The experimental model of type 2 diabetes mellitus caused by a high-fat diet with low-dose streptozotocin in rats

Aim . To develop a pathogenetically reasonable model of type 2 diabetes with marked peripheral insulin resistance and relative insulin deficiency in rats using a high-fat diet and a single injection of streptozotocin in the low dose. Materials and methods. Experiments were conducted on 16 outbred male rats. Type 2 diabetes model in experimental animals was achieved by feeding them with high-fat diet (55% of energy from fat) for 28 days followed by a single injection of streptozotocin (35 mg/kg). The serum glucose and insulin concentrations in rats were measured before streptozotocin administration and at the end of the experiment. To estimate insulin resistance, insulin tolerance test and glucose tolerance test were performed. Total protein, albumin, total and direct bilirubin, urea, uric acid, total cholesterol, high-density lipoproteins and low-density lipoproteins, and activity of alanine aminotransferase and aspartate aminotransferase were measured in the blood serum. Results . A high-fat diet with a single injection of streptozotocin resulted in lipid and protein metabolism disorders and peripheral tissues insulin resistance in experimental animals. Basal insulin levels did not change against the backdrop of high glucose level. Conclusions . These results indicate that feeding rats with a high-fat diet (55% of calories from fats) and a single administration of streptozotocin at a low dose (35 mg/kg) reproduce general pathological processes of type 2 diabetes. This model can be used to study the pathogenesis of type 2 diabetes as well as to investigate the effect of potential hypoglycemic agents.