MolPharm xPharm- The Comprehensive Pharmacology Reference

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Molecular Pharmacology Fast Forward
First published on March 2, 2007; DOI: 10.1124/mol.106.031948

0026-895X/07/7106-1554-1562$20.00
Mol Pharmacol 71:1554-1562, 2007

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
mol.106.031948v1
71/6/1554    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, K. Y.
Right arrow Articles by Cheon, H. G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, K. Y.
Right arrow Articles by Cheon, H. G.

Phosphatase and Tensin Homolog Deleted on Chromosome 10 Suppression Is an Important Process in Peroxisome Proliferator-Activated Receptor-{gamma} Signaling in Adipocytes and Myotubes

Ki Young Kim, Hyun Sill Cho, Won Hoon Jung, Sung Soo Kim, and Hyae Gyeong Cheon

Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Daejeon, Korea

Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) activation enhances insulin sensitivity in type 2 diabetes mellitus. However, downstream mediators of PPAR{gamma} activation in adipocytes and myotubes, the most important cell types involved in glucose homeostasis, remained unclear. Here we show by using two synthetic PPAR{gamma} agonists (rosiglitazone and KR-62776, a novel PPAR{gamma} agonist) that phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a key downstream mediator of PPAR{gamma} signaling. The PPAR{gamma} agonists down-regulated PTEN expression, resulting in glucose uptake increase in differentiated 3T3-L1 adipocytes and C2C12 skeletal muscle cells. In both cells, PTEN knockdown increased glucose uptake, whereas overexpression abolished the agonist-induced effects. The effects of PPAR{gamma} agonists on PTEN expression and glucose uptake disappeared by pretreatment with a PPAR{gamma} antagonist or by knockdown of PPAR{gamma} expression. In vivo treatment of the agonists to C57BL/6J-ob/ob mice resulted in the reduction of PTEN level in both adipose and skeletal muscle tissues and decreased plasma glucose levels. Thus, these results suggest that PTEN suppression is a key mechanism of the PPAR{gamma}-mediated glucose uptake stimulation in insulin-sensitive cells such as adipocytes and skeletal muscle cells, thereby restoring glucose homeostasis in type 2 diabetes.

Received October 19, 2006; accepted March 2, 2007

Address correspondence to: Dr. Hyae Gyeong Cheon, Bio-Organic Science Division, Korea Research Institute of Chemical Technology, Jang-dong 100, Yuseong-gu, Daejeon 305-600, Korea. E-mail: hgcheon{at}krict.re.kr




This article has been cited by other articles:


Home page
 Genes Dev.Home page
A. Lahoz and A. Hall
DLC1: a significant GAP in the cancer genome
Genes & Dev., July 1, 2008; 22(13): 1724 - 1730.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2007 by the American Society for Pharmacology and Experimental Therapeutics