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

Overview

Journal J Diabetes Res

Publisher Wiley

Specialty Endocrinology

Date 2017 Jan 21

PMID 28105440

Citations 11

Authors

Celine Hivelin

Sophie Beraud-Dufour

Christelle Devader

Amar Abderrahmani

Sebastien Moreno

Hamid Moha Ou Maati

Alaeddine Djillani

Catherine Heurteaux

Marc Borsotto

Jean Mazella

Thierry Coppola

Affiliations

Soon will be listed here.

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 pancreatic -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 -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 (Δ ~ 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.

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