Chronic high-fat feeding in rats induces profound whole-body insulin resistance, mainly due to effects in oxidative skeletal muscle. The mechanisms of this reaction remain unclear, but local lipid availability has been implicated. The aim of this study was to examine the influence of three short-term physiological manipulations intended to lower muscle lipid availability on insulin sensitivity in high-fat–fed rats. Adult male Wistar rats fed a high-fat diet for 3 weeks were divided into four groups the day before the study: one group was fed the normal daily high-fat meal (FM); another group was fed an isocaloric low-fat high-glucose meal (GM); a third group was fasted overnight (NM); and a fourth group underwent a single bout of exercise (2-h swim), then were fed the normal high-fat meal (EX). In vivo insulin action was assessed using the hyperinsulinemic glucose clamp (plasma insulin 745 pmol/l, glucose 7.2 mmol/l). Prior exercise, a single low-fat meal, or fasting all significantly increased insulin-stimulated glucose utilization, estimated at either the whole-body level (P < 0.01 vs. FM) or in red quadriceps muscle (EX 18.2, GM 28.1, and NM 19.3 vs. FM 12.6 ± 1.1 μmol · 100 g−1 · min−1; P < 0.05), as well as increased insulin suppressibility of muscle total long-chain fatty acyl-CoA (LCCoA), the metabolically available form of fatty acid (EX 24.0, GM 15.5, and NM 30.6 vs. FM 45.4 nmol/g; P < 0.05). There was a strong inverse correlation between glucose uptake and LC-CoA in red quadriceps during the clamp (r = −0.7, P = 0.001). Muscle triglyceride was significantly reduced by short-term dietary lipid withdrawal (GM −22 and NM −24% vs. FM; P < 0.01), but not prior exercise. We concluded that muscle insulin resistance induced by high-fat feeding is readily ameliorated by three independent, short-term physiological manipulations. The data suggest that insulin resistance is an important factor in the elevated muscle lipid availability induced by chronic high-fat feeding.
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December 01 1997
Diet-Induced Muscle Insulin Resistance in Rats Is Ameliorated by Acute Dietary Lipid Withdrawal or a Single Bout of Exercise: Parallel Relationship Between Insulin Stimulation of Glucose Uptake and Suppression of Long-Chain Fatty Acyl-CoA
Nicholas D Oakes;
Nicholas D Oakes
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Kim S Bell;
Kim S Bell
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Stuart M Furler;
Stuart M Furler
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Souad Camilleri;
Souad Camilleri
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Asish K Saha;
Asish K Saha
Diabetes and Metabolism Unit, Boston University Medical Center
Boston, Massachusetts
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Neil B Ruderman;
Neil B Ruderman
Diabetes and Metabolism Unit, Boston University Medical Center
Boston, Massachusetts
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Donald J Chisholm;
Donald J Chisholm
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Edward W Kraegen
Edward W Kraegen
Garvan Institute of Medical Research, St. Vincent's Hospital
Sydney, Australia
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Address correspondence and reprint requests to Dr. Nicholas D, Oakes, Garvan Institute of Medical Research, St. Vincent's Hospital, Sydney NSW 2010, Australia. E-mail: [email protected].
Diabetes 1997;46(12):2022–2028
Article history
Received:
March 18 1997
Revision Received:
September 03 1997
Accepted:
September 03 1997
PubMed:
9392490
Citation
Nicholas D Oakes, Kim S Bell, Stuart M Furler, Souad Camilleri, Asish K Saha, Neil B Ruderman, Donald J Chisholm, Edward W Kraegen; Diet-Induced Muscle Insulin Resistance in Rats Is Ameliorated by Acute Dietary Lipid Withdrawal or a Single Bout of Exercise: Parallel Relationship Between Insulin Stimulation of Glucose Uptake and Suppression of Long-Chain Fatty Acyl-CoA. Diabetes 1 December 1997; 46 (12): 2022–2028. https://doi.org/10.2337/diab.46.12.2022
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