The Characterization of Fructose-Based High-Fat Diet and Low-Dose Streptozotocin in A Type 2 Diabetes Mellitus Rat Model

Information on the biochemical profiles of new antidiabetic agents from animal models is essential for preclinical trials. This study optimizes and characterizes a high-fat, high-fructose diet (HFFD) and low-dose streptozotocin (STZ)-induced type 2 diabetes mellitus (type 2 DM). Wistar rats were fed an HFFD (2 ml of egg yolk, 2 ml of lard, and fructose at 3.6 g/kg BW) for 2, 4, and 6 weeks (p.o), followed by STZ (35 mg/kg body weight BW, i.p) to measure the biochemical parameters. Non-induction HFFD and STZ were used as a normal control group. HFFD for 2, 4, and 6 weeks before STZ injection and low-dose STZ-induced rats demonstrated an elevation in the body weight, fasting blood glucose, triglyceride, triglyceride/ glucose index, necrosis score, and insulin-negative cells. Moreover, this induction also reduced the number of insulin-positive cells and the percentage of insulin-positive cells. Among all treatments, HFFD for 2 weeks before STZ injection and low-dose STZ succeeded the type 2 DM rat model and showed stability for 3 weeks after STZ induction. These findings imply that feeding Wistar rat HFFD for 2 weeks, followed by a single dose of STZ at 35 mg/kg BW is a reliable and stable diabetic rat model closely resembling the biochemical characteristics of type 2 DM. © © 2025 by Indonesian Journal of Pharmacy (IJP).