Association of the polymorphisms in the 5′‐untranslated region of PTEN gene with type 2 diabetes in a Japanese population

FEBS Letters

Murakami, Shihou³  Fukui, Kazuhito³  Ishihara, Hajime²  Sato, Akira³  Tsuneki, Hiroshi¹  Wada, Tsutomu³  Yamazaki, Katsuya³  Kagawa, Syota¹  Kobayashi, Masashi³  Yaguchi, Saori¹  Kimura, Ikuko¹  Sasaoka, Toshiyasu¹  Urakaze, Masaharu³  Ishiki, Manabu³  Kawagishi, Yukio³  Iwata, Minoru³ 

[1] The Department of Clinical Pharmacology, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan;Sainou Hospital, Toyama 930-0887, Japan;First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan

关键词: Phosphatase and tensin homolog deleted on chromosome 10;    Phosphatidylinositol 3-kinase;    Akt;    Type 2 diabetes;    Polymorphism;   

DOI  :  10.1016/S0014-5793(03)01225-0

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is known to act as a lipid phosphatase hydrolyzing phosphatidylinositol (PI)(3,4,5)P₃ to PI(4,5)P₂. Since the PI3-kinase product, PI(3,4,5)P₃, is an important second messenger leading to the metabolic action of insulin, PTEN functions as a potent negative regulator of insulin signaling and its gene is one of the possible candidates involved in susceptibility to the development of type 2 (non-insulin-dependent) diabetes. In the present study, we investigated the polymorphisms of the PTEN gene in Japanese patients with type 2 diabetes and non-diabetic control subjects. We identified three mutations of the gene in the type 2 diabetes patients. Among these mutations, the frequency of the substitution of C with G at position −9 (−9C→G) (SNP1), located in the untranslated region of exon 1, was significantly higher in type 2 diabetic patients than in control subjects. In addition, transfection of the PTEN gene with SNP1 resulted in a significantly higher expression level of PTEN protein compared with that of the wild-type PTEN gene in Cos1 and Rat1 cells. Furthermore, insulin-induced phosphorylation of Akt in HIRc cells was decreased more greatly by transfection of SNP1 PTEN gene than that of wild-type PTEN gene. These findings suggest that the change of C to G at position −9 of the PTEN gene is associated with the insulin resistance of type 2 diabetes due possibly to a potentiated hydrolysis of the PI3-kinase product.

【 授权许可】

Unknown