Molecular basis of selective PPARgamma modulation for the treatment of Type 2 diabetes.

Details

Serval ID
serval:BIB_9B36E01D61D4
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Molecular basis of selective PPARgamma modulation for the treatment of Type 2 diabetes.
Journal
Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids
Author(s)
Gelman L., Feige J.N., Desvergne B.
ISSN
1388-1981
ISSN-L
1879-2618
Publication state
Published
Issued date
2007
Peer-reviewed
Oui
Volume
1771
Number
8
Pages
1094-1107
Language
english
Abstract
Peroxisome proliferator-activated receptors (PPARs) (alpha, beta/delta and gamma) are lipid sensors capable of adapting gene expression to integrate various lipid signals. As such, PPARs are also very important pharmaceutical targets, and specific synthetic ligands exist for the different isotypes and are either currently used or hold promises in the treatment of major metabolic disorders. In particular, compounds of the class of the thiazolinediones (TZDs) are PPARgamma agonists and potent insulin-sensitizers. The specific but still broad expression patterns of PPARgamma, as well as its implication in numerous pathways, constitutes also a disadvantage regarding drug administration, since this potentially increases the chance to generate side-effects through the activation of the receptor in tissues or cells not affected by the disease. Actually, numerous side effects associated with the administration of TZDs have been reported. Today, a new generation of PPARgamma modulators is being actively developed to activate the receptor more specifically, in a cell and time-dependent manner, in order to induce a specific subset of target genes only and modulate a restricted number of metabolic pathways. We will discuss here why and how the development of such selective PPARgamma modulators is possible, and summarize the results obtained with the published molecules.
Keywords
Diabetes Mellitus, Type 2/drug therapy, Drug Design, Humans, Hypoglycemic Agents/therapeutic use, PPAR gamma/agonists, PPAR gamma/drug effects, Thiazolidinediones/therapeutic use
Pubmed
Web of science
Create date
24/01/2008 15:26
Last modification date
20/08/2019 15:02
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