A Novel Mouse Model of Type 2 Diabetes Using a Medium‒Fat Diet, Fructose, and Streptozotocin to Study the Complications of Human Disease

The study of type 2 diabetes mellitus (T2DM) pathophysiology relies mainly on the use of animal models, the most common of which involves the consumption of high-fat diets comprising 60% calories from fat. Although these models reproduce the onset and most complications associated with T2DM, they do not accurately mimic human dietary patterns, as they lack the addition of carbohydrates such as fructose. This study aimed to develop a C57BL/6 mouse model of T2DM that mimics the disease, as occurs in younger individuals, via a medium-fat diet (34.5% kcal from fat) combined with a 20% fructose solution as drinking water and a single low-dose of streptozotocin (STZ) (100 mg/kg), a diabetogenic drug. At week 20, D + T mice exhibited significant weight gain and elevated fasting blood glucose levels compared with those of control mice and the development of insulin resistance. Similarly, the circulating levels of hepatic enzymes (GPT, GOT, and alkaline phosphatase), total cholesterol, and LDL increased. Multi-organ damage, including reduced pancreatic islet size and number, severe hepatic steatosis, inflammatory infiltration in visceral adipose tissue, and cardiac and renal dysfunction, were also detected. The proposed model replicates T2DM in young mice by combining a medium-fat diet with fructose and STZ.