Metabolic inflexibility and protein lysine acetylation in heart mitochondria of a chronic model of Type 1 diabetes

Diabetic Cardiomyopathy Contractility Bioenergetics
DOI: 10.1042/bj20121038 Publication Date: 2012-10-04T08:28:35Z
ABSTRACT
Diabetic cardiomyopathy refers to the changes in contractility that occur diabetic heart can arise absence of vascular disease. Mitochondrial bioenergetic deficits and increased free radical production are pathological hallmarks cardiomyopathy, but mechanisms causal relationships between mitochondrial progression disease not understood. We evaluated cardiac function a rodent model chronic Type 1 diabetes (OVE26 mice) before onset deficits. found most pronounced change OVE26 mitochondria is severe metabolic inflexibility. This inflexibility characterized by large respiration measured presence non-fatty acid substrates. Metabolic occurred concomitantly with decreased activities PDH (pyruvate dehydrogenase) complex II. Hyper-acetylation protein lysine was also observed. Treatment control acetic anhydride (Ac2O), an acetylating agent, preferentially inhibited substrates superoxide production. have concluded inflexibility, induced discrete enzymatic molecular changes, including hyper-acetylation residues, precedes defects diabetes.
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