Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 387, Issue 4, Pages 651-655Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.07.064
Keywords
Acetate oxidation; Human; Myotubes; Skeletal muscle; Tricarboxylic acid cycle; Type 2 diabetes
Categories
Funding
- Danish Medical Research Council
- Novo Nordisk Foundation
- Danish Diabetes Association
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The diabetic phenotype is complex, requiring elucidation of key initiating defects. It is unknown whether the reduced tricarboxylic acid cycle (TCA) flux in skeletal muscle of obese and obese type 2 diabetic (T2D) subjects is of primary origin. Acetate oxidation (measurement of TCA-flux) was significantly reduced in primary myotube cultures established from T2D versus lean subjects. Acetate oxidation was acutely stimulated by insulin and respiratory uncoupling. Inhibition of TCA flux in lean myotubes by malonate was followed by a measured decline in; acetate oxidation, complete palmitate oxidation, lipid uptake, glycogen synthesis, ATP content and increased glucose uptake, while glucose oxidation was unaffected. Acute TCA inhibition did not induce insulin resistance. Thus the reduced TCA cycle flux in T2D skeletal muscle may be of primary origin. The diabetic phenotype of increased basal glucose uptake and glucose oxidation, the reduced complete lipid oxidation and increased respiratory quotient, are likely to be adaptive responses to the reduced TCA cycle flux. (C) 2009 Published by Elsevier Inc.
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