MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity
Identifieur interne : 005316 ( Main/Exploration ); précédent : 005315; suivant : 005317MicroRNAs contribute to compensatory β cell expansion during pregnancy and obesity
Auteurs : Cécile Jacovetti [Suisse] ; Amar Abderrahmani [France] ; Géraldine Parnaud [Suisse] ; Jean-Christophe Jonas [Belgique] ; Marie-Line Peyot [Canada] ; Marion Cornu [Suisse] ; Ross Laybutt [Australie] ; Emmanuelle Meugnier [France] ; Sophie Rome [France] ; Bernard Thorens [Suisse] ; Marc Prentki [Canada] ; Domenico Bosco [Suisse] ; Romano Regazzi [Suisse]Source :
- The Journal of Clinical Investigation [ 0021-9738 ] ; 2012.
Abstract
Pregnancy and obesity are frequently associated with diminished insulin sensitivity, which is normally compensated for by an expansion of the functional β cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory β cell mass expansion is largely unknown. We found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein–coupled estrogen receptor GPR30 and the glucagon-like peptide 1 (GLP1) receptor. Blockade of miR-338-3p in β cells using specific anti-miR molecules mimicked gene expression changes occurring during β cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory β cell mass expansion occurring under different insulin resistance states.
Url:
DOI: 10.1172/JCI64151
PubMed: 22996663
PubMed Central: 3461923
Affiliations:
- Australie, Belgique, Canada, France, Suisse
- Canton de Vaud, Hauts-de-France, Nord-Pas-de-Calais, Région de Bruxelles-Capitale
- Bruxelles, Lausanne, Lille, Louvain-la-Neuve
- Université catholique de Louvain
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Le document en format XML
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last="Parnaud">Géraldine Parnaud</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Jonas, Jean Christophe" sort="Jonas, Jean Christophe" uniqKey="Jonas J" first="Jean-Christophe" last="Jonas">Jean-Christophe Jonas</name><affiliation wicri:level="4"><nlm:aff id="JCI64151">Université catholique de Louvain, Institut de recherche expérimentale et clinique, Pôle d’endocrinologie, diabète et nutrition, Brussels, Belgium.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Belgique</country><wicri:regionArea>Université catholique de Louvain, Institut de recherche expérimentale et clinique, Pôle d’endocrinologie, diabète et nutrition, Brussels</wicri:regionArea><placeName><settlement type="city">Bruxelles</settlement><region nuts="2">Région de Bruxelles-Capitale</region><settlement type="city">Louvain-la-Neuve</settlement></placeName><orgName type="university">Université catholique de Louvain</orgName></affiliation></author><author><name sortKey="Peyot, Marie Line" sort="Peyot, Marie Line" uniqKey="Peyot M" first="Marie-Line" last="Peyot">Marie-Line Peyot</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Montreal Diabetes Research Center and CRCHUM, Montreal, Quebec, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Montreal Diabetes Research Center and CRCHUM, Montreal, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI64151">Departments of Nutrition and Biochemistry, University of Montreal, Montreal, Quebec, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Departments of Nutrition and Biochemistry, University of Montreal, Montreal, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Cornu, Marion" sort="Cornu, Marion" uniqKey="Cornu M" first="Marion" last="Cornu">Marion Cornu</name><affiliation wicri:level="3"><nlm:aff id="JCI64151">Center for Integrative Genomics, University of Lausanne, Genopode Building, Lausanne, Switzerland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Center for Integrative Genomics, University of Lausanne, Genopode Building, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Laybutt, Ross" sort="Laybutt, Ross" uniqKey="Laybutt R" first="Ross" last="Laybutt">Ross Laybutt</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, New South Wales, Australia.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Australie</country><wicri:regionArea>Diabetes and Obesity Research Program, Garvan Institute of Medical Research, St. Vincent’s Hospital, Sydney, New South Wales</wicri:regionArea><wicri:noRegion>New South Wales</wicri:noRegion></affiliation></author><author><name sortKey="Meugnier, Emmanuelle" sort="Meugnier, Emmanuelle" uniqKey="Meugnier E" first="Emmanuelle" last="Meugnier">Emmanuelle Meugnier</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Laboratory CarMen (INSERM 1060, INRA 1235, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, Oullins, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratory CarMen (INSERM 1060, INRA 1235, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Rome, Sophie" sort="Rome, Sophie" uniqKey="Rome S" first="Sophie" last="Rome">Sophie Rome</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Laboratory CarMen (INSERM 1060, INRA 1235, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, Oullins, France.</nlm:aff><country xml:lang="fr" wicri:curation="lc">France</country><wicri:regionArea>Laboratory CarMen (INSERM 1060, INRA 1235, INSA), University of Lyon, Faculté de Médecine Lyon-Sud, Chemin du Grand Revoyet, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Thorens, Bernard" sort="Thorens, Bernard" uniqKey="Thorens B" first="Bernard" last="Thorens">Bernard Thorens</name><affiliation wicri:level="3"><nlm:aff id="JCI64151">Center for Integrative Genomics, University of Lausanne, Genopode Building, Lausanne, Switzerland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Center for Integrative Genomics, University of Lausanne, Genopode Building, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author><author><name sortKey="Prentki, Marc" sort="Prentki, Marc" uniqKey="Prentki M" first="Marc" last="Prentki">Marc Prentki</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Montreal Diabetes Research Center and CRCHUM, Montreal, Quebec, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Montreal Diabetes Research Center and CRCHUM, Montreal, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="JCI64151">Departments of Nutrition and Biochemistry, University of Montreal, Montreal, Quebec, Canada.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Canada</country><wicri:regionArea>Departments of Nutrition and Biochemistry, University of Montreal, Montreal, Quebec</wicri:regionArea><wicri:noRegion>Quebec</wicri:noRegion></affiliation></author><author><name sortKey="Bosco, Domenico" sort="Bosco, Domenico" uniqKey="Bosco D" first="Domenico" last="Bosco">Domenico Bosco</name><affiliation wicri:level="1"><nlm:aff id="JCI64151">Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva, Switzerland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Cell Isolation and Transplantation Center, Department of Surgery, Geneva University Hospitals and University of Geneva, Geneva</wicri:regionArea><wicri:noRegion>Geneva</wicri:noRegion></affiliation></author><author><name sortKey="Regazzi, Romano" sort="Regazzi, Romano" uniqKey="Regazzi R" first="Romano" last="Regazzi">Romano Regazzi</name><affiliation wicri:level="3"><nlm:aff id="JCI64151">Department of Cell Biology and Morphology, University of Lausanne, Lausanne, Switzerland.</nlm:aff><country xml:lang="fr" wicri:curation="lc">Suisse</country><wicri:regionArea>Department of Cell Biology and Morphology, University of Lausanne, Lausanne</wicri:regionArea><placeName><settlement type="city">Lausanne</settlement><region nuts="3" type="region">Canton de Vaud</region></placeName></affiliation></author></analytic><series><title level="j">The Journal of Clinical Investigation</title><idno type="ISSN">0021-9738</idno><idno type="eISSN">1558-8238</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Pregnancy and obesity are frequently associated with diminished insulin sensitivity, which is normally compensated for by an expansion of the functional β cell mass that prevents chronic hyperglycemia and development of diabetes mellitus. The molecular basis underlying compensatory β cell mass expansion is largely unknown. We found in rodents that β cell mass expansion during pregnancy and obesity is associated with changes in the expression of several islet microRNAs, including miR-338-3p. In isolated pancreatic islets, we recapitulated the decreased miR-338-3p level observed in gestation and obesity by activating the G protein–coupled estrogen receptor GPR30 and the glucagon-like peptide 1 (GLP1) receptor. Blockade of miR-338-3p in β cells using specific anti-miR molecules mimicked gene expression changes occurring during β cell mass expansion and resulted in increased proliferation and improved survival both in vitro and in vivo. These findings point to a major role for miR-338-3p in compensatory β cell mass expansion occurring under different insulin resistance states.</p></div></front></TEI><affiliations><list><country><li>Australie</li><li>Belgique</li><li>Canada</li><li>France</li><li>Suisse</li></country><region><li>Canton de Vaud</li><li>Hauts-de-France</li><li>Nord-Pas-de-Calais</li><li>Région de Bruxelles-Capitale</li></region><settlement><li>Bruxelles</li><li>Lausanne</li><li>Lille</li><li>Louvain-la-Neuve</li></settlement><orgName><li>Université catholique de Louvain</li></orgName></list><tree><country name="Suisse"><region name="Canton de Vaud"><name sortKey="Jacovetti, Cecile" sort="Jacovetti, Cecile" uniqKey="Jacovetti C" first="Cécile" last="Jacovetti">Cécile Jacovetti</name></region><name sortKey="Bosco, Domenico" sort="Bosco, Domenico" uniqKey="Bosco D" first="Domenico" last="Bosco">Domenico Bosco</name><name sortKey="Cornu, Marion" sort="Cornu, Marion" uniqKey="Cornu M" first="Marion" last="Cornu">Marion Cornu</name><name sortKey="Parnaud, Geraldine" sort="Parnaud, Geraldine" uniqKey="Parnaud G" first="Géraldine" last="Parnaud">Géraldine Parnaud</name><name sortKey="Regazzi, Romano" sort="Regazzi, Romano" uniqKey="Regazzi R" first="Romano" last="Regazzi">Romano Regazzi</name><name sortKey="Thorens, Bernard" sort="Thorens, Bernard" uniqKey="Thorens B" first="Bernard" last="Thorens">Bernard Thorens</name></country><country name="France"><region name="Hauts-de-France"><name sortKey="Abderrahmani, Amar" sort="Abderrahmani, Amar" uniqKey="Abderrahmani A" first="Amar" last="Abderrahmani">Amar Abderrahmani</name></region><name sortKey="Meugnier, Emmanuelle" sort="Meugnier, Emmanuelle" uniqKey="Meugnier E" first="Emmanuelle" last="Meugnier">Emmanuelle Meugnier</name><name sortKey="Rome, Sophie" sort="Rome, Sophie" uniqKey="Rome S" first="Sophie" last="Rome">Sophie Rome</name></country><country name="Belgique"><region name="Région de Bruxelles-Capitale"><name sortKey="Jonas, Jean Christophe" sort="Jonas, Jean Christophe" uniqKey="Jonas J" first="Jean-Christophe" last="Jonas">Jean-Christophe Jonas</name></region></country><country name="Canada"><noRegion><name sortKey="Peyot, Marie Line" sort="Peyot, Marie Line" uniqKey="Peyot M" first="Marie-Line" last="Peyot">Marie-Line Peyot</name></noRegion><name sortKey="Peyot, Marie Line" sort="Peyot, Marie Line" uniqKey="Peyot M" first="Marie-Line" last="Peyot">Marie-Line Peyot</name><name sortKey="Prentki, Marc" sort="Prentki, Marc" uniqKey="Prentki M" first="Marc" last="Prentki">Marc Prentki</name><name sortKey="Prentki, Marc" sort="Prentki, Marc" uniqKey="Prentki M" first="Marc" last="Prentki">Marc Prentki</name></country><country name="Australie"><noRegion><name sortKey="Laybutt, Ross" sort="Laybutt, Ross" uniqKey="Laybutt R" first="Ross" last="Laybutt">Ross Laybutt</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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