The study aimed to compare three different experimental type 2 diabetes mellitus (T2DM) models performed on rats. 3 equal groups of 54 Wistar albino rats were randomly categorized as follows; first group: The rats treated by high-fat diet and streptozotocin (35 mg/kg, SC), second group: The rats received drinking water containing 20% fructose, and third group: Nicotinamide (110 mg/kg, IP) and streptozotocin (60 mg/kg, SC) were administered. Six animals from each group were euthanized at 6, 10 and 12 weeks to evaluate the diabetic process in the models. Glucose and HbA1c levels tended to be higher in the third model, though overall profiles were comparable to first model group. In the early phases, the first model group's triglyceride levels were statistically greater than those of the other groups, and its insulin levels dropped over time. The GLUT4, IRS1 and PIK3R expressions in skeletal muscle decreased in the first and third model groups. Based on practical considerations, the third model appeared to be more feasible for long-term studies and showed a better reflection of the T2DM phenotype; however, the first model demonstrated more pronounced effects in the short-term. The findings of this research may provide valuable insights for future studies by guiding researchers in selecting the appropriate experimental model for T2DM research in rats and will be a guide for developing new drugs and treatments in the search.

To Cite This Article: Dik B, Erkoc-Kaya D, Parlak TM, Tufan O and Gokturk F 2025. Molecular and biochemical comparison of various rat models for experimental diabetes induction. Pak Vet J. http://dx.doi.org/10.29261/pakvetj/2025.276