A mechanism for reduced myocardial carnitine levels in diabetic animals.

The effects of substrates, fasting, and diabetes on carnitine transport into the myocardial cells were characterized in perfused adult rat hearts. Increasing the level of acetyl carnitine and decreasing the level of free carnitine by perfusion with various substrates did not alter the rate of carnitine transport. Carnitine transport was enhanced by the perfusion with palmitate. At low work, addition of 1.2 mM palmitate increased carnitine transport by 33%, whereas high work + 1.2 mM palmitate stimulated transport 60% over that of glucose-perfused hearts. The enhancement of carnitine transport correlated with a rise in tissue levels of long-chain acyl carnitine. When the level of long-chain acyl carnitine was increased prior to measurement of carnitine transport, the enhancement of uptake seen with palmitate as substrate was not observed. Carnitine transport in hearts from 48-h-fasted or diabetic animals was not different from transport in hearts of fed animals. Diabetes resulted in decreased tissue levels of carnitine. The decrease was observed after 48 h of severe diabetes and after several weeks of mild diabetes. In each case, low tissue levels of carnitine were associated with reduced serum carnitine. Serum carnitine decreased to a value near the Km for carnitine transport in diabetic animals. It is concluded that a decreased rate of transport due to lower serum carnitine may be responsible for reduced levels of carnitine seen in diabetic hearts.