Modeling type 2 diabetes in rats using high fat diet and streptozotocin

The pathology of type 2 diabetes is complex, with multiple stages culminating in a functional β-cell mass that is insufficient to meet the body's needs. Although the broad outlines of the disease etiology are known, many critical questions remain to be answered before next-generation therapeutics can be developed. In order to further elucidate the pathobiology of this disease, animal models mimicking the pathology of human type 2 diabetes are of great value. One example of a type 2 diabetes animal model is the high-fat diet-fed, streptozotocin (HFD/STZ)-treated rat model. The present review first summarizes the current understanding of the metabolic profile and pathology involved in the different stages of the type 2 diabetes disease progression in humans. Second, the known characteristics of the HFD/STZ rat model are reviewed and compared with the pathophysiology of human type 2 diabetes. Next, the suitability of the HFD/STZ model as a model of type 2 diabetes with a focus on identifying critical caveats and unanswered questions about the model is discussed. The improved understanding of refined animal models will hopefully lead to more relevant preclinical studies and development of improved therapeutics for diabetes. Depending on the amount of residual functional β-cells mass, the HFD/STZ rat model might be a suitable animal model of the final stage of type 2 diabetes.