Nongenetic mouse models of non-insulin-dependent diabetes mellitus
Nongenetic mouse models of non-insulin-dependent diabetes mellitus
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DOI：
10.1016/s0026-0495(98)90027-0
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发表时间：
1998-06-01
影响因子：
9.8
通讯作者：
Reaven, GM
中科院分区：
文献类型：
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作者：
Luo, J;Quan, J;Reaven, GM
这项研究的目的是开发一种非胰岛素依赖型糖尿病(NIDDM)的小鼠模型，该模型接近模拟人类疾病的代谢异常，并且与现有的遗传模型相比具有成本效益。为此，在雄性C57BL/6J或癌症研究所(ICR)小鼠中，通过喂食富含果糖或脂肪的饲料来诱导胰岛素抵抗，并通过向这些小鼠注射不会导致饮食中糖尿病的链脲佐菌素(STZ)来诱导高血糖。在C57BL/6J小鼠中，胰岛素水平最初因富含果糖和脂肪的饮食而增加，然后在注射STZ后下降到与喂食小鼠相当或仍然高于喂养小鼠的水平。与STZ后胰岛素水平的降低有关，饲喂脂肪和果糖的C57BL/6J小鼠出现显著的高血糖，分别达到388+/-38和366+/-58 mg/dL。相比之下，注射等量STZ的喂食小鼠的血糖和胰岛素浓度都没有变化，与喂食ICR的小鼠相比，喂饲脂肪的小鼠注射STZ前后的结果基本相同。虽然没有进行直接比较，但与脂肪喂养的C57BL/6J小鼠相比，脂肪喂养的ICR小鼠对STZ的糖尿病效应的敏感性似乎更高。最后，当使用二甲双胍或甲苯丁胺治疗这些NIDDM实验模型的小鼠时，血糖降低。鉴于这些结果，似乎有理由认为，饮食诱导的胰岛素抵抗和相对较低剂量的STZ在小鼠模型中的结果应该用于研究NIDDM的病理生理学或评估治疗NIDDM的治疗化合物。版权所有(C)1998年，W.B.桑德斯公司。
The purpose of the study was to develop a mouse model of non-insulin-dependent diabetes mellitus (NIDDM) that closely simulates the metabolic abnormalities of the human disease and is also cost-effective compared with the genetic models currently available. For this purpose, insulin resistance was induced in male C57BL/6J or Institute of Cancer Research (ICR) mice by feeding diets enriched in either fructose or fat, and hyperglycemia was induced by injecting these mice with a dose of streptozotocin (STZ) that does not cause diabetes in chow-fed mice. In the case of C57BL/6J mice, insulin levels initially increased in response to the fructose-and fat-enriched diets and then decreased to levels comparable to or still higher than those in chow-fed mice following STZ injection. Associated with the decrease in insulin levels following STZ, fat-fed and fructose-fed C57BL/6J mice became significantly hyperglycemic, reaching values of 388 +/- 38 and 366 +/- 58 mg/dL, respectively. In contrast, neither plasma glucose nor insulin concentrations changed in chow-fed mice injected with an identical amount of STZ, Essentially identical findings were seen before and after STZ injection in fat-fed compared with chow-fed ICR mice. Although a direct comparison was not made, sensitivity to the diabetogenic effects of STZ appeared to be greater in fat-fed ICR compared with fat-fed C57BL/6J mice. Finally, plasma glucose decreased when mice with these experimental models of NIDDM were treated with either metformin or tolbutamide, Given these results, it seems reasonable to suggest that the combination of dietary-induced insulin resistance and relatively low-dose STZ results in mouse models that should be of use in studying the pathophysiology of NIDDM or in evaluating therapeutic compounds for the treatment of NIDDM. Copyright (C) 1998 by W.B. Saunders Company.