Development of a High-Fat Diet and Low-Dose Streptozotocin-Induced Rat Model for Type 2 Diabetes Mellitus

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder marked by persistent hyperglycemia, insulin resistance, and progressive pancreatic β-cell dysfunction. Despite the global rise in T2DM prevalence, the development of reliable and reproducible animal models that closely mimic human disease pathology remains a significant challenge in diabetes research. A combination of dietary and chemical induction is often employed to replicate the multifactorial pathogenesis of T2DM. OBJECTIVE: The study aims to create and verify a robust rat model of T2DM utilizing a high-fat diet (HFD) in combination with low-dose streptozotocin (STZ) injections at 25mg/kg, reproducing important aspects such as hyperglycemia, insulin resistance, and β-cell dysfunction. METHODS: Male Sprague-Dawley rats were randomly assigned to two groups: normal control (NC) and diabetic control (DC). The DC group received an HFD for 4 weeks followed by two intraperitoneal STZ injections (25 mg/kg) at a 5-day interval. Metabolic parameters including fasting blood glucose (FBG), serum cholesterol, creatinine, HbA1c, and HOMA-IR were assessed. RESULTS: The diabetic rats demonstrated significant increases in FBG, cholesterol, creatinine, and HbA1c compared to controls (p < 0.05), indicating successful induction of diabetes. Additionally, HOMA-IR values were significantly elevated in the diabetic group compared to the control group, confirming the presence of insulin resistance. This increase reflects impaired glucose utilization due to high-fat diet–induced metabolic stress and partial β-cell dysfunction. No mortality or severe complications were observed during the induction process. CONCLUSION: The HFD-STZ model effectively reproduced the dual pathology of insulin resistance and pancreatic β-cell dysfunction observed in human T2DM. This model provides a reliable platform for evaluating antidiabetic therapies and investigating disease mechanisms in preclinical studies.