Characteristic features of insulin secretion in the streptozotocin-induced NIDDM rat model.

Male Wistar neonatal rats at age 1.5 days (Streptozotocin [STZ] group 1) and 5 days (STZ group 2) received a subcutaneous injection of 90 mg/kg STZ. After 10 weeks, the rats were subjected to an oral glucose tolerance test (OGTT) (2 g/kg) in a conscious state. The pancreas perfusion experiments were conducted 2 weeks after the OGTT. There was no statistical difference in insulin response between the STZ group 1 and the control group. On the contrary, in the STZ group 2, the plasma glucose response to OGTT showed a typical diabetic pattern, and the plasma insulin response was markedly blunted. In the isolated perfused rat pancreas, the infusion of glucose evoked a biphasic insulin secretion, but the peak insulin levels induced by 16.7 mmol/L glucose in the STZ group 1 were significantly lower than in the controls. We further investigated characteristics of insulin secretion in response to different secretagogues in these animal models using isolated islets. The insulin content of the islets of the STZ group 1 were about one half that of the control group. Insulin secretion in the STZ group 1 was impaired in response to glucose stimulation, but remained normal in response to arginine and forskolin. These results suggest that insulin secretion of non-insulin-dependent diabetes mellitus (NIDDM) rat model is selectively impaired in response to glucose stimulation, possibly due to a disorder of signaling mechanism other than adenylate cyclase.