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Am J Physiol Endocrinol Metab (November 3, 2009). doi:10.1152/ajpendo.00317.2009
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RESEARCH ARTICLE

Deficiency of Electron Transport Chain in Human Skeletal Muscle Mitochondria in Type 2 Diabetes Mellitus and Obesity

Vladimir B. Ritov,1,* Elizabeth V. Menshikova,1 Koichiro Azuma,1 Richard J Wood,1 Frederico G.S. Toledo,1 Bret H. Goodpaster,1 Neil B. Ruderman,2 and David E. Kelley1

1University of Pittsburgh 2Boston University Medical Center

Submitted 15 May 2009 ; revised 27 October 2009 ; accepted in final form 27 October 2009

Background Insulin resistance in skeletal muscle in obesity and T2DM is associated with reduced muscle oxidative capacity, reduced expression in nuclear genes responsible for oxidative metabolism, and reduced activity of mitochondrial electron transport chain. The presented study was undertaken to analyze mitochondria content and mitochondrial enzyme profile in skeletal muscle of sedentary lean individuals and to compare that with our previous data on obese or obese T2DM group. Study Design and Methods Frozen skeletal muscle biopsies obtained from lean volunteers were used to estimate cardiolipin content, mtDNA (markers of mitochondrial mass), NADH-oxidase activity of mitochondrial electron transport chain (ETC) and activity of citrate synthase and β-hydroxyacyl-CoA dehydrogenase (β-HAD): key enzymes of TCA cycle and β-oxidation pathway, respectively. Frozen biopsies collected from obese or T2DM individuals in our previous studies were used to estimate activity of β-HAD. The obtained data were complemented by data from our previous studies and statistically analyzed to compare mitochondria content and mitochondrial enzyme profile in lean, obese or T2DM cohort. Results The total activity of NADH oxidase was significantly reduced in obese or T2DM subjects. The cardiolipin content for lean or obese group was similar and, although for T2DM group cardiolipin showed a tendency to decline, it was statistically insignificant. The total activity of citrate synthase for lean and T2DM group was similar; however it was significantly increased in obese group. Activity of β-HAD and mtDNA content was similar for all three groups. Conclusions. The total activity of NADH-oxidase in biopsy for lean group is significantly higher than corresponding activity for obese or T2DM cohort. The specific activity of NADH-oxidase (per mg cardiolipin) and NADH-oxidase/citrate synthase and NADH-oxidase/β-HAD ratios are reduced by 2-3 folds in both T2DM and obesity.

mitochondria; skeletal muscle; insulin resistance; obesity


* University of Pittsburgh ritov{at}pitt.edu






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