An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma).
J Biol Chem
; 270(22): 12953-6, 1995 Jun 02.
Article
in En
| MEDLINE
| ID: mdl-7768881
ABSTRACT
Thiazolidinedione derivatives are antidiabetic agents that increase the insulin sensitivity of target tissues in animal models of non-insulin-dependent diabetes mellitus. In vitro, thiazolidinediones promote adipocyte differentiation of preadipocyte and mesenchymal stem cell lines; however, the molecular basis for this adipogenic effect has remained unclear. Here, we report that thiazolidinediones are potent and selective activators of peroxisome proliferator-activated receptor gamma (PPAR gamma), a member of the nuclear receptor superfamily recently shown to function in adipogenesis. The most potent of these agents, BRL49653, binds to PPAR gamma with a Kd of approximately 40 nM. Treatment of pluripotent C3H10T1/2 stem cells with BRL49653 results in efficient differentiation to adipocytes. These data are the first demonstration of a high affinity PPAR ligand and provide strong evidence that PPAR gamma is a molecular target for the adipogenic effects of thiazolidinediones. Furthermore, these data raise the intriguing possibility that PPAR gamma is a target for the therapeutic actions of this class of compounds.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Thiazoles
/
Transcription Factors
/
Receptors, Cytoplasmic and Nuclear
/
Thiazolidinediones
/
Hypoglycemic Agents
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
1995
Document type:
Article
Affiliation country:
United States