Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation
Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2011-11, Vol.108 (48), p.19264-19269 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Rovira, Meritxell Huang, Wei Yusuff, Shamila Shim, Joong Sup Ferrante, Anthony A Liu, Jun O Parsons, Michael J |
| description | Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis. |
| doi_str_mv | 10.1073/pnas.1113081108 |
| format | Article |
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We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.1113081108</identifier><identifier>PMID: 22084084</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Acetanilides - pharmacology ; Animals ; Animals, Genetically Modified ; autoimmunity ; Biological Sciences ; Biosynthesis ; Caffeic Acids - pharmacology ; Cell Differentiation - drug effects ; Cell Line, Tumor ; Cell lines ; Cell Proliferation ; Cells ; Cellular differentiation ; Danio rerio ; Diabetes ; Dimethyl Sulfoxide ; DNA Primers - genetics ; Dose-Response Relationship, Drug ; Drug Discovery - methods ; drugs ; Endocrine cells ; Epirizole - pharmacology ; Exocrine cells ; FDA approval ; fish ; Fluorescent Antibody Technique ; Green Fluorescent Proteins ; guanosine triphosphate ; Guanosine Triphosphate - biosynthesis ; HMGB1 Protein - metabolism ; Insulin ; insulin-dependent diabetes mellitus ; Insulin-Secreting Cells - cytology ; Insulin-Secreting Cells - drug effects ; islets of Langerhans ; Larva - drug effects ; Larvae ; Larval development ; mechanism of action ; Microscopy, Confocal ; Mycophenolic Acid - pharmacology ; p-Aminoazobenzene - analogs & derivatives ; p-Aminoazobenzene - pharmacology ; Pancreas ; Pharmaceutical Preparations - metabolism ; Progenitor cells ; Real-Time Polymerase Chain Reaction ; retinoic acid ; Sulfanilic Acids - pharmacology ; swimming ; Tretinoin - metabolism ; Type 1 diabetes mellitus ; Zebrafish</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2011-11, Vol.108 (48), p.19264-19269</ispartof><rights>copyright © 1993—2008 National Academy of Sciences of the United States of America</rights><rights>Copyright National Academy of Sciences Nov 29, 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c490t-230b555179736015a260bf19f32c397753cdf2f7b6ee00b48480901ef7475f1e3</citedby><cites>FETCH-LOGICAL-c490t-230b555179736015a260bf19f32c397753cdf2f7b6ee00b48480901ef7475f1e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/108/48.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/23066752$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/23066752$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,727,780,784,803,885,27924,27925,53791,53793,58017,58250</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22084084$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rovira, Meritxell</creatorcontrib><creatorcontrib>Huang, Wei</creatorcontrib><creatorcontrib>Yusuff, Shamila</creatorcontrib><creatorcontrib>Shim, Joong Sup</creatorcontrib><creatorcontrib>Ferrante, Anthony A</creatorcontrib><creatorcontrib>Liu, Jun O</creatorcontrib><creatorcontrib>Parsons, Michael J</creatorcontrib><title>Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.</description><subject>Acetanilides - pharmacology</subject><subject>Animals</subject><subject>Animals, Genetically Modified</subject><subject>autoimmunity</subject><subject>Biological Sciences</subject><subject>Biosynthesis</subject><subject>Caffeic Acids - pharmacology</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Cell Proliferation</subject><subject>Cells</subject><subject>Cellular differentiation</subject><subject>Danio rerio</subject><subject>Diabetes</subject><subject>Dimethyl Sulfoxide</subject><subject>DNA Primers - genetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Discovery - methods</subject><subject>drugs</subject><subject>Endocrine cells</subject><subject>Epirizole - pharmacology</subject><subject>Exocrine cells</subject><subject>FDA approval</subject><subject>fish</subject><subject>Fluorescent Antibody Technique</subject><subject>Green Fluorescent Proteins</subject><subject>guanosine triphosphate</subject><subject>Guanosine Triphosphate - biosynthesis</subject><subject>HMGB1 Protein - metabolism</subject><subject>Insulin</subject><subject>insulin-dependent diabetes mellitus</subject><subject>Insulin-Secreting Cells - cytology</subject><subject>Insulin-Secreting Cells - drug effects</subject><subject>islets of Langerhans</subject><subject>Larva - drug effects</subject><subject>Larvae</subject><subject>Larval development</subject><subject>mechanism of action</subject><subject>Microscopy, Confocal</subject><subject>Mycophenolic Acid - pharmacology</subject><subject>p-Aminoazobenzene - analogs & derivatives</subject><subject>p-Aminoazobenzene - pharmacology</subject><subject>Pancreas</subject><subject>Pharmaceutical Preparations - metabolism</subject><subject>Progenitor cells</subject><subject>Real-Time Polymerase Chain Reaction</subject><subject>retinoic acid</subject><subject>Sulfanilic Acids - pharmacology</subject><subject>swimming</subject><subject>Tretinoin - metabolism</subject><subject>Type 1 diabetes mellitus</subject><subject>Zebrafish</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkc1vEzEUxC0EomnhzAmwuG_7_LFr-4JUBQpIlThAz5bjtRNHib3Yu0U98L_jVdIGJEs-zO_NG3sQekPgkoBgV0M05ZIQwkASAvIZWhBQpOm4gudoAUBFIznlZ-i8lC0AqFbCS3RGKUhezwL9WW7cPlizw8Vm5yIOvYtj8MEVfPPpujHDkNO963Gfp3XBJvZ4NHntRjyYcfPbPBQ8bsyIQ-wn6_CQnU02pKlUPVZHMwaLXeyTzSE63AfvXZ43VCHFV-iFN7viXh_vC3R38_nn8mtz-_3Lt-X1bWPrQ8aGMli1bUuEEqwD0hrawcoT5Rm1TAnRMtt76sWqcw5gxSWXoIA4L7hoPXHsAn08-A7Tau96WwNks9NDDnuTH3QyQf-vxLDR63SvGaWSM14NPhwNcvo1uTLqbZpyrJm1AlG_EyRU6OoA2ZxKyc4_LSCg57r0XJc-1VUn3v2b64l_7KcC-AjMkyc7qbnURNFuRt4ekG0ZUz5ZMOg60dKqvz_o3iRt1jkUffeDAuEARHZKEvYXb5KwlQ</recordid><startdate>20111129</startdate><enddate>20111129</enddate><creator>Rovira, Meritxell</creator><creator>Huang, Wei</creator><creator>Yusuff, Shamila</creator><creator>Shim, Joong Sup</creator><creator>Ferrante, Anthony A</creator><creator>Liu, Jun O</creator><creator>Parsons, Michael J</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><scope>FBQ</scope><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>7QG</scope><scope>7QL</scope><scope>7QP</scope><scope>7QR</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TK</scope><scope>7TM</scope><scope>7TO</scope><scope>7U9</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>H94</scope><scope>M7N</scope><scope>P64</scope><scope>RC3</scope><scope>5PM</scope></search><sort><creationdate>20111129</creationdate><title>Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation</title><author>Rovira, Meritxell ; Huang, Wei ; Yusuff, Shamila ; Shim, Joong Sup ; Ferrante, Anthony A ; Liu, Jun O ; Parsons, Michael J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c490t-230b555179736015a260bf19f32c397753cdf2f7b6ee00b48480901ef7475f1e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Acetanilides - pharmacology</topic><topic>Animals</topic><topic>Animals, Genetically Modified</topic><topic>autoimmunity</topic><topic>Biological Sciences</topic><topic>Biosynthesis</topic><topic>Caffeic Acids - pharmacology</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell lines</topic><topic>Cell Proliferation</topic><topic>Cells</topic><topic>Cellular differentiation</topic><topic>Danio rerio</topic><topic>Diabetes</topic><topic>Dimethyl Sulfoxide</topic><topic>DNA Primers - genetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Discovery - methods</topic><topic>drugs</topic><topic>Endocrine cells</topic><topic>Epirizole - pharmacology</topic><topic>Exocrine cells</topic><topic>FDA approval</topic><topic>fish</topic><topic>Fluorescent Antibody Technique</topic><topic>Green Fluorescent Proteins</topic><topic>guanosine triphosphate</topic><topic>Guanosine Triphosphate - biosynthesis</topic><topic>HMGB1 Protein - metabolism</topic><topic>Insulin</topic><topic>insulin-dependent diabetes mellitus</topic><topic>Insulin-Secreting Cells - cytology</topic><topic>Insulin-Secreting Cells - drug effects</topic><topic>islets of Langerhans</topic><topic>Larva - drug effects</topic><topic>Larvae</topic><topic>Larval development</topic><topic>mechanism of action</topic><topic>Microscopy, Confocal</topic><topic>Mycophenolic Acid - pharmacology</topic><topic>p-Aminoazobenzene - analogs & derivatives</topic><topic>p-Aminoazobenzene - pharmacology</topic><topic>Pancreas</topic><topic>Pharmaceutical Preparations - metabolism</topic><topic>Progenitor cells</topic><topic>Real-Time Polymerase Chain Reaction</topic><topic>retinoic acid</topic><topic>Sulfanilic Acids - pharmacology</topic><topic>swimming</topic><topic>Tretinoin - metabolism</topic><topic>Type 1 diabetes mellitus</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rovira, Meritxell</creatorcontrib><creatorcontrib>Huang, Wei</creatorcontrib><creatorcontrib>Yusuff, Shamila</creatorcontrib><creatorcontrib>Shim, Joong Sup</creatorcontrib><creatorcontrib>Ferrante, Anthony A</creatorcontrib><creatorcontrib>Liu, Jun O</creatorcontrib><creatorcontrib>Parsons, Michael J</creatorcontrib><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Chemoreception Abstracts</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rovira, Meritxell</au><au>Huang, Wei</au><au>Yusuff, Shamila</au><au>Shim, Joong Sup</au><au>Ferrante, Anthony A</au><au>Liu, Jun O</au><au>Parsons, Michael J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2011-11-29</date><risdate>2011</risdate><volume>108</volume><issue>48</issue><spage>19264</spage><epage>19269</epage><pages>19264-19269</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>Pancreatic β-cells are an essential source of insulin and their destruction because of autoimmunity causes type I diabetes. We conducted a chemical screen to identify compounds that would induce the differentiation of insulin-producing β-cells in vivo. To do this screen, we brought together the use of transgenic zebrafish as a model of β-cell differentiation, a unique multiwell plate that allows easy visualization of lateral views of swimming larval fish and a library of clinical drugs. We identified six hits that can induce precocious differentiation of secondary islets in larval zebrafish. Three of these six hits were known drugs with a considerable background of published data on mechanism of action. Using pharmacological approaches, we have identified and characterized two unique pathways in β-cell differentiation in the zebrafish, including down-regulation of GTP production and retinoic acid biosynthesis.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>22084084</pmid><doi>10.1073/pnas.1113081108</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Acetanilides - pharmacology Animals Animals, Genetically Modified autoimmunity Biological Sciences Biosynthesis Caffeic Acids - pharmacology Cell Differentiation - drug effects Cell Line, Tumor Cell lines Cell Proliferation Cells Cellular differentiation Danio rerio Diabetes Dimethyl Sulfoxide DNA Primers - genetics Dose-Response Relationship, Drug Drug Discovery - methods drugs Endocrine cells Epirizole - pharmacology Exocrine cells FDA approval fish Fluorescent Antibody Technique Green Fluorescent Proteins guanosine triphosphate Guanosine Triphosphate - biosynthesis HMGB1 Protein - metabolism Insulin insulin-dependent diabetes mellitus Insulin-Secreting Cells - cytology Insulin-Secreting Cells - drug effects islets of Langerhans Larva - drug effects Larvae Larval development mechanism of action Microscopy, Confocal Mycophenolic Acid - pharmacology p-Aminoazobenzene - analogs & derivatives p-Aminoazobenzene - pharmacology Pancreas Pharmaceutical Preparations - metabolism Progenitor cells Real-Time Polymerase Chain Reaction retinoic acid Sulfanilic Acids - pharmacology swimming Tretinoin - metabolism Type 1 diabetes mellitus Zebrafish |
| title | Chemical screen identifies FDA-approved drugs and target pathways that induce precocious pancreatic endocrine differentiation |
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