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High Fat Diet Insulin Resistance Mechanism

Mechanism By Which Dietary Fat Can Raise Blood Glucose And Insulin

Mechanism By Which Dietary Fat Can Raise Blood Glucose And Insulin

Mechanism By Which Dietary Fat Can Raise Blood Glucose And Insulin Back in 2008 , I began writing about the effect of dietary fat on insulin sensitivity, and blood levels of glucose and insulin. Heres one of the studies: It was a small randomized crossover study on healthy subjects that compared: High-fat diet (40% carbohydrate, 45% fat) High-carb diet (55% carbohydrate, 30% fat) During the oral-glucose-tolerance test, both glucose and insulin rose to higher concentrations after the high-fat diet than after the high-carb diet, showing lower glucose tolerance and insulin sensitivity with the high-fat diet. Over the years I learned that saturated fat decreased insulin sensitivity more than other fats, e.g. the KANWU Study . One mechanism by which dietary fat decreases insulin sensitivity, raising blood glucose and insulin levels is through reduced action of the glucose transporter GLUT4. There seems to be both a reduced expression of the GLUT4 gene, and a reduced translocation or movement of GLUT4 to the cell membrane in the presence of a high-fat, especially high-saturated fat diet. (GLUT4 is one of the glucose transport proteins that move glucose from the bloodstream into muscle and fat cells. Its insertion into the membrane is controlled by insulin. See diagram.) When glucose cannot enter cells, blood glucose levels rise. When normal amounts of insulin fail to clear blood of glucose, the pancreas responds by releasing more. The result is impaired glucose tolerance, hyperinsulinemia, and eventual development of type 2 diabetes. Over time, compensatory insulin output from beta cells in the pancreas diminishes and a person with type 2 diabetes may find themselves injecting insulin instead of just taking oral meds. Here are some studies and reviews that address this: 1. A Continue reading >>

Insulin Resistance

Insulin Resistance

Insulin resistance (IR) is a pathological condition in which cells fail to respond normally to the hormone insulin. The body produces insulin when glucose starts to be released into the bloodstream from the digestion of carbohydrates in the diet. Normally this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy. The concentration of glucose in the blood decreases as a result, staying within the normal range even when a large amount of carbohydrates is consumed. When the body produces insulin under conditions of insulin resistance, the cells are resistant to the insulin and are unable to use it as effectively, leading to high blood sugar. Beta cells in the pancreas subsequently increase their production of insulin, further contributing to a high blood insulin level. This often remains undetected and can contribute to the development of type 2 diabetes or latent autoimmune diabetes of adults.[1] Although this type of chronic insulin resistance is harmful, during acute illness it is actually a well-evolved protective mechanism. Recent investigations have revealed that insulin resistance helps to conserve the brain's glucose supply by preventing muscles from taking up excessive glucose.[2] In theory, insulin resistance should even be strengthened under harsh metabolic conditions such as pregnancy, during which the expanding fetal brain demands more glucose. People who develop type 2 diabetes usually pass through earlier stages of insulin resistance and prediabetes, although those often go undiagnosed. Insulin resistance is a syndrome (a set of signs and symptoms) resulting from reduced insulin activity; it is also part of a larger constellation of symptoms called the metabolic syndrome. Insuli Continue reading >>

What Causes Insulin Resistance? Lipid Overload

What Causes Insulin Resistance? Lipid Overload

Over the past year I have interacted with hundreds of people with diabetes, and have come to learn one very important lesson that has changed my view of diabetes altogether. This realization came to me early on in my career as a nutrition and fitness coach for people with diabetes, and continues to hold true. While insulin resistance is a condition that is most commonly associated with type 2 diabetes, an increasing body of evidence is now shedding light on the fact that insulin resistance is a common thread that underlies many health conditions previously unassociated with blood sugar, including (but not limited to) heart disease, diabetes, atherosclerosis, the metabolic syndrome, obesity and cancer. What that means is simple: insulin resistance significantly increases your risk for the development of a collection of health conditions that can significantly reduce your quality of life and decrease your life expectancy. Watch this video for a synopsis of the causes of insulin resistance: What is insulin and why should you care? Insulin is a hormone which is released by the pancreas in response to rising blood glucose. When you consume carbohydrates, the glucose that enters the bloodstream knocks on the door of the beta cells in the pancreas as a signal to make insulin. Insulin serves as the key that unlocks the door to allow glucose to enter body tissues. Insulin tells your cells “Yoo hoo! Pick up this glucose. It’s all over the place.” Without insulin, cells in the liver, muscle, and fat have a difficult time vacuuming up glucose from the blood. These tissues are capable to vacuuming up only a small percentage (5-10%) of the glucose in circulation without the help of insulin. When insulin is present, the amount of glucose that can be transported into tissues sign Continue reading >>

Estrogens Protect Against High-fat Diet-induced Insulin Resistance And Glucose Intolerance In Mice

Estrogens Protect Against High-fat Diet-induced Insulin Resistance And Glucose Intolerance In Mice

Estrogens Protect against High-Fat Diet-Induced Insulin Resistance and Glucose Intolerance in Mice Team 9 (E.R., H.C., J.-F.A., P.G.), Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 858 et Universite de Toulouse, Institut de Medecine Moleculaire de Rangueil, Institut Federatif de Recherche (IFR) 31, Toulouse, France Department of Team 2 (E.R., A.W., R.B.), INSERM Unite 858, Institut de Medecine Moleculaire de Rangueil, IFR31, 31432 Toulouse, France Search for other works by this author on: Department of Team 2 (E.R., A.W., R.B.), INSERM Unite 858, Institut de Medecine Moleculaire de Rangueil, IFR31, 31432 Toulouse, France Search for other works by this author on: Team 9 (E.R., H.C., J.-F.A., P.G.), Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 858 et Universite de Toulouse, Institut de Medecine Moleculaire de Rangueil, Institut Federatif de Recherche (IFR) 31, Toulouse, France Search for other works by this author on: Team 9 (E.R., H.C., J.-F.A., P.G.), Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 858 et Universite de Toulouse, Institut de Medecine Moleculaire de Rangueil, Institut Federatif de Recherche (IFR) 31, Toulouse, France Search for other works by this author on: Department of Team 2 (E.R., A.W., R.B.), INSERM Unite 858, Institut de Medecine Moleculaire de Rangueil, IFR31, 31432 Toulouse, France Search for other works by this author on: Team 9 (E.R., H.C., J.-F.A., P.G.), Institut National de la Sante et de la Recherche Medicale (INSERM) Unite 858 et Universite de Toulouse, Institut de Medecine Moleculaire de Rangueil, Institut Federatif de Recherche (IFR) 31, Toulouse, France Service de Diabetologie (P.G.), Pole Cardio-Vasculaire et Metabolique, Centre Hospitalier Universitaire d Continue reading >>

High-fructose And High-fat Diet-induced Insulin Resistance Enhances Atherosclerosis In Watanabe Heritable Hyperlipidemic Rabbits

High-fructose And High-fat Diet-induced Insulin Resistance Enhances Atherosclerosis In Watanabe Heritable Hyperlipidemic Rabbits

High-fructose and high-fat diet-induced insulin resistance enhances atherosclerosis in Watanabe heritable hyperlipidemic rabbits Individuals with insulin resistance and resulting impaired glucose tolerance along with type 2 diabetes showed an increased prevalence of atherosclerosis. Our aim in this study was to address whether diet-induced insulin resistance plays any roles in the development of aortic and coronary atherosclerosis in hyperlipidemic rabbits. We fed Watanabe heritable hyperlipidemic (WHHL) rabbits with a high-fructose and high-fat diet (HFFD) with restricted normal calories and compared the lesions of both aortic and coronary atherosclerosis with those of control WHHL rabbits fed a normal chow diet. HFFD-fed WHHL rabbits showed insulin resistance and impaired glucose tolerance accompanied by elevated plasma lipid levels and accumulation of adipose tissue even though their body weight was unchanged compared to the control rabbits. At 8 weeks, the aortic gross lesion area of HFFD-fed WHHL rabbits was increased by 40 % over the controls and their lesions were characterized by increased number of macrophages and smooth muscle cells. At 16 weeks, the lesions of HFFD-fed WHHL rabbits showed more advanced lesions such as lipid core formation and calcification. In addition, coronary atherosclerosis was significantly increased in HFFD-fed WHHL rabbits. These results suggest that insulin resistance accelerates lesion formation of atherosclerosis. Insulin ResistanceCoronary AtherosclerosisCholesteryl Ester Transfer ProteinMicrosomal Triglyceride Transfer ProteinAdvanced Lesion Insulin resistance (IR) is frequently associated with many metabolic diseases such as obesity, hypertriglyceridemia, type 2 diabetes, and metabolic syndrome [ 1 ]. Individuals with underlying Continue reading >>

High-fat Diet-induced Insulin Resistance In Single Skeletal Muscle Fibers Is Fiber Type Selective

High-fat Diet-induced Insulin Resistance In Single Skeletal Muscle Fibers Is Fiber Type Selective

Skeletal muscle is the major site for insulin-stimulated glucose disposal, and muscle insulin resistance confers many negative health outcomes. Muscle is composed of multiple fiber types, and conventional analysis of whole muscles cannot elucidate fiber type differences at the cellular level. Previous research demonstrated that a brief (two weeks) high fat diet (HFD) caused insulin resistance in rat skeletal muscle. The primary aim of this study was to determine in rat skeletal muscle the influence of a brief (two weeks) HFD on glucose uptake (GU) ± insulin in single fibers that were also characterized for fiber type. Epitrochlearis muscles were incubated with [3H]-2-deoxyglucose (2DG) ± 100 µU/ml insulin. Fiber type (myosin heavy chain expression) and 2DG accumulation were measured in whole muscles and single fibers. Although fiber type composition of whole muscles did not differ between diet groups, GU of insulin-stimulated whole muscles from LFD rats significantly exceeded HFD values (P < 0.005). For HFD versus LFD rats, GU of insulin-stimulated single fibers was significantly (P < 0.05) lower for IIA, IIAX, IIBX, IIB, and approached significance for IIX (P = 0.100), but not type I (P = 0.776) fibers. These results revealed HFD-induced insulin resistance was attributable to fiber type selective insulin resistance and independent of altered fiber type composition. Skeletal muscle is the major site for insulin-stimulated glucose disposal1, and skeletal muscle insulin resistance is a primary and essential event in the progression to type 2 diabetes2. Even in the absence of type 2 diabetes, insulin resistance confers negative health outcomes3. It is important to understand the processes responsible for insulin resistance of the skeletal muscle to develop interventions Continue reading >>

Cellular Mechanism By Which Estradiol Protects Female Ovariectomized Mice From High-fat Diet-induced Hepatic And Muscle Insulin Resistance

Cellular Mechanism By Which Estradiol Protects Female Ovariectomized Mice From High-fat Diet-induced Hepatic And Muscle Insulin Resistance

Cellular Mechanism by Which Estradiol Protects Female Ovariectomized Mice From High-Fat Diet-Induced Hepatic and Muscle Insulin Resistance Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Department of Physiology and Biophysics (J.P.G.C., C.R.O.C.), Institute of Biomedical Sciences, University of So Paulo, 05508-900 So Paulo, Brazil Search for other works by this author on: Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Search for other works by this author on: Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Howard Hughes Medical Institute (H.-Y.L., G.I.S.), Yale University School of Medicine, New Haven, Connecticut 06536-9812 Search for other works by this author on: Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Search for other works by this author on: Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Search for other works by this author on: Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Search for other works by this author on: Department of Internal Medicine (J.P.G.C., F.R.J., H.-Y.L., S.K., B.A.G., M.K., V.T.S., K.F.P., M.J.J., G.I.S.), New Haven, Connecticut 06536-9812 Search for other works by this author on: Department of Physiology and Biophysics (J.P.G.C., C.R.O.C.), Institu Continue reading >>

High-fat Diet Induces Hepatic Insulin Resistance And Impairment Of Synaptic Plasticity

High-fat Diet Induces Hepatic Insulin Resistance And Impairment Of Synaptic Plasticity

High-Fat Diet Induces Hepatic Insulin Resistance and Impairment of Synaptic Plasticity Zhigang Liu , Ishan Y. Patil , Tianyi Jiang , Harsh Sancheti , John P. Walsh , Bangyan L. Stiles , Fei Yin , Enrique Cadenas Affiliations: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America, College of Food Science and Engineering, Northwest A&F University, Yangling, China Affiliation: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America Affiliation: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America Affiliation: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America Affiliation: Davis School of Gerontology and Program in Neuroscience, University of Southern California, Los Angeles, CA, 90089, United States of America Affiliation: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America Affiliation: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America Affiliation: Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, 90089, United States of America High-fat diet (HFD)-induced obesity is associated with insulin resistance, which may affect brain synaptic plasticity through impairment of insulin-sensitive processes underlying neuronal survival, learning, and memory. The experimental model consis Continue reading >>

High-fat Diets Cause Insulin Resistance Despite An Increase In Muscle Mitochondria

High-fat Diets Cause Insulin Resistance Despite An Increase In Muscle Mitochondria

High-fat diets cause insulin resistance despite an increase in muscle mitochondria We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. High-fat diets cause insulin resistance despite an increase in muscle mitochondria Chad R. Hancock, Dong-Ho Han, [...], and John O. Holloszy It has been hypothesized that insulin resistance is mediated by a deficiency of mitochondria in skeletal muscle. In keeping with this hypothesis, high-fat diets that cause insulin resistance have been reported to result in a decrease in muscle mitochondria. In contrast, we found that feeding rats high-fat diets that cause muscle insulin resistance results in a concomitant gradual increase in muscle mitochondria. This adaptation appears to be mediated by activation of peroxisome proliferator-activated receptor (PPAR) by fatty acids, which results in a gradual, posttranscriptionally regulated increase in PPAR coactivator 1 (PGC-1) protein expression. Similarly, overexpression of PPAR results in a large increase in PGC-1 protein in the absence of any increase in PGC-1 mRNA. We interpret our findings as evidence that raising free fatty acids results in an increase in mitochondria by activating PPAR, which mediates a posttranscriptional increase in PGC-1. Our findings argue against the concept that insulin resistance is mediated by a deficiency of muscle mitochondria. Keywords: mitochondrial biogenesis, mitochondrial dysfunction, PPAR, skeletal muscle, PGC-1 It has b Continue reading >>

Odontella Aurita-enriched Diet Prevents High Fat Diet-induced Liver Insulin Resistance

Odontella Aurita-enriched Diet Prevents High Fat Diet-induced Liver Insulin Resistance

Odontella aurita-enriched diet prevents high fat diet-induced liver insulin resistance 1Unit Mixte de Recherche, Neuroendocrinolgie Molculaire de la Prise Alimentaire, NeuroPSI UMR9197, University Paris-Sud, Orsay, France 2Centre National de la Recherche Scientifique, NeuroPSI Institute, Unit Mixte de Recherche 9197, Orsay, France 3Laboratoire de Virologie, Microbiologie, Qualit/Ecotoxicologie et Biodiversit, University Hassan II, Casablanca, Morocco Correspondence should be addressed to M Taouis; Email: mohammed.taouis{at}u-psud.fr The beneficial effect of polyunsaturated omega-3 fatty acid (w-3 FA) consumption regarding cardiovascular diseases, insulin resistance and inflammation has been widely reported. Fish oil is considered as the main source of commercialized w-3 FAs, and other alternative sources have been reported such as linseed or microalgae. However, despite numerous reports, the underlying mechanisms of action of w-3 FAs on insulin resistance are still not clearly established, especially those from microalgae. Here, we report that Odontella aurita, a microalga rich in w-3 FAs eicosapentaenoic acid, prevents high fat diet-induced insulin resistance and inflammation in the liver of Wistar rats. Indeed, a high fat diet (HFD) increased plasma insulin levels associated with the impairment of insulin receptor signaling and the up-regulation of toll-like receptor 4 (TLR4) expressions. Importantly, Odontella aurita-enriched HFD (HFOA) reduces body weight and plasma insulin levels and maintains normal insulin receptor expression and responsiveness. Furthermore, HFOA decreased TLR4 expression, JNK/p38 phosphorylation and pro-inflammatory factors. In conclusion, we demonstrate for the first time, to our knowledge, that diet supplementation with whole Ondontella aurit Continue reading >>

High-fat Load: Mechanism(s) Of Insulin Resistance In Skeletal Muscle

High-fat Load: Mechanism(s) Of Insulin Resistance In Skeletal Muscle

High-fat load: mechanism(s) of insulin resistance in skeletal muscle We are experimenting with display styles that make it easier to read articles in PMC. The ePub format uses eBook readers, which have several "ease of reading" features already built in. The ePub format is best viewed in the iBooks reader. You may notice problems with the display of certain parts of an article in other eReaders. Generating an ePub file may take a long time, please be patient. High-fat load: mechanism(s) of insulin resistance in skeletal muscle D S Lark, K H Fisher-Wellman, and P D Neufer Skeletal muscle from sedentary obese patients is characterized by depressed electron transport activity, reduced expression of genes required for oxidative metabolism, altered mitochondrial morphology and lower overall mitochondrial content. These findings imply that obesity, or more likely the metabolic imbalance that causes obesity, leads to a progressive decline in mitochondrial function, eventually culminating in mitochondrial dissolution or mitoptosis. A decrease in the sensitivity of skeletal muscle to insulin represents one of the earliest maladies associated with high dietary fat intake and weight gain. Considerable evidence has accumulated to suggest that the cytosolic ectopic accumulation of fatty acid metabolites, including diacylglycerol and ceramides, underlies the development of insulin resistance in skeletal muscle. However, an alternative mechanism has recently been evolving, which places the etiology of insulin resistance in the context of cellular/mitochondrial bioenergetics and redox systems biology. Overnutrition, particularly from high-fat diets, generates fuel overload within the mitochondria, resulting in the accumulation of partially oxidized acylcarnitines, increased mitochondr Continue reading >>

High Fat Diet Induces Central Obesity, Insulin Resistance And Microvascular Dysfunction In Hamsters

High Fat Diet Induces Central Obesity, Insulin Resistance And Microvascular Dysfunction In Hamsters

Volume 82, Issue 3 , November 2011, Pages 416-422 High fat diet induces central obesity, insulin resistance and microvascular dysfunction in hamsters Microvascular dysfunction is an early finding in obesity possibly related to co-morbidities like diabetes and hypertension. Therefore we have investigated changes on microvascular function, body composition, glucose and insulin tolerance tests (GTT and ITT) on male hamsters fed either with high fat (HFD, n=20) or standard (Control, n=21) diet during 16weeks. Total body fat and protein content were determined by carcass analysis, aorta eNOS and iNOS expression by immunoblotting assay and mean blood pressure (MAP) and heart rate (HR) by an arterial catheter. Microvascular reactivity in response to acetylcholine and sodium nitroprusside, functional capillary density (FCD), capillary recruitment induced by a hyperinsulinemic status and macromolecular permeability after 30min ischemia was assessed on either cheek pouch or cremaster muscle preparations. Compared to Control, HFD animals have shown increased visceral fat (6.00.8 vs. 13.80.6g/100g BW), impaired endothelial dependent vasodilatation, decreased FCD (11.31.3 vs. 6.81.2/field) and capillary recruitment during hyperinsulinemia and increased macromolecular permeability after ischemia/reperfusion (86.45.2 vs.105.25.1leaks/cm2), iNOS expression and insulin resistance. MAP, HR, endothelial independent vasodilatation and eNOS expression were not different between groups. Our results have shown that HFD elicits an increase on visceral fat deposition, microvascular dysfunction and insulin resistance in hamsters. We have studied microcirculatory effects of high fat diet in hamsters High fat diet blunted arteriolar response to acetylcholine and induced iNOS expression in aorta. Continue reading >>

A High Fat Diet Impairs Stimulation Of Glucose Transport In Muscle

A High Fat Diet Impairs Stimulation Of Glucose Transport In Muscle

A High Fat Diet Impairs Stimulation of Glucose Transport in Muscle FUNCTIONAL EVALUATION OF POTENTIAL MECHANISMS * A high fat diet causes resistance of skeletal muscle glucose transport to insulin and contractions. We tested the hypothesis that fat feeding causes a change in plasma membrane composition that interferes with functioning of glucose transporters and/or insulin receptors. Epitrochlearis muscles of rats fed a high (50% of calories) fat diet for 8 weeks showed 50% decreases in insulin- and contraction-stimulated 3-O-methylglucose transport. Similar decreases in stimulated glucose transport activity occurred in muscles of wild-type mice with 4 weeks of fat feeding. In contrast, GLUT1 overexpressing muscles of transgenic mice fed a high fat diet showed no decreases in their high rates of glucose transport, providing evidence against impaired glucose transporter function. Insulin-stimulated system A amino acid transport, insulin receptor (IR) tyrosine kinase activity, and insulin-stimulated IR and IRS-1 tyrosine phosphorylation were all normal in muscles of rats fed the high fat diet for 8 weeks. However, after 30 weeks on the high fat diet, there was a significant reduction in insulin-stimulated tyrosine phosphorylation in muscle. The increases in GLUT4 at the cell surface induced by insulin or muscle contractions, measured with the 3H-labeled 2-N-4-(1-azi-2,2,2-trifluoroethyl)-benzoyl-1,3-bis-(d-mannose-4-yloxy)-2-propylamine photolabel, were 2636% smaller in muscles of the 8-week high fat-fed rats as compared with control rats. Our findings provide evidence that (a) impairment of muscle glucose transport by 8 weeks of high fat feeding is not due to plasma membrane composition-related reductions in glucose transporter or insulin receptor function, (b) a defect Continue reading >>

Mechanisms Of Fatty Acid-induced Insulin Resistance In Muscle And Liver

Mechanisms Of Fatty Acid-induced Insulin Resistance In Muscle And Liver

1University of Ain Shams – Department of Biochemistry – Faculty of Science, Cairo – Egypt 2University Health Network, Canada 3Hospital for Sick Children, Canada 4Mount Sinai Hospital, Canada 5University of Toronto, Toronto, Canada Corresponding Author: Rafik Ragheb University of Toronto, Toronto – Canada Tel/Fax: 1-905-2099660 E-mail: [email protected] Citation: Ragheb R, Medhat AM (2011) Mechanisms of Fatty Acid-Induced Insulin Resistance in Muscle and Liver. J Diabetes Metab 2:127. doi:10.4172/2155-6156.1000127 Copyright: © 2011 Ragheb R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Visit for more related articles at Journal of Diabetes & Metabolism Abstract Insulin Resistance occurs as a result of disturbances in lipid metabolism and increased levels of circulating fatty acids that accumulate within the insulin sensitive tissues such as muscle, liver and adipose tissues. Increased fatty acid flux has been suggested to be strongly associated with insulin resistant states such as obesity and type 2-diabetes. Fatty acids appear to cause this defect in glucose transport by inhibiting insulin -stimulated tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) and reducing IRS-1 associated phosphatidyl-inositol 3-kinase activity that implicate other insulin signaling components downstream of the insulin signaling cascade. A number of different metabolic abnormalities may increase intramyocellular or intrahepatic fatty acid metabolites that induce the disease state of insulin resistance through a number of different cellular mechanisms. The current review Continue reading >>

The Mechanism Of Cetp-mediated Protection From High-fat Diet-induced Insulin Resistance Palmisano, Brian T. Vanderbilt University Medical Center, Nashville, Tn, United States

The Mechanism Of Cetp-mediated Protection From High-fat Diet-induced Insulin Resistance Palmisano, Brian T. Vanderbilt University Medical Center, Nashville, Tn, United States

The Mechanism of Cetp-Mediated Protection from High-Fat Diet-Induced Insulin Resistance Obesity causes insulin resistance, which increases the risk of Type 2 Diabetes (T2D) and Coronary Heart Disease (CHD). Although weight loss is a primary goal in clinical management of obesity, long-term weight loss is rarely sustained. Therefore, it is imperative to understand pathways that might ameliorate the impact of obesity on T2D and CHD. We discovered that transgenic expression of Cholesteryl Ester Transfer Protein (Cetp) protects against high-fat diet (HFD)-induced insulin resistance in female mice in the setting of obesity. Cetp traffics triglyceride and cholesteryl ester (CE) between plasma lipoproteins, culminating in delivery of CE to the liver for secretion as bile - termed reverse cholesterol transport (RCT). Cetp inhibitors raise high- density lipoprotein (HDL) but fail to reduce risk for CHD, which may indicate that Cetp has non-HDL functions. Mice lack Cetp, so we used transgenic mice expressing Cetp to define how Cetp impacts insulin resistance. Using the hyperinsulinemic-euglycemic clamp technique, we found that Cetp protects against insulin resistance in females, but not males following 4 weeks of HFD. This protection was despite a similar degree of obesity. The objective of this proposal is to understand how Cetp protects against insulin resistance in diet-induced obese mice. Our discovery represents a novel and beneficial function of Cetp with regard to obesity pathophysiology. Despite high-fat feeding, Cetp expression preserved insulin signaling pathways in liver and muscle and insulin-mediated downregulation of mRNA for gluconeogenic genes Phosphoenopyruvate Carboxykinase (Pck1) and Glucose-6-Phosphatase (G6pc). We found that Cetp increased mRNA of the bile a Continue reading >>

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