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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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/3142175 |
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| author | Céline Hivelin Sophie Béraud-Dufour Christelle Devader Amar Abderrahmani Sébastien Moreno Hamid Moha ou Maati Alaeddine Djillani Catherine Heurteaux Marc Borsotto Jean Mazella Thierry Coppola |
| author_facet | Céline Hivelin Sophie Béraud-Dufour Christelle Devader Amar Abderrahmani Sébastien Moreno Hamid Moha ou Maati Alaeddine Djillani Catherine Heurteaux Marc Borsotto Jean Mazella Thierry Coppola |
| author_sort | Céline Hivelin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-5ce0b490bc014551ba4a958c50acb044 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-5ce0b490bc014551ba4a958c50acb0442025-02-03T05:43:51ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/31421753142175Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker SpadinCéline Hivelin0Sophie Béraud-Dufour1Christelle Devader2Amar Abderrahmani3Sébastien Moreno4Hamid Moha ou Maati5Alaeddine Djillani6Catherine Heurteaux7Marc Borsotto8Jean Mazella9Thierry Coppola10CNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, CHU Lille, Institut Pasteur de Lille, UMR 8199-EGID, Université Lille, 59000 Lille, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceDépartement de Physiologie, Institut de Génomique Fonctionnelle (IGF), CNRS/INSERM UMR5203, Université de Montpellier, Montpellier, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceCNRS, Inserm, IPMC, Université Côte d’Azur, Valbonne, FranceInhibition 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.http://dx.doi.org/10.1155/2016/3142175 |
| spellingShingle | Céline Hivelin Sophie Béraud-Dufour Christelle Devader Amar Abderrahmani Sébastien Moreno Hamid Moha ou Maati Alaeddine Djillani Catherine Heurteaux Marc Borsotto Jean Mazella Thierry Coppola Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin Journal of Diabetes Research |
| title | Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin |
| title_full | Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin |
| title_fullStr | Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin |
| title_full_unstemmed | Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin |
| title_short | Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin |
| title_sort | potentiation of calcium influx and insulin secretion in pancreatic beta cell by the specific trek 1 blocker spadin |
| url | http://dx.doi.org/10.1155/2016/3142175 |
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