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dc.contributor.authorArifin, SAen_US
dc.contributor.authorPaternoster, Sen_US
dc.contributor.authorCarlessi, Ren_US
dc.contributor.authorCasari, Ien_US
dc.contributor.authorEkberg, JHen_US
dc.contributor.authorMaffucci, Ten_US
dc.contributor.authorNewsholme, Pen_US
dc.contributor.authorRosenkilde, MMen_US
dc.contributor.authorFalasca, Men_US
dc.date.accessioned2018-08-07T10:22:18Z
dc.date.available2018-06-02en_US
dc.date.issued2018-09en_US
dc.date.submitted2018-08-01T10:46:39.221Z
dc.identifier.issn1388-1981en_US
dc.identifier.urihttp://qmro.qmul.ac.uk/xmlui/handle/123456789/43084
dc.description.abstractThe gastrointestinal tract is increasingly viewed as critical in controlling glucose metabolism, because of its role in secreting multiple glucoregulatory hormones, such as glucagon like peptide-1 (GLP-1). Here we investigate the molecular pathways behind the GLP-1- and insulin-secreting capabilities of a novel GPR119 agonist, Oleoyl-lysophosphatidylinositol (Oleoyl-LPI). Oleoyl-LPI is the only LPI species able to potently stimulate the release of GLP-1 in vitro, from murine and human L-cells, and ex-vivo from murine colonic primary cell preparations. Here we show that Oleoyl-LPI mediates GLP-1 secretion through GPR119 as this activity is ablated in cells lacking GPR119 and in colonic primary cell preparation from GPR119-/- mice. Similarly, Oleoyl-LPI-mediated insulin secretion is impaired in islets isolated from GPR119-/- mice. On the other hand, GLP-1 secretion is not impaired in cells lacking GPR55 in vitro or in colonic primary cell preparation from GPR55-/- mice. We therefore conclude that GPR119 is the Oleoyl-LPI receptor, upstream of ERK1/2 and cAMP/PKA/CREB pathways, where primarily ERK1/2 is required for GLP-1 secretion, while CREB activation appears dispensable.en_US
dc.description.sponsorshipWork in the Falasca lab is supported by Diabetes Australia. S.A.A. received a full SLAI scholarship from Ministry of Higher Learning, Malaysia. S.P. is supported by the Curtin University Health Sciences Faculty International Research Scholarships. We thank Prof David Baker for the GPR55−/− mice.en_US
dc.format.extent1132 - 1141en_US
dc.languageengen_US
dc.language.isoenen_US
dc.relation.ispartofBiochim Biophys Acta Mol Cell Biol Lipidsen_US
dc.rights© 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectGPR119en_US
dc.subjectGPR55en_US
dc.subjectGlucagon-like peptide-1 (GLP-1)en_US
dc.subjectL-cellsen_US
dc.subjectLysophosphatidylinositol (LPI)en_US
dc.subjectMixed colonic preparationen_US
dc.subjectAnimalsen_US
dc.subjectCell Lineen_US
dc.subjectCell Line, Tumoren_US
dc.subjectCyclic AMPen_US
dc.subjectCyclic AMP Response Element-Binding Proteinen_US
dc.subjectCyclic AMP-Dependent Protein Kinasesen_US
dc.subjectEnteroendocrine Cellsen_US
dc.subjectEpithelial Cellsen_US
dc.subjectGene Expression Regulationen_US
dc.subjectGlucagon-Like Peptide 1en_US
dc.subjectHumansen_US
dc.subjectInsulinen_US
dc.subjectInsulin Secretionen_US
dc.subjectIslets of Langerhansen_US
dc.subjectLysophospholipidsen_US
dc.subjectMiceen_US
dc.subjectMice, Inbred C57BLen_US
dc.subjectMitogen-Activated Protein Kinase 1en_US
dc.subjectMitogen-Activated Protein Kinase 3en_US
dc.subjectOleic Acidsen_US
dc.subjectPrimary Cell Cultureen_US
dc.subjectReceptors, Cannabinoiden_US
dc.subjectReceptors, G-Protein-Coupleden_US
dc.subjectSignal Transductionen_US
dc.titleOleoyl-lysophosphatidylinositol enhances glucagon-like peptide-1 secretion from enteroendocrine L-cells through GPR119.en_US
dc.typeArticle
dc.identifier.doi10.1016/j.bbalip.2018.06.007en_US
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/29883799en_US
pubs.issue9en_US
pubs.notesNot knownen_US
pubs.publication-statusPublisheden_US
pubs.volume1863en_US
dcterms.dateAccepted2018-06-02en_US


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