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

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
• Journal: Nihon yakurigaku zasshi. Folia pharmacologica Japonica (Nihon Yakurigaku Zasshi) Vol. 122 Issue 4 Pg. 317-24 (Oct 2003) ISSN: 0015-5691 [Print] 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)