[过氧化物酶体增殖物激活受体γ在2型糖尿病发病中的作用]

[The role of PPARgamma in the onset of type 2 diabetes].

作者信息

Hara Kazuo, Yamauchi Toshimasa, Kubota Naoto, Tobe Kazuyuki, Yamazaki Tsutomu, Nagai Ryozo, Kadowaki Takashi

机构信息

Department of Clinical Bioinformatics, Graduate School of Medicine, University of Tokyo, Japan.

出版信息

Nihon Yakurigaku Zasshi. 2003 Oct;122(4):317-24. doi: 10.1254/fpj.122.317.

DOI:10.1254/fpj.122.317

PMID:14501167

Abstract

We have investigated the role of PPARgamma and its related genes on the pathogenesis of type 2 diabetes. Heterozygous PPARgamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet, whose phenotypes were abrogated by PPARgamma agonist treatment. Moreover, a Pro12Ala polymorphism in the human PPARgamma 2 gene, which has been reported to cause a reduction in the PPARgamma activity, was associated with decreased risk of type 2 diabetes in Japanese. The protective effect of this polymorphism against type 2 diabetes has been confirmed by meta-analysis using reports in various ethnic groups. Taken together with these results, PPARgamma is a thrifty gene mediating type 2 diabetes both in mice and humans. Indeed, pharmacological inhibitors of PPARgamma/RXR ameliorates high-fat diet-induced insulin resistance in animal models of type 2 diabetes.

摘要

我们研究了过氧化物酶体增殖物激活受体γ（PPARγ）及其相关基因在2型糖尿病发病机制中的作用。杂合子PPARγ缺陷小鼠在高脂饮食下因脂肪细胞肥大而免受胰岛素抵抗的发展，其表型通过PPARγ激动剂治疗而消除。此外，据报道人类PPARγ2基因中的Pro12Ala多态性会导致PPARγ活性降低，在日本人中与2型糖尿病风险降低相关。通过对不同种族群体报告的荟萃分析证实了这种多态性对2型糖尿病的保护作用。综合这些结果，PPARγ是一种在小鼠和人类中介导2型糖尿病的节俭基因。实际上，PPARγ/RXR的药理抑制剂可改善2型糖尿病动物模型中高脂饮食诱导的胰岛素抵抗。