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dc.contributor.authorKheder, MH
dc.contributor.authorBailey, SR
dc.contributor.authorDudley, KJ
dc.contributor.authorSillence, MN
dc.contributor.authorde Laat, MA
dc.date.accessioned2020-12-18T03:42:14Z
dc.date.available2020-12-18T03:42:14Z
dc.date.issued2018-01-29
dc.identifierpii: 4316
dc.identifier.citationKheder, M. H., Bailey, S. R., Dudley, K. J., Sillence, M. N. & de Laat, M. A. (2018). Equine glucagon-like peptide-1 receptor physiology. PEERJ, 6 (1), https://doi.org/10.7717/peerj.4316.
dc.identifier.issn2167-8359
dc.identifier.urihttp://hdl.handle.net/11343/255884
dc.description.abstractBackground: Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated. Methods: Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified in vitro. Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism in vitro, using concentration-response experiments. Results: The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced (P = 0.08) insulin secretion by 27%. Discussion: The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation.
dc.languageEnglish
dc.publisherPEERJ INC
dc.titleEquine glucagon-like peptide-1 receptor physiology
dc.typeJournal Article
dc.identifier.doi10.7717/peerj.4316
melbourne.affiliation.departmentVeterinary Biosciences
melbourne.source.titlePeerJ
melbourne.source.volume6
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1305243
melbourne.contributor.authorBailey, Simon
dc.identifier.eissn2167-8359
melbourne.accessrightsOpen Access


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