Effects of insulin resistance on substrate utilization during exercise in overweight women

During exercise, obese individuals oxidize less glycogen and more fat than their lean counterparts, but the shift in substrate use may be mediated by insulin resistance rather than body fat per se. In addition, individuals with Type 2 diabetes are not resistant to contraction-mediated glucose uptake during exercise, but in vivo studies uncomplicated by hyperglycemia are lacking. The purpose of this study was to compare blood glucose uptake and the balance between carbohydrate and fat utilization during exercise in insulin-resistant (IR) and insulin-sensitive (IS) women of equivalent body fatness and maximal oxygen consumption (V̇o2 max). Twelve overweight sedentary women were divided into two groups with similar body mass index (IR = 28.5 ± 1.6, IS = 27.5 ± 1.9), lean mass (IR = 42.4 ± 1.8 kg, IS = 41.5 ± 1.9 kg), and V̇o2 max (IR = 29.7 ± 3.5 ml·kg−1·min−1, IS = 30.7 ± 3.9 ml·kg−1·min−1) but a markedly different composite insulin sensitivity index (IR = 3.0 ± 0.7, IS = 7.7 ± 0.9). Blood glucose kinetics and substrate oxidation were assessed by stable isotope dilution and indirect calorimetry during 50 min of treadmill walking at 45% V̇o2 max. Total carbohydrate oxidation and estimated muscle glycogen use were significantly lower in the IR group. Blood glucose uptake was the same in the IR and IS groups. These data suggest that insulin resistance, independent of body fat, spares muscle glycogen and shifts substrate oxidation toward less carbohydrate use during exercise. Insulin-resistant individuals with normoglycemia appear to have no defect in blood glucose uptake during exercise.

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Rosemary Extract Activates AMPK, Inhibits mTOR and Attenuates the High Glucose and High Insulin-Induced Muscle Cell Insulin Resistance

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2020-0592 ◽

2021 ◽

Author(s):

Hesham Shamshoum ◽

Filip Vlavcheski ◽

Rebecca E.K. MacPherson ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Plasma Membrane ◽

Blood Glucose ◽

Glucose Uptake ◽

Muscle Cell ◽

High Glucose ◽

Serine Phosphorylation ◽

Rosemary Extract ◽

Insulin Levels ◽

High Insulin

Impaired action of insulin in skeletal muscle, termed insulin resistance, leads to increased blood glucose levels resulting in compensatory increase in insulin levels. The elevated blood glucose and insulin levels exacerbate insulin resistance and contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). In previous studies we found attenuation of free fatty acid-induced muscle cell insulin resistance by rosemary extract (RE). In the present study we investigated the effects of RE on high glucose (HG) and high insulin (HI)-induced muscle cell insulin resistance. Exposure of L6 myotubes to 25 mM glucose and 100 nM insulin for 24 h, to mimic hyperglycemia and hyperinsulinemia, abolished the acute insulin-stimulated glucose uptake, increased the serine phosphorylation of IRS-1 and the phosphorylation/ activation of mTOR and p70S6K. Treatment with RE significantly improved the insulin-stimulated glucose uptake and increased the acute insulin-stimulated tyrosine phosphorylation while reduced the HG+HI-induced serine phosphorylation of IRS-1 and phosphorylation of mTOR and p70S6K. Additionally, treatment with RE significantly increased the phosphorylation of AMPK, its downstream effector ACC and the plasma membrane GLUT4 levels. Our data indicate a potential of RE to counteract muscle cell insulin resistance and more studies are required to investigate its effectiveness in vivo. Novelty: • Rosemary extract (RE) phosphorylated muscle cell AMPK and ACC under both normal and high glucose (HG)/high insulin (HI) conditions. • The HG/HI-induced serine phosphorylation of IRS-1 and activation of mTOR and p70S6K were attenuated by RE. • RE increased the insulin-stimulated glucose uptake by enhancing GLUT4 glucose transporter translocation to plasma membrane.

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Hemodynamic actions of insulin

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1994.267.2.e187 ◽

1994 ◽

Vol 267 (2) ◽

pp. E187-E202 ◽

Cited By ~ 65

Author(s):

A. D. Baron

Keyword(s):

Nitric Oxide ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Glucose Uptake ◽

Pressor Response ◽

Physiological Role ◽

Oxide System ◽

Maximal Response ◽

Insulin Resistant ◽

The Right

There is accumulating evidence that insulin has a physiological role to vasodilate skeletal muscle vasculature in humans. This effect occurs in a dose-dependent fashion within a half-maximal response of approximately 40 microU/ml. This vasodilating action is impaired in states of insulin resistance such as obesity, non-insulin-dependent diabetes, and elevated blood pressure. The precise physiological role of insulin-mediated vasodilation is not known. Data indicate that the degree of skeletal muscle perfusion can be an important determinant of insulin-mediated glucose uptake. Therefore, it is possible that insulin-mediated vasodilation is an integral aspect of insulin's overall action to stimulate glucose uptake; thus defective vasodilation could potentially contribute to insulin resistance. In addition, insulin-mediated vasodilation may play a role in the regulation of vascular tone. Data are provided to indicate that the pressor response to systemic norepinephrine infusions is increased in obese insulin-resistant subjects. Moreover, the normal effect of insulin to shift the norepinephrine pressor dose-response curve to the right is impaired in these patients. Therefore, impaired insulin-mediated vasodilation could further contribute to the increased prevalence of hypertension observed in states of insulin resistance. Finally, data are presented to indicate that, via a yet unknown interaction with the endothelium, insulin is able to increase nitric oxide synthesis and release and through this mechanism vasodilate. It is interesting to speculate that states of insulin resistance might also be associated with a defect in insulin's action to modulate the nitric oxide system.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hypoglycemic Effect of Vitexin in C57BL/6J Mice and HepG2 Models

Journal of Food Quality ◽

10.1155/2021/5535476 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Weidong Xu ◽

Jiayao Li ◽

Weipeng Qi ◽

Ye Peng

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Blood Glucose ◽

Glucose Uptake ◽

Lipid Content ◽

Hepg2 Cells ◽

Body Weight Gain ◽

Tnf Α ◽

Hepatic Lipid Content

Apigenin-8-C-glucoside (vitexin), a natural phytochemical contained in hawthorn, has been reported to have versatile beneficial bioactivities, such as antioxidation, anticancer property, and adipogenesis inhibition. The present research aimed to determine the influence of vitexin on insulin resistance elicited by HFD in mice and HepG2 cells. Vitexin markedly alleviated body weight gain and improved glucose and insulin intolerance induced by HFD. Vitexin partially normalized blood glucose, cholesterol, TNF-α, and hepatic lipid content. Moreover, vitexin recovered the reduced glucose uptake induced by glucosamine. The present results indicate that vitexin prevents HFD-induced insulin resistance.

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Pioglitazone improves insulin resistance and decreases blood pressure in adult patients with congenital adrenal hyperplasia

Acta Endocrinologica ◽

10.1530/eje-09-0523 ◽

2009 ◽

Vol 161 (6) ◽

pp. 887-894 ◽

Cited By ~ 7

Author(s):

Jeanne Margot Kroese ◽

Christiaan F Mooij ◽

Marinette van der Graaf ◽

Ad R M M Hermus ◽

Cees J Tack

Keyword(s):

Insulin Resistance ◽

Blood Pressure ◽

Insulin Sensitivity ◽

Body Fat ◽

Matched Control ◽

Fat Distribution ◽

Body Fat Distribution ◽

Adrenal Hyperplasia ◽

Insulin Resistant ◽

Steroid Profiles

ContextPatients with congenital adrenal hyperplasia (CAH) are chronically treated with supraphysiological doses of glucocorticoids, which are known to induce insulin resistance. Thiazolidinediones might reverse this effect and improve insulin sensitivity.ObjectivesTo assess insulin sensitivity in CAH patients and the effect of pioglitazone treatment on insulin sensitivity in CAH patients. Secondary objectives were the effects of treatment with pioglitazone on blood pressure, body fat distribution, lipid, and steroid profiles.DesignRandomized placebo controlled crossover trial.ParticipantsTwelve CAH patients and 12 body mass and age-matched control subjects.InterventionSixteen-week treatment with pioglitazone (45 mg/day) or placebo.Main outcome measureInsulin sensitivity measured by euglycemic clamp and oral glucose tolerance test. Further measures were 24-h blood pressure profiles, body fat distribution measured by magnetic resonance imaging, dual energy x-ray absorptiometry (DEXA) and bioimpedance procedures, liver fat by magnetic resonance spectroscopy, lipid, and steroid profiles.ResultsCAH patients were insulin resistant compared with healthy controls. Treatment with pioglitazone significantly improved insulin sensitivity in CAH patients (glucose infusion rate (GIR) from 28.5±11.6 to 38.9±11.0 μmol/kg per min, P=0.000, GIR in controls 46.2±23.4 μmol/kg per min, P<0.05 versus CAH). Treatment with pioglitazone decreased blood pressure (systolic: 124.0±13.6 vs 127.0±14.9 mmHg, P<0.001, diastolic: 72.8±11.5 vs 77.4±12.6 mmHg, P<0.001). No changes in body fat distribution, lipid, and steroid profiles were observed.ConclusionsCAH patients are insulin resistant compared with matched control subjects. Treatment with pioglitazone improves insulin sensitivity and decreases blood pressure in CAH patients.

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Abstract P636: Insulin Resistance in Obesity Results in Postprandial Salt and Water Loss

Hypertension ◽

10.1161/hyp.68.suppl_1.p636 ◽

2016 ◽

Vol 68 (suppl_1) ◽

Author(s):

Debra L Irsik ◽

Ashley R Washington ◽

Rabei Alaisami ◽

Michael W Brands

Keyword(s):

Insulin Resistance ◽

Blood Glucose ◽

Water Loss ◽

Urine Volume ◽

Zucker Rats ◽

Sprague Dawley ◽

Insulin Resistant ◽

Dual Channel ◽

Obese Rats ◽

Postprandial Insulin

Obesity and insulin resistance contribute to the development of metabolic syndrome, a growing epidemic in our country. The obese Zucker rat is an experimental model of this disease. Previously, using Sprague Dawley rats, we have shown that the normal postprandial rise in insulin acts physiologically to prevent renal salt and water wasting after meals. This study tested whether the effects of postprandial insulin would be attenuated in insulin resistant rats and result in excess salt and water loss. Chronic artery and vein catheters were implanted in male lean and obese Zucker rats for infusion and blood sampling. Rats were housed in metabolic cages and their catheters were connected to dual-channel Instech swivels for access. Over a 24-hr period of ad libitum eating, blood glucose was not different between obese and lean rats (127±7 vs. 120±3 mg/dl) but obese rats were hyperinsulinemic (14.86 vs. 0.98 ng/ml). Obese rats had significantly greater urine volume than lean controls (22.5±1.2 vs. 14.7±0.9 ml) despite similar water intakes. Obese rats tended to excrete more Na+ than lean controls (3.46±0.15 vs. 2.97±0.35 mEq) with equal amounts of Na+ intake. To evaluate the response to a single meal while controlling for blood glucose, fasted rats were administered a glucose bolus (as 50% dextrose) that yielded peak levels of blood glucose that were not different in the two groups (589±11 vs. 596 ±3 mg/dl at t=5 min.). Plasma insulin increased from fasting in both groups to 26.35 and 9.34 ng/ml in obese and lean controls, respectively. Over the 4-hour period following the glucose administration, obese rats had significantly greater urine volume (8.6±1.3 vs. 2.2 ±0.6 ml) and Na+ excretion (0.53±0.11 vs. 0.25±0.09 mEq) than lean controls. This suggests that insulin resistance of obesity may impair the ability of postprandial insulin to participate in maintenance of Na+ and water homeostasis, but the potential role of insulin resistance specifically within the kidney requires further study.

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Prevalence and Clinical Characteristics of Children and Adolescents with Metabolically Healthy Obesity: Role of Insulin Sensitivity

Life ◽

10.3390/life10080127 ◽

2020 ◽

Vol 10 (8) ◽

pp. 127 ◽

Cited By ~ 1

Author(s):

Federica Vinciguerra ◽

Andrea Tumminia ◽

Roberto Baratta ◽

Alfredo Ferro ◽

Salvatore Alaimo ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Children And Adolescents ◽

Metabolic Phenotype ◽

Sensitivity Index ◽

Insulinogenic Index ◽

Model Assessment ◽

Insulin Resistant ◽

Metabolically Healthy

Obesity represents a major risk factor for metabolic disorders, but some individuals, “metabolically healthy” (MHO), show less clinical evidence of these complications, in contrast to “metabolically unhealthy” (MUO) individuals. The aim of this cross-sectional study is to assess the prevalence of the MHO phenotype in a cohort of 246 overweight/obese Italian children and adolescents, and to evaluate their characteristics and the role of insulin resistance. Homeostasis model assessment–insulin resistance (HOMA-IR), insulin sensitivity index (ISI), insulinogenic index (IGI) and disposition index (DI) were all calculated from the Oral Glucose Tolerance Test (OGTT). MHO was defined by either: (1) HOMA-IR < 2.5 (MHO-IRes), or (2) absence of the criteria for metabolic syndrome (MHO-MetS). The MHO prevalence, according to MHO-MetS or MHO-IRes criteria, was 37.4% and 15.8%, respectively. ISI was the strongest predictor of the MHO phenotype, independently associated with both MHO-IRes and MHO-MetS. The MHO-MetS group was further subdivided into insulin sensitive or insulin resistant on the basis of HOMA-IR (either < or ≥ 2.5). Insulin sensitive MHO-MetS patients had a better metabolic profile compared to both insulin resistant MHO-MetS and MUO-MetS individuals. These data underscore the relevance of insulin sensitivity to identifying, among young individuals with overweight/obesity, the ones who have a more favorable metabolic phenotype.

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Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

Journal of Applied Physiology ◽

10.1152/japplphysiol.01438.2005 ◽

2006 ◽

Vol 100 (5) ◽

pp. 1467-1474 ◽

Cited By ~ 203

Author(s):

Jong Sam Lee ◽

Srijan K. Pinnamaneni ◽

Su Ju Eo ◽

In Ho Cho ◽

Jae Hwan Pyo ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Fatty Acids ◽

Insulin Sensitivity ◽

Polyunsaturated Fatty Acids ◽

Glucose Uptake ◽

High Fat ◽

Insulin Resistant ◽

L6 Myotubes ◽

Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

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Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle

Diabetology & Metabolic Syndrome ◽

10.1186/s13098-019-0499-6 ◽

2019 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Amirhosein Khoshi ◽

Golnaz Goodarzi ◽

Rezvan Mohammadi ◽

Roghaye Arezumand ◽

Meysam Moghbeli ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Glucose Uptake ◽

Alpha Synuclein ◽

C2c12 Cells ◽

Diabetic Mice ◽

Insulin Metabolism ◽

Insulin Resistant ◽

Type 2 Diabetic

Abstract Background Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice. Materials and methods Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet + low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess the SNCA expression. Results The obtained results have showed a significant ~ 27% decrease in SNCA expression level in muscle tissue of diabetic mice (P = 0.022). Moreover, there was a significant change of SNCA expression in insulin-resistant C2C12 cells (P < 0.001). Conclusion Type 2 diabetes due to insulin-resistance can decrease SNCA gene expression in muscles. In addition to the role of SNCA in cell susceptibility to insulin and glucose uptake, the SNCA expression can also be affected by insulin metabolism.

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Attenuation of Free Fatty Acid-Induced Muscle Insulin Resistance by Rosemary Extract

Nutrients ◽

10.3390/nu10111623 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1623 ◽

Cited By ~ 6

Author(s):

Filip Vlavcheski ◽

Evangelia Tsiani

Keyword(s):

Insulin Resistance ◽

Glucose Uptake ◽

Muscle Cell ◽

Serine Phosphorylation ◽

Rosemary Extract ◽

Muscle Insulin Resistance ◽

Insulin Resistant ◽

L6 Myotubes ◽

P70 S6k ◽

Amp Activated Protein Kinase

Elevated blood free fatty acids (FFAs), as seen in obesity, impair muscle insulin action leading to insulin resistance and Type 2 diabetes mellitus. Serine phosphorylation of the insulin receptor substrate (IRS) is linked to insulin resistance and a number of serine/threonine kinases including JNK, mTOR and p70 S6K have been implicated in this process. Activation of the energy sensor AMP-activated protein kinase (AMPK) increases muscle glucose uptake, and in recent years AMPK has been viewed as an important target to counteract insulin resistance. We reported recently that rosemary extract (RE) increased muscle cell glucose uptake and activated AMPK. However, the effect of RE on FFA-induced muscle insulin resistance has never been examined. In the current study, we investigated the effect of RE in palmitate-induced insulin resistant L6 myotubes. Exposure of myotubes to palmitate reduced the insulin-stimulated glucose uptake, increased serine phosphorylation of IRS-1, and decreased the insulin-stimulated phosphorylation of Akt. Importantly, exposure to RE abolished these effects and the insulin-stimulated glucose uptake was restored. Treatment with palmitate increased the phosphorylation/activation of JNK, mTOR and p70 S6K whereas RE completely abolished these effects. RE increased the phosphorylation of AMPK even in the presence of palmitate. Our data indicate that rosemary extract has the potential to counteract the palmitate-induced muscle cell insulin resistance and further studies are required to explore its antidiabetic properties.

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PCB126-mediated effects on adipocyte energy metabolism and adipokine secretion may result in abnormal glucose uptake in muscle cells

10.1101/2020.07.07.192245 ◽

2020 ◽

Author(s):

Audrey Caron ◽

Fozia Ahmed ◽

Vian Peshdary ◽

Léa Garneau ◽

Ella Atlas ◽

...

Keyword(s):

Insulin Resistance ◽

Energy Metabolism ◽

Glucose Uptake ◽

Mitochondrial Function ◽

Muscle Metabolism ◽

Insulin Resistant ◽

Mediated Effects ◽

Tnf Α ◽

Coplanar Polychlorinated Biphenyls ◽

Amp Activated Protein Kinase

AbstractBackgroundExposure to coplanar polychlorinated biphenyls (PCBs) is linked to the development of insulin resistance. Previous studies suggested that PCB126 alters muscle mitochondrial function through an indirect mechanism. Since PCBs are stored in fat, we hypothesized that PCB126 alters adipokine secretion, which in turn affects muscle metabolism.ObjectivesThe objectives of this study were: 1) To study the impacts of PCB126 exposure on adipocyte cytokine/adipokine secretion; 2) To determine whether adipocyte-derived factors alter glucose metabolism and mitochondrial function in myotubes when exposed to PCB126; 3) To determine whether pre-established insulin resistance alters the metabolic responses of adipocytes exposed to PCB126 and the communication between adipocytes and myotubes.Method3T3-L1 adipocytes were exposed to PCB126 (1-100 nM) in two insulin sensitivity conditions (insulin sensitive (IS) and insulin resistant (IR) adipocytes), followed by the measurement of secreted adipokines, mitochondrial function and insulin-stimulated glucose uptake. Communication between adipocytes and myotubes was reproduced by exposing C2C12 or mouse primary myotubes to conditioned medium (CM) derived from IS or IR 3T3-L1 adipocytes exposed to PCB126. Mitochondrial function and insulin-stimulated glucose uptake were then determined in myotubes.ResultsPCB126 significantly increased adipokine (adiponectin, IL-6, MCP-1, TNF-α) secretion and decreased mitochondrial function, glucose uptake and glycolysis in IR but not in IS 3T3-L1 adipocytes. Altered energy metabolism in IR 3T3-L1 adipocytes was linked to decreased phosphorylation of AMP-activated protein kinase (p-AMPK) and increased superoxide dismutase 2 levels, an enzyme involved in reactive oxygen species detoxification. Exposure of myotubes to CM from PCB126-treated IR adipocytes decreased glucose uptake, without altering glycolysis or mitochondrial function. Interestingly, p-AMPK levels were increased rather than decreased in myotubes exposed to the CM of PCB126-treated IR adipocytes.ConclusionTaken together, these data suggest that increased adipokine secretion from IR adipocytes exposed to PCB126 may explain impaired glucose uptake in myotubes.

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