Development and Characterization of a Low-Protein Diet– and Low-Dose Streptozotocin–Induced Rat Model of Type 2 Diabetes Mellitus in Wistar Rats

Aim: To develop an experimental model of type 2 diabetes mellitus (T2DM) in rats using a low-protein diet (LPD) and streptozotocin. Methodology: Malnutrition was established in male Wistar rats immediately after weaning by feeding them a LPD containing 10% protein. The control group received a standard pellet diet containing 18% protein. After malnutrition was established, increasing doses of streptozotocin (STZ) were administered to induce diabetes in the LPD group. Fasting blood glucose (FBG) was measured 72 hours after the STZ challenge and monitored weekly thereafter. At the end of the study, an oral glucose tolerance test (OGTT) was performed. Serum insulin and lipid profile were also estimated. Rats were euthanized to collect the pancreas for histopathological examination. Key findings: The cardinal signs of diabetes were evident in LPD rats receiving 40 mg/kg and higher doses of STZ compared with the control group. The increase in FBG in the LPD + STZ groups was proportional to the STZ dose. Increased OGTT and HOMA-IR values indicated impaired glucose tolerance in these rats. Further, hyperinsulinemia and dyslipidemia confirmed the development of insulin resistance. Additional evidence come from histopathology, where pancreatic islet cell atrophy was evident in the protein-malnourished rats. Damage to the pancreatic islet cells worsened with increasing doses of STZ. Significance: Protein malnutrition (PMN) is a risk factor for the development of T2DM.