Alteration of the apparent Ki of carnitine palmitoyltransferase for malonyl-CoA by the diabetic state and reversal by insulin.

The effects of streptozotocin-induced diabetes and the subsequent treatment of diabetic animals with insulin were studied using a dose of streptozotocin that produces highly ketotic animals 48 h after injection. Carnitine palmitoyltransferase of diabetic animals had apparent Ki values for malonyl-CoA that were approximately 10 times greater than control animals, indicating a greatly decreased affinity for malonyl-CoA in the diabetic state. Subsequent treatment of diabetic animals with insulin for 5 days produced non-ketotic animals with normal blood glucose, and the affinity of carnitine palmitoyltransferase for malonyl-CoA was increased to the control level. Treatment of other groups of ketotic diabetic animals with insulin produced substantial changes in the carnitine palmitoyltransferase apparent Ki value for malonyl-CoA within 4 h. These results suggest that insulin modulates the ketotic state, at least in part, by increasing the affinity of carnitine palmitoyltransferase for malonyl-CoA to bring about inhibition of fatty acid oxidation and ketogenesis.