Journal ArticleDOI
Influence of dietary fat composition on development of insulin resistance in rats. Relationship to muscle triglyceride and omega-3 fatty acids in muscle phospholipid.
Leonard H Storlien,Arthur B. Jenkins,Donald J. Chisholm,Wendy S. Pascoe,Sue Khouri,Edward W. Kraegen +5 more
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TLDR
It is concluded that the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats and impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose–fatty acid cycle involvement.Abstract:
High levels of some but not all dietary fats lead to insulin resistance in rats. The aim of this study was to investigate the important determinants underlying this observation. Insulin action was assessed with the euglycemic clamp. Diets high in saturated, monounsaturated (ω-9), or polyunsaturated (ω-6) fatty acids led to severe insulin resistance; glucose infusion rates [GIR] to maintain euglycemia at ∼1000 pM insulin were 6.2 ± 0.9, 8.9 ± 0.9, and 9.7 ± 0.4 mg · kg −1 · min −1 , respectively, versus 16.1 ± 1.0 mg · kg −1 · min −1 in chow-fed controls. Substituting 11% of fatty acids in the polyunsaturated fat diet with long-chain ω-3 fatty acids from fish oils normalized insulin action (GIR 15.0 ± 1.3 mg · kg −1 · min −1 ). Similar replacement with short-chain ω-3 (α-linolenic acid, 18:3ω3) was ineffective in the polyunsaturated diet (GIR 9.9 ± 0.5 mg · kg −1 · min −1 ) but completely prevented the insulin resistance induced by a saturated-fat diet (GIR 16.0 ± 1.5 mg · kg −1 · min −1 ) and did so in both the liver and peripheral tissues. Insulin sensitivity in skeletal muscle was inversely correlated with mean muscle triglyceride accumulation ( r = 0.95 and 0.86 for soleus and red quadriceps, respectively; both P = 0.01). Furthermore, percentage of long-chain ω-3 fatty acid in phospholipid measured in red quadriceps correlated highly with insulin action in that muscle ( r = 0.97). We conclude that 1 ) the particular fatty acids and the lipid environment in which they are presented in high-fat diets determine insulin sensitivity in rats; 2 ) impaired insulin action in skeletal muscle relates to triglyceride accumulation, suggesting intracellular glucose–fatty acid cycle involvement; and 3 ) long-chain ω-3 fatty acids in phospholipid of skeletal muscle may be important for efficient insulin action.read more
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Journal ArticleDOI
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle *
Chunli Yu,Yan Chen,Gary W. Cline,Dongyan Zhang,Haihong Zong,Yanlin Wang,Raynald Bergeron,Jason K. Kim,Samuel W. Cushman,Gregory J. Cooney,Bronwyn Atcheson,Morris F. White,Edward W. Kraegen,Gerald I. Shulman +13 more
TL;DR: The hypothesis that an increase in plasma fatty acid concentration results in a increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-θ leading to increased IRS-1 Ser307 phosphorylation is supported.
Journal ArticleDOI
Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study.
Martin Krššák,Falk Petersen K,Alan Dresner,Loretta DiPietro,Suzanne M. Vogel,Douglas L. Rothman,Michael Roden,Gerald I. Shulman +7 more
TL;DR: Results show that intramyocellular lipid concentration, as assessed non invasively by localized 1H NMR spectroscopy, is a good indicator of whole body insulin sensitivity in non-diabetic, non-obese humans.
Journal ArticleDOI
Skeletal Muscle Triglyceride Levels Are Inversely Related to Insulin Action
D. A. Pan,Stephen Lillioja,A. D. Kriketos,M R Milner,Louise A. Baur,C Bogardus,Arthur B. Jenkins,Leonard H Storlien,Leonard H Storlien +8 more
TL;DR: The results suggest that in this human population, as in animal models, skeletal muscle insulin sensitivity is strongly influenced by local supplies of triglycerides, as well as by remote depots and circulating lipids.
Journal ArticleDOI
Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver
E. Dale Abel,Odile D. Peroni,Jason K. Kim,Young-Bum Kim,Olivier Boss,Ed Hadro,Timo Minnemann,Gerald I. Shulman,Barbara B. Kahn +8 more
TL;DR: Downregulation of GLUT4 and glucose transport selectively in adipose tissue can cause insulin resistance and thereby increase the risk of developing diabetes, as well as developing glucose intolerance and hyperinsulinaemia.
Journal ArticleDOI
High-fat diets: modeling the metabolic disorders of human obesity in rodents.
TL;DR: In this review, metabolic data obtained with different HF diet approaches are compiled and whole‐body and organ‐specific diet effects are analyzed.
References
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Role of Insulin Resistance in Human Disease
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Immunoassay of Insulin: Two Antibody System: Plasma Insulin Levels of Normal, Subdiabetic and Diabetic Rats
Carl R Morgan,Arnold Lazarow +1 more
TL;DR: A two antibody system of insulin assay for immunoassay of insulin induces the production of specific nonprecipitating antibodies, both in experimental animals and in humans.
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Hindlimb muscle fiber populations of five mammals
TL;DR: It was found that the soleus and vastus intermedius muscles had the highest proportion of slow oxidative fibers in all five species, demonstrating the constancy of muscle fiber profiles dependent upon anatomical position and functional utilization.
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Comparison of Monounsaturated Fatty Acids and Carbohydrates for Lowering Plasma Cholesterol
TL;DR: A diet rich in monounsaturated fatty acids appears to be at least as effective in lowering plasma cholesterol as a diet low in fat and high in carbohydrate in short-term studies in which liquid diets are used and body weight is kept constant.