Establishment and Evaluation of Rat Models of Type 2 Diabetes Mellitus

Objective: To establish an animal model similar to the metabolic abnormalities of human type 2 diabetes mellitus with insulin resistance.Methods: Adult male Wistar rats were fed with high-fatty(59% of calories-fat) diet that contained unsaturated fatty acid for 5 weeks to induce insulin resistance, then streptozotion(STZ, 25 mg/kg) was injected intraperitoneally to result in insulin secretion defect and hyperglycemia. euglycemic-hyperinsulinemic clamp technique was performed in rats to estimate their insulin sensitivity.Results: Glucose infusion rates(GIR) in the rats with high-fat diet decreased and fast plasma insulin increased compared with the control group. Based on the high-fat diet, the rats were injected intraperitoneally with low-dose streptozotocin to establish type 2 diabetes mellitus model. One week after STZ injection,blood glucose moderate increased, plasma insulin decreased but still higher than that in regular chow-fed rats, with insulin resistance and dyslipidemia still existed. GIR was obviously lower in rats with the high-fatty diet group and the high fatty plus low dose STZ injection group than that of the control group. Conclusion: Type 2 diabetes mellitus animal model is successfully reproduced by using the high fatty diet plus low dose STZ injection.It may provide a perfect animal model for investigating type 2 diabetic mechanism and pharmacology, also be used to research insulin resistance and related diseases of human beings.