Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1
AuthorsEmery, Edward C.
Habib, Abdella M.
Fischer, Michael J.M.
Gribble, Fiona M.
King’s College London
University College London
University of Erlangen-Nuremberg
MetadataShow full item record
AbstractStimulus-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 GLP-1. By microarray and quantitative PCR 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 (mustard oil), carvacrol, and polyunsaturated fatty acids, which 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.
CitationEmery EC, Diakogiannaki E, Gentry C, Psichas A, Habib AM, Bevan S, Fischer MJM, Reimann F, Gribble FM (2015) 'Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1', Diabetes, 64 (4), pp.1202-1210.
PublisherAmerican Diabetes Association Inc.
PubMed Central IDPMC4375100
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