VARIABILITY OF THE STREPTOZOTOCIN–NICOTINAMIDE MODEL OF EXPERIMENTAL DIABETES IN YOUNG SPRAGUE–DAWLEY RATS: A PRELIMINARY VALIDATION STUDY

Abstract

The streptozotocin–nicotinamide (STZ–NIA) model is widely used to induce experimental type 2 diabetes mellitus (T2DM), but its metabolic outcome may vary according to the induction protocol. This study evaluated the response to an initial and a modified STZ–NIA protocol in young Sprague–Dawley rats, with particular emphasis on blood glucose and body weight. Materials and methods: Rats were allocated to control and STZ–NIA groups. The initial protocol consisted of NIA pretreatment followed by STZ administration. As persistent hyperglycemia was not achieved, the protocol was modified by reducing NIA exposure and increasing the STZ dose. Blood glucose was measured longitudinally, and body weight was monitored throughout the experimental period. Parametric and non-parametric statistical analyses were performed. Results: The initial protocol did not induce persistent hyperglycemia. Following protocol modification, the STZ–NIA group showed significant temporal variation in blood glucose, with the most pronounced increase occurring after the second induction phase. However, this response was transient, with glucose levels subsequently returning toward baseline. Glycemia remained comparatively stable in control animals. Body weight increased in both groups throughout the study, with no significant difference in absolute or relative weight gain between groups. Conclusions: The modified STZ–NIA protocol produced a transient metabolic response but did not establish a stable diabetic phenotype. These findings are consistent with an important role of the balance between STZ-induced β-cell injury and NIA-mediated protection in determining the metabolic response. Longitudinal glucose monitoring and further optimization of the induction protocol, together with direct assessment of pancreatic β-cell integrity and insulin-related parameters, are warranted to establish a reproducible model for subsequent pharmacological studies.