title: Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin.
abstract: Inhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for the treatment of depression. Since these channels are expressed in pancreaticβ-cells, we investigated their role in the control of insulin secretion and glucose homeostasis. In this study, we confirmed the expression of TREK-1 channels in the insulin secreting MIN6-B1β-cell line and in mouse islets. We found that their blockade by SPA potentiated insulin secretion induced by potassium chloride dependent membrane depolarization. Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential (ΔVm~ 12 mV) and increased the cytosolic calcium concentration. In mice, administration of SPA enhanced the plasma insulin level stimulated by glucose, confirming its secretagogue effect observed in vitro. Taken together, this work identifies SPA as a novel potential pharmacological agent able to control insulin secretion and glucose homeostasis.
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Hivelin
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Béraud-Dufour
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Devader
authors.affiliation: CNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199-EGID, Université Lille, 59000 Lille, France.
authors.forename: Amar
authors.identifier: 0000-0003-0752-0343
authors.initials: A
authors.lastname: Abderrahmani
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Moreno
authors.affiliation: Département de Physiologie, Institut de Génomique Fonctionnelle (IGF), CNRS/INSERM UMR5203, Université de Montpellier, Montpellier, France.
authors.forename: Hamid
authors.initials: H
authors.lastname: Moha Ou Maati
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Alaeddine
authors.initials: A
authors.lastname: Djillani
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Heurteaux
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Borsotto
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Jean
authors.identifier: 0000-0002-5627-0742
authors.initials: J
authors.lastname: Mazella
authors.affiliation: CNRS, Inserm, IPMC, Université Côte d'Azur, Valbonne, France.
authors.forename: Thierry
authors.identifier: 0000-0003-1018-722X
authors.initials: T
authors.lastname: Coppola
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D003600:Cytosol / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D010455:Peptides / Q000494:pharmacology*; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*
chemical_list: D007328:Insulin; D010455:Peptides; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1; C551795:spadin peptide; D005947:Glucose; D002118:Calcium