The use of High-Fat/Carbohydrate Diet-Fed and Streptozotocin-Treated Mice as a Suitable Animal Model of Type 2 Diabetes Mellitus

Abstract

This study defined a mouse model of type 2 diabetes that closely simulated the development and metabolic  abnormalities of the human disease. Male C57BL/6J mice were fed with diet enriched in fat and simple carbohydrate  for 6 weeks and then injected with streptozotocin (STZ, 150 mg/kg intraperitoneally) to develop type  2 diabetes. High-fat/carbohydrate-fed mice showed similar blood glucose concentrations to chow-fed mice, but  higher insulin concentrations (P<0.01). Hyperglycemia (17.6±3.27 mmol/L) was observed in these mice after  STZ injection, and the insulin concentrations decreased to the level comparable to, or still higher than, the normal.  The model mice showed impaired glucose tolerance in the oral glucose tolerance test (OGTT), and insulin  resistance in the insulin tolerance test (ITT). Moreover, these animals had lower glycogen storage (P<0.001),  higher serum free fatty acid (P<0.001), and higher triglycerides (P<0.05) levels compared with control mice.  Furthermore, the model mice were sensitive to the glucose lowering effect of metformin. In conclusion, this  mouse model could be considered as one of the suitable animal models for type 2 diabetes mellitus, and hence  can reasonably be used for type 2 diabetes pathophysiological research and therapeutic-compound evaluation.