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Diabetes. 2015 Apr;64(4):1202-10. doi: 10.2337/db14-0737. Epub 2014 Oct 16.

Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1.

Author information

  • 1Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K.
  • 2Wolfson Centre for Age-Related Diseases, King's College London, London, U.K.
  • 3Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London, U.K.
  • 4Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany.
  • 5Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K. fmg23@cam.ac.uk fr222@cam.ac.uk.

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.

PMID:
25325736
PMCID:
PMC4375100
DOI:
10.2337/db14-0737
[PubMed - indexed for MEDLINE]
Free PMC Article
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