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Choi, Jang Hyun
Lab of Diabetes and Metabolism (LDM)
Research Interests
  • Diabetes, Metabolic Disorders, PPARg, Gene Regulation, Anti-Diabetic Drug

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Antidiabetic actions of a non-agonist PPAR gamma ligand blocking Cdk5-mediated phosphorylation

Cited 137 times inthomson ciCited 130 times inthomson ci
Title
Antidiabetic actions of a non-agonist PPAR gamma ligand blocking Cdk5-mediated phosphorylation
Author
Choi, Jang HyunBanks, Alexander S.Kamenecka, Theodore M.Busby, Scott A.Chalmers, Michael J.Kumar, NareshKuruvilla, Dana S.Shin, YouseungHe, YuanjunBruning, John B.Marciano, David P.Cameron, Michael D.Laznik, DinaJurczak, Michael J.Schuerer, Stephan C.Vidovic, DusicaShulman, Gerald I.Spiegelman, Bruce M.Griffin, Patrick R.
Issue Date
2011-09
Publisher
NATURE PUBLISHING GROUP
Citation
NATURE, v.477, no.7365, pp.477 - 481
Abstract
PPAR gamma is the functioning receptor for the thiazolidinedione (TZD) class of antidiabetes drugs including rosiglitazone and pioglitazone(1). These drugs are full classical agonists for this nuclear receptor, but recent data have shown that many PPAR gamma-based drugs have a separate biochemical activity, blocking the obesity-linked phosphorylation of PPAR gamma by Cdk5 (ref. 2). Here we describe novel synthetic compounds that have a unique mode of binding to PPAR gamma, completely lack classical transcriptional agonism and block the Cdk5-mediated phosphorylation in cultured adipocytes and in insulin-resistant mice. Moreover, one such compound, SR1664, has potent antidiabetic activity while not causing the fluid retention and weight gain that are serious side effects of many of the PPAR gamma drugs. Unlike TZDs, SR1664 also does not interfere with bone formation in culture. These data illustrate that new classes of antidiabetes drugs can be developed by specifically targeting the Cdk5-mediated phosphorylation of PPAR gamma.
URI
https://scholarworks.unist.ac.kr/handle/201301/7222
URL
http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80053131732
DOI
10.1038/nature10383
ISSN
0028-0836
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