Establishment and pathophysiological characterization of type 2 diabetic mouse model produced by streptozotocin and nicotinamide

This study was performed in order to establish a mouse model that represents the non-obese type 2 diabetes reflecting a majority of diabetic patients among Asian races and to show its pathophysiological profiles. Streptozotocin (STZ) was administered to C57BL/6J mice with or without nicotinamide (120 or 240 mg/kg, STZ/NA120 or STZ/NA240), twice with an interval of 2 d, and plasma glucose concentration, body weight, water intake, insulin contents and insulin signal-related proteins were monitored. STZ-induced hyperglycemia (fasting and nonfasting), body weight loss and polyposia were significantly depressed by NA dose-dependently. In STZ/NA120 and STZ/NA240 mice, pancreatic insulin content was retained by 28 and 43% of normal control (10.5 +/- 0.93 mu U/ml), respectively, and histological damage of pancreatic beta cells was also less severe than that observed in STZ mice. When given the calorie-controlled high fat diet, the STZ/NA mice caused hyperlipidemia, and significantly increased insulin resistance. These observations suggest that the combined administration of STZ and NA causes partial depletion of pancreatic insulin and that the high fat constituents lead to insulin resistance in this model. The present mouse model, therefore, well exhibits the recent diabetic pathophysiological characteristics of a majority of Asian patients.