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

  • Cambridge University Hospitals NHS Foundation Trust
    ,
  • King's College London
    ,
  • University College London
    ,
  • Friedrich-Alexander University Erlangen-Nürnberg
Research Output: Contribution to journal Article Peer-review

Sustainable Development Goals

  • SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well

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.

Publication Information

Output type

Research Output: Contribution to journal Article Peer-review

Original language

English

Pages from-to (Number of pages)

Pages 1202-1210

Journal (Volume, Issue Number)

Diabetes (Volume 64, Issue 4)

Publication milestones

  • Accepted/In press - 08/10/2014
  • Published - 16/10/2014

Publication status

Published - 16/10/2014

ISSN

0012-1797

External Publication IDs

  • handle.net: 10547/624684
  • Scopus: 84962022105

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