Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin

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 pancreatic β-cells, we investigated their role in the control of insulin secretion and glucose homeostasis. In...

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Bibliographic Details
Published in:Journal of diabetes research 2016-01, Vol.2016 (2016), p.1-9
Main Authors: Mazella, J., Coppola, Thierry, Borsotto, Marc, Djillani, Alaeddine, Moha ou Maati, Hamid, Moreno, Sébastien, Abderrahmani, Amar, Devader, Christelle, Béraud-Dufour, Sophie, Hivelin, Céline, Heurteaux, Catherine
Format: Article
Language:English
Subjects:
Animals
Antibodies
Calcium - metabolism
Cell Line
Cytosol - metabolism
Experiments
Glucose
Glucose - pharmacology
Insulin
Insulin - metabolism
Insulin Secretion
Insulin-Secreting Cells - drug effects
Insulin-Secreting Cells - metabolism
Islets of Langerhans - drug effects
Islets of Langerhans - metabolism
Kinases
Laboratory animals
Life Sciences
Male
Membrane Potentials - drug effects
Mice
Pancreas
Penicillin
Peptides
Peptides - pharmacology
Potassium
Potassium Channels, Tandem Pore Domain - metabolism
Proteins
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Summary: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 pancreatic β-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-B1 β-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.
ISSN:2314-6745
2314-6753
2314-6753
DOI:10.1155/2016/3142175