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J Appl Physiol (August 13, 2004). doi:10.1152/japplphysiol.00686.2004
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Submitted on July 2, 2004
Accepted on August 4, 2004

Enzymatic regulation of glucose disposal in human skeletal muscle following a high fat, low carbohydrate diet

Tanya L. Pehleman1, Sandra J. Peters2, George J. F. Heigenhauser3, and Lawrence L. Spriet1*

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

* To whom correspondence should be addressed. E-mail: lspriet{at}uoguelph.ca.

Whole body glucose disposal and skeletal muscle hexokinase, glycogen synthase (GS), pyruvate dehydrogenase (PDH)and PDH kinase (PDK)activities were measured in aerobically trained males following 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 following 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 2-fold and 1.25-fold, respectively following 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/min) before the OGTT versus CON. During the OGTT, GS and PDH activation increased by the same magnitude in both diets, such that PDH activation remained lower during the OGTT (0.60 ± 0.11 vs. 1.04 ± 0.09 mmol acetyl-CoA/kg/min). These data demonstrate that the decreased glucose disposal during the OGTT following 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.




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