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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), pp.1192-1196
Main Authors: Deng, Tuo, Shan, Song, Li, Zhi-Bin, Wu, Zhong-Wen, Liao, Chen-Zhong, Ko, Ben, Lu, Xian-Ping, Cheng, Jing, Ning, Zhi-Qiang
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cited_by cdi_FETCH-LOGICAL-c499t-47de8c156bbfbf66bed2c10e6299876839178d7c00e41f9c792611d510968ff3
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container_title Biological & pharmaceutical bulletin
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creator Deng, Tuo
Shan, Song
Li, Zhi-Bin
Wu, Zhong-Wen
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Ko, Ben
Lu, Xian-Ping
Cheng, Jing
Ning, Zhi-Qiang
description 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.
doi_str_mv 10.1248/bpb.28.1192
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source Full-Text Journals in Chemistry (Open access)
subjects Alkenes - pharmacology
Animals
Base Sequence
Blood Glucose - analysis
Diabetes Mellitus, Experimental - blood
Dimerization
DNA Primers
Mice
Naphthalenes - pharmacology
peroxisome proliferator-activated receptor
Peroxisome Proliferator-Activated Receptors - agonists
retinoid X receptor
Retinoids - pharmacology
Reverse Transcriptase Polymerase Chain Reaction
synthetic compound
type 2 diabetes
title A New Retinoid-Like Compound That Activates Peroxisome Proliferator-Activated Receptors and Lowers Blood Glucose in Diabetic Mice
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