Referenced in: none

Automatically associated channels: TRP , TRPA , TRPA1

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

Authors: Edward C Emery, Eleftheria Diakogiannaki, Clive Gentry, Arianna Psichas, Abdella M Habib, Stuart Bevan, Michael J M Fischer, Frank Reimann, Fiona M Gribble

Journal, date & volume: Diabetes, 2014 Oct 16 , ,

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/25325736

Abstract
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 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.