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

Emery EC, Diakogiannaki E, Gentry C, Psichas A, Habib AM, Bevan S, Fischer M, Reimann F, Gribble FM (2015)

Publication Type: Journal article

Publication year: 2015

Journal

Diabetes American Diabetes Association

Book Volume: 64

Pages Range: 1202-10

Journal Issue: 4

DOI: 10.2337/db14-0737

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.

Authors with CRIS profile

Michael Fischer Medizinische Fakultät

Involved external institutions

King’s College London GB United Kingdom (GB) Addenbrooke's Hospital GB United Kingdom (GB) University College London (UCL) GB United Kingdom (GB)

How to cite

APA:

Emery, E.C., Diakogiannaki, E., Gentry, C., Psichas, A., Habib, A.M., Bevan, S.,... Gribble, F.M. (2015). Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1. Diabetes, 64(4), 1202-10. https://doi.org/10.2337/db14-0737

MLA:

Emery, Edward C., et al. "Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1." Diabetes 64.4 (2015): 1202-10.

BibTeX: Download