Effects of Antidiabetic Drugs on Glucose Tolerance in Streptozotocin-nicotinamide-induced Mildly Diabetic and Streptozotocin-induced Severely Diabetic Mice

In this study, streptozotocin-nicotinamide-induced mildly diabetic mice and streptozotocin-induced severely diabetic mice were created to compare their characteristics and to investigate the effects of antidiabetic drugs on glucose tolerance. In severely diabetic mice, the pancreatic insulin content decreased to approximately 10% of levels found in normal mice. These mice also showed a decrease in body weight, a marked increase in nonfasting blood glucose levels and urinary glucose excretion, and a marked decline in glucose tolerance due to insulin secretory deficiency. In contrast, the pancreatic insulin content was approximately 50% of normal levels in mildly diabetic mice. These mice did not show any change in body weight, but displayed a mild increase in nonfasting blood glucose levels and urinary glucose excretion, and a mild decline in glucose tolerance due to loss of early-phase insulin secretion. Administration of antidiabetic drugs, namely voglibose, metformin, glibenclamide, sitagliptin and insulin, significantly improved glucose tolerance in mildly diabetic mice. In severely diabetic mice, voglibose, metformin and insulin significantly improved glucose tolerance, but no significant effect was observed for glibenclamide and sitagliptin due to a decreased insulinotropic effect. These results demonstrate that streptozotocin-nicotinamide-induced mildly diabetic mice have many pathological features resembling type 2 diabetes, and can serve as models for the pharmacological evaluation of many antidiabetic drugs.