Jejunal Proteins Secreted by db/db Mice or Insulin-Resistant Humans Impair the Insulin Signaling and Determine Insulin Resistance
Identifieur interne : 001A37 ( Pmc/Checkpoint ); précédent : 001A36; suivant : 001A38Jejunal Proteins Secreted by db/db Mice or Insulin-Resistant Humans Impair the Insulin Signaling and Determine Insulin Resistance
Auteurs : Serenella Salinari [Italie] ; Cyrille Debard [France] ; Alessandro Bertuzzi [Italie] ; Christine Durand [France] ; Paul Zimmet [Australie] ; Hubert Vidal [France] ; Geltrude Mingrone [Italie]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
Two recent studies demonstrated that bariatric surgery induced remission of type 2 diabetes very soon after surgery and far too early to be attributed to weight loss. In this study, we sought to explore the mechanism/s of this phenomenon by testing the effects of proteins from the duodenum-jejunum conditioned-medium (CM) of
These findings show that jejunal proteins either from
Url:
DOI: 10.1371/journal.pone.0056258
PubMed: 23437106
PubMed Central: 3577828
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Jejunal Proteins Secreted by <italic>db/db</italic> Mice or Insulin-Resistant Humans Impair the Insulin Signaling and Determine Insulin Resistance</title><author><name sortKey="Salinari, Serenella" sort="Salinari, Serenella" uniqKey="Salinari S" first="Serenella" last="Salinari">Serenella Salinari</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Computer and System Science, University of Rome “Sapienza”, Rome, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Computer and System Science, University of Rome “Sapienza”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Debard, Cyrille" sort="Debard, Cyrille" uniqKey="Debard C" first="Cyrille" last="Debard">Cyrille Debard</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Bertuzzi, Alessandro" sort="Bertuzzi, Alessandro" uniqKey="Bertuzzi A" first="Alessandro" last="Bertuzzi">Alessandro Bertuzzi</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Institute of Systems Analysis and Computer Science, National Research Council, Rome, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Systems Analysis and Computer Science, National Research Council, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Durand, Christine" sort="Durand, Christine" uniqKey="Durand C" first="Christine" last="Durand">Christine Durand</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Zimmet, Paul" sort="Zimmet, Paul" uniqKey="Zimmet P" first="Paul" last="Zimmet">Paul Zimmet</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Vidal, Hubert" sort="Vidal, Hubert" uniqKey="Vidal H" first="Hubert" last="Vidal">Hubert Vidal</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Mingrone, Geltrude" sort="Mingrone, Geltrude" uniqKey="Mingrone G" first="Geltrude" last="Mingrone">Geltrude Mingrone</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Department of Internal Medicine, Catholic University, School of Medicine, Rome, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Internal Medicine, Catholic University, School of Medicine, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23437106</idno><idno type="pmc">3577828</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3577828</idno><idno type="RBID">PMC:3577828</idno><idno type="doi">10.1371/journal.pone.0056258</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">002A66</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">002A66</idno><idno type="wicri:Area/Pmc/Curation">002916</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">002916</idno><idno type="wicri:Area/Pmc/Checkpoint">001A37</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">001A37</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Jejunal Proteins Secreted by <italic>db/db</italic> Mice or Insulin-Resistant Humans Impair the Insulin Signaling and Determine Insulin Resistance</title><author><name sortKey="Salinari, Serenella" sort="Salinari, Serenella" uniqKey="Salinari S" first="Serenella" last="Salinari">Serenella Salinari</name><affiliation wicri:level="3"><nlm:aff id="aff1"><addr-line>Department of Computer and System Science, University of Rome “Sapienza”, Rome, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Computer and System Science, University of Rome “Sapienza”, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Debard, Cyrille" sort="Debard, Cyrille" uniqKey="Debard C" first="Cyrille" last="Debard">Cyrille Debard</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Bertuzzi, Alessandro" sort="Bertuzzi, Alessandro" uniqKey="Bertuzzi A" first="Alessandro" last="Bertuzzi">Alessandro Bertuzzi</name><affiliation wicri:level="3"><nlm:aff id="aff3"><addr-line>Institute of Systems Analysis and Computer Science, National Research Council, Rome, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Institute of Systems Analysis and Computer Science, National Research Council, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author><author><name sortKey="Durand, Christine" sort="Durand, Christine" uniqKey="Durand C" first="Christine" last="Durand">Christine Durand</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Zimmet, Paul" sort="Zimmet, Paul" uniqKey="Zimmet P" first="Paul" last="Zimmet">Paul Zimmet</name><affiliation wicri:level="1"><nlm:aff id="aff4"><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria</wicri:regionArea><wicri:noRegion>Victoria</wicri:noRegion></affiliation></author><author><name sortKey="Vidal, Hubert" sort="Vidal, Hubert" uniqKey="Vidal H" first="Hubert" last="Vidal">Hubert Vidal</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins</wicri:regionArea><wicri:noRegion>Oullins</wicri:noRegion><wicri:noRegion>Oullins</wicri:noRegion></affiliation></author><author><name sortKey="Mingrone, Geltrude" sort="Mingrone, Geltrude" uniqKey="Mingrone G" first="Geltrude" last="Mingrone">Geltrude Mingrone</name><affiliation wicri:level="3"><nlm:aff id="aff5"><addr-line>Department of Internal Medicine, Catholic University, School of Medicine, Rome, Italy</addr-line></nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea>Department of Internal Medicine, Catholic University, School of Medicine, Rome</wicri:regionArea><placeName><settlement type="city">Rome</settlement><region nuts="2">Latium</region></placeName></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec><title>Background</title><p>Two recent studies demonstrated that bariatric surgery induced remission of type 2 diabetes very soon after surgery and far too early to be attributed to weight loss. In this study, we sought to explore the mechanism/s of this phenomenon by testing the effects of proteins from the duodenum-jejunum conditioned-medium (CM) of <italic>db/db</italic> or Swiss mice on glucose uptake <italic>in vivo</italic> in Swiss mice and <italic>in vitro</italic> in both Swiss mice soleus and L6 cells. We studied the effect of sera and CM proteins from insulin resistant (IR) and insulin-sensitive subjects on insulin signaling in human myoblasts.</p></sec><sec><title>Methodology/Principal Findings</title><p><italic>db/db</italic> proteins induced massive IR either <italic>in vivo</italic> or <italic>in vitro</italic>, while Swiss proteins did not. In L6 cells, only <italic>db/db</italic> proteins produced a noticeable increase in basal <sup>473</sup>Ser-Akt phosphorylation, lack of GSK3β inhibition and a reduced basal <sup>389</sup>Thr-p70-S6K1 phosphorylation. Human IR serum markedly increased basal <sup>473</sup>Ser-Akt phosphorylation in a dose-dependent manner. Human CM IR proteins increased by about twofold both basal and insulin-stimulated <sup>473</sup>Ser-Akt. Basal <sup>9</sup>Ser-GSK3β phosphorylation was increased by IR subjects serum with a smaller potentiating effect of insulin.</p></sec><sec><title>Conclusions</title><p>These findings show that jejunal proteins either from <italic>db/db</italic> mice or from insulin resistant subjects impair muscle insulin signaling, thus inducing insulin resistance.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Defronzo, Ra" uniqKey="Defronzo R">RA DeFronzo</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Kasuga, M" uniqKey="Kasuga M">M Kasuga</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Prentki, M" uniqKey="Prentki M">M Prentki</name></author><author><name sortKey="Nolan, Cj" uniqKey="Nolan C">CJ Nolan</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Guidone, C" uniqKey="Guidone C">C Guidone</name></author><author><name 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<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23437106</article-id><article-id pub-id-type="pmc">3577828</article-id><article-id pub-id-type="publisher-id">PONE-D-12-32700</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0056258</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Anatomy and Physiology</subject><subj-group><subject>Endocrine System</subject><subj-group><subject>Endocrine Physiology</subject><subj-group><subject>Insulin</subject></subj-group></subj-group></subj-group></subj-group><subj-group><subject>Model Organisms</subject><subj-group><subject>Animal Models</subject><subj-group><subject>Mouse</subject></subj-group></subj-group></subj-group><subj-group><subject>Molecular Cell Biology</subject><subj-group><subject>Signal Transduction</subject><subj-group><subject>Signaling Cascades</subject><subj-group><subject>Akt Signaling Cascade</subject><subject>Insulin Signaling Cascade</subject></subj-group></subj-group></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Anatomy and Physiology</subject><subj-group><subject>Endocrine System</subject><subj-group><subject>Diabetic Endocrinology</subject></subj-group></subj-group></subj-group><subj-group><subject>Endocrinology</subject><subj-group><subject>Endocrine Physiology</subject><subj-group><subject>Insulin</subject></subj-group></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Jejunal Proteins Secreted by <italic>db/db</italic> Mice or Insulin-Resistant Humans Impair the Insulin Signaling and Determine Insulin Resistance</article-title><alt-title alt-title-type="running-head">Jejunal Factors and Insulin Resistance</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Salinari</surname><given-names>Serenella</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Debard</surname><given-names>Cyrille</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bertuzzi</surname><given-names>Alessandro</given-names></name><xref ref-type="aff" rid="aff3"><sup>3</sup></xref></contrib><contrib contrib-type="author"><name><surname>Durand</surname><given-names>Christine</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Zimmet</surname><given-names>Paul</given-names></name><xref ref-type="aff" rid="aff4"><sup>4</sup></xref></contrib><contrib contrib-type="author"><name><surname>Vidal</surname><given-names>Hubert</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Mingrone</surname><given-names>Geltrude</given-names></name><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Department of Computer and System Science, University of Rome “Sapienza”, Rome, Italy</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Lyon 1 University, CarMeN Laboratory, INSERM U1060, Oullins, France</addr-line></aff><aff id="aff3"><label>3</label><addr-line>Institute of Systems Analysis and Computer Science, National Research Council, Rome, Italy</addr-line></aff><aff id="aff4"><label>4</label><addr-line>Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia</addr-line></aff><aff id="aff5"><label>5</label><addr-line>Department of Internal Medicine, Catholic University, School of Medicine, Rome, Italy</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Federici</surname><given-names>Massimo</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>University of Tor Vergata, Italy</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>gmingrone@rm.unicatt.it</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: GM SS AB HV. Performed the experiments: C. Debard C. Durand HV. Analyzed the data: SS AB. Contributed reagents/materials/analysis tools: HV GM. Wrote the paper: GM SS AB HV PZ.</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>20</day><month>2</month><year>2013</year></pub-date><volume>8</volume><issue>2</issue><elocation-id>e56258</elocation-id><history><date date-type="received"><day>22</day><month>10</month><year>2012</year></date><date date-type="accepted"><day>7</day><month>1</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Salinari et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><sec><title>Background</title><p>Two recent studies demonstrated that bariatric surgery induced remission of type 2 diabetes very soon after surgery and far too early to be attributed to weight loss. In this study, we sought to explore the mechanism/s of this phenomenon by testing the effects of proteins from the duodenum-jejunum conditioned-medium (CM) of <italic>db/db</italic> or Swiss mice on glucose uptake <italic>in vivo</italic> in Swiss mice and <italic>in vitro</italic> in both Swiss mice soleus and L6 cells. We studied the effect of sera and CM proteins from insulin resistant (IR) and insulin-sensitive subjects on insulin signaling in human myoblasts.</p></sec><sec><title>Methodology/Principal Findings</title><p><italic>db/db</italic> proteins induced massive IR either <italic>in vivo</italic> or <italic>in vitro</italic>, while Swiss proteins did not. In L6 cells, only <italic>db/db</italic> proteins produced a noticeable increase in basal <sup>473</sup>Ser-Akt phosphorylation, lack of GSK3β inhibition and a reduced basal <sup>389</sup>Thr-p70-S6K1 phosphorylation. Human IR serum markedly increased basal <sup>473</sup>Ser-Akt phosphorylation in a dose-dependent manner. Human CM IR proteins increased by about twofold both basal and insulin-stimulated <sup>473</sup>Ser-Akt. Basal <sup>9</sup>Ser-GSK3β phosphorylation was increased by IR subjects serum with a smaller potentiating effect of insulin.</p></sec><sec><title>Conclusions</title><p>These findings show that jejunal proteins either from <italic>db/db</italic> mice or from insulin resistant subjects impair muscle insulin signaling, thus inducing insulin resistance.</p></sec></abstract><funding-group><funding-statement>Financed by the Catholic University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="12"></page-count></counts></article-meta></front></pmc><affiliations><list><country><li>Australie</li><li>France</li><li>Italie</li></country><region><li>Latium</li></region><settlement><li>Rome</li></settlement></list><tree><country name="Italie"><region name="Latium"><name sortKey="Salinari, Serenella" sort="Salinari, Serenella" uniqKey="Salinari S" first="Serenella" last="Salinari">Serenella Salinari</name></region><name sortKey="Bertuzzi, Alessandro" sort="Bertuzzi, Alessandro" uniqKey="Bertuzzi A" first="Alessandro" last="Bertuzzi">Alessandro Bertuzzi</name><name sortKey="Mingrone, Geltrude" sort="Mingrone, Geltrude" uniqKey="Mingrone G" first="Geltrude" last="Mingrone">Geltrude Mingrone</name></country><country name="France"><noRegion><name sortKey="Debard, Cyrille" sort="Debard, Cyrille" uniqKey="Debard C" first="Cyrille" last="Debard">Cyrille Debard</name></noRegion><name sortKey="Durand, Christine" sort="Durand, Christine" uniqKey="Durand C" first="Christine" last="Durand">Christine Durand</name><name sortKey="Vidal, Hubert" sort="Vidal, Hubert" uniqKey="Vidal H" first="Hubert" last="Vidal">Hubert Vidal</name></country><country name="Australie"><noRegion><name sortKey="Zimmet, Paul" sort="Zimmet, Paul" uniqKey="Zimmet P" first="Paul" last="Zimmet">Paul Zimmet</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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