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Disturbances in mitochondrial metabolism of energy substrates in left ventricle of patients with type 2 diabetes

Diabetes mellitus type 2 (DM2) is associated with a greatly increased risk for cardiac disease, originating both from vascular causes (ischemic heart disease) and metabolic disturbance itself (diabetic cardiomyopathy). Myocardial metabolism of DM2 patients was thus far studied using indirect approaches in vivo, and direct methods in human atrium in vitro, with some controversial findings regarding fatty acid utilization. However, no studies exist that directly investigated a mitochondrial substrate utilization in left ventricular tissue obtained from living patients. Mitochondrial fatty acid (palmitoylcarnitine) and carbohydrate (pyruvate) oxidation were measured in permeabilized left ventricular fibers obtained from patients undergoing coronary artery bypass grafting surgery, whom either had DM2 or were not diabetic (Ctl). There was no difference between the two groups in the oxidation of pyruvate (10 mmol/l). However, mitochondrial oxidation rate of palmitoylcarnitine (40 mol/l) in DM group was significantly decreased. There was no difference in activity of citrate synthase or pyruvate dehidrogenase, and no difference in expression of individual complexes of electron transfer chain. In conclusion, the novelty this study is the direct observation that left ventricle of patients with DM2 exhibits significantly decreased oxidation rate of fatty acids, while the oxidation of carbohydrate is unaffected. This is associated with unchanged mitochondrial content and expression of mitochondrial respiratory chain complexes. Such mitochondrial disturbances can result in excessive intracellular accumulation of lipids in diabetic hearts, which is thought to contribute to pathogenesis of diabetic cardiomyopathy.

mitochondrial metabolism; type 2 diabetes; fatty acid oxidation; myocardium

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