L-PROPIONYLCARNITINE ENHANCEMENT OF SUBSTRATE OXIDATION AND MITOCHONDRIAL RESPIRATION IN THE DIABETIC RAT-HEART

This study was designed to determine whether L-propionylcarnitine (LPC ) treatment is beneficial in preventing the depression in cardiac func tion from occurring in chronic diabetes. Diabetes was induced by tail vein injection of streptozotocin (60 mg/kg), Two weeks later, treatmen t was initialed by supplementing the drinking water with LPC at the co ncentration of 1 mg/ml. Following a 6-week treatment period, myocardia l substrate utilization and cardiac function were determined in isolat ed working hearts. In a separate group of hearts, the effects of LPC t reatment on mitochondrial respiration were also determined. The result s showed that diabetic hearts, compared with those of controls, oxidiz ed glucose at a much lower rate, but oxidized palmitate at a similar r ate. The effect of diabetes compared to controls was also characterize d by a pronounced decrease in cardiac pump function, Following treatme nt with LPC, however, there was a marked increase in the rates at whic h glucose and palmitate were oxidized by diabetic hearts, and a signif icant improvement in cardiac pump performance, In addition, the depres sion of cardiac mitochondrial respiration seen in diabetes was prevent ed with LPC treatment. Our findings show that the depression of cardia c pump function by diabetes can be prevented with chronic LPC treatmen t, Possible mechanisms for this beneficial effect include an energetic ally favorable shift in glucose and fatty acid metabolism. (C) 1996 Ac ademic Press Limited