CHANGES IN THE SUBCELLULAR-DISTRIBUTION OF FREE CARNITINE AND ITS ACYL DERIVATIVES IN DIABETIC RAT HEARTS FOLLOWING TREATMENT WITH L-CARNITINE

Carnitine deficiency has been demonstrated in diabetic hearts, and it is also well known that L-carnitine administration has a beneficial ef fect on cardiac function. Carnitine treatment would be expected to red uce the accumulation of long-chain acylcarnitine. However, many report s have shown that myocardial long-chain acylcarnitine levels were incr eased following treatment with L-carnitine in whole-heart studies. Sin ce acylcarnitine exists in both the mitochondrial and cytosolic compar tments, it is difficult to investigate changes in subcellular distribu tion by studying whole-heart preparations. The present study investiga ted the myocardial subcellular distribution of carnitine and its acyl derivatives in diabetic rats with or without L-carnitine treatment. Ap proximately 90% of total cellular carnitine was located in the cytosol in the diabetic hearts. Both mitochondrial and cytosolic levels of fr ee carnitine and short-chain acylcarnitine were significantly decrease d in the diabetic heart. However, the mitochondrial level of long-chai n acylcarnitine was significantly increased. L-carnitine treatment red uced the mitochondrial level of long-chain acylcarnitine, but the cyto solic level of long-chain acylcarnitine was significantly increased. T hese results show that L-carnitine treatment prevents the accumulation of long-chain acylcarnitine in the mitochondrial space and then reduc es the detergent effect of long-chain acylcarnitine on the mitochondri al membrane. We suggest that it is a possible mechanism of the benefic ial effect of L-carnitine treatment on the diabetic heart.