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一种新的2型糖尿病大鼠模型:高脂喂养、链脲佐菌素处理的大鼠。

A new rat model of type 2 diabetes: the fat-fed, streptozotocin-treated rat.

作者信息

Reed M J, Meszaros K, Entes L J, Claypool M D, Pinkett J G, Gadbois T M, Reaven G M

机构信息

Shaman Pharmaceuticals, South San Francisco, CA 94080-4812, USA.

出版信息

Metabolism. 2000 Nov;49(11):1390-4. doi: 10.1053/meta.2000.17721.

Abstract

This study was initiated to develop an animal model of type 2 diabetes in a non-obese, outbred rat strain that replicates the natural history and metabolic characteristics of the human syndrome and is suitable for pharmaceutical research. Male Sprague-Dawley rats (n = 31), 7 weeks old, were fed normal chow (12% of calories as fat), or high-fat diet (40% of calories as fat) for 2 weeks and then injected with streptozotocin (STZ, 50 mg/kg intravenously). Before STZ injection, fat-fed rats had similar glucose concentrations to chow-fed rats, but significantly higher insulin, free fatty acid (FFA), and triglyceride (TG) concentrations (P < .01 to .0001). Plasma insulin concentrations in response to oral glucose (2 g/kg) were increased 2-fold by fat feeding (P < .01), and adipocyte glucose clearance under maximal insulin stimulation was significantly reduced (P < .001), suggesting that fat feeding induced insulin resistance. STZ injection increased glucose (P < .05), insulin (P < .05), FFA (P < .05), and TG (P < .0001) concentrations in fat-fed rats (Fat-fed/STZ rats) compared with chow-fed, STZ-injected rats (Chow-fed/STZ rats). Fat-fed/STZ rats were not insulin deficient compared with normal chow-fed rats, but had hyperglycemia and a somewhat higher insulin response to an oral glucose challenge (both P < .05). In addition, insulin-stimulated adipocyte glucose clearance was reduced in Fat-fed/STZ rats compared with both chow-fed and Chow-fed/STZ rats (P < .001). Finally, Fat-fed/STZ rats were sensitive to the glucose lowering effects of metformin and troglitazone. In conclusion, Fat-fed/STZ rats provide a novel animal model for type 2 diabetes, simulates the human syndrome, and is suitable for the testing of antidiabetic compounds.

摘要

本研究旨在开发一种非肥胖远交系大鼠的2型糖尿病动物模型,该模型可复制人类综合征的自然病史和代谢特征,适用于药物研究。选用7周龄雄性斯普拉格-道利大鼠(n = 31),分别给予普通饲料(脂肪提供12%的热量)或高脂饲料(脂肪提供40%的热量)喂养2周,然后静脉注射链脲佐菌素(STZ,50 mg/kg)。在注射STZ之前,高脂饲料喂养的大鼠血糖浓度与普通饲料喂养的大鼠相似,但胰岛素、游离脂肪酸(FFA)和甘油三酯(TG)浓度显著更高(P <.01至.0001)。高脂饲料喂养使口服葡萄糖(2 g/kg)后血浆胰岛素浓度增加2倍(P <.01),最大胰岛素刺激下脂肪细胞的葡萄糖清除率显著降低(P <.001),提示高脂饲料喂养诱导了胰岛素抵抗。与普通饲料喂养且注射STZ的大鼠(普通饲料/STZ大鼠)相比,注射STZ使高脂饲料喂养的大鼠(高脂饲料/STZ大鼠)的血糖(P <.05)、胰岛素(P <.05)、FFA(P <.05)和TG(P <.0001)浓度升高。与正常普通饲料喂养的大鼠相比,高脂饲料/STZ大鼠并非胰岛素缺乏,但存在高血糖,且对口服葡萄糖刺激的胰岛素反应略高(均P <.05)。此外,与普通饲料喂养的大鼠和普通饲料/STZ大鼠相比,高脂饲料/STZ大鼠胰岛素刺激的脂肪细胞葡萄糖清除率降低(P <.001)。最后,高脂饲料/STZ大鼠对二甲双胍和曲格列酮的降糖作用敏感。总之,高脂饲料/STZ大鼠为2型糖尿病提供了一种新型动物模型,模拟了人类综合征,适用于抗糖尿病化合物的测试。

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