Preferential inhibition of lactate oxidation relative to glucose oxidationin the rat heart following diabetes

Objective: Alterations in myocardial metabolism occur early after the onset of diabetes suggesting that they may play a role in the development of car diac dysfunction. Inhibition of myocardial pyruvate dehydrogenase (PDH). gl ucose transport and glycolysis have all been reported following diabetes. I n vivo lactate is also a potential source of energy for the heart and its o xidation should not be affected by changes in glucose transport and glycoly sis. Therefore, the objective of this study, was to test the hypothesis tha t following diabetes the inhibition of glucose oxidation would be greater t han the inhibition of lactate oxidation, Methods: Hearts from control and o ne-week-old diabetic rats were perfused with [1-C-13]glucose (11 mmol/l) al one, [1-C-13]glucose plus lactate (0.5 mmol/l) or glucose plus [3-C-13]lact ate (0.5 or 1.0 mmol/l) as substrates. Glucose and lactate oxidation rates were determined by combining C-13-NMR glutamate isotopomer analysis of tiss ue extracts with measurements of oxygen consumption, Results: In diabetic h earts perfused with glucose alone, glucose oxidation was decreased compared to controls (0.31+/-0.08 vs. 0.71+/-0.11 mu moles/min/g wet weight; p<0.05 ). Surprisingly, in hearts perfused with glucose plus 0.5 mmol/l lactate, t here was no difference in glucose oxidation between control and diabetic gr oups (0.201+/-0.05 vs. 0.16+/-0.03 mu moles/min/g wet weight respectively), However, under these conditions lactate oxidation was markedly reduced in the diabetic group (0.89+/-0.18 vs. 0.24+/-0.05 mu moles/min/g wet weight: p<0.05). At 1.0 mmol/l lactate oxidation was still significantly depressed in the diabetic group. Conclusion: There was a greater decrease in lactate oxidation relative to glucose oxidation in hearts from diabetic animals. Th ese results demonstrate that diabetes lends to a specific inhibition of lac tate oxidation independent of its effects on pyruvate dehydrogenase. (C) 19 99 Elsevier Science B.V. All rights reserved.