Heat shock protein (Hsp)60 and
IGF-1 receptor signaling protect cardiac muscle against injury. The abundance of cardiac
IGF-1 receptor can be upregulated by Hsp60, but how diabetes modulates cardiac muscle Hsp60 has not yet been defined. We investigated the changes of Hsp60 and
IGF-1 receptor signaling in the diabetic myocardium and studied how diabetes modulates Hsp60 and
IGF-1 receptor in diabetic myocardium. In the
streptozotocin (STZ)-induced diabetic rat, downregulation of Hsp60 and
IGF-1 receptor occurred 4 days after induction of diabetes.
IGF-1 activation of
IGF-1 receptor,
Mek, and Akt were reduced accordingly in the diabetic myocardium. The independent effect of
insulin and
hyperglycemia on Hsp60 was investigated in primary cardiomyocytes. Incubating cardiomyocytes with
insulin was associated with dose-dependent increase of
Hsp60 protein. In contrast, the abundance of Hsp60 was not affected by high concentration of
glucose in these cells. To further determine the independent effects of
hyperglycemia and
insulin deficiency on the changes of myocardial Hsp60 and
IGF-1 receptor, we used
phlorizin to normalize
blood glucose in diabetic rats. In the
phlorizin-treated diabetic rats, myocardial Hsp60 was lower than that of the normal controls. In contrast,
insulin treatment normalized myocardial Hsp60 in the diabetic rats. Because
phlorizin does not alter insulin secretion, Hsp60 expression was modulated by
insulin and not by
hyperglycemia. Similar changes of Hsp60 and
IGF-1 receptor were observed in the skeletal muscle of STZ-induced diabetic rats. These findings suggest that
insulin deficiency is a novel mechanism that leads to downregulation of Hsp60 in diabetic muscle tissues. The development of
diabetic cardiomyopathy might have involved downregulation of Hsp60 and subsequent reduction of
IGF-1 receptor signaling.