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Biochemistry Research International
Volume 2012 (2012), Article ID 716056, 6 pages
Research Article

Reduced TCA Flux in Diabetic Myotubes: Determined by Single Defects?

1Laboratory of Molecular Physiology, Department of Pathology, Odense University Hospital, 5000 Odense, Denmark
2Department of Endocrinology, Odense University Hospital, 5000 Odense, Denmark

Received 9 November 2011; Revised 3 January 2012; Accepted 12 January 2012

Academic Editor: Paul R. Gooley

Copyright © 2012 Michael Gaster. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The diabetic phenotype is complex, requiring elucidation of key initiating defects. Diabetic myotubes express a primary reduced tricarboxylic acid (TCA) cycle flux but at present it is unclear in which part of the TCA cycle the defect is localised. In order to localise the defect we studied ATP production in isolated mitochondria from substrates entering the TCA cycle at various points. ATP production was measured by luminescence with or without concomitant ATP utilisation by hexokinase in mitochondria isolated from myotubes established from eight lean and eight type 2 diabetic subjects. The ATP production of investigated substrate combinations was significantly reduced in mitochondria isolated from type 2 diabetic subjects compared to lean. However, when ATP synthesis rates at different substrate combinations were normalized to the corresponding individual pyruvate-malate rate, there was no significant difference between groups. These results show that the primary reduced TCA cycle flux in diabetic myotubes is not explained by defects in specific part of the TCA cycle but rather results from a general downregulation of the TCA cycle.