Effects of insulin, palmitate, and acetate on lipolysis of endogenous triacylglycerols were studied in the isolated perfused hearts of control and ketotic diabetic rats. In the absence of fatty acid, the rate and net amount of lipolysis were increased in diabetic hearts. After 120 min of perfusion, the residual triacylglycerol content was similar in both hearts, suggesting that the accumulation of triacylglycerols in the heart of ketotic diabetic rats was due to the expansion of the mobiliza-ble fraction. Insulin, in physiologic concentrations, inhibited triacylglycerol lipolysis in control hearts, provided glucose was present in the perfusate. In diabetic hearts perfused with glucose, insulin up to 500 μU/ml did not inhibit triacylglycerol lipolysis.
A physiologic concentration of palmitate (0.5 mM) completely inhibited triacylglycerol lipolysis in both control and diabetic hearts. Palmitate inhibition of lipolysis in both control and diabetic hearts could be observed in absence of perfusate glucose. Heart intra-cellular lipoprotein lipase activity was determined to check whether the inhibitory actions of insulin and palmitate could be explained by reduction in this lipase activity. Perfusion of control hearts with insulin and glucose had no effect on the lipase activity. Lipase activity of the control heart was unaffected and that of the diabetic heart was inhibited after perfusion with palmitate. The results of this study show (1) insulin in physiologic concentrations inhibits heart triacylglycerol lipolysis probably through increased glucose transport and glycolysis; (2) inclusion of palmitate in the perfusate results in inhibition of triacylglycerol lipolysis in both control and diabetic hearts and in the case of the diabetic heart, the palmitate effect is due to the inhibition of the intracellular lipoprotein lipase activity; and (3) an increased synthesis of triacylglycerol coupled with an inhibition of its lipolysis by free fatty acids and ketone bodies may explain the accumulation of triacylglycerols in the hearts of diabetic rats.
