Development of a Type 2 Diabetes Mellitus Model in Rats with Administration of High-Fat Diet and Streptozotocin

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, insulin resistance, and β-cell dysfunction. Despite various efforts, the development of a stable and reproducible T2DM model remains a challenge for fundamental and clinical research due to variability in model methodologies and outcomes. OBJECTIVE: This study aimed to optimize an induced rat model of T2DM characterized by insulin resistance and β-cell degeneration using a combination of a high-fat diet (HFD) and low-dose streptozotocin (STZ)@ 25mg/kg injections. METHODS: Male Sprague-Dawley rats were divided into two groups. The normal control (NC) group was fed standard chow for four weeks and received vehicle injections, while the diabetic control (DC) group was fed a high-fat diet for four weeks and administered two intraperitoneal injections of STZ (25 mg/kg) at a five-day interval. Rats with fasting blood glucose levels ≥250 mg/dL were classified as diabetic. Key parameters—including body weight, fasting blood glucose, serum cholesterol, serum creatinine, and HbA1c—were measured. RESULTS: Rats subjected to HFD feeding followed by STZ injections exhibited significant increases in fasting blood glucose, total serum cholesterol, serum creatinine, and HbA1c levels compared to normal controls (p < 0.05), confirming the successful induction of a diabetic state. The model demonstrated features of insulin resistance, hyperglycemia, dyslipidemia, and early renal alterations, replicating key aspects of human T2DM pathophysiology. CONCLUSION: A combination of high-fat diet and low-dose STZ administration successfully developed a robust and reproducible rat model of T2DM characterized by insulin resistance and β-cell destruction. This improved experimental model provides a valuable platform for future research into the mechanisms and therapeutic interventions of T2DM.