Diabetes mellitus (DM) is a chronic metabolic disorder characterized by persistent hyperglycaemia resulting from impaired insulin secretion, insulin action, or both. Experimental rat models are widely used in preclinical diabetes research because they allow rapid and reproducible evaluation of disease mechanisms and therapeutic interventions. Among the available models, the combination of streptozotocin (STZ) and nicotinamide (NA) is commonly employed to induce a condition resembling type 2 diabetes mellitus (T2DM) through partial pancreatic β-cell damage while preserving residual insulin function. This literature review aimed to evaluate the effects of different STZ–NA induction doses on blood glucose levels in rats and to identify the most reproducible protocol for T2DM induction. A literature review was conducted using studies retrieved from scientific databases, including PubMed, NCBI, ScienceDirect, and PLOS One. A total of 21 studies met the inclusion criteria and were included in the qualitative synthesis. Across the included studies, successful diabetes induction was generally defined by hyperglycaemia; however, diagnostic thresholds varied, ranging from fasting blood glucose levels 126 mg/dL to random blood glucose levels ≥200 mg/dL. Most STZ–NA dose combinations successfully induced diabetic conditions, with post-induction glucose levels commonly exceeding 200 mg/dL. The combination of STZ 60 mg/kgBW and NA 120 mg/kgBW was the most frequently reported regimen and consistently produced stable hyperglycaemia, typically ≥200 mg/dL, while avoiding complete pancreatic β-cell destruction. Overall, the available evidence suggests that STZ 60 mg/kgBW combined with NA 120 mg/kgBW represents the most consistent protocol for establishing a T2DM rat model.
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