Changes in cardiac protein kinase C activities and isozymes in streptozotocin-induced diabetes

To understand cardiac dysfunction in diabetes, the activity of protein kina se C (PKC) and protein contents of its isozymes (PKC-alpha, -beta, -epsilon , and -zeta) were examined in diabetic rats upon injection of streptozotoci n (65 mg/kg iv). The hearts were removed at 1, 2, 4, and 8 wk, and some of the 6-wk diabetic animals had been injected with insulin (3 U/day) for 2 wk . The Ca2+-dependent PKC activity was increased by 43 and 51% in the homoge nate fraction and 31 and 70% in the cytosolic fraction from the 4- and 8-wk diabetic hearts, respectively, in comparison with control values. The Ca2-independent PKC activity was increased by 24 and 32% in the homogenate fra ction and 52 and 89% in the cytosolic fraction from the 4- and 8-wk diabeti c hearts, respectively, in comparison with control values. The relative pro tein contents of PKC-alpha, -beta, -epsilon, and -zeta isozymes were increa sed by 43, 31, 48, and 38%, respectively, in the homogenate fraction and by 126, 119, 148, and 129%, respectively, in the cytosolic fraction of the 8- wk diabetic heart. The observed changes in heart homogenate and cytosolic f ractions were partially reversible upon treatment of the diabetic rats with insulin. The results suggest that the increased myocardial PKC activity an d increased protein contents of the cytosolic PKC isozymes are associated w ith subcellular alterations and cardiac dysfunction in the diabetic heart.