Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1.
Diabetes
; 64(4): 1202-10, 2015 Apr.
Article
em En
| MEDLINE
| ID: mdl-25325736
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Células Enteroendócrinas
/
Peptídeo 1 Semelhante ao Glucagon
/
Canais de Potencial de Receptor Transitório
/
Intestino Delgado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Diabetes
Ano de publicação:
2015
Tipo de documento:
Article
País de publicação:
Estados Unidos