Insulin Secretory Dysfunction as the Underlying Mechanism of Diabetogenesis in Neonatal Streptozotocin-Induced Type 2 Diabetes Model Rats

Background: Neonatal Streptozotocin (n-STZ) rats are widely used as models for type 2 diabetes mellitus, but the basic defects of diabetes (insulin secretion and resistance) have not yet been adequately characterized in all species of such rats. Materials and Methods: In this study, the basic defects were studied in a group of neonatal streptozotocin-induced type-2 (n-2 STZ) diabetic models of Long Evans rats. The model rats were produced with a single intraperitoneal injection of streptozotocin to 48 hr old pups. Glucose and lipid levels were measured using the standard method. Insulin was measured by ELISA. The intestinal perfusion method was followed to check for the intestinal absorption of glucose. Insulin secretory capacity and resistance were measured using the Homeostasis Model Assessment (HOMA) and Insulin Sensitivity Index (ISI) methods. Results: Type 2 diabetic rats showed significantly higher blood glucose levels at fasting (p<0.001) and at 90 min (p<0.001). Significantly high levels of total cholesterol (p=0.002), triglycerides (p=0.04), and low levels of HDL cholesterol (p=0.04) were observed in diabetic rats compared to control. Glucose absorption in the intestine was found to be significantly higher in almost all the perfusate samples. The diabetic rats had significantly lower serum insulin levels as compared to the control at fasting and at the 90 min period (p<0.001) after oral glucose load. In diabetic rats, insulin secretory capacity (HOMA%B) and ISI composite were notably lower (p<0.001) and insulin sensitivity (HOMA%S) was significantly higher (p<0.001) compared to control. Conclusion: n-2 STZ Long Evans rats showed glycemic and lipidemic abnormalities due to insulin secretory dysfunction which could not be balanced by inadequate compensatory decrease in insulin resistance. Experimental scientists are required to be aware of this basic defect when interpreting their data on such animals.