Modelling type 2 diabetes in rats via high-lipid diet and streptozotocin-induced insulin resistance and β-cell dysfunction assessed by C-peptide

Streptozotocin, that has a selective pharmacological toxicity toward pancreatic beta cells, in addition to high lipid diet (HLD) has been widely used to induce T2DM. However, no evidence has shown that superior dose of streptozotocin (STZ) to establish T2DM. This study was initiated to develop an animal model (Wister Albino rats) of T2DM with suitable dose of STZ. Total fifty male rats (210 ± 20 g) were arbitrarily divided into 10 groups (n = 5). Two groups were control group fed normal diet (ND) and high lipid diet (HLD). The remaining rats were induced with STZ at 20, 40, 60 and 80 mg/kg body weight, with each dose tested under ND and HLD conditions. Body weight, blood glucose, HbA1c, serum insulin, C-peptide, pancreatic glucokinase, serum triglycerides (TG), total cholesterol (TC), antioxidant enzymes (SOD, CAT, GSH, MDA) and pancreatic histology. 80 mg/kg STZ group rats expired within 7 days. After 28 days of experiment, Blood glucose was markedly raised up. Insulin and C-peptide levels were lower in STZ/HLD fed groups (P < 0.001) rats. Pancreatic glucokinase activity significantly decreased (P < 0.05). SOD, CAT, GSH and TG, TC increased significantly in STZ/HLD treated groups (P < 0.01). We observed that, β- cells were present in STZ/HLD fed rats pancreas and insulin secretion is higher than ND fed rats. We concluded that, HLD with 40mg STZ/Kg b.w. rats provide a novel animal model for T2DM without any contradictions and is suitable for the testing of antidiabetic compounds.