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Acute activation of pyruvate dehydrogenase increases glucose oxidation in muscle without changing glucose uptake


Pyruvate dehydrogenase (PDH) activity is a key component of the glucose/fatty acid cycle hypothesis for the regulation of glucose uptake and metabolism. We have investigated whether acute activation of PDH in muscle can alleviate the insulin resistance caused by feeding animals a high-fat diet (HFD). The importance of PDH activity in muscle glucose disposal under insulin-stimulated conditions was determined by infusing the PDH kinase inhibitor dichloroacetate (DCA) into HFD-fed Wistar rats during a hyperinsulinemic-euglycemic clamp. Acute DCA infusion did not alter glucose infusion rate, glucose disappearance, or hepatic glucose production but did decrease plasma lactate levels. DCA substantially increased muscle PDH activity; however, this did not improve insulin-stimulated glucose uptake in insulin-resistant muscle of HFD rats. DCA infusion increased the flux of pyruvate to acetyl-CoA and reduced glucose incorporation into glycogen and alanine in muscle. Similarly, in isolated muscle, DCA treatment increased glucose oxidation and decreased glycogen synthesis without changing glucose uptake. These results suggest that, although PDH activity controls the conversion of pyruvate to acetyl-CoA for oxidation, this has little effect on glucose uptake into muscle under insulin-stimulated conditions.

Type Journal
ISBN 1522-1555 (Electronic) 0193-1849 (Linking)
Authors Small, L.; Brandon, A. E.; Quek, L. E.; Krycer, J. R.; James, D. E.; Turner, N.; Cooney, G. J.
Responsible Garvan Author (missing name)
Published Date 2018-08-01
Published Volume 315
Published Issue 2
Published Pages E258-E266
Status Always Electronic
DOI 10.1152/ajpendo.00386.2017
URL link to publisher's version
OpenAccess link to author's accepted manuscript version