2387-P: Optimizing STZ Dose to Create a Physiologically Relevant Type 1 Diabetes Model for Drug Evaluation

Introduction and Objective: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by the progressive loss of insulin-producing β-cells. Currently, several animal models are used to study T1D, with the STZ (streptozotocin) model being one of the most widely used. STZ-induced models offer rapid and reproducible evaluation of β-cell destruction; however, excessive β-cell destruction may hinder the effectiveness of potential therapeutics and may not fully mimic the human form of T1D.To assess the β-cell destruction induced by different doses of STZ, we establish a moderately injured β-cell T1D model that supports therapeutic efficacy. Methods: Rats were administered STZ at doses of 15, 40, and 60 mg/kg. Blood glucose levels and insulin immunohistochemistry were monitored throughout the experiment to assess β-cell destruction. Results: At a dose of 15 mg/kg, STZ did not induce sufficient β-cell destruction to establish a T1D model. In contrast, a 60 mg/kg dose led to significant β-cell damage, with a % Sum of Islet area (Islet area/Pancreas area) of 0.22. The 40 mg/kg dose resulted in a moderate increase in blood glucose levels and an intermediate β-cell damage level, with a % Sum of Islet area of 0.67, making it a suitable model for studying the therapeutic effects of drugs targeting T1D. Conclusion: A 40 mg/kg STZ dose induces moderate β-cell destruction, creating a more physiologically relevant model for T1D that can be used to evaluate therapeutic interventions without the extreme β-cell loss seen with higher STZ doses. This model may better mimic human T1D and allow for more accurate testing of potential therapie Disclosure H. Qi: Employee; Current; WuXi AppTex. Y. Li: None.