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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 |
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creator | Deng, Tuo Shan, Song Li, Zhi-Bin Wu, Zhong-Wen Liao, Chen-Zhong 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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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.</description><identifier>ISSN: 0918-6158</identifier><identifier>EISSN: 1347-5215</identifier><identifier>DOI: 10.1248/bpb.28.1192</identifier><identifier>PMID: 15997096</identifier><language>eng</language><publisher>Japan: The Pharmaceutical Society of Japan</publisher><subject>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</subject><ispartof>Biological and Pharmaceutical Bulletin, 2005, Vol.28(7), pp.1192-1196</ispartof><rights>2005 The Pharmaceutical Society of Japan</rights><rights>Copyright Japan Science and Technology Agency 2005</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c499t-47de8c156bbfbf66bed2c10e6299876839178d7c00e41f9c792611d510968ff3</citedby><cites>FETCH-LOGICAL-c499t-47de8c156bbfbf66bed2c10e6299876839178d7c00e41f9c792611d510968ff3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15997096$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Deng, Tuo</creatorcontrib><creatorcontrib>Shan, Song</creatorcontrib><creatorcontrib>Li, Zhi-Bin</creatorcontrib><creatorcontrib>Wu, Zhong-Wen</creatorcontrib><creatorcontrib>Liao, Chen-Zhong</creatorcontrib><creatorcontrib>Ko, Ben</creatorcontrib><creatorcontrib>Lu, Xian-Ping</creatorcontrib><creatorcontrib>Cheng, Jing</creatorcontrib><creatorcontrib>Ning, Zhi-Qiang</creatorcontrib><title>A New Retinoid-Like Compound That Activates Peroxisome Proliferator-Activated Receptors and Lowers Blood Glucose in Diabetic Mice</title><title>Biological & pharmaceutical bulletin</title><addtitle>Biol Pharm Bull</addtitle><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. 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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.</description><subject>Alkenes - pharmacology</subject><subject>Animals</subject><subject>Base Sequence</subject><subject>Blood Glucose - analysis</subject><subject>Diabetes Mellitus, Experimental - blood</subject><subject>Dimerization</subject><subject>DNA Primers</subject><subject>Mice</subject><subject>Naphthalenes - pharmacology</subject><subject>peroxisome proliferator-activated receptor</subject><subject>Peroxisome Proliferator-Activated Receptors - agonists</subject><subject>retinoid X receptor</subject><subject>Retinoids - pharmacology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>synthetic compound</subject><subject>type 2 diabetes</subject><issn>0918-6158</issn><issn>1347-5215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNpdkUtv1DAURi1ERaeFFXtkCYkNyuCbhx87hgFKpQEqNHvLcW6ohyQOdkLLsv-8Hs20SGxsyz4-vtcfIS-BLSEv5bt6rJe5XAKo_AlZQFGKrMqhekoWTIHMOFTylJzFuGOMCZYXz8gpVEoJpviC3K3oN7yhP3Byg3dNtnG_kK59P_p5aOj22kx0ZSf3x0wY6RUGf-ui75FeBd-5FoOZfMgeiCZ5LI5pK1KTrm_8Dablh877hl50s_URqRvoR2fq9KClX53F5-SkNV3EF8f5nGw_f9quv2Sb7xeX69Ums6VSU1aKBqWFitd1W7ec19jkFhjyXCkpuCwUCNkIyxiW0CorVM4BmgpSm7Jti3Py5qAdg_89Y5x076LFrjMD-jlqLhkDJVQCX_8H7vwchlSahrJURcmZkol6e6Bs8DEGbPUYXG_CXw1M72PRKRadS72PJdGvjs657rH5xx5zSMD7A7CLk_mJj4AJ6Zs6fJCJw7B3Ph7ZaxM0DsU9baqfvA</recordid><startdate>20050701</startdate><enddate>20050701</enddate><creator>Deng, Tuo</creator><creator>Shan, Song</creator><creator>Li, Zhi-Bin</creator><creator>Wu, Zhong-Wen</creator><creator>Liao, Chen-Zhong</creator><creator>Ko, Ben</creator><creator>Lu, Xian-Ping</creator><creator>Cheng, Jing</creator><creator>Ning, Zhi-Qiang</creator><general>The Pharmaceutical Society of Japan</general><general>Japan Science and Technology Agency</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7QR</scope><scope>7TK</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20050701</creationdate><title>A New Retinoid-Like Compound That Activates Peroxisome Proliferator-Activated Receptors and Lowers Blood Glucose in Diabetic Mice</title><author>Deng, Tuo ; Shan, Song ; Li, Zhi-Bin ; Wu, Zhong-Wen ; Liao, Chen-Zhong ; Ko, Ben ; Lu, Xian-Ping ; Cheng, Jing ; Ning, Zhi-Qiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c499t-47de8c156bbfbf66bed2c10e6299876839178d7c00e41f9c792611d510968ff3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Alkenes - pharmacology</topic><topic>Animals</topic><topic>Base Sequence</topic><topic>Blood Glucose - analysis</topic><topic>Diabetes Mellitus, Experimental - blood</topic><topic>Dimerization</topic><topic>DNA Primers</topic><topic>Mice</topic><topic>Naphthalenes - pharmacology</topic><topic>peroxisome proliferator-activated receptor</topic><topic>Peroxisome Proliferator-Activated Receptors - agonists</topic><topic>retinoid X receptor</topic><topic>Retinoids - pharmacology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>synthetic compound</topic><topic>type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Deng, Tuo</creatorcontrib><creatorcontrib>Shan, Song</creatorcontrib><creatorcontrib>Li, Zhi-Bin</creatorcontrib><creatorcontrib>Wu, Zhong-Wen</creatorcontrib><creatorcontrib>Liao, Chen-Zhong</creatorcontrib><creatorcontrib>Ko, Ben</creatorcontrib><creatorcontrib>Lu, Xian-Ping</creatorcontrib><creatorcontrib>Cheng, Jing</creatorcontrib><creatorcontrib>Ning, Zhi-Qiang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Biological & pharmaceutical bulletin</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Deng, Tuo</au><au>Shan, Song</au><au>Li, Zhi-Bin</au><au>Wu, Zhong-Wen</au><au>Liao, Chen-Zhong</au><au>Ko, Ben</au><au>Lu, Xian-Ping</au><au>Cheng, Jing</au><au>Ning, Zhi-Qiang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A New Retinoid-Like Compound That Activates Peroxisome Proliferator-Activated Receptors and Lowers Blood Glucose in Diabetic Mice</atitle><jtitle>Biological & pharmaceutical bulletin</jtitle><addtitle>Biol Pharm Bull</addtitle><date>2005-07-01</date><risdate>2005</risdate><volume>28</volume><issue>7</issue><spage>1192</spage><epage>1196</epage><pages>1192-1196</pages><issn>0918-6158</issn><eissn>1347-5215</eissn><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.</abstract><cop>Japan</cop><pub>The Pharmaceutical Society of Japan</pub><pmid>15997096</pmid><doi>10.1248/bpb.28.1192</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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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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