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dc.contributor.authorPais, Ramonaen
dc.contributor.authorGribble, Fionaen
dc.contributor.authorReimann, Franken
dc.date.accessioned2015-08-18T14:13:42Z
dc.date.available2015-08-18T14:13:42Z
dc.date.issued2015-07-26en
dc.identifier.citationPais et al. Peptides (2015) Vol. 77, pp. 9–15. DOI: 10.1016/j.peptides.2015.07.019en
dc.identifier.issn0196-9781
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/250302
dc.description.abstractGlucagon like peptide-1 is an insulinotropic hormone released from intestinal L-cells in response to food ingestion. Here, we investigated mechanisms underlying the sensing of peptones by primary small intestinal L-cells. Meat, casein and vegetable-derived peptones (5mg/ml), the L-amino acids Phe, Trp, Gln and Ala (20 mM each), and the dipeptide glycine-sarcosine (20 mM) stimulated GLP-1 secretion from primary cultures prepared from the small intestine. Further mechanistic studies were performed with meat peptone, and revealed the elevation of intracellular calcium in L-cells. Inhibition of the calcium sensing receptor (CaSR), transient receptor potential (TRP) channels and Q-type voltage gated calcium channels (VGCC) significantly attenuated peptone-stimulated GLP-1 release and reduced intracellular Ca2+ responses. CaSR inhibition also attenuated the GLP-1 secretory response to Gln. Targeting these pathways in L-cells could be used to increase endogenous production of GLP-1 and offer exploitable avenues for the development of therapeutics to treat diabetes and obesity.
dc.description.sponsorshipThis work was funded by grants from the Wellcome Trust (WT088357/Z/09/Z and WT084210/Z/07/Z), the MRC Metabolic Diseases Unit (MRC_MC_UU_12012/3) and Full4Health (FP7/2011-2015, grant agreement n° 266408).
dc.languageEnglishen
dc.language.isoenen
dc.publisherElsevier
dc.rightsAttribution 2.0 UK: England & Wales*
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/uk/*
dc.titleSignalling pathways involved in the detection of peptones by murine small intestinal enteroendocrine L-cellsen
dc.typeArticle
dc.description.versionThis is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.peptides.2015.07.019en
prism.endingPage15
prism.publicationDate2015en
prism.publicationNamePeptidesen
prism.startingPage9
prism.volume77en
dc.rioxxterms.funderWellcome Trust
dc.rioxxterms.funderMRC
dc.rioxxterms.projectidWT088357/Z/09/Z
dc.rioxxterms.projectidWT084210/Z/07/Z
dc.rioxxterms.projectidMRC_MC_UU_12012/3
dcterms.dateAccepted2015-07-20en
rioxxterms.versionofrecord10.1016/j.peptides.2015.07.019en
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2015-07-26en
dc.contributor.orcidGribble, Fiona [0000-0002-4232-2898]
dc.contributor.orcidReimann, Frank [0000-0001-9399-6377]
dc.identifier.eissn1873-5169
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12012/3)
pubs.funder-project-idMRC (MC_UU_12012/5)


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Attribution 2.0 UK: England & Wales
Except where otherwise noted, this item's licence is described as Attribution 2.0 UK: England & Wales