Regulation of glucose uptake by muscles. 10. Effects of alloxan-diabetes, starvation, hypophysectomy and adrenalectomy, and of fatty acids, ketone bodies and pyruvate, on the glycerol output and concentrations of free fatty acids, long-chain fatty acyl-coenzyme A, glycerol phosphate and citrate-cycle intermediates in rat heart and diaphragm muscles

Abstract

The concentration of long-chain fatty acyl-CoA in perfused rat heart is increased by alloxan-diabetes, by starvation and by the addition of palmitate in vitro to the perfusion medium. In diabetes the concentration of fatty acyl-CoA can be returned to normal levels by treatment of the diabetic rat with insulin. The concentration of free fatty acids in the perfused rat heart is increased by diabetes, and in rat hemidiaphragms by diabetes and starvation. In hypophysectomized rats the concentration of free fatty acids in hemidiaphragms was not increased by the induction of diabetes. The output of glycerol by perfused rat heart was increased by diabetes and starvation. Prior hypophysectomy or adrenalectomy or treatment with insulin prevented diabetes from increasing the glycerol output. In rat hemidiaphragms the glycerol output was similarly increased by diabetes in normal but not in hypophysectomized rats. Treatment of hypophysectomized alloxan-diabetic rats with growth hormone and cortisol led to an increase in the glycerol output by hemidiaphragms. The concentration of glycerol phosphate in rat heart and rat hemidiaphragms was decreased by diabetes and by starvation. Prior adrenalectomy or treatment of the rat with insulin prevented diabetes from lowering the concentration of glycerol phosphate. It is concluded that there is increased provision of fatty acids for respiration in heart and diaphragm muscle of alloxan-diabetic and starved rats in vitro, due in part to an increased rate of lipolysis and possibly in part to a diminished rate of re-esterification of fatty acid. In perfused hearts from diabetic rats or in hearts from normal fed rats perfused with medium containing fatty acids or ketone bodies the concentrations of acetyl-CoA, citrate and isocitrate are increased. These changes in concentrations are attributed to an increased rate of oxidation of fatty acids and ketone bodies to acetyl-CoA. These findings are consistent with the view that an increased rate of oxidation of fatty acids and ketone bodies is responsible for abnormalities of glucose phosphorylation, fructose 6-phosphate phosphorylation, and pyruvate oxidation in muscles of diabetic rats.