The Glucagon-like peptide-1 receptor agonist, exendin-4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome

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dc.contributor.author O'Brien, Rebecca
dc.contributor.author O'Malley, Dervla
dc.date.accessioned 2019-11-08T12:54:49Z
dc.date.available 2019-11-08T12:54:49Z
dc.date.issued 2019-10-11
dc.identifier.citation O'Brien, R. and O'Malley, D. (2019) 'The Glucagon-like peptide-1 receptor agonist, exendin-4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome', Neurogastroenterology and Motility. doi: 10.1111/nmo.13738 en
dc.identifier.issn 1350-1925
dc.identifier.uri http://hdl.handle.net/10468/8980
dc.identifier.doi 10.1111/nmo.13738 en
dc.description.abstract Background: Glucagon-like peptide-1 (GLP-1) is beneficial in relieving pain-related symptoms of Irritable bowel syndrome (IBS), a prevalent, multi-factorial functional bowel disorder characterized by diarrhea and/or constipation, abdominal bloating, and pain. Activation of myenteric neurons has been implicated in the inhibitory effects of GLP-1 on gastrointestinal motility; however, the mechanisms of action underlying this are not clear. Methods: A rat model of IBS was used to examine physiological changes evoked by intraperitoneal administration of a GLP-1 receptor agonist, exendin-4. Behavioral and physiological analysis of stress-sensitive Wister Kyoto (WKY) rats was used to determine if administration of exendin-4, in the presence or absence of neutralizing interleukin-6 receptor monoclonal antibodies, modified IBS-like symptoms. Immunofluorescence, calcium imaging, and Western blotting techniques were used to investigate the potential role of enteric neural plexi and tight junction protein expression in this effect. Key Results: Consistent with the expression of GLP-1 and interleukin-6 receptors in both submucosal and myenteric ganglia, exendin-4 and interleukin-6 stimulated calcium responses in these neurons. In vivo administration of exendin-4 normalized stress-induced defecation and visceral pain sensitivity in WKY rats. No additional changes were noted in rats co-treated with exendin-4 and anti-interleukin-6 receptor antibodies. Mucosal expression of occludin, a tight junction protein, was decreased by exendin-4. Centrally regulated anxiety-like behaviors were not modified. Conclusions and Inferences: These data suggest that intraperitoneal injection of exendin-4 improves bowel dysfunction in WKY rats without impacting on centrally regulated anxiety-like behaviors. Modulation of enteric neuronal function and tight junction expression appear to underlie the functional benefits of this intervention. en
dc.description.sponsorship University College Cork (School of Medicine TRAP funding) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher John Wiley & Sons Ltd. en
dc.relation.uri https://onlinelibrary.wiley.com/doi/abs/10.1111/nmo.13738
dc.rights © 2019, John Wiley & Sons Ltd. This is the peer reviewed version of the following article: O'Brien, R. and O'Malley, D. (2019) 'The Glucagon-like peptide-1 receptor agonist, exendin-4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome', Neurogastroenterology and Motility, doi: 10.1111/nmo.13738, which has been published in final form at https://doi.org/10.1111/nmo.13738. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. en
dc.subject Colorectal distension en
dc.subject Open field en
dc.subject Stress en
dc.subject Wister Kyoto en
dc.subject Exendin‐4 en
dc.subject Glucagon‐like peptide‐1 en
dc.subject Interleukin‐6 en
dc.title The Glucagon-like peptide-1 receptor agonist, exendin-4, ameliorated gastrointestinal dysfunction in the Wistar Kyoto rat model of Irritable Bowel Syndrome en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Dervla O'Malley, Physiology, University College Cork, Cork, Ireland. +353-21-490-3000 Email: d.omalley@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2020-10-11
dc.date.updated 2019-11-08T12:43:33Z
dc.description.version Accepted Version en
dc.internal.rssid 499911637
dc.contributor.funder University College Cork en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Neurogastroenterology and Motility en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress d.omalley@ucc.ie en
dc.identifier.articleid e13738 en
dc.internal.bibliocheck In press. Check vol / issue / page range. Amend citation and copyright statement as necessary. en
dc.identifier.eissn 1365-2982


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