Streptozotocin/High Fat Diet Model of Type 2 Diabetes
Recently, non-genetic rodent models have been developed which combine exposure to a high-fat diet with low doses of streptozotocin (STZ), a toxin that specifically targets the insulin–producing β-cells of the pancreas and destroys them through alkylation of DNA. These models are popular because they more closely mirror the metabolic disturbances observed in type 2 diabetic patients when compared to monogenetic rodent models of diabetes/obesity or dietary-induced obese rats and mice alone (which model insulin resistance but are not overtly diabetic).
High fat fed animals treated with STZ display significantly increased plasma glucose, blood HbA1c levels and urinary glucose excretion compared to vehicle-treated control animals and impaired glucose tolerance following a glucose challenge. Plasma insulin levels are markedly reduced both before and after a glucose load and STZ markedly reduces pancreatic insulin, consistent with the destruction of insulin-secreting β-cells. The STZ/high fat model can therefore be used to screen for the beneficial effects of novel antidiabetic compounds on glycaemic control and to assess the ability of novel antidiabetic drugs to preserve β-cell function.
Furthermore, as STZ induces diabetic nephropathy (demonstrated by urinary microalbuminuria and kidney pathology) and diabetic peripheral neuropathy (demonstrated by mechanical allodynia) in high fat fed animals, the model can be used to evaluate novel treatments for the complications associated with diabetes.
