Effects of Anoxia and Low Free Fatty Acid on Myocardial Energy Metabolism in Streptozotocin-Diabetic Rats

To investigate anaerobic glycolysis and glucose oxidation in the diabetic heart, we studied the effects of anoxia and low exogenous free fatty acid (FFA) on myocardial adenosine triphosphate (ATP) content in the isolated perfused heart from streptozotocin-diabetic rats. The perfusate consisted of Krebs-Ringer buffer (pH 7.4) containing 5 mM glucose and 0.30 mM or 0.05 mM FFA, equilibrated with 95% O2 + 5% CO2 or 95% N2 + 5% CO2 gas. Under aerobic conditions, glucose uptake, lactate production and glucose oxidation by the diabetic heart were reduced by 68, 57 and 53% of the control, respectively, and FFA oxidation by the diabetic heart was increased by 67% of the control. Under anoxic conditions, the increments in glucose uptake and lactate production by the diabetic heart were much smaller than those by the control (2.6 and 9.5 mumol/g/30 min vs. 11.4 and 40 mumol/g/30 min, respectively). The ATP content in the diabetic myocardium was decreased more rapidly in the anoxic perfusion than that in the control. In the aerobic perfusion, the ATP content in the control myocardium was maintained for 60 min at low FFA (0.05 mM) in the perfusate. The ATP content in the diabetic myocardium was reduced after 40 min at low FFA but was well maintained for 60 min by the addition of 0.30 mM FFA. Thus the ATP content in aerobic diabetic myocardium was not well maintained when exogenous FFA supply was depleted. These results suggest that diabetic hearts have a primary defect in the stimulation of glycolysis and glucose oxidation, which does not result from increased FFA utilization.