НОВАЯ МОДЕЛЬ САХАРНОГО ДИАБЕТА 2-ГО ТИПА И ДИАБЕТИЧЕСКОЙ НЕФРОПАТИИ У КРЫС

Non-genetic rat models of diabetic nephropathy are most commonly reproduced by using streptozotocin. However, administration of high doses of streptozotocin might have significant disadvantages such as severe hyperglycemia due to insulinopenic condition. Nevertheless, certain significant metabolic factors besides hyperglycemia, such as insulin resistance, obesity, dyslipidemia, and hypertension plays a crucial role in the onset and progression of diabetic nephropathy in type 2 diabetes mellitus. Hereby, we have described a novel model of type 2 diabetes and nephropathy in rats that is characterized by morphofunctional changes similar to relatively early stages of human diabetic nephropathy. Starting at 3 weeks after right-side nephrectomy, adult male Wistar rats were fed for 5 weeks the high-fat diet containing beef tallow and then successively received nicotinamide (230 mg/kg) and streptozotocin (65 mg/kg) intraperitoneally in 15-min interval. Control nondiabetic uninephrectomized rats received vehicle and were fed normal chow. With described model we observed the development of mild hyperglycemia, overweight, slight significant increase in insulin resistance, and dyslipidemia which resulted in a gradual decrease in renal function up to significant reduced creatinine clearance and elevated albuminuria, and confirmed diabetic nephropathy by validated electron and light microscopic morphological criteria at week 30 of the study.