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Stimulation of glucagon-like peptide-1 secretion downstream of the ligand-gated ion channel TRPA1

Diabetes (New York, N.Y.), 2014-10, Vol.64 (4), p.1202-1210 [Peer Reviewed Journal]

ISSN: 0012-1797 ;EISSN: 1939-327X ;DOI: 10.2337/db14-0737 ;PMID: 25325736

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  • Title:
    Stimulation of glucagon-like peptide-1 secretion downstream of the ligand-gated ion channel TRPA1
  • Author: Emery, Edward C. ; Diakogiannaki, Eleftheria ; Gentry, Clive ; Psichas, Arianna ; Habib, Abdella M. ; Bevan, Stuart ; Fischer, Michael J. M. ; Reimann, Frank ; Gribble, Fiona M.
  • Is Part Of: Diabetes (New York, N.Y.), 2014-10, Vol.64 (4), p.1202-1210
  • Description: Stimulus-coupled incretin secretion from enteroendocrine cells plays a fundamental role in glucose homeostasis, and could be targeted for the treatment of type-2 diabetes. Here, we investigated the expression and function of transient receptor potential (TRP) ion channels in enteroendocrine L-cells producing glucagon-like peptide-1 (GLP-1). By microarray and qPCR analysis we identified trpa1 as an L-cell enriched transcript in the small intestine. Calcium imaging of primary L-cells and the model cell line GLUTag revealed responses triggered by the TRPA1 agonists allyl-isothiocyanate (AITC, mustard oil), carvacrol and polyunsaturated fatty acids, that were blocked by TRPA1 antagonists. Electrophysiology in GLUTag cells showed that carvacrol induced a current with characteristics typical of TRPA1 and triggered the firing of action potentials. TRPA1 activation caused an increase in GLP-1 secretion from primary murine intestinal cultures and GLUTag cells; an effect that was abolished in cultures from trpa1 −/− mice or by pharmacological TRPA1 inhibition. These findings present TRPA1 as a novel sensory mechanism in enteroendocrine L-cells, coupled to the facilitation of GLP-1 release, which may be exploitable as a target for treating diabetes.
  • Language: English
  • Identifier: ISSN: 0012-1797
    EISSN: 1939-327X
    DOI: 10.2337/db14-0737
    PMID: 25325736
  • Source: PubMed Central (Open access)
    Alma/SFX Local Collection
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