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dc.contributor.authorKuhre, Rune Een
dc.contributor.authorWewer Albrechtsen, Nicolai Jen
dc.contributor.authorLarsen, Olaven
dc.contributor.authorJepsen, Sara Len
dc.contributor.authorBalk-Møller, Emilieen
dc.contributor.authorAndersen, Daniel Ben
dc.contributor.authorDeacon, Carolyn Fen
dc.contributor.authorSchoonjans, Kristinaen
dc.contributor.authorReimann, Franken
dc.contributor.authorGribble, Fionaen
dc.contributor.authorAlbrechtsen, Reidaren
dc.contributor.authorHartmann, Boletteen
dc.contributor.authorRosenkilde, Mette Men
dc.contributor.authorHolst, Jens Jen
dc.date.accessioned2018-06-05T13:26:37Z
dc.date.available2018-06-05T13:26:37Z
dc.date.issued2018-05en
dc.identifier.issn2212-8778
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/276623
dc.description.abstractObjective: Bile acids (BAs) facilitate fat absorption and may play a role in glucose and metabolism regulation, stimulating the secretion of gut hormones. The relative importance and mechanisms involved in BA-stimulated secretion of appetite and metabolism regulating hormones from the gut and pancreas is not well described and was the purpose of this study. Methods: The effects of bile acids on the secretion of gut and pancreatic hormones was studied in rats and compared to the most well described nutritional secretagogue: glucose. The molecular mechanisms that underlie the secretion was studied by isolated perfused rat and mouse small intestine and pancreas preparations and supported by immunohistochemistry, expression analysis and pharmacological studies. Results: Bile acids robustly stimulate secretion of not only the incretin hormones, glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1), but also glucagon and insulin in vivo, to levels comparable to those resulting from glucose stimulation. The mechanisms of GLP-1, neurotensin and peptide YY (PYY) secretion was secondary to intestinal absorption and depended on activation of basolateral membrane TGR5 receptors on the L-cells in the following order of potency: Litocholic acid >DeoxyCholicAcid>ChenoDCA>CA. Thus BAs did not stimulate secretion of GLP-1 and PYY from perfused small intestine in TGR5 K.O. mice but stimulated robust resposes in wild type littermates. TGR5 is not expressed on alpha cells or beta cells, and BAs had no direct effects on glucagon or insulin secretion from the perfused pancreas. Conclusion: BAs should be considered not only as fat emulsifiers but also as important regulators of appetite- and metabolism-regulating hormones by activation of basolateral intestinal TGR5.
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherElsevier
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 International*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectIntestinal Mucosaen
dc.subjectPancreasen
dc.subjectCells, Cultureden
dc.subjectCOS Cellsen
dc.subjectAnimalsen
dc.subjectMice, Inbred C57BLen
dc.subjectMiceen
dc.subjectRatsen
dc.subjectRats, Wistaren
dc.subjectBile Acids and Saltsen
dc.subjectGastric Inhibitory Polypeptideen
dc.subjectPeptide YYen
dc.subjectReceptors, G-Protein-Coupleden
dc.subjectMaleen
dc.subjectGlucagon-Like Peptide 1en
dc.subjectChlorocebus aethiopsen
dc.titleBile acids are important direct and indirect regulators of the secretion of appetite- and metabolism-regulating hormones from the gut and pancreas.en
dc.typeArticle
prism.endingPage95
prism.publicationDate2018en
prism.publicationNameMolecular metabolismen
prism.startingPage84
prism.volume11en
dc.identifier.doi10.17863/CAM.23923
dcterms.dateAccepted2018-03-13en
rioxxterms.versionofrecord10.1016/j.molmet.2018.03.007en
rioxxterms.versionVoR*
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2018-05en
dc.contributor.orcidWewer Albrechtsen, Nicolai J [0000-0003-4230-5753]
dc.contributor.orcidLarsen, Olav [0000-0001-9054-4690]
dc.contributor.orcidAndersen, Daniel B [0000-0001-7944-9342]
dc.contributor.orcidDeacon, Carolyn F [0000-0003-2611-5642]
dc.contributor.orcidReimann, Frank [0000-0001-9399-6377]
dc.contributor.orcidGribble, Fiona [0000-0002-4232-2898]
dc.contributor.orcidHartmann, Bolette [0000-0001-8509-2036]
dc.contributor.orcidRosenkilde, Mette M [0000-0001-9600-3254]
dc.contributor.orcidHolst, Jens J [0000-0001-6853-3805]
dc.identifier.eissn2212-8778
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12012/3)
pubs.funder-project-idWELLCOME TRUST (106262/Z/14/Z & 106263/Z/14/Z)
pubs.funder-project-idEC FP7 CP (266408)
cam.orpheus.successThu Jan 30 12:59:04 GMT 2020 - The item has an open VoR version.*
rioxxterms.freetoread.startdate2100-01-01


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Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's licence is described as Attribution-NonCommercial-NoDerivatives 4.0 International