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First published on March 2, 2007; DOI: 10.1124/mol.106.031948

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Received for publication October 19, 2006.
Revised January 30, 2007.
Accepted for publication March 2, 2007.

PTEN suppression is an important process in PPAR{gamma} signaling in adipocytes and myotubes

Ki Young Kim 1, Hyun Sill Cho 1, Won Hoon Jung 1, Sung Soo Kim 1, Hyae Gyeong Cheon 1*

1 Korea Research Institute of Chemical Technology

* Address correspondence to: E-mail: hgcheon{at}krict.re.kr

Abstract

Peroxisome proliferator-activated receptor-{gamma} (PPAR{gamma}) activation enhances insulin sensitivity in type 2 diabetes mellitus. However, downstream mediators of PPAR{gamma} effects 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 PTEN is a key downstream mediator of PPAR{gamma} signaling. The PPAR{gamma} agonists downregulated PTEN expression resulting in glucose uptake increase in differentiated 3T3-L1 adipocytes and C2C12 skeletal muscle cells. In the cells, PTEN knockdown increased glucose uptake, whereas overexpression abolished the agonists-induced effects. The effects of PPAR{gamma} agonists on PTEN expression and glucose uptake disappeared by pretreatment with a PPAR{gamma} antagonist. In vivo treatment of the agonists to ob/ob mice resulted in the reduction of PTEN level in both adipose and skeletal muscle tissues, along with 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.


Key words: PPARs, Protein Phosphatases (other), RNA/siRNA


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