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J Appl Physiol 98: 100-107, 2005. First published August 13, 2004; doi:10.1152/japplphysiol.00686.2004
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Enzymatic regulation of glucose disposal in human skeletal muscle after a high-fat, low-carbohydrate diet

Tanya L. Pehleman,1 Sandra J. Peters,2 George J. F. Heigenhauser,3 and Lawrence L. Spriet1

1Department of Human Biology and Nutritional Sciences, University of Guelph, Guelph, Ontario; 2Faculty of Applied Health Sciences, Brock University, St. Catharines, Ontario; and 3Department of Medicine, McMaster University, Hamilton, Ontario, Canada

Submitted 2 July 2004 ; accepted in final form 8 August 2004

Whole body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH), and PDH kinase (PDK) activities were measured in aerobically trained men after a standardized control diet (Con; 51% carbohydrate, 29% fat, and 20% protein of total energy intake) and a 56-h eucaloric, high-fat, low-carbohydrate diet (HF/LC; 5% carbohydrate, 73% fat, and 22% protein). An oral glucose tolerance test (OGTT; 1 g/kg) was administered after the Con and HF/LC diets with vastus lateralis muscle biopsies sampled pre-OGTT and 75 min after ingestion of the oral glucose load. The 90-min area under the blood glucose and plasma insulin concentration vs. time curves increased by 2-fold and 1.25-fold, respectively, after the HF/LC diet. The pre-OGTT fraction of GS in its active form and the maximal activity of hexokinase were not affected by the HF/LC diet. However, the HF/LC diet increased PDK activity (0.19 ± 0.05 vs. 0.08 ± 0.02 min–1) and decreased PDH activation (0.38 ± 0.08 vs. 0.79 ± 0.10 mmol acetyl-CoA·kg wet muscle–1·min–1) before the OGTT vs. Con. During the OGTT, GS and PDH activation increased by the same magnitude in both diets, such that PDH activation remained lower during the HF/LC OGTT (0.60 ± 0.11 vs. 1.04 ± 0.09 mmol acetyl-CoA·kg–1·min–1). These data demonstrate that the decreased glucose disposal during the OGTT after the 56-h HF/LC diet was in part related to decreased oxidative carbohydrate disposal in skeletal muscle and not to decreased glycogen storage. The rapid increase in PDK activity during the HF/LC diet appeared to account for the reduced potential for oxidative carbohydrate disposal.

oxidative glucose disposal; pyruvate dehydrogenase activity; pyruvate dehydrogenase kinase activity; glycogen synthase activity; hexokinase activity



Address for reprint requests and other correspondence: L. L. Spriet, Dept. of Human Biology and Nutritional Sciences, University of Guelph, Guelph, ON, Canada N1G 2W1 (E-mail: lspriet{at}uoguelph.ca)




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