Department of Pharmacy, Faculty of Health Sciences, The Open University of Sri Lanka, Sri Lanka.
Department of Biochemistry, Faculty of Medicine, University of Ruhuna, Sri Lanka.
J Pharmacol Toxicol Methods. 2022 Jan-Feb;113:107144. doi: 10.1016/j.vascn.2021.107144. Epub 2021 Dec 9.
The development of a stable disease model with an adequate biochemical profile is crucial for the preclinical investigation of new antidiabetic agents. This study aimed at optimization and characterization of high fat diet (HFD) fed streptozotocin (STZ) induced type 2 diabetes mellitus (type 2 DM) Wistar rat model. Wistar rats fed with HFD for four weeks received STZ (30, 40, and 50 mg/kg, intraperitoneal). Diabetic rats were observed for four more weeks and sacrificed. Non- injected healthy Wistar rats and HFD-fed rats were used as control groups. The glucose status and the lipid profile of the model were assessed. STZ-induced rats showed significant dose-dependent alterations in fasting serum insulin and glucose, homeostatic model assessment- insulin resistance (HOMA-IR), HOMA- β cell function (HOMA- β), quantitative insulin sensitivity check index (QUICKI), total cholesterol (TC), triglycerides (TG) and atherogenic index (AI). STZ 50 mg/kg group rats showed significant increase in glycated hemoglobin (HbA), low density lipoprotein cholesterol (LDL-C) and very low density lipoprotein cholesterol (VLDL-C) levels compared to healthy rats. The atherogenic risk index (ARI), the Castelli risk index-I (CRII), and CRI-II were significantly (p < 0.05) high in the STZ 40 mg/kg and 50 mg/kg group rats. Results suggest that the Wistar rats fed with HFD rich in saturated fat for four weeks followed by a single intraperitoneal dose of 50 mg/kg of STZ would produce a stable diabetic model which closely mimic biochemical features of type 2 DM. Key messages: Wistar rats fed with HFD rich in saturated fat for four weeks followed by a single intraperitoneal dose of 50 mg/kg STZ would produce a stable diabetic model that closely mimics the biochemical characteristics of type 2 DM characterized by insulin resistance, relative insulin deficiency and impaired β cell function.
建立具有适当生化特征的稳定疾病模型对于新的抗糖尿病药物的临床前研究至关重要。本研究旨在优化和表征高脂肪饮食（HFD）喂养的链脲佐菌素（STZ）诱导的 2 型糖尿病（2 型 DM）Wistar 大鼠模型。四周围喂高脂肪饮食的 Wistar 大鼠接受腹腔内注射 STZ（30、40 和 50mg/kg）。观察糖尿病大鼠四周后并进行处死。未注射健康 Wistar 大鼠和 HFD 喂养大鼠作为对照组。评估模型的葡萄糖状态和脂质谱。STZ 诱导的大鼠空腹血清胰岛素和葡萄糖、稳态模型评估-胰岛素抵抗（HOMA-IR）、HOMA-β细胞功能（HOMA-β）、定量胰岛素敏感性检查指数（QUICKI）、总胆固醇（TC）、三酰甘油（TG）和致动脉粥样硬化指数（AI）均呈现显著的剂量依赖性改变。与健康大鼠相比，STZ 50mg/kg 组大鼠的糖化血红蛋白（HbA）、低密度脂蛋白胆固醇（LDL-C）和极低密度脂蛋白胆固醇（VLDL-C）水平显著升高。STZ 40mg/kg 和 50mg/kg 组大鼠的致动脉粥样硬化风险指数（ARI）、Castelli 风险指数-I（CRII）和 CRI-II 均显著升高（p<0.05）。结果表明，四周围喂富含饱和脂肪的 HFD 后，大鼠单次腹腔注射 50mg/kg 的 STZ 可产生稳定的糖尿病模型，该模型密切模拟 2 型 DM 的生化特征。关键信息：四周围喂富含饱和脂肪的 HFD 后，大鼠单次腹腔注射 50mg/kg 的 STZ 可产生稳定的糖尿病模型，该模型模拟 2 型 DM 的生化特征，表现为胰岛素抵抗、相对胰岛素缺乏和β细胞功能受损。
