Effects of prostaglandin E1 in diabetic heart.

Isolated perfused hearts from normal and alloxan-diabetic rats were studied to determine the effects of prostaglandin E1 (PGE1) on phosphorylase activation in the insulin-deficient state. Perfusion of hearts from normal and diabetic rats with 3 X 10(-5) M PGE1 for the final 2 min resulted in activation to the same extent of adenosine 3',5'-cyclic monophosphate (cAMP) accumulation, cAMP-sensitive protein kinase, and phosphorylase kinase. Although phosphorylase activation was somewhat suppressed in both the normal and diabetic heart, PGE1 produced a 36% increase in phosphorylase a in normal hearts and a 44% increase in phosphorylase a in diabetic hearts. The decreased effectiveness of phosphorylase activation by PGE1 appears to be located beyond activation of phosphorylase kinase and perhaps involves an alteration in phosphorylase sensitivity to phosphorylase kinase. Further, the activation of phosphorylase by phosphorylase kinase is hypersensitive in hearts of diabetic rats, perhaps due to a diabetes-related alteration in calcium metabolism.