ATP Production and TCA Activity are Stimulated by Propionyl-L-Carnitine in the Diabetic Rat Heart

Abstract

The beneficial effect of propionyl-L-carnitine (PLC) on cardiac function in diabetes mellitus is well documented. This study was designed to determine whether the improvement in cardiac function mediated by PLC in the diabetic rat heart is associated with an increase in ATP production and tricarboxylic acid (TCA) cycle activity. Diabetes was induced by an intravenous injection of streptozotocin (60 mg/kg). Following diagnosis of diabetes, treatment was initiated by supplementing the drinking water with PLC at a concentration of 1 g/L for a period of 6 weeks. ATP production and TCA cycle activity were determined from oxidative rates of glucose and palmitate measured in isolated working hearts from control and diabetic animals. The effect of diabetes was associated with a decrease in heart function, expressed as rate-pressure product (RPP), and in rates of myocardial glucose oxidation. Rates of palmitate oxidation in diabetic hearts were similar to those of control hearts. In PLC-treated diabetic hearts, rates of both glucose and palmitate oxidation were increased and a significant improvement in RPP was observed. As a result, overall ATP production and TCA cycle activity from glucose and palmitate oxidation were increased in diabetic hearts. Our results indicate that the depression in RPP in the diabetic rat heart can be prevented with chronic PLC treatment. Increases in glucose and palmitate utilization with resultant increases in ATP production and TCA cycle activity may explain the benefit of PLC on diabetic rat heart function.