A New Retinoid-Like Compound That Activates Peroxisome Proliferator-Activated Receptors and Lowers Blood Glucose in Diabetic Mice

Retinoid X receptor (RXR) forms heterodimers with peroxisome proliferator-activated receptors (PPARs, with subtypes of α, δ and γ), and the heterodimers can be activated by either an RXR or a PPAR subtype-specific ligand. Based on the chemical structure of the RXR natural ligand, 9-cis-retinoic acid...

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Published in:Biological & Pharmaceutical Bulletin 2005, Vol.28 (7), p.1192-1196
Main Authors: Tuo DWNGa, b, Song SHANb, Zhi-Bin LIb, Zhong-Wen WUb, Chen-Zhong LIAOb, Ben KOc, Xian-Ping LUb, Jing CHENGa, Zhi-Qiang NINGb
Format: Article
Language:Japanese
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Summary:Retinoid X receptor (RXR) forms heterodimers with peroxisome proliferator-activated receptors (PPARs, with subtypes of α, δ and γ), and the heterodimers can be activated by either an RXR or a PPAR subtype-specific ligand. Based on the chemical structure of the RXR natural ligand, 9-cis-retinoic acid (9-cis-RA), we designed and synthesized a retinoid-like compound, CS018. In vitro characterizations by cell-based reporter gene assays indicated that CS018 activated RXR homodimers and the heterodimers of RXR with PPARs, but not with farnesoid X-activated receptor (FXR) and liver X-activated receptor (LXR). Furthermore, RT-PCR results showed that CS018 induced the expression of the PPARγ target genes, CD36 and lipoprotein lipase (LPL). In vivo studies on the diabetic db/db mice demonstrated that CS018 dramatically lowered the animal blood glucose levels. CS018 thus may represent a new retinoid-like compound that activates RXR/PPARs and has potential therapeutic applications in type 2 diabetes and other metabolic diseases.
ISSN:0918-6158