A novel mouse model for studying complications related to type 2 diabetes using a medium-fat diet, fructose, and streptozotocin

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 in drinking water. The aim of this study was to develop a mouse model for studying complications related to T2DM. To this end, male C57BL/6 mice were fed a medium-fat diet (34.5% kcal from fat), given 20% fructose in drinking water, and injected with a single low dose of streptozotocin (STZ; 100 mg/kg) (D + T). At week 20, D + T mice exhibited significant weight gain, elevated fasting blood glucose levels, and the development of insulin resistance compared with control mice. Furthermore, the circulating levels of liver 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, was also detected. The proposed model replicates T2DM-associated complications in young mice by combining a medium-fat diet with fructose and STZ.