Assessment of Pharmacological Responses to an Anti-diabetic Drug in a New Obese Type 2 Diabetic Rat Model

INTRODUCTION: The number of diabetic patients has recently been increasing worldwide, and numerous anti-diabetic drugs have been developed to induce good glycemic control. In particular, metformin, which exhibits glucose-lowering effects by suppressing gluconeogenesis in the liver, is widely used as a first line oral anti-diabetic drug for type 2 diabetes mellitus. MATERIAL AND METHODS: In this study, the pharmacological effects of metformin were investigated using female and male Spontaneously Diabetic Torii (SDT) fatty rats, a new obese type 2 diabetic model. RESULTS: Two experiments were performed: an assessment of repeated treatment with metformin in female SDT fatty rats 5 to 13 weeks of age (experiment 1), and an assessment of repeated treatment with metformin in male SDT fatty rats 6 to 10 weeks of age (experiment 2). In female SDT fatty rats, metformin treatment led to good glycemic control, increases in sensory nerve conduction velocity, and improvements in pancreatic abnormalities such as irregular boundaries and vacuole form of islets. In male SDT fatty rats, metformin decreased blood glucose levels 4 weeks after treatment. CONCLUSION: Metformin treatment led to maintained good glycemic control and improved neuropathy and pancreatic lesions in female SDT fatty rats. The SDT fatty rat is useful for the development of novel anti-diabetic agents that show potential to improve glucose metabolic disorders in the liver.