Preparation and Validation of a Home-Made AIN-93 Modified High-FatDiet/ Streptozotocin Model for Type 2 Diabetes Research

Introduction: Cost-effective and reliable experimental models are essential for studying Type 2 Diabetes Mellitus (T2DM). This study aimed to develop and validate a costeffective T2DM rat model using a home-made High-Fat Diet (HFD) derived from the AIN-93 diet combined with low-dose Streptozotocin (STZ), and to assess its metabolic and physiological effects. Methods: Forty male Sprague-Dawley rats were used. After one week of acclimatization, 10 rats were sacrificed as a normal baseline group. The remaining 30 were fed a home-made HFD for three weeks, followed by STZ injection (35 mg/kg). Ten rats were sacrificed at week 3 (baseline T2DM group), and 17 at week 5 (progressed T2DM group); three rats died before study completion. Results: Diabetic groups showed significant increases in body and liver weights, fasting glucose, insulin, Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), leptin, glucagon, Phosphoenolpyruvate Carboxykinase (PEPCK), Glucose-6-Phosphatase (G-6-Pase), and serum lipids, along with reduced Glucagon-Like Peptide-1(GLP-1) levels (P ≤ 0.05). Significant differences between the 3-week and 5-week T2DM groups confirmed disease progression. Discussion: The model effectively reproduced key features of early-stage T2DM, including insulin resistance, β-cell dysfunction, dyslipidemia, and increased hepatic gluconeogenesis. Elevated leptin and reduced GLP-1 levels further support the model’s physiological relevance. The results validate the use of a modified AIN-93-based home-made HFD as a low-cost, reliable approach for T2DM research. Conclusion: A home-made HFD combined with STZ successfully induces T2DM in rats and produces consistent metabolic alterations. This low-cost model offers a practical tool for diabetes research, particularly in resource-limited settings.