hardware with different software versions was used at the six centers. Measurements followed a standard operating procedure: (1) seven healthy young children were brought to each of the six centers for sRaw measurements; and (2) 105 healthy preschool children (52 boys; mean age, 5.1 years; interquartile range, 4.3 to 6.0) were recruited locally for sRaw measurements. (1) The sRaw of the seven-children study group was significantly lower at two centers compared with the other four centers, and one center had significantly higher sRaw than all the other centers (p factory settings of the software was subsequently discovered in one of the deviating centers. (2) Normative data (105 preschool children) were generated and were without significant difference between centers and independent of height, weight, age, and gender. We subsequently pooled these normative data (105 children) with our previous data from 121 healthy young children (overall mean sRaw, 1.27; SD, 0.25). Control using biological standards revealed errors in the factory setting and highlights the need for developing methods for verification of resistance measures to assure accuracy. Normative data were subsequently generated. Importantly, other centers using such normative data should first consider proper calibration before applying reference values.

  3. Human perceptual overestimation of whole body roll tilt in hypergravity.

    Science.gov (United States)

    Clark, Torin K; Newman, Michael C; Oman, Charles M; Merfeld, Daniel M; Young, Laurence R

    2015-04-01

    Hypergravity provides a unique environment to study human perception of orientation. We utilized a long-radius centrifuge to study perception of both static and dynamic whole body roll tilt in hypergravity, across a range of angles, frequencies, and net gravito-inertial levels (referred to as G levels). While studies of static tilt perception in hypergravity have been published, this is the first to measure dynamic tilt perception (i.e., with time-varying canal stimulation) in hypergravity using a continuous matching task. In complete darkness, subjects reported their orientation perception using a haptic task, whereby they attempted to align a hand-held bar with their perceived horizontal. Static roll tilt was overestimated in hypergravity, with more overestimation at larger angles and higher G levels, across the conditions tested (overestimated by ∼35% per additional G level, P < 0.001). As our primary contribution, we show that dynamic roll tilt was also consistently overestimated in hypergravity (P < 0.001) at all angles and frequencies tested, again with more overestimation at higher G levels. The overestimation was similar to that for static tilts at low angular velocities but decreased at higher angular velocities (P = 0.006), consistent with semicircular canal sensory integration. To match our findings, we propose a modification to a previous Observer-type canal-otolith interaction model. Specifically, our data were better modeled by including the hypothesis that the central nervous system treats otolith stimulation in the utricular plane differently than stimulation out of the utricular plane. This modified model was able to simulate quantitatively both the static and the dynamic roll tilt overestimation in hypergravity measured experimentally. Copyright © 2015 the American Physiological Society.

  4. Contribution of anaerobic energy expenditure to whole body thermogenesis

    Directory of Open Access Journals (Sweden)

    Scott Christopher B

    2005-06-01

    Full Text Available Abstract Heat production serves as the standard measurement for the determination of energy expenditure and efficiency in animals. Estimations of metabolic heat production have traditionally focused on gas exchange (oxygen uptake and carbon dioxide production although direct heat measurements may include an anaerobic component particularly when carbohydrate is oxidized. Stoichiometric interpretations of the ratio of carbon dioxide production to oxygen uptake suggest that both anaerobic and aerobic heat production and, by inference, all energy expenditure – can be accounted for with a measurement of oxygen uptake as 21.1 kJ per liter of oxygen. This manuscript incorporates contemporary bioenergetic interpretations of anaerobic and aerobic ATP turnover to promote the independence of these disparate types of metabolic energy transfer: each has different reactants and products, uses dissimilar enzymes, involves different types of biochemical reactions, takes place in separate cellular compartments, exploits different types of gradients and ultimately each operates with distinct efficiency. The 21.1 kJ per liter of oxygen for carbohydrate oxidation includes a small anaerobic heat component as part of anaerobic energy transfer. Faster rates of ATP turnover that exceed mitochondrial respiration and that are supported by rapid glycolytic phosphorylation with lactate production result in heat production that is independent of oxygen uptake. Simultaneous direct and indirect calorimetry has revealed that this anaerobic heat does not disappear when lactate is later oxidized and so oxygen uptake does not adequately measure anaerobic efficiency or energy expenditure (as was suggested by the "oxygen debt" hypothesis. An estimate of anaerobic energy transfer supplements the measurement of oxygen uptake and may improve the interpretation of whole-body energy expenditure.

  5. Dietary glycemic index and glycemic load, carbohydrate and fiber intake, and measures of insulin sensitivity, secretion, and adiposity in the Insulin Resistance Atherosclerosis Study.

    Science.gov (United States)

    Liese, Angela D; Schulz, Mandy; Fang, Fang; Wolever, Thomas M S; D'Agostino, Ralph B; Sparks, Karen C; Mayer-Davis, Elizabeth J

    2005-12-01

    We studied the association of digestible carbohydrates, fiber intake, glycemic index, and glycemic load with insulin sensitivity (S(I)), fasting insulin, acute insulin response (AIR), disposition index, BMI, and waist circumference. Data on 979 adults with normal (67%) and impaired (33%) glucose tolerance from the Insulin Resistance Atherosclerosis Study (1992-1994) were analyzed. Usual dietary intake was assessed via a 114-item interviewer-administered food frequency questionnaire from which nutrient intakes were estimated. Published glycemic index values were assigned to food items and average dietary glycemic index and glycemic load calculated per subject. S(I) and AIR were determined by frequently sampled intravenous glucose tolerance test. Disposition index was calculated by multiplying S(I) with AIR. Multiple linear regression modeling was employed. No association was observed between glycemic index and S(I), fasting insulin, AIR, disposition index, BMI, or waist circumference after adjustment for demographic characteristics or family history of diabetes, energy expenditure, and smoking. Associations observed for digestible carbohydrates and glycemic load, respectively, with S(I), insulin secretion, and adiposity (adjusted for demographics and main confounders) were entirely explained by energy intake. In contrast, fiber was associated positively with S(I) and disposition index and inversely with fasting insulin, BMI, and waist circumference but not with AIR. Carbohydrates as reflected in glycemic index and glycemic load may not be related to measures of insulin sensitivity, insulin secretion, and adiposity. Fiber intake may not only have beneficial effects on insulin sensitivity and adiposity, but also on pancreatic functionality.

  6. Measurement of hepatic insulin sensitivity early after the bypass of the proximal small bowel in humans.

    Science.gov (United States)

    Miras, A D; Herring, R; Vusirikala, A; Shojaee-Moradi, F; Jackson, N C; Chandaria, S; Jackson, S N; Goldstone, A P; Hakim, N; Patel, A G; Umpleby, A M; Le Roux, C W

    2017-03-01

    Unlike gastric banding or sleeve gastrectomy procedures, intestinal bypass procedures, Roux-en-Y gastric bypass in particular, lead to rapid improvements in glycaemia early after surgery. The bypass of the proximal small bowel may have weight loss and even caloric restriction-independent glucose-lowering properties on hepatic insulin sensitivity. In this first human mechanistic study, we examined this hypothesis by investigating the early effects of the duodeno-jejunal bypass liner (DJBL; GI Dynamics, USA) on the hepatic insulin sensitivity by using the gold standard euglycaemic hyperinsulinaemic clamp methodology. Seven patients with obesity underwent measurement of hepatic insulin sensitivity at baseline, 1 week after a low-calorie liquid diet and after a further 1 week following insertion of the DJBL whilst on the same diet. Duodeno-jejunal bypass liner did not improve the insulin sensitivity of hepatic glucose production beyond the improvements achieved with caloric restriction. Caloric restriction may be the predominant driver of early increases in hepatic insulin sensitivity after the endoscopic bypass of the proximal small bowel. The same mechanism may be at play after Roux-en-Y gastric bypass and explain, at least in part, the rapid improvements in glycaemia.

  7. Prolactin Promotes Adipose Tissue Fitness and Insulin Sensitivity in Obese Males.

    Science.gov (United States)

    Ruiz-Herrera, Xarubet; de Los Ríos, Ericka A; Díaz, Juan M; Lerma-Alvarado, Ricardo M; Martínez de la Escalera, Lucía; López-Barrera, Fernando; Lemini, María; Arnold, Edith; Martínez de la Escalera, Gonzalo; Clapp, Carmen; Macotela, Yazmín

    2017-01-01

    Excessive accumulation of body fat triggers insulin resistance and features of the metabolic syndrome. Recently, evidence has accumulated that obesity, type 2 diabetes, and metabolic syndrome are associated with reduced levels of serum prolactin (PRL) in humans and rodents, raising the question of whether low PRL levels contribute to metabolic dysfunction. Here, we have addressed this question by investigating the role of PRL in insulin sensitivity and adipose tissue fitness in obese rodents and humans. In diet-induced obese rats, treatment with PRL delivered via osmotic mini-pumps, improved insulin sensitivity, prevented adipocyte hypertrophy, and reduced inflammatory cytokine expression in visceral fat. PRL also induced increased expression of Pparg and Xbp1s in visceral adipose tissue and elevated circulating adiponectin levels. Conversely, PRL receptor null mice challenged with a high-fat diet developed greater insulin resistance, glucose intolerance, and increased adipocyte hypertrophy compared with wild-type mice. In humans, serum PRL values correlated positively with systemic adiponectin levels and were reduced in insulin-resistant patients. Furthermore, PRL circulating levels and PRL produced by adipose tissue correlated directly with the expression of PPARG, ADIPOQ, and GLUT4 in human visceral and sc adipose tissue. Thus, PRL, acting through its cognate receptors, promotes healthy adipose tissue function and systemic insulin sensitivity. Increasing the levels of PRL in the circulation may have therapeutic potential against obesity-induced metabolic diseases. Copyright © 2017 by the Endocrine Society.

  8. Triggered release of insulin from glucose-sensitive enzyme multilayer shells.

    Science.gov (United States)

    Qi, Wei; Yan, Xuehai; Fei, Jinbo; Wang, Anhe; Cui, Yue; Li, Junbai

    2009-05-01

    A glucose-sensitive multilayer shell, which was fabricated by the layer-by-layer (LbL) assembly method, can be used as a carrier for the encapsulation and controlled release of insulin. In the present report, glucose oxidase (GOD) and catalase (CAT) were assembled on insulin particles alternately via glutaraldehyde (GA) cross-linking. The resulting core-shell system has been proven to be glucose-sensitive. When the external glucose was introduced, the release ratio of insulin from the protein multilayer can be increased observably. This is likely attributed to the catalysis interaction of CAT/GOD shells to glucose, which leads to the production of H(+) and thus drops the pH of the microenvironment. Under the acidic conditions, on the one hand, a part of C=N bond formed from Schiff base reaction can be broken and thus increasing the permeability of the capsule wall. On the other hand, the solubility of insulin can also be increased. The above factors may be the key control to increase the release of insulin from the multilayer. Therefore, such CAT/GOD multilayer may have a great potential as a glucose-sensitive release carrier for insulin, and may open the way for the further application of LbL capsules in the drug delivery and controlled release, etc.

  9. Whole-body vibration in underground load-haul-dump vehicles

    Energy Technology Data Exchange (ETDEWEB)

    Village, J.; Morrison, J.B.; Leong, D.K.N. (Simon Fraser University, Burnaby, BC (Canada). School of Kinesiology)

    1989-10-01

    A study was conducted to determine whole-body vibration (WBV) measurements at the seat plan of load-haul-dump (LHD) vehicles of 3-5, 5-, 6- and 8-yard capacity, at two underground mines. The vibration levels of heavy equipment have been reported to coincide with the most sensitive frequencies of the body and can have detrimental effects on vision, equilibrium, and manual dexterity. They can also be related to muscular fatigue, back injuries, and digestive and circulatory disorders. Data collected was compared with ISO standards; and an evaluation of the findings was conducted with respect to LHD accident and injury data, and information available in the literature on WBV. 26 refs., 8 figs., 4 tabs.

  10. Design of the superconducting magnet for 9.4 Tesla whole-body magnetic resonance imaging

    Science.gov (United States)

    Li, Y.; Wang, Q.; Dai, Y.; Ni, Z.; Zhu, X.; Li, L.; Zhao, B.; Chen, S.

    2017-02-01

    A superconducting magnet for 9.4 Tesla whole-body magnetic resonance imaging is designed and fabricated in Institute of Electrical Engineering, Chinese Academy of Sciences. In this paper, the electromagnetic design methods of the main coils and compensating coils are presented. Sensitivity analysis is performed for all superconducting coils. The design of the superconducting shimming coils is also presented and the design of electromagnetic decoupling of the Z2 coils from the main coils is introduced. Stress and strain analysis with both averaged and detailed models is performed with finite element method. A quench simulation code with anisotropic continuum model and control volume method is developed by us and is verified by experimental study. By means of the quench simulation code, the quench protection system for the 9.4 T magnet is designed for the main coils, the compensating coils and the shimming coils. The magnet cryostat design with zero helium boiling-off technology is also introduced.

  11. Quantitative whole-body MRI in familial partial lipodystrophy type 2: changes in adipose tissue distribution coincide with biochemical improvement.

    LENUS (Irish Health Repository)

    McLaughlin, Patrick D

    2012-11-01

    OBJECTIVE: Familial partial lipodystrophy type 2 (Online Mendelian Inheritance in Man no. 151660) is a systemic disorder characterized by regional lipoatrophy and lipohypertrophy, severe insulin resistance, and early cardiovascular death. At initial presentation, whole-body MRI allows the radiologist to accurately characterize patients with familial partial lipodystrophy and helps differentiate familial partial lipodystrophy from many other subtypes of lipodystophy. We present the findings of serial quantitative MRI analysis in two patients with familial partial lipodystrophy type 2 and outline the objective imaging changes that occur during medical therapy with oral rosiglitazone. CONCLUSION: Cervical adipose volume and visceral adipose area increased by 105% and 60% in the two patients and hepatic fat fraction decreased by 55% during a 21-month period of medical therapy. These changes coincided with a decrease in biochemical indexes of insulin resistance. Whole body quantitative MRI may therefore help to demonstrate the subclinical changes in fat deposition that occur as a result of novel treatment of familial partial lipodystrophy and with continued research may play a role in guiding the choice, duration, and intensity of novel medical therapy.

  12. Comparison of atlas-based techniques for whole-body bone segmentation

    DEFF Research Database (Denmark)

    Arabi, Hossein; Zaidi, Habib

    2017-01-01

    We evaluate the accuracy of whole-body bone extraction from whole-body MR images using a number of atlas-based segmentation methods. The motivation behind this work is to find the most promising approach for the purpose of MRI-guided derivation of PET attenuation maps in whole-body PET/MRI...... out in terms of estimating bone extraction accuracy from whole-body MRI using standard metrics, such as Dice similarity (DSC) and relative volume difference (RVD) considering bony structures obtained from intensity thresholding of the reference CT images as the ground truth. Considering the Dice...

  13. 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.

  14. Evaluation of insulin secretion and action in New World camelids.

    Science.gov (United States)

    Firshman, Anna M; Cebra, Christopher K; Schanbacher, Barbara J; Seaquist, Elizabeth R

    2013-01-01

    To measure and compare insulin secretion and sensitivity in healthy alpacas and llamas via glucose clamping techniques. 8 llamas and 8 alpacas. Hyperinsulinemic euglycemic clamping (HEC) and hyperglycemic clamping (HGC) were performed on each camelid in a crossover design with a minimum 48-hour washout period between clamping procedures. The HEC technique was performed to measure insulin sensitivity. Insulin was infused IV at 6 mU/min/kg for 4 hours, and an IV infusion of glucose was adjusted to maintain blood glucose concentration at 150 mg/dL. Concentrations of blood glucose and plasma insulin were determined throughout. The HGC technique was performed to assess insulin secretion in response to exogenous glucose infusion. An IV infusion of glucose was administered to maintain blood glucose concentration at 320 mg/dL for 3 hours, and concentrations of blood glucose and plasma insulin were determined throughout. Alpacas and llamas were not significantly different with respect to whole-body insulin sensitivity during HEC or in pancreatic β-cell response during HGC. Alpacas and llamas had markedly lower insulin sensitivity during HEC and markedly lower pancreatic β-cell response during HGC, in comparison with many other species. New World camelids had lower glucose-induced insulin secretion and marked insulin resistance in comparison with other species. This likely contributes to the disorders of fat and glucose metabolism that are common to camelids.

  15. A Small Insulinomimetic Molecule Also Improves Insulin Sensitivity in Diabetic Mice.

    Directory of Open Access Journals (Sweden)

    Sandip Mukherjee

    Full Text Available Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O22(dmpz], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1.17μM thus activating insulin receptor tyrosine kinase and its downstream signaling molecules resulting increased uptake of [14C] 2 Deoxy-glucose. Oral administration of dmp to streptozotocin treated BALB/c mice lowers blood glucose level and markedly stimulates glucose and fatty acid uptake by skeletal muscle and adipose tissue respectively. In db/db mice, it greatly improves insulin sensitivity through excess expression of PPARγ and its target genes i.e. adiponectin, CD36 and aP2. Study on the underlying mechanism demonstrated that excess expression of Wnt3a decreased PPARγ whereas dmp suppression of Wnt3a gene increased PPARγ expression which subsequently augmented adiponectin. Increased production of adiponectin in db/db mice due to dmp effected lowering of circulatory TG and FFA levels, activates AMPK in skeletal muscle and this stimulates mitochondrial biogenesis and bioenergetics. Decrease of lipid load along with increased mitochondrial activity greatly improves energy homeostasis which has been found to be correlated with the increased insulin sensitivity. The results obtained with dmp, therefore, strongly indicate that dmp could be a potential candidate for insulin replacement therapy.

  16. 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....

  17. Effects of Lactobacillus acidophilus NCFM on insulin sensitivity and the systemic inflammatory response in human subjects

    DEFF Research Database (Denmark)

    Andreasen, Anne Sofie; Larsen, Nadja; Pedersen-Skovsgaard, Theis

    2010-01-01

    According to animal studies, intake of probiotic bacteria may improve glucose homeostasis. We hypothesised that probiotic bacteria improve insulin sensitivity by attenuating systemic inflammation. Therefore, the effects of oral supplementation with the probiotic bacterium Lactobacillus acidophilus...... course with either L. acidophilus NCFM or placebo. L. acidophilus was detected in stool samples by denaturating gradient gel electrophoresis and real-time PCR. Separated by the 4-week intervention period, two hyperinsulinaemic-euglycaemic clamps were performed to estimate insulin sensitivity. Furthermore......, the systemic inflammatory response was evaluated by subjecting the participants to Escherichia coli lipopolysaccharide injection (0·3 ng/kg) before and after the treatment course. L. acidophilus NCFM was detected in 75 % of the faecal samples after treatment with the probiotic bacterium. Insulin sensitivity...

  18. 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

  19. Central Administration of Galanin Receptor 1 Agonist Boosted Insulin Sensitivity in Adipose Cells of Diabetic Rats.

    Science.gov (United States)

    Zhang, Zhenwen; Fang, Penghua; He, Biao; Guo, Lili; Runesson, Johan; Langel, Ülo; Shi, Mingyi; Zhu, Yan; Bo, Ping

    2016-01-01

    Our previous studies testified the beneficial effect of central galanin on insulin sensitivity of type 2 diabetic rats. The aim of the study was further to investigate whether central M617, a galanin receptor 1 agonist, can benefit insulin sensitivity. The effects of intracerebroventricular administration of M617 on insulin sensitivity and insulin signaling were evaluated in adipose tissues of type 2 diabetic rats. The results showed that central injection of M617 significantly increased plasma adiponectin contents, glucose infusion rates in hyperinsulinemic-euglycemic clamp tests, GLUT4 mRNA expression levels, GLUT4 contents in plasma membranes, and total cell membranes of the adipose cells but reduced the plasma C-reactive protein concentration in nondiabetic and diabetic rats. The ratios of GLUT4 contents were higher in plasma membranes to total cell membranes in both nondiabetic and diabetic M617 groups than each control. In addition, the central administration of M617 enhanced the ratios of pAkt/Akt and pAS160/AS160, but not phosphorylative cAMP response element-binding protein (pCREB)/CREB in the adipose cells of nondiabetic and diabetic rats. These results suggest that excitation of central galanin receptor 1 facilitates insulin sensitivity via activation of the Akt/AS160 signaling pathway in the fat cells of type 2 diabetic rats.

  20. Effect of cabergoline on insulin sensitivity, inflammation, and carotid intima media thickness in patients with prolactinoma.

    Science.gov (United States)

    Inancli, Serap Soytac; Usluogullari, Alper; Ustu, Yusuf; Caner, Sedat; Tam, Abbas Ali; Ersoy, Reyhan; Cakir, Bekir

    2013-08-01

    The aim of this study was to evaluate the effect of Cabergoline on insulin sensitivity, inflammatory markers, and carotid intima media thickness in prolactinoma patients. Twenty-one female, newly diagnosed patients with prolactinoma were included in the study. None of the patients were treated previously. Cabergoline was given as treatment, starting with 0.5 mg/day and tapered necessarily. Blood samples were taken for prolactin, highly sensitive C-reactive protein, homocysteine, total cholesterol, low density lipoprotein (LDL) cholesterol, fasting glucose, insulin, and HOMA (homeostasis model assessment of insulin resistance) score was calculated, prior to and 6 months after starting treatment. The body mass index (BMI) was measured and carotid intima media thickness (CIMT) was evaluated for each patient prior to and 6 months after the treatment. The prolactin levels and LDL decreased significantly after cabergoline treatment. Insulin sensitivity improved independently from the decrease in prolactin levels and BMI. The significant decrease in homocysteine and hs-CRP was not related with the decrease in prolactin levels. The significant decrease in CIMT was independent from the decrease in prolactin levels, HOMA score, and BMI. Our data suggest that cabergoline treatment causes an improvement in insulin sensitivity and inflammatory markers and causes a decrease in CIMT independent from the decrease in prolactin, LDL cholesterol, and BMI. We conclude that short term cabergoline treatment can improve endothelial function independently from the changes in metabolic disturbances and inflammatory markers.

  1. Can diffusion-weighted whole-body MRI replace contrast-enhanced CT for initial staging of Hodgkin lymphoma in children and adolescents?

    Science.gov (United States)

    Regacini, Rodrigo; Puchnick, Andrea; Luisi, Flavio Augusto Vercillo; Lederman, Henrique Manoel

    2018-01-23

    Although positron emission tomography with 18F-fluoro-2-deoxyglucose (FDG-PET/CT) has been recommended as the method of choice for lymphoma staging, it has limited availability in several countries, therefore, studies comparing whole-body magnetic resonance imaging (MRI) to conventional staging methods or to FDG-PET/CT are an important tool to establish whole-body MRI as an alternative to these methods. To compare whole-body MRI versus conventional imaging methods for staging of Hodgkin lymphoma in children and adolescents. The study included 22 patients ages 5 to 21 years. Staging was performed using conventional imaging methods and whole-body MRI. Conventional imaging methods were defined as computed tomography (CT) of the neck, chest, abdomen and pelvis and ultrasonography of the neck and/or abdomen. We calculated the sensitivity of these methods for Hodgkin lymphoma staging and their sensitivity and specificity for detecting sites of nodal and extranodal involvement. The sensitivity of whole-body MRI for Hodgkin lymphoma staging was superior to that of conventional imaging methods (95.5% vs. 86.4%, respectively), but both methods had similar sensitivity and specificity for detecting involvement of nodal sites (99.1% and 100% vs. 97.3% and 100%, respectively) and extranodal sites (90.5% and 98.7% vs. 90.5% and 99.4%, respectively). Whole-body MRI has excellent sensitivity for staging of Hodgkin lymphoma in children and adolescents. It can thus be considered an alternative for this purpose, particularly because it does not expose patients to ionizing radiation.

  2. 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...

  3. 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....

  4. 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...

  5. Guidelines for Whole-Body Vibration Health Surveillance

    Science.gov (United States)

    POPE, M.; MAGNUSSON, M.; LUNDSTRÖM, R.; HULSHOF, C.; VERBEEK, J.; BOVENZI, M.

    2002-05-01

    examination, which includes recording any change in exposure to WBV. The findings for the individual should be compared with previous examinations. Group data should also be compiled periodically. Medical removal may be considered along with re-placement in working practices without exposure to WBV. This paper presents opinions on health surveillance for whole-body vibration developed within a working group of partners funded on a European Community Network (BIOMED2 concerted action BMH4-CT98-3251: Research network on detection and prevention of injuries due to occupational vibration exposures). The health surveillance protocol and the draft questionnaire with explanation comments are presented for wider consideration by the science community and others before being considered appropriate for implementation.

  6. Acute effects of stochastic resonance whole body vibration.

    Science.gov (United States)

    Elfering, Achim; Zahno, Jasmine; Taeymans, Jan; Blasimann, Angela; Radlinger, Lorenz

    2013-01-01

    To investigate the acute effects of stochastic resonance whole body vibration (SR-WBV) training to identify possible explanations for preventive effects against musculoskeletal disorders. Twenty-three healthy, female students participated in this quasi-experimental pilot study. Acute physiological and psychological effects of SR-WBV training were examined using electromyography of descending trapezius (TD) muscle, heart rate variability (HRV), different skin parameters (temperature, redness and blood flow) and self-report questionnaires. All subjects conducted a sham SR-WBV training at a low intensity (2 Hz with noise level 0) and a verum SR-WBV training at a higher intensity (6 Hz with noise level 4). They were tested before, during and after the training. Conclusions were drawn on the basis of analysis of variance. Twenty-three healthy, female students participated in this study (age = 22.4 ± 2.1 years; body mass index = 21.6 ± 2.2 kg/m(2)). Muscular activity of the TD and energy expenditure rose during verum SR-WBV compared to baseline and sham SR-WBV (all P < 0.05). Muscular relaxation after verum SR-WBV was higher than at baseline and after sham SR-WBV (all P < 0.05). During verum SR-WBV the levels of HRV were similar to those observed during sham SR-WBV. The same applies for most of the skin characteristics, while microcirculation of the skin of the middle back was higher during verum compared to sham SR-WBV (P < 0.001). Skin redness showed significant changes over the three measurement points only in the middle back area (P = 0.022). There was a significant rise from baseline to verum SR-WBV (0.86 ± 0.25 perfusion units; P = 0.008). The self-reported chronic pain grade indicators of pain, stiffness, well-being, and muscle relaxation showed a mixed pattern across conditions. Muscle and joint stiffness (P = 0.018) and muscular relaxation did significantly change from baseline to different conditions of SR-WBV (P < 0.001). Moreover, muscle relaxation after

  7. Whole-body vibration therapy in intensive care patients: A feasibility and safety study.

    Science.gov (United States)

    Boeselt, Tobias; Nell, Christoph; Kehr, Katahrina; Holland, Angélique; Dresel, Marc; Greulich, Timm; Tackenberg, Björn; Kenn, Klaus; Boeder, Johannes; Klapdor, Benjamin; Kirschbaum, Andreas; Vogelmeier, Claus; Alter, Peter; Koczulla, Andreas Rembert

    2016-03-01

    Admission to the intensive care unit is associated with sustained loss of muscle mass, reduced quality of life and increased mortality. Early rehabilitation measures may counteract this process. New approaches to rehabilitation while the patient remains in bed are whole-body vibration alone and whole-body vibration with a dumbbell. The aims of this study are to determine the safety of whole-body vibration for patients admitted to the intensive care unit, and to compare the effects of these techniques in intensive care unit patients and healthy subjects. Twelve intensive care unit patients and 12 healthy subjects using whole-body vibration for the first time were examined while lying in bed. First both groups performed whole body vibration over 3 min. In a second step whole body vibration with dumbbell was performed. In order to determine the safety of the training intensity, heart rate, oxygen saturation and blood pressure were measured. The study was approved by the Marburg ethics committee. There were minor reversible and transient increases in diastolic blood pressure (p = 0.005) and heart rate (p = 0.001) in the control group with whole-body vibration with a dumbbell. In intensive care patients receiving whole-body vibration alone, there were increases in diastolic blood pressure (p = 0.011) and heart rate (p vibration and whole-body vibration with a dumbbell for intensive care unit in-bed patients. No clinically significant safety problems were found. Whole-body vibration and whole-body vibration with a dumbbell might therefore be alternative methods for use in early in-bed rehabilitation, not only for hospitalized patients.

  8. 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.

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

    Science.gov (United States)

    Wiria, Aprilianto E; Hamid, Firdaus; Wammes, Linda J; Prasetyani, Margaretta A; Dekkers, Olaf M; May, Linda; Kaisar, Maria M M; Verweij, Jaco J; Guigas, Bruno; Partono, Felix; Sartono, Erliyani; Supali, Taniawati; Yazdanbakhsh, Maria; Smit, Johannes W A

    2015-01-01

    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.

  10. PDE 5 inhibitor improves insulin sensitivity by enhancing mitochondrial function in adipocytes.

    Science.gov (United States)

    Yu, Hea Min; Chung, Hyo Kyun; Kim, Koon Soon; Lee, Jae Min; Hong, Jun Hwa; Park, Kang Seo

    2017-11-04

    Adipocytes are involved in many metabolic disorders. It was recently reported that phosphodiesterase type 5 (PDE5) is expressed in human adipose tissue. In addition, PDE5 inhibitors have been shown to improve insulin sensitivity in humans. However, the mechanism underlying the role of PDE5 inhibitors as an insulin sensitizer remains largely unknown. The present study was undertaken to investigate the role of the PDE5 inhibitor udenafil in insulin signaling in adipocytes and whether this is mediated through the regulation of mitochondrial function. To study the mechanism underlying the insulin sensitizing action of PDE5 inhibitors, we evaluated quantitative changes in protein or mRNA levels of mitochondrial oxidative phosphorylation (OxPhos) complex, oxygen consumption rate (OCR), and fatty acid oxidation with varying udenafil concentrations in 3T3-L1 cells. Our cell study suggested that udenafil enhanced the insulin signaling pathway in 3T3-L1 cells. Following udenafil treatment, basal mitochondrial OCR, maximal OxPhos capacity, and OxPhos gene expression significantly increased. Finally, we examined whether udenafil can affect the fatty acid oxidation process. Treatment of 3T3-L1 cells with udenafil (10 and 20 μM) significantly increased fatty acid oxidation rate in a dose-dependent manner. In addition, the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) significantly increased. We demonstrated that the PDE5 inhibitor udenafil enhances insulin sensitivity by improving mitochondrial function in 3T3-L1 cells. This might be the mechanism underlying the PDE5 inhibitor-enhanced insulin signaling in adipocytes. This also suggests that udenafil may provide benefit in the treatment of type 2 diabetes and other related cardiovascular diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Short-Term Moderate Sleep Restriction Decreases Insulin Sensitivity in Young Healthy Adults

    Science.gov (United States)

    Wang, Xuewen; Greer, Julian; Porter, Ryan R.; Kaur, Kamaljeet; Youngstedt, Shawn D.

    2017-01-01

    Context and Purpose The literature suggests that severe sleep loss of more than a few hours a night decreases glucose tolerance and insulin sensitivity. The aim of this study was to determine whether moderate sleep restriction had similar effects. Methods Fifteen healthy non-obese (BMI=24.5±3.4 kg/m2) young adults (20.6±1.3 years) completed two 2-hour oral glucose tolerance tests (OGTT): one was after 3 days of time-in-bed restriction by 1–3 hours each night, and the other was after 3 days of ad libitum sleep. Glucose and insulin concentrations during OGTT, and fasting glucagon and cortisol concentrations were determined. The homeostasis model of insulin resistance (HOMA-IR), Matsuda index, and the quantitative insulin sensitivity check index (QUICKI) were calculated. Results The total time-in-bed during the sleep restriction and the ad libitum phase was 5.98±0.76 and 7.98±0.54 hours/day, and total sleep time was 5.16±0.49 and 6.65±0.64 hours/day, respectively. Glucose concentrations before and 30, 60, 90, and 120 minutes following consumption of glucose and area under the curve were not different for the two OGTT (p > 0.10 for all). Insulin concentration at fasting and area under the curve during the OGTT were significantly higher (p = 0.034 and 0.038, respectively) following restricted sleep than following ad libitum sleep. Fasting glucagon concentration was also higher (p = 0.003). The HOMA-IR, Matsuda index, and QUICKI all suggested decreased insulin sensitivity following restricted sleep. Conclusion Short-term moderate sleep restriction reduced insulin sensitivity compared to ad libitum sleep in this group of healthy young adults. PMID:28819636

  12. Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity

    Science.gov (United States)

    Shaham, Oded; Wei, Ru; Wang, Thomas J; Ricciardi, Catherine; Lewis, Gregory D; Vasan, Ramachandran S; Carr, Steven A; Thadhani, Ravi; Gerszten, Robert E; Mootha, Vamsi K

    2008-01-01

    Glucose ingestion after an overnight fast triggers an insulin-dependent, homeostatic program that is altered in diabetes. The full spectrum of biochemical changes associated with this transition is currently unknown. We have developed a mass spectrometry-based strategy to simultaneously measure 191 metabolites following glucose ingestion. In two groups of healthy individuals (n=22 and 25), 18 plasma metabolites changed reproducibly, including bile acids, urea cycle intermediates, and purine degradation products, none of which were previously linked to glucose homeostasis. The metabolite dynamics also revealed insulin's known actions along four key axes—proteolysis, lipolysis, ketogenesis, and glycolysis—reflecting a switch from catabolism to anabolism. In pre-diabetics (n=25), we observed a blunted response in all four axes that correlated with insulin resistance. Multivariate analysis revealed that declines in glycerol and leucine/isoleucine (markers of lipolysis and proteolysis, respectively) jointly provide the strongest predictor of insulin sensitivity. This observation indicates that some humans are selectively resistant to insulin's suppression of proteolysis, whereas others, to insulin's suppression of lipolysis. Our findings lay the groundwork for using metabolic profiling to define an individual's 'insulin response profile', which could have value in predicting diabetes, its complications, and in guiding therapy. PMID:18682704

  13. Substrate Metabolism and Insulin Sensitivity During Fasting in Obese Human Subjects: Impact of GH Blockade.

    Science.gov (United States)

    Pedersen, Morten Høgild; Svart, Mads Vandsted; Lebeck, Janne; Bidlingmaier, Martin; Stødkilde-Jørgensen, Hans; Pedersen, Steen Bønløkke; Møller, Niels; Jessen, Niels; Jørgensen, Jens O L

    2017-04-01

    Insulin resistance and metabolic inflexibility are features of obesity and are amplified by fasting. Growth hormone (GH) secretion increases during fasting and GH causes insulin resistance. To study the metabolic effects of GH blockade during fasting in obese subjects. Nine obese males were studied thrice in a randomized design: (1) after an overnight fast (control), (2) after 72 hour fasting (fasting), and (3) after 72 hour fasting with GH blockade (pegvisomant) [fasting plus GH antagonist (GHA)]. Each study day consisted of a 4-hour basal period followed by a 2-hour hyperinsulinemic, euglycemic clamp combined with indirect calorimetry, assessment of glucose and palmitate turnover, and muscle and fat biopsies. GH levels increased with fasting (P fasting-induced reduction of serum insulin-like growth factor I was enhanced by GHA (P Fasting increased lipolysis and lipid oxidation independent of GHA, but fasting plus GHA caused a more pronounced suppression of lipid intermediates in response to hyperinsulinemic, euglycemic clamp. Fasting-induced insulin resistance was abrogated by GHA (P Fasting plus GHA also caused elevated glycerol levels and reduced levels of counterregulatory hormones. Fasting significantly reduced the expression of antilipolytic signals in adipose tissue independent of GHA. Suppression of GH activity during fasting in obese subjects reverses insulin resistance and amplifies insulin-stimulated suppression of lipid intermediates, indicating that GH is an important regulator of substrate metabolism, insulin sensitivity, and metabolic flexibility also in obese subjects.

  14. Modulation of Insulin Sensitivity of Hepatocytes by the Pharmacological Downregulation of Phospholipase D

    Directory of Open Access Journals (Sweden)

    Nataliya A. Babenko

    2015-01-01

    Full Text Available Background. The role of phospholipase D (PLD as a positive modulator of glucose uptake activation by insulin in muscle and adipose cells has been demonstrated. The role of PLD in the regulation of glucose metabolism by insulin in the primary hepatocytes has been determined in this study. Methods. For this purpose, we studied effects of inhibitors of PLD on glucose uptake and glycogen synthesis stimulation by insulin. To determine the PLD activity, the method based on determination of products of transphosphatidylation reaction, phosphatidylethanol or phosphatidylbutanol, was used. Results. Inhibition of PLD by a general antagonist (1-butanol or specific inhibitor, halopemide, or N-hexanoylsphingosine, or by cellular ceramides accumulated in doxorubicin-treated hepatocytes decreased insulin-stimulated glucose metabolism. Doxorubicin-induced hepatocytes resistance to insulin action could be abolished by inhibition of ceramide production. Halopemide could nullify this effect. Addition of propranolol, as well as inhibitors of phosphatidylinositol 3-kinase (PI3-kinase (wortmannin, LY294002 or suppressors of Akt phosphorylation/activity, luteolin-7-O-glucoside or apigenin-7-O-glucoside, to the culture media could block cell response to insulin action. Conclusion. PLD plays an important role in the insulin signaling in the hepatocytes. PLD is activated downstream of PI3-kinase and Akt and is highly sensitive to ceramide content in the liver cells.

  15. Neutral lipid storage disease with myopathy: a whole-body nuclear MRI and metabolic study.

    Science.gov (United States)

    Laforêt, Pascal; Stojkovic, Tanya; Bassez, Guillaume; Carlier, Pierre G; Clément, Karine; Wahbi, Karim; Petit, François M; Eymard, Bruno; Carlier, Robert-Yves

    2013-02-01

    Neutral lipid storage disease with myopathy (NLSDM) is caused by a mutation in the gene encoding adipose triglyceride lipase (ATGL), and is characterized by the presence of numerous triglyceride-containing cytoplasmic droplets in type I muscle fibers. Major clinical manifestations concern the heart and skeletal muscle, and some patients also present diabetes mellitus. We report the clinical, metabolic, and whole-body nuclear magnetic resonance imaging findings of three patients with NLSDM. Muscle MRI study was consistent with previous descriptions, and allowed to show a common pattern of fatty replacement. Muscle changes predominated in the paravertebral muscles, both compartments of legs, and posterior compartment of the thighs. A more variable distribution of muscle involvement was observed on upper limbs, with marked asymmetry in one patient, and alterations predominating on supra and infra spinatus, biceps brachialis and anterior compartment of arms. Cardiac NMR studies revealed anomalies despite normal echocardiography in two patients. Endocrine studies showed low leptin and adiponectine levels, a moderate increase in insulin levels at fasting state, and even greater increase after oral glucose tolerance test in one patient. Two patients had elevated triglycerides and low cholesterol-HDL. Based on these analyses, regular control of cardiometabolic risks appear mandatory in the clinical follow-up of these subjects. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Whole body [{sup 11}C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates

    Energy Technology Data Exchange (ETDEWEB)

    Murthy, Rajan [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States); Harris, Paul; Leibel, Rudolph [Columbia University College of Physicians and Surgeons, Department of Medicine, New York, NY (United States); Simpson, Norman; Parsey, Ramin [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); Van Heertum, Ronald [Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States); Mann, J.J. [Columbia University College of Physicians and Surgeons, Department of Psychiatry, New York, NY (United States); Columbia University College of Physicians and Surgeons, Department of Radiology, New York, NY (United States); New York State Psychiatric Institute, Department of Neuroscience, Division of Brain Imaging, New York, NY (United States)

    2008-04-15

    Vesicular monoamine transporter type 2 abundance quantified using the radiotracer [{sup 11}C]-dihydrotetrabenazine (DTBZ) has been used to study diagnosis and pathogenesis of dementia and psychiatric disorders in humans. In addition, it may be a surrogate marker for insulin-producing pancreatic beta cell mass, useful for longitudinal measurements using positron emission tomography to track progression of autoimmune diabetes. To support the feasibility of long-term repeated administrations, we estimate the biodistribution and dosimetry of [{sup 11}C]-DTBZ in humans. Five baboon studies were acquired using a Siemens ECAT camera. After transmission scanning, 165-210 MBq of [{sup 11}C]-DTBZ were injected, and dynamic whole body emission scans were conducted. Time-activity data were used to obtain residence times and estimate absorbed radiation dose according to the MIRD model. Most of the injected tracer localized to the liver and the lungs, followed by the intestines, brain, and kidneys. The highest estimated absorbed radiation dose was in the stomach wall. The largest radiation dose from [{sup 11}C]-DTBZ is to the stomach wall. This dose estimate, as well as the radiation dose to other radiosensitive organs, must be considered in evaluating the risks of multiple administrations. (orig.)

  17. 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.

  18. 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

    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...... (to 86.7%). HOMA beta-cell function increased between years 4 and 3 before diagnosis (from 85.0% to 92.6%) and then decreased until diagnosis (to 62.4%). INTERPRETATION: In this study, we show changes in glucose concentrations, insulin sensitivity, and insulin secretion as much as 3-6 years before......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...

  19. Glucose effectiveness and insulin sensitivity measurements derived from the non-insulin-assisted minimal model and the clamp techniques are concordant

    DEFF Research Database (Denmark)

    Henriksen, Jan Erik; Alford, Frank; Ward, Glenn

    2010-01-01

    We investigated the concordance between glucose effectiveness (SG) and insulin sensitivity (SI), derived from the unmodified dynamic non-insulin-assisted intravenous glucose tolerance test (IVGTT) implemented by SG(MM) and SI(MM); simulation analysis and modelling/conversational interaction (SAAM....../CONSAM) versus the eu/hyperglycaemic basal insulinaemic and the euglycaemic hyperinsulinaemic clamp (SG(CLAMP) and SI(CLAMP))....

  20. 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

  1. Chronic hyperinsulinemia reduces insulin sensitivity and metabolic functions of brown adipocyte.

    Science.gov (United States)

    Rajan, Sujith; Shankar, Kripa; Beg, Muheeb; Varshney, Salil; Gupta, Abhishek; Srivastava, Ankita; Kumar, Durgesh; Mishra, Raj K; Hussain, Zakir; Gayen, Jiaur R; Gaikwad, Anil N

    2016-09-01

    The growing pandemics of diabetes have become a real threat to world economy. Hyperinsulinemia and insulin resistance are closely associated with the pathophysiology of type 2 diabetes. In pretext of brown adipocytes being considered as the therapeutic strategy for the treatment of obesity and insulin resistance, we have tried to understand the effect of hyperinsulinemia on brown adipocyte function. We here with for the first time report that hyperinsulinemia-induced insulin resistance in brown adipocyte is also accompanied with reduced insulin sensitivity and brown adipocyte characteristics. CI treatment decreased expression of brown adipocyte-specific markers (such as PRDM16, PGC1α, and UCP1) and mitochondrial content as well as activity. CI-treated brown adipocytes showed drastic decrease in oxygen consumption rate (OCR) and spare respiratory capacity. Morphological study indicates increased accumulation of lipid droplets in CI-treated brown adipocytes. We have further validated these findings in vivo in C57BL/6 mice implanted with mini-osmotic insulin pump for 8weeks. CI treatment in mice leads to increased body weight gain, fat mass and impaired glucose intolerance with reduced energy expenditure and insulin sensitivity. CI-treated mice showed decreased BAT characteristics and function. We also observed increased inflammation and ER stress markers in BAT of CI-treated animals. The above results conclude that hyperinsulinemia has deleterious effect on brown adipocyte function, making it susceptible to insulin resistance. Thus, the above findings have greater implication in designing approaches for the treatment of insulin resistance and diabetes via recruitment of brown adipocytes. © 2016 Society for Endocrinology.

  2. Segmentation and Visual Analysis of Whole-Body Mouse Skeleton microSPECT

    NARCIS (Netherlands)

    A. Khmelinskii (Artem); H.C. Groen (Harald); M. Baiker (Martin); M. de Jong (Marion); B.P.F. Lelieveldt (Boudewijn)

    2012-01-01

    textabstractWhole-body SPECT small animal imaging is used to study cancer, and plays an important role in the development of new drugs. Comparing and exploring whole-body datasets can be a difficult and time-consuming task due to the inherent heterogeneity of the data (high volume/throughput,

  3. Segmentation and visual analysis of whole-body mouse skeleton microSPECT

    NARCIS (Netherlands)

    Khmelinskii, A.; Groen, H.C.; De Jong, M.; Lelieveldt, B.P.F.

    2012-01-01

    Whole-body SPECT small animal imaging is used to study cancer, and plays an important role in the development of new drugs. Comparing and exploring whole-body datasets can be a difficult and time-consuming task due to the inherent heterogeneity of the data (high volume/throughput, multi-modality,

  4. Oak Ridge National Laboratory whole-body counter: internal operating procedure manual

    Energy Technology Data Exchange (ETDEWEB)

    Berger, C.D.; Lane, B.H.

    1982-08-01

    The general purpose of the ORNL Whole Body Counter is to provide a rapid estimation of the type and quantity of radionuclide deposited in the human body. This report contains a review of the equipment in use at the facility and the procedure for its operation, the standard procedure for performing a routine whole body count, and a discussion of interpretation of results.

  5. Disruption of TBP-2 ameliorates insulin sensitivity and secretion without affecting obesity.

    Science.gov (United States)

    Yoshihara, Eiji; Fujimoto, Shimpei; Inagaki, Nobuya; Okawa, Katsuya; Masaki, So; Yodoi, Junji; Masutani, Hiroshi

    2010-11-23

    Type 2 diabetes mellitus (T2DM) is characterized by defects in both insulin sensitivity and glucose-stimulated insulin secretion (GSIS) and is often accompanied by obesity. In this study, we show that disruption of thioredoxin binding protein-2 (TBP-2, also called Txnip) in obese mice (ob/ob) dramatically improves hyperglycaemia and glucose intolerance, without affecting obesity or adipocytokine concentrations. TBP-2-deficient ob/ob mice exhibited enhanced insulin sensitivity with activated insulin receptor substrate-1/Akt signalling in skeletal muscle and GSIS in islets compared with ob/ob mice. The elevation of uncoupling protein-2 (UCP-2) expression in ob/ob islets was downregulated by TBP-2 deficiency. TBP-2 overexpression suppressed glucose-induced adenosine triphosphate production, Ca(2+) influx and GSIS. In β-cells, TBP-2 enhanced the expression level and transcriptional activity of UCP-2 by recruitment of peroxisome proliferator-activated receptor-γ co-activator-1α to the UCP-2 promoter. Thus, TBP-2 is a key regulatory molecule of both insulin sensitivity and GSIS in diabetes, raising the possibility that inhibition of TBP-2 may be a novel therapeutic approach for T2DM.

  6. Muscle Arnt/Hif1β Is Dispensable in Myofiber Type Determination, Vascularization and Insulin Sensitivity.

    Directory of Open Access Journals (Sweden)

    Pierre-Marie Badin

    Full Text Available Aryl Hydrocarbon Receptor Nuclear Translocator/ hypoxia-inducible factor 1 beta (ARNT/ HIF1β, a member of bHLH-PAS family of transcriptional factors, plays a critical role in metabolic homeostasis, insulin resistance and glucose intolerance. The contributions of ARNT in pancreas, liver and adipose tissue to energy balance through gene regulation have been described. Surprisingly, the impact of ARNT signaling in the skeletal muscles, one of the major organs involved in glucose disposal, has not been investigated, especially in type II diabetes. Here we report that ARNT is expressed in the skeletal muscles, particularly in the energy-efficient oxidative slow-twitch myofibers, which are characterized by increased oxidative capacity, mitochondrial content, vascular supply and insulin sensitivity. However, muscle-specific deletion of ARNT did not change myofiber type distribution, oxidative capacity, mitochondrial content, capillarity, or the expression of genes associated with these features. Consequently, the lack of ARNT in the skeletal muscle did not affect weight gain, lean/fat mass, insulin sensitivity and glucose tolerance in lean mice, nor did it impact insulin resistance and glucose intolerance in high fat diet-induced obesity. Therefore, skeletal muscle ARNT is dispensable for controlling muscle fiber type and metabolic regulation, as well as diet-induced weight control, insulin sensitivity and glucose tolerance.

  7. Muscle Arnt/Hif1β Is Dispensable in Myofiber Type Determination, Vascularization and Insulin Sensitivity.

    Science.gov (United States)

    Badin, Pierre-Marie; Sopariwala, Danesh H; Lorca, Sabina; Narkar, Vihang A

    2016-01-01

    Aryl Hydrocarbon Receptor Nuclear Translocator/ hypoxia-inducible factor 1 beta (ARNT/ HIF1β), a member of bHLH-PAS family of transcriptional factors, plays a critical role in metabolic homeostasis, insulin resistance and glucose intolerance. The contributions of ARNT in pancreas, liver and adipose tissue to energy balance through gene regulation have been described. Surprisingly, the impact of ARNT signaling in the skeletal muscles, one of the major organs involved in glucose disposal, has not been investigated, especially in type II diabetes. Here we report that ARNT is expressed in the skeletal muscles, particularly in the energy-efficient oxidative slow-twitch myofibers, which are characterized by increased oxidative capacity, mitochondrial content, vascular supply and insulin sensitivity. However, muscle-specific deletion of ARNT did not change myofiber type distribution, oxidative capacity, mitochondrial content, capillarity, or the expression of genes associated with these features. Consequently, the lack of ARNT in the skeletal muscle did not affect weight gain, lean/fat mass, insulin sensitivity and glucose tolerance in lean mice, nor did it impact insulin resistance and glucose intolerance in high fat diet-induced obesity. Therefore, skeletal muscle ARNT is dispensable for controlling muscle fiber type and metabolic regulation, as well as diet-induced weight control, insulin sensitivity and glucose tolerance.

  8. Effect of Low Salt Diet on Insulin Resistance in Salt Sensitive versus Salt Resistant Hypertension

    Science.gov (United States)

    Garg, Rajesh; Sun, Bei; Williams, Jonathan

    2014-01-01

    Accumulating evidence shows an increase in insulin resistance on salt restriction. We compared the effect of low salt diet on insulin resistance in salt sensitive versus salt resistant hypertensive subjects. We also evaluated the relationship between salt sensitivity of blood pressure and salt sensitivity of insulin resistance in a multivariate regression model. Studies were conducted after one week of high salt (200 mmol/day Na) and one week of low salt (10 mmol/day Na) diet. Salt sensitivity was defined as the fall in systolic blood pressure >15mmHg on low salt diet. The study includes 389 subjects (44% Females, 16% Blacks, BMI 28.5±4.2 Kg/m2). As expected, blood pressure was lower on low salt (129±16/78±9 mmHg) as compared to high salt diet (145±18/86±10 mmHg). Fasting plasma glucose, insulin and HOMA were higher on low salt diet (95.4±19.4 mg/dl, 10.8±7.3 mIU/L and 2.6±1.9) as compared to high salt diet (90.6±10.8 mg/dl, 9.4±5.8 mIU/L and 2.1±1.4) (p salt sensitive (N=193) versus salt resistant (N=196) subjects on either diet. Increase in HOMA on low salt diet was 0.5±1.4 in salt sensitive and 0.4±1.5 in salt resistant subjects (p=NS). On multivariate regression analysis, change in systolic blood pressure was not associated with change in HOMA after including age, BMI, sex, change in serum and urine aldosterone and cortisol into the model. We conclude that the increase in insulin resistance on low salt diet is not affected by salt sensitivity of blood pressure. PMID:25185125

  9. A DXA Whole Body Composition Cross-Calibration Experience: Evaluation With Humans, Spine, and Whole Body Phantoms.

    Science.gov (United States)

    Krueger, Diane; Libber, Jessie; Sanfilippo, Jennifer; Yu, Hui Jing; Horvath, Blaine; Miller, Colin G; Binkley, Neil

    2016-01-01

    New densitometer installation requires cross-calibration for accurate longitudinal assessment. When replacing a unit with the same model, the International Society for Clinical Densitometry recommends cross-calibrating by scanning phantoms 10 times on each instrument and states that spine bone mineral density (BMD) should be within 1%, whereas total body lean, fat, and %fat mass should be within 2% of the prior instrument. However, there is limited validation that these recommendations provide adequate total body cross-calibration. Here, we report a total body cross-calibration experience with phantoms and humans. Cross-calibration between an existing and new Lunar iDXA was performed using 3 encapsulated spine phantoms (GE [GE Lunar, Madison, WI], BioClinica [BioClinica Inc, Princeton, NJ], and Hologic [Hologic Inc, Bedford, MA]), 1 total body composition phantom (BioClinica), and 30 human volunteers. Thirty scans of each phantom and a total body scan of human volunteers were obtained on each instrument. All spine phantom BMD means were similar (within 1%; phantom (BBCP) BMD and bone mineral content (BMC) values were within 2% with biases of 0.005 g/cm2 and -3.4 g. However, lean and fat mass and %fat differed by 4.6%-7.7% with biases of +463 g, -496 g, and -2.8%, respectively. In vivo comparison supported BBCP data; BMD and BMC were within ∼2%, but lean and fat mass and %fat differed from 1.6% to 4.9% with biases of +833 g, -860 g, and -1.1%. As all body composition comparisons exceeded the recommended 2%, the new densitometer was recalibrated. After recalibration, in vivo bias was lower (phantoms, despite good BMD and BMC agreement, did not detect substantial lean and fat differences observed using BBCP and in vivo assessments. Consequently, spine phantoms are inadequate for dual-energy X-ray absorptiometry whole body composition cross-calibration. Copyright © 2016 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights

  10. Whole-body MRI in the detection of bone marrow infiltration in patients with plasma cell neoplasms in comparison to the radiological skeletal survey

    Energy Technology Data Exchange (ETDEWEB)

    Ghanem, Nadir; Lohrmann, Christian; Pache, Gregor; Uhl, Markus; Saueressig, Ulrich; Kotter, Elmar; Langer, Mathias [University Hospital Freiburg, Department of Diagnostic Radiology, Freiburg (Germany); Engelhardt, Monika [University Hospital Freiburg, Department of Hematology and Oncology, Freiburg (Germany)

    2006-05-15

    To compare the diagnostic value of whole-body MRI versus radiological skeletal survey (RSS) in staging patients with plasma cell neoplasms (PCN) and to evaluate the possible therapeutic impact of the replacement of RSS by whole-body MRI. Fifty-four patients with PCN [multiple myeloma (MM), n=47; monoclonal gammopathy of unknown significance (MGUS), n=7] were studied by whole-body MRI and RSS in a monocenter prospective analysis from August 2002 to May 2004. The MRIs were performed using a rolling table platform ''AngioSURF'' for unlimited field of view with a 1.5-T system (Magnetom Sonata/Maestro Class, Siemens Medical Solutions, Erlangen, Germany). A coronal STIR sequence (TR5500-4230/TE102-94/TI160) was used for imaging of the different body regions, including the head, neck, thorax, abdomen, pelvis and upper and lower extremities. The RSS consisted of eight different projections of the axial and appendicular skeleton. In 41/54 (74%) patients, the results of the whole-body MRI and RSS were concordant. In 11/54 (20%) patients, both imaging techniques were negative. Bone involvement was observed in 30/54 (55%) patients; however, whole-body MRI revealed this more extensively than the RSS in 27/30 (90%) patients with concordant positive imaging findings. In 3/30 (10%) patients, both imaging techniques demonstrated a similar extent of bone marrow infiltration. In 10/54 (19%) patients, the whole-body MRI was superior to RSS in detecting bone marrow infiltration, whereas the RSS was negative. In 3/54 (6%) patients, the RSS was proven to be false positive by the clinical course, whereas the whole-body MRI was truly negative. Whole-body MRI is a fast and highly effective method for staging PCN patients by the use of a rolling table platform. Moreover, it is more sensitive and specific than RSS and reveals bone marrow infiltration and extensive disease more reliably. Therefore, whole-body MRI should be performed as an additional method of exactly

  11. 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......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...

  12. 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...... that only the diameter (and not the number) of individual subsarcolemmal LDs was negatively associated with insulin sensitivity (R2 = 0.20, P = 0.03, n = 29). Despite 34% (P = 0.004) fewer LDs, the diameter of individual subsarcolemmal LDs was 20% (P = 0.0004) larger in type 2 fibers than in type 1 fibers....... Furthermore, aerobic training decreased the size of subsarcolemmal LDs in the type 2fibers, and ESA treatment lowered the number of both intermyofibrillar and subsarcolemmal LDs in the type 1fibers. In conclusion, the size of individual subsarcolemmal LDs may be involved in the mechanism by which LDs...

  13. Arsenic exposure is associated with diminished insulin sensitivity in non-diabetic Amish adults.

    Science.gov (United States)

    Park, Sung Kyun; Peng, Qing; Bielak, Lawrence F; Silver, Kristi D; Peyser, Patricia A; Mitchell, Braxton D

    2016-09-01

    Substantial evidence supports an association between diabetes and arsenic at high exposure levels, but results are mixed at low exposure levels. The aetiology of diabetes involves insulin resistance and β-cell dysfunction. However, only a few epidemiologic studies have examined measures of insulin resistance and β-cell function in relation to arsenic exposure, and no studies have tested for associations with the oral glucose tolerance test (OGTT). We examined the association between urinary total arsenic and OGTT-based markers of insulin sensitivity and β-cell function. We studied 221 non-diabetic adults (mean age = 52.5 years) from the Amish Family Diabetes Study. We computed OGTT-based validated measures of insulin sensitivity and β-cell function. Generalized estimating equations accounting for sibship were used to estimate associations. After adjusting for age, sex, waist-to-hip ratio and urinary creatinine, an interquartile range increase in urinary total arsenic (6.24 µg/L) was significantly, inversely associated with two insulin sensitivity measures (Stumvoll metabolic clearance rate = -0.23 mg/(kg min), (95% CI: -0.38, -0.089), p = 0.0015; Stumvoll insulin sensitivity index = -0.0029 µmol/(kg min pM), (95% CI: -0.0047, -0.0011), p = 0.0015). Urinary total arsenic was also significantly associated with higher fasting glucose levels (0.57 mg/dL (95% CI: 0.06, 1.09) per interquartile range increase, p = 0.029). No significant associations were found between urinary total arsenic and β-cell function measures. This preliminary study found that urinary total arsenic was associated with insulin sensitivity but not β-cell function measures, suggesting that low-level arsenic exposure may influence diabetes risk through impairing insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

  14. PUFAs acutely affect triacylglycerol-derived skeletal muscle fatty acid uptake and increase postprandial insulin sensitivity

    NARCIS (Netherlands)

    Jans, A.; Konings, E.; Goossens, G.H.; Bouwman, F.G.; Moors, C.C.; Boekschoten, M.V.; Afman, L.A.; Muller, M.R.; Mariman, E.C.; Blaak, E.E.

    2012-01-01

    Background: Dietary fat quality may influence skeletal muscle lipid processing and fat accumulation, thereby modulating insulin sensitivity. Objective: The objective was to examine the acute effects of meals with various fatty acid (FA) compositions on skeletal muscle FA processing and postprandial

  15. 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

  16. 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) cm3 , Pfat %, 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.

  17. Acute caffeine ingestion reduces insulin sensitivity in healthy subjects: a systematic review and meta-analysis.

    Science.gov (United States)

    Shi, Xiuqin; Xue, Wenhua; Liang, Shuhong; Zhao, Jie; Zhang, Xiaojian

    2016-12-28

    According to previous meta-analyses, coffee consumption reduces the risk of type 2 diabetes mellitus. However, the underlying mechanism remains unknown. Whether caffeine, the key ingredient in coffee, has a beneficial effect on the glycemic homeostasis and the anti-diabetic effect is particularly controversial. The aim of this study was to summarize the effect of acute caffeine ingestion on insulin sensitivity in healthy men. A comprehensive literature search for papers published before April 2016 was conducted in EMBASE, PubMed, and Cochrane Library databases. Randomized controlled trials (RCTs) that investigated the effect of caffeine on insulin sensitivity in healthy humans without diabetes were included. A random effects meta-analysis was conducted using Review Manager 5.3. The search yielded 7 RCTs in which caffeine intake was the single variant. Compared with placebo, caffeine intake significantly decreased the insulin sensitivity index, with a standardized mean difference of -2.06 (95% confidence interval -2.67 to -1.44, I2 = 49%, P for heterogeneity = 0.06). Acute caffeine ingestion reduces insulin sensitivity in healthy subjects. Thus, in the short term, caffeine might shift glycemic homeostasis toward hyperglycemia. Long-term trials investigating the role of caffeine in the anti-diabetic effect of coffee are needed.

  18. Moderate alcohol consumption increases insulin sensitivity and ADIPOQ expression in postmenopausal women: A randomised, crossover trial

    NARCIS (Netherlands)

    Joosten, M.M.; Beulens, J.W.J.; Kersten, S.; Hendriks, H.F.J.

    2008-01-01

    Aims/hypothesis: To determine whether 6 weeks of daily, moderate alcohol consumption increases expression of the gene encoding adiponectin (ADIPOQ) and plasma levels of the protein, and improves insulin sensitivity in postmenopausal women. Methods: In a randomised, open-label, crossover trial

  19. 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

  20. Enhanced insulin sensitivity in skeletal muscle and liver by physiological overexpression of SIRT6

    Directory of Open Access Journals (Sweden)

    Jason G. Anderson

    2015-11-01

    Conclusions: Our data indicate that moderate, physiological overexpression of SIRT6 enhances insulin sensitivity in skeletal muscle and liver, engendering protective actions against diet-induced T2DM. Hence, the present study provides support for the anti-T2DM effect of SIRT6 and suggests SIRT6 as a putative molecular target for anti-T2DM treatment.

  1. 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

    low insulin sensitivity. Methods: 25 middle aged male participants were matched for lean body mass and recruited into three groups; type 2 diabetes patients (T2D), impaired glu- cose tolerance (IGT), and healthy sedentary controls (CON) according to their glucose tolerance and VO2peak. A muscle biopsy...

  2. Exercise Improves Insulin Sensitivity in the Absence of Changes in Cytokines

    NARCIS (Netherlands)

    Verheggen, R.J.; Poelkens, F.; Roerink, S.H.; Ramakers, R.E.; Catoire, M.; Hermus, A.R.; Thijssen, D.H.; Hopman, M.T.

    2016-01-01

    PURPOSE: The benefits of aerobic exercise training on insulin sensitivity in subjects with metabolic syndrome (MetS) are, at least in part, associated with changes in cytokines. Recent studies identified novel cytokines (e.g., fractalkine, omentin, and osteopontin) that are strongly involved in

  3. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus

    NARCIS (Netherlands)

    Hanssen, M.J.W.; Hoeks, J.; Brans, B.; Boekschoten, M.V.; Kersten, A.H.

    2015-01-01

    Cold exposure may be a potential therapy for diabetes by increasing brown adipose tissue (BAT) mass and activity. Here we report that 10 d of cold acclimation (14–15 °C) increased peripheral insulin sensitivity by ~43% in eight type 2 diabetes subjects. Basal skeletal muscle GLUT4 translocation

  4. Effects of different degrees of insulin sensitivity on endothelial function in obese patients.

    Science.gov (United States)

    Galvão, Roberto; Plavnik, Frida Liane; Ribeiro, Fernando Flexa; Ajzen, Sérgio Aron; Christofalo, Dejaldo M de J; Kohlmann, Osvaldo

    2012-01-01

    Obesity derived from intra-abdominal fat deposition tends to increase hormonal and cytokine production, thus worsening insulin sensitivity and leading to endothelial dysfunction. Hyperinsulinemia is considered an independent risk factor for ischemic heart disease and cause of endothelial dysfunction in healthy individuals. To assess the impact of different degrees of insulin resistance, measured by HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), on endothelial function in obese, non-diabetic patients without prior history of cardiovascular events and different metabolic syndrome components. Forty obese individuals were submitted to anthropometric measurements, BP measurements at office and ABPM and laboratory tests, in addition to non-invasive ultrasound assessment of endothelial function. Patients were divided into 3 groups according to the level of insulin resistance: patients with HOMA-IR values from 0.590 to 1.082 were assigned to Group 1 (n=13), from 1.083 to 1.410 to Group 2 (n=14) and from 1.610 to 2.510 to Group 3 (n=13). We found a significant difference in flow-mediated dilation in group 3 compared to group 1 (9.2 ± 7.0 vs 18.0 ± 7.5 %, p=0.006). There was a negative correlation between endothelial function and insulin, HOMA-IR and triglycerides. Our data suggest that mild changes in insulin resistance levels assessed by HOMA-IR may have an impact on vasodilatatory endothelial function in uncomplicated obese individuals with different cardiovascular risk factors.

  5. [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.

  6. Whole Body Vibration at Different Exposure Frequencies: Infrared Thermography and Physiological Effects

    Directory of Open Access Journals (Sweden)

    Anelise Sonza

    2015-01-01

    Full Text Available The aim of this study was to investigate the effects of whole body vibration (WBV on physiological parameters, cutaneous temperature, tactile sensitivity, and balance. Twenty-four healthy adults (25.3±2.6 years participated in four WBV sessions. They spent 15 minutes on a vibration platform in the vertical mode at four different frequencies (31, 35, 40, and 44 Hz with 1 mm of amplitude. All variables were measured before and after WBV exposure. Pressure sensation in five anatomical regions and both feet was determined using Von Frey monofilaments. Postural sway was measured using a force plate. Cutaneous temperature was obtained with an infrared camera. WBV influences the discharge of the skin touch-pressure receptors, decreasing sensitivity at all measured frequencies and foot regions (P≤0.05. Regarding balance, no differences were found after 20 minutes of WBV at frequencies of 31 and 35 Hz. At 40 and 44 Hz, participants showed higher anterior-posterior center of pressure (COP velocity and length. The cutaneous temperature of the lower limbs decreased during and 10 minutes after WBV. WBV decreases touch-pressure sensitivity at all measured frequencies 10 min after exposure. This may be related to the impaired balance at higher frequencies since these variables have a role in maintaining postural stability. Vasoconstriction might explain the decreased lower limb temperature.

  7. Saffron (Crocus sativus L.) increases glucose uptake and insulin sensitivity in muscle cells via multipathway mechanisms.

    Science.gov (United States)

    Kang, Changkeun; Lee, Hyunkyoung; Jung, Eun-Sun; Seyedian, Ramin; Jo, MiNa; Kim, Jehein; Kim, Jong-Shu; Kim, Euikyung

    2012-12-15

    Saffron (Crocus sativus Linn.) has been an important subject of research in the past two decades because of its various biological properties, including anti-cancer, anti-inflammatory, and anti-atherosclerotic activities. On the other hand, the molecular bases of its actions have been scarcely understood. Here, we elucidated the mechanism of the hypoglycemic actions of saffron through investigating its signaling pathways associated with glucose metabolism in C(2)C(12) skeletal muscle cells. Saffron strongly enhanced glucose uptake and the phosphorylation of AMPK (AMP-activated protein kinase)/ACC (acetyl-CoA carboxylase) and MAPKs (mitogen-activated protein kinases), but not PI 3-kinase (Phosphatidylinositol 3-kinase)/Akt. Interestingly, the co-treatment of saffron and insulin further improved the insulin sensitivity via both insulin-independent (AMPK/ACC and MAPKs) and insulin-dependent (PI 3-kinase/Akt and mTOR) pathways. It also suggested that there is a crosstalk between the two signaling pathways of glucose metabolism in skeletal muscle cells. These results could be confirmed from the findings of GLUT4 translocation. Taken together, AMPK plays a major role in the effects of saffron on glucose uptake and insulin sensitivity in skeletal muscle cells. Our study provides important insights for the possible mechanism of action of saffron and its potential as a therapeutic agent in diabetic patients. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. ELOVL6 Genetic Variation Is Related to Insulin Sensitivity: A New Candidate Gene in Energy Metabolism

    Science.gov (United States)

    Morcillo, Sonsoles; Martín-Núñez, Gracia María; Rojo-Martínez, Gemma; Almaraz, María Cruz; García-Escobar, Eva; Mansego, María Luisa; de Marco, Griselda; Chaves, Felipe J.; Soriguer, Federico

    2011-01-01

    Background The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1). Objective We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain. Design We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex. Results Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001). Conclusions Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study. PMID:21701577

  9. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids.

    Science.gov (United States)

    Fu, Xianghui; Dong, Bingning; Tian, Yan; Lefebvre, Philippe; Meng, Zhipeng; Wang, Xichun; Pattou, François; Han, Weidong; Wang, Xiaoqiong; Lou, Fang; Jove, Richard; Staels, Bart; Moore, David D; Huang, Wendong

    2015-06-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet-fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D.

  10. 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...... to an intravenous glucose-glucagon challenge as well as an oral glucose load. Already within 1 week, RYGB reduced basal glucose production, improved basal hepatic insulin sensitivity and increased insulin clearance highlighting the liver as an important organ responsible for the early effects on glucose metabolism...... in response to oral glucose, underscoring the importance of the changed gut anatomy....

  11. 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

    follow-up data from the Inter99 study were used. Individuals with normal glucose tolerance (NGT) at baseline and i-IFG, i-IGT, combined IFG/IGT, or NGT at the 5-year follow-up were examined with an oral glucose tolerance test (n = 3,145). Insulin sensitivity index (ISI), homeostasis model assessment......OBJECTIVE: The aim of this study was to describe the natural history of insulin secretion and insulin sensitivity in the development of isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), and combined IFG/IGT. RESEARCH DESIGN AND METHODS: Baseline and 5-year...

  12. Cryo-sectioning of mice for whole-body imaging of drugs and metabolites with desorption electrospray ionization mass spectrometry imaging - a simplified approach

    DEFF Research Database (Denmark)

    Okutan, Seda; Hansen, Harald S; Janfelt, Christian

    2016-01-01

    A method is presented for whole-body imaging of drugs and metabolites in mice with desorption electrospray ionization mass spectrometry imaging (DESI-MSI). Unlike most previous approaches to whole-body imaging which are based on cryo-sectioning using a cryo-macrotome, the presented approach...... bodyweight which is comparable to the normal prescribed human dose. The simultaneous imaging of endogenous and exogenous compounds facilitates registration of the drug images to certain organs in the body by colored-overlay of the two types of images. The method represents a relatively low-cost approach...... to simple, sensitive and highly selective whole-body imaging in drug distribution and metabolism studies....

  13. Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling.

    Science.gov (United States)

    Høeg, Louise D; Sjøberg, Kim A; Jeppesen, Jacob; Jensen, Thomas E; Frøsig, Christian; Birk, Jesper B; Bisiani, Bruno; Hiscock, Natalie; Pilegaard, Henriette; Wojtaszewski, Jørgen F P; Richter, Erik A; Kiens, Bente

    2011-01-01

    We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance. Insulin sensitivity of whole-body and leg glucose disposal was studied in 16 young well-matched healthy men and women infused with intralipid or saline for 7 h. Muscle biopsies were obtained before and during a euglycemic-hyperinsulinemic clamp (1.42 mU · kg⁻¹ · min⁻¹). Intralipid infusion reduced whole-body glucose infusion rate by 26% in women and 38% in men (P insulin-stimulated leg glucose uptake was reduced significantly less in women (45%) than men (60%) after intralipid infusion. Hepatic glucose production was decreased during the clamp similarly in women and men irrespective of intralipid infusion. Intralipid did not impair insulin or AMPK signaling in muscle and subcutaneous fat, did not cause accumulation of muscle lipid intermediates, and did not impair insulin-stimulated glycogen synthase activity in muscle or increase plasma concentrations of inflammatory cytokines. In vitro glucose transport in giant sarcolemmal vesicles was not decreased by acute exposure to fatty acids. Leg lactate release was increased and respiratory exchange ratio was decreased by intralipid. Intralipid infusion causes less insulin resistance of muscle glucose uptake in women than in men. This insulin resistance is not due to decreased canonical insulin signaling, accumulation of lipid intermediates, inflammation, or direct inhibition of GLUT activity. Rather, a higher leg lactate release and lower glucose oxidation with intralipid infusion may suggest a metabolic feedback regulation of glucose metabolism.

  14. Ectopic Fat Deposition on Insulin Sensitivity: Correlation of Hepatocellular Lipid Content and M Value

    Directory of Open Access Journals (Sweden)

    Beverly S. Hong

    2016-01-01

    Full Text Available Purpose. This study aimed to explore the relationship among insulin sensitivity and ectopic fat depots in participants with different glucose status. Methods. Fifty-nine men and women were enrolled in this study: 29 with normal glucose tolerance (NGT, 17 with impaired glucose tolerance (IGT, and 13 with type 2 diabetes mellitus (T2DM. All participants underwent a hyperinsulinemic-euglycemic clamp to assess the insulin sensitivity index (M value and magnetic resonance imaging to measure the hepatocellular lipid content (HCL, skeletal muscle fat content including intramyocellular lipid (IMCL and extramyocellular lipid (EMCL of tibialis anterior (ta, and soleus muscle (sol. Results. The M value of NGT group was higher than those of IGT and T2DM groups (P=0.001. Participants with T2DM had the highest HCL and IMCL (ta compared with those in NGT and IGT groups (P=0.001. The M value had an inverse relationship with HCL (r=-0.789, P=0.001, IMCL (sol (r=-0.427, P=0.002, and IMCL (ta (r=-0.419, P=0.002. Stepwise linear regression analysis showed that HCL (standardized β=-0.416; P=0.001 had an independent relationship with M value. Conclusions. Hepatocellular lipid content deposition happens earlier than skeletal muscle fat deposition. HCL is an independent risk factor for insulin resistance and may be used to evaluate the risk of developing T2DM as a noninvasive marker of insulin sensitivity index.

  15. The Association between Alcohol Consumption and β-Cell Function and Insulin Sensitivity in Korean Population.

    Science.gov (United States)

    Yoo, Min-Gyu; Kim, Hyo-Jin; Jang, Han Byul; Lee, Hye-Ja; Park, Sang Ick

    2016-11-14

    This cross-sectional study was performed to examine the association between alcohol consumption and insulin secretion and sensitivity using the Korean Genome and Epidemiology Study. Alcohol consumption levels were categorized into four groups: (i) abstainers, (ii) low (consumption. β-cell function and insulin sensitivity were estimated using the insulinogenic index (IGI60), and Matsuda insulin sensitivity index (ISI), respectively. IGI60 and ISI were dichotomized into high and low groups using median cut-off values and four groups were defined (G-I: high IGI60/high ISI; G-II: high IGI60/low ISI; G-III: low IGI60/high ISI; and G-IV: low IGI60/low ISI). Men consumed 26.5 g alcohol per day on average, whereas women only consumed 5.7 g/day, so women were excluded from subsequent analyses due to their low drinking levels. Alcohol consumption was positively associated with high-density lipoprotein (HDL) cholesterol, aspartate aminotransferase (AST), and triglycerides (TG) in men, but was negatively associated with IGI60 (p function (G-III) with high alcohol consumption. In addition, alcohol consumption increased HDL cholesterol in the four groups (p consumption increased the risk of high cholesterol and TG. In individuals with decreased β-cell function (G-III), alcohol consumption increased the risk of high TG and high AST levels. High alcohol consumption was significantly associated with reduced insulin secretion. In addition, alcohol consumption was related to some metabolic risk factors depending on insulin secretion or sensitivity.

  16. Effects of Dietary Garlic Extracts on Whole Body Amino Acid and Fatty Acid Composition, Muscle Free Amino Acid Profiles and Blood Plasma Changes in Juvenile Sterlet Sturgeon,

    Directory of Open Access Journals (Sweden)

    Dong-Hoon Lee

    2012-10-01

    Full Text Available A series of studies were carried out to investigate the supplemental effects of dietary garlic extracts (GE on whole body amino acids, whole body and muscle free amino acids, fatty acid composition and blood plasma changes in 6 month old juvenile sterlet sturgeon (Acipenser ruthenus. In the first experiment, fish with an average body weight of 59.6 g were randomly allotted to each of 10 tanks (two groups of five replicates, 20 fish/tank and fed diets with (0.5% or without (control GE respectively, at the level of 2% of fish body weight per day for 5 wks. Whole body amino acid composition between the GE and control groups were not different (p>0.05. Among free amino acids in muscle, L-glutamic acid, L-alanine, L-valine, L-leucine and L-phenylalanine were significantly (p0.05 were noticed at 12 h (74.6 vs 73.0. Plasma insulin concentrations (μIU/ml between the two groups were significantly (p<0.05 different at 1 (10.56 vs 5.06 and 24 h (32.56 vs 2.96 after feeding. The present results suggested that dietary garlic extracts could increase dietary glucose utilization through the insulin secretion, which result in improved fish body quality and feed utilization by juvenile sterlet sturgeon.

  17. Increased insulin and leptin sensitivity in mice lacking acyl CoA:diacylglycerol acyltransferase 1.

    Science.gov (United States)

    Chen, Hubert C; Smith, Steven J; Ladha, Zuleika; Jensen, Dalan R; Ferreira, Luis D; Pulawa, Leslie K; McGuire, James G; Pitas, Robert E; Eckel, Robert H; Farese, Robert V

    2002-04-01

    Acyl coenzyme A:diacylglycerol acyltransferase 1 (DGAT1) is one of two known DGAT enzymes that catalyze the final step in mammalian triglyceride synthesis. DGAT1-deficient mice are resistant to diet-induced obesity through a mechanism involving increased energy expenditure. Here we show that these mice have decreased levels of tissue triglycerides, as well as increased sensitivity to insulin and to leptin. Importantly, DGAT1 deficiency protects against insulin resistance and obesity in agouti yellow mice, a model of severe leptin resistance. In contrast, DGAT1 deficiency did not affect energy and glucose metabolism in leptin-deficient (ob/ob) mice, possibly due in part to a compensatory upregulation of DGAT2 expression in the absence of leptin. Our results suggest that inhibition of DGAT1 may be useful in treating insulin resistance and leptin resistance in human obesity.

  18. Early Pregnancy-Associated Plasma Protein A Concentrations Are Associated With Third Trimester Insulin Sensitivity.

    Science.gov (United States)

    Petry, Clive J; Ong, Ken K; Hughes, Ieuan A; Acerini, Carlo L; Frystyk, Jan; Dunger, David B

    2017-06-01

    First or early second trimester pregnancy-associated plasma protein A (PAPP-A) concentrations have previously been shown to be lower in women who subsequently develop gestational diabetes mellitus (GDM) and gestational hypertension. We therefore sought to investigate why circulating PAPP-A concentrations are related to the subsequent risk of GDM and gestational hypertension. We measured serum PAPP-A concentrations around week 15 of pregnancy and related these to indices derived from week 28 oral glucose tolerance tests and blood pressures across pregnancy in the Cambridge Baby Growth Study cohort. Increased PAPP-A concentrations were associated with reduced GDM risk [odds ratio 0.623 (0.453, 0.856), P = 3.5 × 10-3, n = 777] and reduced mean arterial blood pressures (β = -0.202 to -0.177, P = 1.7 to 6.9 × 10-3, n = 347 to 355). They were also negatively associated with week 28 fasting (β = -0.149, P = 6.6 × 10-4, n = 777) and 60-minute (β = -0.188, P = 1.5 × 10-5, n = 777) oral glucose tolerance test glucose concentrations. These associations were underpinned by the strong associations between increased week 15 PAPP-A concentrations and decreased week 28 insulin resistance (homeostasis model assessment of insulin resistance: β = -0.319, P = 1.7 × 10-13, n = 768), as well as increased insulin secretion relative to insulin sensitivity (insulin disposition index: β = 0.202, P = 6.5 × 10-6, n = 731). These results suggest that links between PAPP-A concentrations in early pregnancy and subsequent glucose concentrations and blood pressures may be mediated by changes in insulin sensitivity (and secretion).

  19. Improved insulin sensitivity and islet function after PPARdelta activation in diabetic db/db mice.

    Science.gov (United States)

    Winzell, Maria Sörhede; Wulff, Erik Max; Olsen, Grith Skytte; Sauerberg, Per; Gotfredsen, Carsten F; Ahrén, Bo

    2010-01-25

    The peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily. Several reports have shown that PPARdelta is involved in lipid metabolism, increasing fat oxidation and depleting lipid accumulation. Whether PPARdelta is involved in the regulation of glucose metabolism is not completely understood. In this study, we examined effects of long-term PPARdelta activation on glycemic control, islet function and insulin sensitivity in diabetic db/db mice. Male db/db mice were administered orally once daily with a selective and partial PPARdelta agonist (NNC 61-5920, 30 mg/kg) for eight weeks; control mice received vehicle. Fasting and non-fasting plasma glucose were reduced, reflected in reduced hemoglobinA(1c) (3.6+/-1.6% vs. 5.4+/-1.8 in db/db controls, P<0.05) and furthermore, the AUC(glucose) after oral glucose (3g/kg) was reduced by 67% (P<0.05) after long-term PPARdelta activation. Following intravenous glucose (1g/kg), glucose tolerance was improved after PPARdelta activation (K(G) 1.3+/-0.6 vs. -0.05+/-0.7 %/min, P=0.048). Insulin sensitivity, measured as the glucose clearance after intravenous injection of glucose (1g/kg) and insulin (0.75 or 1.0 U/kg), during inhibition of endogenous insulin secretion by diazoxide (25mg/kg), was improved (K(G) 2.9+/-0.6 vs. 1.3+/-0.3 %/min in controls, P<0.05) despite lower insulin levels. Furthermore, islets isolated from PPARdelta agonist treated mice demonstrated improved glucose responsiveness as well as improved cellular topography. In conclusion, PPARdelta agonism alleviates insulin resistance and improves islet function and topography, resulting in improved glycemia in diabetic db/db mice. This suggests that activation of PPARdelta improves glucose metabolism and may therefore potentially be target for treatment of type 2 diabetes.

  20. Suppression of PC-1/ENPP-1 expression improves insulin sensitivity in vitro and in vivo.

    Science.gov (United States)

    Zhou, Heather H; Chin, Chen-Ni; Wu, Margaret; Ni, Weihua; Quan, Shuo; Liu, Franklin; Dallas-Yang, Qing; Ellsworth, Kenneth; Ho, Thu; Zhang, Aiwu; Natasha, Tajneen; Li, Jing; Chapman, Kevin; Strohl, William; Li, Cai; Wang, I-Ming; Berger, Joel; An, Zhiqiang; Zhang, Bei B; Jiang, Guoqiang

    2009-08-15

    Plasma cell membrane glycoprotein-1, or ectonucleotide pyrophosphatase/phosphodieterase (PC-1/ENPP1) has been shown to inhibit insulin signaling in cultured cells in vitro and in transgenic mice in vivo when overexpressed. Furthermore, both genetic polymorphism and increased expression of PC-1 have been reported to be associated with type 2 diabetes in humans. Thus it was proposed that PC-1 inhibition represents a potential strategy for the treatment of type 2 diabetes. However, it has not been proven that suppression of PC-1 expression or inhibition of its function will actually improve insulin sensitivity. We show in the current study that transient overexpression of PC-1 inhibits insulin-stimulated insulin receptor tyrosine phosphorylation in HEK293 cells, while knockdown of PC-1 with siRNA significantly increases insulin-stimulated Akt phosphorylation in HuH7 human hepatoma cells. Adenoviral vector expressing a short hairpin RNA against mouse PC-1 (PC-1shRNA) was utilized to efficiently knockdown PC-1 expression in the livers of db/db mice. In comparison with db/db mice treated with a control virus, db/db mice treated with the PC-1shRNA adenovirus had approximately 80% lower hepatic PC-1 mRNA levels, approximately 30% lower ambient fed plasma glucose, approximately 25% lower fasting plasma glucose, and significantly improved oral glucose tolerance. Taken together, these results demonstrate that suppression of PC-1 expression improves insulin sensitivity in vitro and in an animal model of diabetes, supporting the proposition that PC-1 inhibition is a potential therapeutic approach for the treatment of type 2 diabetes.

  1. Changes of insulin sensitivity and secretion after bariatric/metabolic surgery.

    Science.gov (United States)

    Mingrone, Geltrude; Cummings, David E

    2016-07-01

    Type 2 diabetes (T2D) is classically characterized by failure of pancreatic β-cell function and insulin secretion to compensate for a prevailing level of insulin resistance, typically associated with visceral obesity. Although this is usually a chronic, progressive disease in which delay of end-organ complications is the primary therapeutic goal for medical and behavioral approaches, several types of bariatric surgery, especially those that include intestinal bypass components, exert powerful antidiabetes effects to yield remission of T2D in most cases. It has become increasingly clear that in addition to the known benefits of acute caloric restriction and chronic weight loss to ameliorate T2D, bariatric/metabolic operations also engage a variety of weight-independent mechanisms to improve glucose homeostasis, enhancing insulin sensitivity and secretion to varying degrees depending on the specific operation. In this paper, we review the effects of Roux-en-Y gastric bypass, biliopancreatic diversion, and vertical sleeve gastrectomy on the primary determinants of glucose homeostasis: insulin sensitivity, insulin secretion, and, to the lesser extent that it is known, insulin-independent glucose disposal. A full understanding of these effects should help optimize surgical and device-based designs to provide maximal antidiabetes impact, and it holds the promise to identify targets for possible novel diabetes pharmacotherapeutics. These insights also contribute to the conceptual rationale for use of bariatric operations as "metabolic surgery," employed primarily to treat T2D, including among patients not obese enough to qualify for surgery based on traditional criteria related to high body mass index. Copyright © 2016 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.

  2. Fasting serum levels of ferritin are associated with impaired pancreatic beta cell function and decreased insulin sensitivity

    DEFF Research Database (Denmark)

    Bonfils, Linéa; Ellervik, Christina; Friedrich, Nele

    2015-01-01

    Aims/hypothesis: Elevated serum ferritin levels are associated with an increased risk of type 2 diabetes, but the nature of this association remains elusive. The aim of this study was to test the hypothesis that an elevated fasting serum ferritin level is associated with an increased risk of type...... ferritin levels are associated with surrogate measures of both impaired beta cell function and decreased insulin sensitivity. Menopause seems to modify the association with insulin sensitivity....... diabetes due to its association with impaired beta cell function and decreased insulin sensitivity. Methods: We investigated 6,392 individuals from the Danish general population. Surrogate measures of beta cell function and insulin sensitivity were calculated for approximately 6,100 individuals based...... glucose levels at 0, 30 and 120 min (p beta cell function estimated as the insulinogenic index and corrected insulin response (p 

  3. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture

    DEFF Research Database (Denmark)

    Benrick, Anna; Kokosar, Milana; Hu, Min

    2017-01-01

    measured by euglycemic-hyperinsulinemic clamp during and after 45 min of low-frequency EA in 21 overweight/obese women with polycystic ovary syndrome (PCOS) and 21 controls matched for age, weight, and body mass index (experiment 1) and in rats receiving autonomic receptor blockers (experiment 2). GIR...... was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS...... of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.-Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M...

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

    Science.gov (United States)

    Zheng, Xianjie; Niu, Sen

    2018-01-29

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

  5. Meal-induced insulin sensitization is preserved after acute olanzapine administration in female Sprague-Dawley rats.

    Science.gov (United States)

    Kovács, Diána; Hegedűs, Csaba; Kiss, Rita; Sári, Réka; Németh, József; Szilvássy, Zoltán; Peitl, Barna

    2015-05-01

    Olanzapine, an atypical antipsychotic, can acutely induce fasting insulin resistance, but we do not know whether it is able to modulate the meal-induced insulin sensitization (MIS). Two main experimental groups (control and olanzapine-treated) were created with two subgroups (fasted and re-fed) within each. After oral vehicle/olanzapine administration, the first meal size and duration and the total amount of consumed food was recorded in conscious rats. Then, under anaesthesia, the carotid artery and jugular vein was prepared and cannulated to obtain samples for blood glucose and hormone determination as well as for insulin/glucose infusion, respectively. Basal insulin sensitivity and MIS was determined by homeostasis model assessment (HOMA) calculation and by rapid insulin sensitivity test, respectively. In fasted animals, olanzapine increased blood glucose and plasma insulin and reduced basal insulin sensitivity, but it failed to modify other hormone levels. Postprandial leptin and glucose-dependent insulinotropic polypeptide (GIP) levels increased, and ghrelin level decreased significantly (p rats. Furthermore, the MIS was preserved after acute olanzapine treatment. The blunted postprandial ghrelin and insulin response could contribute to the effect of olanzapine on feeding behaviour. Pharmacological induction of MIS may improve the olanzapine-induced insulin resistance.

  6. 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.

  7. Signal Processing Methods for Removing the Effects of Whole Body Vibration upon Speech

    Science.gov (United States)

    Bitner, Rachel M.; Begault, Durand R.

    2014-01-01

    Humans may be exposed to whole-body vibration in environments where clear speech communications are crucial, particularly during the launch phases of space flight and in high-performance aircraft. Prior research has shown that high levels of vibration cause a decrease in speech intelligibility. However, the effects of whole-body vibration upon speech are not well understood, and no attempt has been made to restore speech distorted by whole-body vibration. In this paper, a model for speech under whole-body vibration is proposed and a method to remove its effect is described. The method described reduces the perceptual effects of vibration, yields higher ASR accuracy scores, and may significantly improve intelligibility. Possible applications include incorporation within communication systems to improve radio-communication systems in environments such a spaceflight, aviation, or off-road vehicle operations.

  8. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

    LENUS (Irish Health Repository)

    Shortt, Conor P

    2009-04-01

    The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma.

  9. Possible Mechanisms of Low Back Pain due to Whole-Body Vibration

    Science.gov (United States)

    Pope, M. H.; Wilder, D. G.; Magnusson, M.

    1998-08-01

    The investigators describe their multifaceted approach to the study of the relationship between whole-body vibration and low back pain.In vitroexperiments, using percutaneous pin-mounted accelerometers have shown that the natural frequency is at 4·5 Hz. The frequency response was affected by posture, seating, and seat-back inclination. The response appears to be largely determined by the rocking of the pelvis. Electromyographic studies have shown that muscle fatigue occurs under whole body vibration. After whole body vibration exposure the muscle response to a sudden load has greater latency. Vehicle driving may be a reason for low back pain or herniated nucleus pulposus. Prolonged seating exposure, coupled with the whole body vibration should be reduced for those recovering from these problems. Vibration attenuating seats, and correct ergonomic layout of the cabs may reduce the risks of recurrence.

  10. Mouse whole-body organ mapping by non-rigid registration approach

    Science.gov (United States)

    Xiao, Di; Zahra, David; Bourgeat, Pierrick; Berghofer, Paula; Acosta Tamayo, Oscar; Green, Heather; Gregoire, Marie Claude; Salvado, Olivier

    2011-03-01

    Automatic small animal whole-body organ registration is challenging because of subject's joint structure, posture and position difference and loss of reference features. In this paper, an improved 3D shape context based non-rigid registration method is applied for mouse whole-body skeleton registration and lung registration. A geodesic path based non-rigid registration method is proposed for mouse torso skin registration. Based on the above registration methods, a novel non-rigid registration framework is proposed for mouse whole-body organ mapping from an atlas to new scanned CT data. A preliminary experiment was performed to test the method on lung and skin registration. A whole-body organ mapping was performed on three target data and the selected organs were compared with the manual outlining results. The robust of the method has been demonstrated.

  11. Various performance-enhancing effects from the same intensity of whole-body vibration training

    Directory of Open Access Journals (Sweden)

    Paohung Chung

    2017-09-01

    Conclusion: All frequency and amplitude settings in the 8-week whole-body vibration training increased muscle strength, but different settings resulted in various neuromuscular adaptations despite the same intensity.

  12. Severe insulin-resistant diabetes mellitus in patients with congenital muscle fiber type disproportion myopathy

    DEFF Research Database (Denmark)

    Vestergaard, H; Klein, H H; Hansen, T

    1995-01-01

    severe insulin resistance of both liver and peripheral tissues. The impaired insulin-stimulated glucose disposal to peripheral tissues was primarily due to reduced nonoxidative glucose metabolism. These changes were paralleled by reduced basal values of muscle GS total activity, allosterical activation...... heterogeneity. Concomitant endocrine dysfunctions have not been described. We report the findings of altered insulin secretion and insulin action in two brothers affected with CFTDM and glucose intolerance as well as in their nonconsanguineous glucose-tolerant parents. Results are compared with those of six...... normoglycemic control subjects. All study participants underwent an oral glucose tolerance test to estimate insulin secretion. The oldest boy and his parents volunteered for studies of whole-body insulin sensitivity consisting of a 4-h euglycemic hyperinsulinemic clamp in combination with indirect calorimetry...

  13. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women.

    Science.gov (United States)

    Muscelli, Elza; Kozàkovà, Michaela; Flyvbjerg, Allan; Kyriakopoulou, Konstantina; Astiarraga, Brenno D; Glintborg, Dorte; Konrad, Thomas; Favuzzi, Angela; Petrie, Jhon

    2009-04-01

    The mechanisms by which menopause may influence the systemic subclinical atherosclerosis are unexplained. The aim of this cross-sectional study was to evaluate the associations between early menopause, established cardiovascular (c-v) risk factors, metabolic parameters (insulin secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid artery (CCA) luminal diameter, and IMT in different carotid segments were measured in digitized ultrasound images. Insulin sensitivity and secretion were assessed using the euglycemic hyperinsulinemic clamp technique and oral glucose tolerance test (OGTT). Insulin secretion was reconstructed by mathematical modeling. CCA diameter (5.55 +/- 0.46 vs. 5.21+/- 0.51 mm, P women, whereas CCA IMT/diameter ratio and IMT in other carotid segments did not differ between the groups. By multivariate models, independent predictors of CCA diameter were menopause and body weight (cumulative R2 = 0.37) and independent correlates of CCA IMT were luminal diameter, systolic BP and low-density lipoprotein (LDL) cholesterol (cumulative R2 = 0.48). Fasting insulin, insulin secretion, and sensitivity and plasma adiponectin were similar in the two groups and were not related to carotid IMT. Early menopause is associated with CCA remodeling, characterized by a proportional increase in luminal diameter and wall thickness, independent of atherosclerotic risk factors and metabolic variables.

  14. Actions of PPARgamma agonism on adipose tissue remodeling, insulin sensitivity, and lipemia in absence of glucocorticoids.

    Science.gov (United States)

    Berthiaume, Magalie; Sell, Henrike; Lalonde, Josée; Gélinas, Yves; Tchernof, André; Richard, Denis; Deshaies, Yves

    2004-11-01

    Peroxisome proliferator-activated receptor gamma (PPARgamma) agonists improve insulin sensitivity and lipemia partly through enhancing adipose tissue proliferation and capacity for lipid retention. The agonists also reduce local adipose glucocorticoid production, which may in turn contribute to their metabolic actions. This study assessed the effects of a PPARgamma agonist in the absence of glucocorticoids (adrenalectomy, ADX). Intact, ADX, and intact pair-fed (PF) rats were treated with the PPARgamma agonist rosiglitazone (RSG) for 2 wk. RSG increased inguinal (subcutaneous) white (50%) and brown adipose tissue (6-fold) weight but not that of retroperitoneal (visceral) white adipose tissue. ADX but not PF reduced fat accretion in both inguinal and retroperitoneal adipose depots but did not affect brown adipose mass. RSG no longer increased inguinal weight in ADX and PF rats but increased brown adipose mass, albeit less so than in intact rats. RSG increased cell proliferation in white (3-fold) and brown adipose tissue (6-fold), as assessed microscopically and by total DNA, an effect that was attenuated but not abrogated by ADX. RSG reduced the expression of the glucocorticoid-activating enzyme 11beta-hydroxysteroid dehydrogenase 1 (11beta-HSD1) in all adipose depots. RSG improved insulin sensitivity (reduction in fasting insulin and homeostasis model assessment of insulin resistance, both -50%) and triacylglycerolemia (-75%) regardless of the glucocorticoid status, these effects being fully additive to those of ADX and PF. In conclusion, RSG partially retained its ability to induce white and brown adipose cell proliferation and brown adipose fat accretion and further improved insulin sensitivity and lipemia in ADX rats, such effects being therefore independent from the PPARgamma-mediated modulation of glucocorticoids. Copyright 2004 American Physiological Society

  15. 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.

  16. A simple intravenous glucose tolerance test for assessment of insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Ljunggren Stefan

    2011-05-01

    Full Text Available Abstract Background The aim of the study was to find a simple intravenous glucose tolerance test (IVGTT that can be used to estimate insulin sensitivity. Methods In 20 healthy volunteers aged between 18 and 51 years (mean, 28 comparisons were made between kinetic parameters derived from a 12-sample, 75-min IVGTT and the Mbw (glucose uptake obtained during a hyperinsulinemic euglycemic glucose clamp. Plasma glucose was used to calculate the volume of distribution (Vd and the clearance (CL of the injected glucose bolus. The plasma insulin response was quantified by the area under the curve (AUCins. Uptake of glucose during the clamp was corrected for body weight (Mbw. Results There was a 7-fold variation in Mbw. Algorithms based on the slope of the glucose-elimination curve (CL/Vd in combination with AUCins obtained during the IVGTT showed statistically significant correlations with Mbw, the linearity being r2 = 0.63-0.83. The best algorithms were associated with a 25-75th prediction error ranging from -10% to +10%. Sampling could be shortened to 30-40 min without loss of linearity or precision. Conclusion Simple measures of glucose and insulin kinetics during an IVGTT can predict between 2/3 and 4/5 of the insulin sensitivity.

  17. Beneficial impact of sleep extension on fasting insulin sensitivity in adults with habitual sleep restriction.

    Science.gov (United States)

    Leproult, Rachel; Deliens, Gaétane; Gilson, Médhi; Peigneux, Philippe

    2015-05-01

    A link between sleep loss and increased risk for the development of diabetes is now well recognized. The current study investigates whether sleep extension under real-life conditions is a feasible intervention with a beneficial impact on glucose metabolism in healthy adults who are chronically sleep restricted. Intervention study. Sixteen healthy non-obese volunteers (25 [23, 27.8] years old, 3 men). Two weeks of habitual time in bed followed by 6 weeks during which participants were instructed to increase their time in bed by one hour per day. Continuous actigraphy monitoring and daily sleep logs during the entire study. Glucose and insulin were assayed on a single morning blood sample at the end of habitual time in bed and at the end of sleep extension. Home polysomnography was performed during one weekday of habitual time in bed and after 40 days of sleep extension. Sleep time during weekdays increased (mean actigraphic data: +44 ± 34 minutes, P sleep time correlated with changes in glucose (r = +0.53, P = 0.041) and insulin levels (r = -0.60, P = 0.025), as well as with indices of insulin sensitivity (r = +0.76, P = 0.002). In healthy adults who are chronically sleep restricted, a simple low cost intervention such as sleep extension is feasible and is associated with improvements in fasting insulin sensitivity. © 2015 Associated Professional Sleep Societies, LLC.

  18. 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.

  19. Timing of Gun Fire Influences Sprinters’ Multiple Joint Reaction Times of Whole Body in Block Start

    OpenAIRE

    Mitsuo Otsuka; Toshiyuki Kurihara; Tadao Isaka

    2017-01-01

    Experienced sprinters are specifically adapted to pre-planning an advanced motor program. Herein, sprinters are able to immediately accelerate their center of mass forward with a whole-body coordinated motion, following a steady state crouched position. We examined the effect of variable timing of reaction signals on multiple joint reaction times (RT) and whole-body RT for specialist sprinters. Twenty well-experienced male sprinters performed five start-dashes from a block start under five va...

  20. Detection of multifocal osteonecrosis in an adolescent with dermatomyositis using whole-body MRI

    Energy Technology Data Exchange (ETDEWEB)

    Castro, Tania C.M.; Terreri, Maria Teresa A.; Hilario, Maria Odete E. [Federal University of Sao Paulo, Department of Pediatrics, Division of Allergy, Clinical Immunology and Rheumatology, Sao Paulo, SP (Brazil); Lederman, Henrique [Federal University of Sao Paulo, Image Diagnosis Department, Sao Paulo (Brazil); Kaste, Sue C. [St. Jude Children' s Research Hospital, Department of Radiological Sciences, Division of Diagnostic Imaging, Memphis, TN (United States)

    2010-09-15

    Osteonecrosis is a well-recognized complication of corticosteroid use resulting in significant morbidity, often requiring surgical intervention. Whole-body MRI is a promising method that allows imaging of the whole patient in a reasonable time without the use of ionizing radiation. This technique has the potential for evaluating nonmalignant multifocal skeletal disease like osteonecrosis. This case highlights the value of whole-body MR in an adolescent with dermatomyositis who developed multifocal osteonecrosis. (orig.)

  1. A High Resolution Clinical PET with Breast and Whole Body Transfigurations

    Science.gov (United States)

    2006-08-01

    continues to be difficult, whether the density is a result of fibrocystic diseases or young age. Accurate detection of very small breast tumors (2...DAMD17-02-1-0461 TITLE: A High Resolution Clinical PET with Breast and Whole Body Transfigurations PRINCIPAL INVESTIGATOR: Wai-Hoi...SUBTITLE 5a. CONTRACT NUMBER A High Resolution Clinical PET with Breast and Whole Body Transfigurations 5b. GRANT NUMBER DAMD17-02-1-0461

  2. Detection of multifocal osteonecrosis in an adolescent with dermatomyositis using whole-body MRI.

    Science.gov (United States)

    Castro, Tania C M; Lederman, Henrique; Terreri, Maria Teresa A; Kaste, Sue C; Hilario, Maria Odete E

    2010-09-01

    Osteonecrosis is a well-recognized complication of corticosteroid use resulting in significant morbidity, often requiring surgical intervention. Whole-body MRI is a promising method that allows imaging of the whole patient in a reasonable time without the use of ionizing radiation. This technique has the potential for evaluating nonmalignant multifocal skeletal disease like osteonecrosis. This case highlights the value of whole-body MR in an adolescent with dermatomyositis who developed multifocal osteonecrosis.

  3. Whole-body irradiation transiently diminishes the adrenocorticotropin response to recombinant human interleukin-1{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Perlstein, R.S.; Mehta, N.R.; Neta, R.; Whitnall, M.H. [Armed Forces Radiobiology Research Institute, Bethesda, MD (United States); Mougey, E.H. [Walter Reed Army Institute of Research, Washington, DC (United States)

    1995-03-01

    Recombinant human interleukin-1{alpha} (rhIL-1{alpha}) has significant potential as a radioprotector and/or treatment for radiation-induced hematopoietic injury. Both IL-1 and whole-body ionizing irradiation acutely stimulate the hypothalamic-pituitary-adrenal axis. We therefore assessed the interaction of whole-body irradiation and rhIL-1{alpha} in altering the functioning of the axis in mice. Specifically, we determined the adrenocorticotropin (ACTH) and corticosterone responses to rhIL-1{alpha} administered just before and hours to days after whole-body or sham irradiation. Our results indicate that whole-body irradiation does not potentiate the rhIL-1{alpha}-induced increase in ACTH levels at the doses used. In fact, the rhIL-1{alpha}-induced increase in plasma ACTH is transiently impaired when the cytokine is administered 5 h after, but not 1 h before, exposure to whole-body irradiation. The ACTH response may be inhibited by elevated corticosterone levels after whole-body irradiation, or by other radiation-induced effects on the pituitary gland and hypothalamus. 36 refs., 3 figs.

  4. Basic study of entire whole-body PET scanners based on the OpenPET geometry

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Eiji, E-mail: rush@nirs.go.j [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan); Yamaya, Taiga; Nishikido, Fumihiko; Inadama, Naoko; Murayama, Hideo [National Institute of Radiological Sciences, 4-9-1 Inage-ku, Chiba 263-8555 (Japan)

    2010-09-21

    A conventional PET scanner has a 15-25 cm axial field-of-view (FOV) and images a whole body using about six bed positions. An OpenPET geometry can extend the axial FOV with a limited number of detectors. The entire whole-body PET scanner must be able to process a large amount of data effectively. In this work, we study feasibility of the fully 3D entire whole-body PET scanner using the GATE simulation. The OpenPET has 12 block detector rings with the ring diameter of 840 mm and each block detector ring consists of 48 depth-of-interaction (DOI) detectors. The OpenPET has the axial length of 895.95 mm with five parts of 58.95 mm open gaps. The OpenPET has higher single data loss than a conventional PET scanner at grouping circuits. NECR of the OpenPET decreases by single data loss. But single data loss is mitigated by separating the axially arranged detector into two parts. Also, multiple coincidences are found to be important for the entire whole-body PET scanner. The entire whole-body PET scanner with the OpenPET geometry promises to provide a large axial FOV with the open space and to have sufficient performance values. But single data loss at the grouping circuits and multiple coincidences are limited to the peak noise equivalent count rate (NECR) for the entire whole-body PET scanner.

  5. Adipose Cell Size and Regional Fat Deposition as Predictors of Metabolic Response to Overfeeding in Insulin-Resistant and Insulin-Sensitive Humans.

    Science.gov (United States)

    McLaughlin, Tracey; Craig, Colleen; Liu, Li-Fen; Perelman, Dalia; Allister, Candice; Spielman, Daniel; Cushman, Samuel W

    2016-05-01

    Obesity is associated with insulin resistance, but significant variability exists between similarly obese individuals, pointing to qualitative characteristics of body fat as potential mediators. To test the hypothesis that obese, insulin-sensitive (IS) individuals possess adaptive adipose cell/tissue responses, we measured subcutaneous adipose cell size, insulin suppression of lipolysis, and regional fat responses to short-term overfeeding in BMI-matched overweight/obese individuals classified as IS or insulin resistant (IR). At baseline, IR subjects exhibited significantly greater visceral adipose tissue (VAT), intrahepatic lipid (IHL), plasma free fatty acids, adipose cell diameter, and percentage of small adipose cells. With weight gain (3.1 ± 1.4 kg), IR subjects demonstrated no significant change in adipose cell size, VAT, or insulin suppression of lipolysis and only 8% worsening of insulin-mediated glucose uptake (IMGU). Alternatively, IS subjects demonstrated significant adipose cell enlargement; decrease in the percentage of small adipose cells; increase in VAT, IHL, and lipolysis; 45% worsening of IMGU; and decreased expression of lipid metabolism genes. Smaller baseline adipose cell size and greater enlargement with weight gain predicted decline in IMGU, as did increase in IHL and VAT and decrease in insulin suppression of lipolysis. Weight gain in IS humans causes maladaptive changes in adipose cells, regional fat distribution, and insulin resistance. The correlation between development of insulin resistance and changes in adipose cell size, VAT, IHL, and insulin suppression of lipolysis highlight these factors as potential mediators between obesity and insulin resistance. © 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.

  6. Fibroblast Growth Factor 21 Improves Insulin Sensitivity and Synergizes with Insulin in Human Adipose Stem Cell-Derived (hASC) Adipocytes

    Science.gov (United States)

    Lee, Darwin V.; Li, Dongmei; Yan, Qingyun; Zhu, Yimin; Goodwin, Bryan; Calle, Roberto; Brenner, Martin B.; Talukdar, Saswata

    2014-01-01

    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. PMID:25365322

  7. 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.

  8. 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

  9. The influence of reduced insulin sensitivity via short-term reductions in physical activity on cardiac baroreflex sensitivity during acute hyperglycemia.

    Science.gov (United States)

    Holwerda, S W; Reynolds, L J; Restaino, R M; Credeur, D P; Leidy, H J; Thyfault, J P; Fadel, P J

    2015-12-15

    Reduced insulin sensitivity and impaired glycemic control are among the consequences of physical inactivity and have been associated with reduced cardiac baroreflex sensitivity (BRS). However, the effect of reduced insulin sensitivity and acute hyperglycemia following glucose consumption on cardiac BRS in young, healthy subjects has not been well characterized. We hypothesized that a reduction in insulin sensitivity via reductions in physical activity would reduce cardiac BRS at rest and following an oral glucose tolerance test (OGTT). Nine recreationally active men (23 ± 1 yr; >10,000 steps/day) underwent 5 days of reduced daily physical activity (RA5) by refraining from planned exercise and reducing daily steps (insulin alone on cardiac BRS using a 120-min hyperinsulinemic-euglycemic clamp. Insulin sensitivity (Matsuda index) was significantly reduced following RA5 (BL 9.2 ± 1.3 vs. RA5 6.4 ± 1.1, P insulin can impair spontaneous cardiac BRS in young, healthy subjects, and that reductions in cardiac BRS following acute hyperglycemia are unaffected by reduced insulin sensitivity via short-term reductions in physical activity. Copyright © 2015 the American Physiological Society.

  10. Design and performance evaluation of a whole-body Ingenuity TF PET-MRI system

    Energy Technology Data Exchange (ETDEWEB)

    Zaidi, H; Ratib, O [Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Ojha, N; Morich, M; Griesmer, J; Hu, Z; Maniawski, P; Shao, L [Philips Healthcare, Cleveland, OH (United States); Izquierdo-Garcia, D; Fayad, Z A, E-mail: habib.zaidi@hcuge.ch [Translational and Molecular Imaging Institute, Mount Sinai School of Medicine, New York (United States)

    2011-05-21

    The Ingenuity TF PET-MRI is a newly released whole-body hybrid PET-MR imaging system with a Philips time-of-flight GEMINI TF PET and Achieva 3T X-series MRI system. Compared to PET-CT, modifications to the positron emission tomography (PET) gantry were made to avoid mutual system interference and deliver uncompromising performance which is equivalent to the standalone systems. The PET gantry was redesigned to introduce magnetic shielding for the photomultiplier tubes (PMTs). Stringent electromagnetic noise requirements of the MR system necessitated the removal of PET gantry electronics to be housed in the PET-MR equipment room. We report the standard NEMA measurements for the PET scanner. PET imaging and performance measurements were done at Geneva University Hospital as described in the NEMA Standards NU 2-2007 manual. The scatter fraction (SF) and noise equivalent count rate (NECR) measurements with the NEMA cylinder (20 cm diameter) were repeated for two larger cylinders (27 cm and 35 cm diameter), which better represent average and heavy patients. A NEMA/IEC torso phantom was used for overall assessment of image quality. The transverse and axial resolution near the center was 4.7 mm. Timing and energy resolution of the PET-MR system were measured to be 525 ps and 12%, respectively. The results were comparable to PET-CT systems demonstrating that the effect of design modifications required on the PET system to remove the harmful effect of the magnetic field on the PMTs was negligible. The absolute sensitivity of this scanner was 7.0 cps kBq{sup -1}, whereas SF was 26%. NECR measurements performed with cylinders having three different diameters, and image quality measurements performed with IEC phantom yielded excellent results. The Ingenuity TF PET-MRI represents the first commercial whole-body hybrid PET-MRI system. The performance of the PET subsystem was comparable to the GEMINI TF PET-CT system using phantom and patient studies. It is conceived that

  11. 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

  12. The effect of menopause on carotid artery remodeling, insulin sensitivity, and plasma adiponectin in healthy women

    DEFF Research Database (Denmark)

    Muscelli, Elza; Kozàkovà, Michaela; Flyvbjerg, Allan

    2009-01-01

    secretion and sensitivity, plasma adiponectin), and carotid intima-media thickness (IMT) in healthy women. METHODS: In 74 menopausal women (mean age = 51 +/- 3 years, mean duration of menopause = 2.9 +/- 1.2 years) and in 74 nonmenopausal women comparable for age and body mass index (BMI), common carotid...... artery (CCA) luminal diameter, and IMT in different carotid segments were measured in digitized ultrasound images. Insulin sensitivity and secretion were assessed using the euglycemic hyperinsulinemic clamp technique and oral glucose tolerance test (OGTT). Insulin secretion was reconstructed...... by mathematical modeling. RESULTS: CCA diameter (5.55 +/- 0.46 vs. 5.21+/- 0.51 mm, P IMT (608 +/- 78 vs. 576 +/- 74 microm, P IMT/diameter ratio and IMT in other carotid...

  13. Cinnamon extract improves insulin sensitivity in the brain and lowers liver fat in mouse models of obesity.

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

  14. 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

    Objectives 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. Methods 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. Results 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. Conclusions 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. PMID:24643026

  15. 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 trig