| 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. |
| Authors | Kazuo Hara, Toshimasa Yamauchi, Naoto Kubota, Kazuyuki Tobe, Tsutomu Yamazaki, Ryozo Nagai, Takashi Kadowaki
(Affiliation: Department of Clinical Bioinformatics, Graduate School of Medicine, University of Tokyo, Japan.)
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| Journal | Nippon yakurigaku zasshi. Folia pharmacologica Japonica
(Nippon Yakurigaku Zasshi)
Vol. 122
Issue 4
Pg. 317-24
(Oct 2003)
ISSN: 0015-5691 Japan |
| PMID | 14501167
(Publication Type: English Abstract, Journal Article, Review)
|
| Chemical References |
- Receptors, Cytoplasmic and Nuclear
- Transcription Factors
|
| Topics |
- Animals
- Diabetes Mellitus, Type 2
(genetics)
- Humans
- Insulin Resistance
(genetics)
- Mice
- Polymorphism, Genetic
- Receptors, Cytoplasmic and Nuclear
(genetics, physiology)
- Transcription Factors
(genetics, physiology)
|
