Effect of experimental diabetes on rat cardiac cAMP, phosphorylase, and inotropy.

The isolated perfused working rat heart was used to study experimental diabetes-induced alterations in the effect of isoproterenol on adenosine 3',5'-cyclic monophosphate (cAMP) content, inotropy, and phosphorylase activity. Experimental diabetes was induced by intravenous injection of either alloxan (40 mg/kg) or streptozotocin (50 mg/kg). There were no changes in either basal cAMP levels or in isoproterenol-induced cAMP levels in hearts from diabetic rats at either 3 days or 100-120 days after induction of diabetes. Maximum changes produced by isoproterenol in positive and negative dP/dt developments of diabetic rat hearts were also not different from control at either time point. However, phosphorylase was activated to a significantly greater extent by isoproterenol in hearts obtained from acute as well as chronic diabetic rats. Chronic diabetic rat hearts exhibited significantly higher total phosphorylase activity. Diabetic rat hearts had slightly but not significantly higher basal phosphorylase a activity. Furthermore, prostaglandin E1 activated phosphorylase in diabetic rat hearts but not in control rat hearts. Acute metabolic derangements and alterations in Ca2+ homeostasis caused by diabetes could be the underlying causes for this phosphorylase response. Thyroid hormone levels were depressed in diabetic rats. However, hypothyroidism is probably not responsible for the alterations in phosphorylase activity.