| First Author | Emery EC | Year | 2015 |
| Journal | Diabetes | Volume | 64 |
| Issue | 4 | Pages | 1202-10 |
| PubMed ID | 25325736 | Mgi Jnum | J:246159 |
| Mgi Id | MGI:5924538 | Doi | 10.2337/db14-0737 |
| Citation | Emery EC, et al. (2015) Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1. Diabetes 64(4):1202-10 |
| abstractText | 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. |
