Your browser doesn't support javascript.
loading
Stimulation of GLP-1 secretion downstream of the ligand-gated ion channel TRPA1.
Emery, Edward C; Diakogiannaki, Eleftheria; Gentry, Clive; Psichas, Arianna; Habib, Abdella M; Bevan, Stuart; Fischer, Michael J M; Reimann, Frank; Gribble, Fiona M.
Afiliação
  • Emery EC; Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K.
  • Diakogiannaki E; Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K.
  • Gentry C; Wolfson Centre for Age-Related Diseases, King's College London, London, U.K.
  • Psichas A; Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K.
  • Habib AM; Molecular Nociception Group, Wolfson Institute for Biomedical Research, University College London, London, U.K.
  • Bevan S; Wolfson Centre for Age-Related Diseases, King's College London, London, U.K.
  • Fischer MJ; Institute of Physiology and Pathophysiology, University of Erlangen-Nuremberg, Erlangen, Germany.
  • Reimann F; Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K. fmg23@cam.ac.uk fr222@cam.ac.uk.
  • Gribble FM; Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, U.K. fmg23@cam.ac.uk fr222@cam.ac.uk.
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.
Assuntos

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

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