A new retinoid-like compound that activates peroxisome proliferator- activated receptors and lowers blood glucose in diabetic mice

Tuo Deng, Song Shan, Zhi Bin Li, Zhong Wen Wu, Chen Zhong Liao, Ben Ko, Xian Ping Lu, Jing Cheng, Zhi Qiang Ning

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1192-1196
Number of pages5
JournalBiological and Pharmaceutical Bulletin
Volume28
Issue number7
DOIs
StatePublished - Jul 2005

Keywords

  • Peroxisome proliferator-activated receptor
  • Retinoid X receptor
  • Synthetic compound
  • Type 2 diabetes

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology, Toxicology and Pharmaceutics(all)

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