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

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  • Additional Information
    • Source:
      Publisher: Hindawi Limited Country of Publication: England NLM ID: 101605237 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2314-6753 (Electronic) NLM ISO Abbreviation: J Diabetes Res Subsets: MEDLINE
    • Publication Information:
      Publication: <2019>-: London, United Kingdom : Hindawi Limited
      Original Publication: Nasr City, Cairo : Hindawi Publishing Corporation, [2013]-
    • Subject Terms:
      Calcium/*metabolism ; Insulin/*metabolism ; Insulin-Secreting Cells/*drug effects ; Islets of Langerhans/*drug effects ; Peptides/*pharmacology ; Potassium Channels, Tandem Pore Domain/*metabolism; Animals ; Cell Line ; Cytosol/metabolism ; Glucose/pharmacology ; Insulin Secretion ; Insulin-Secreting Cells/metabolism ; Islets of Langerhans/metabolism ; Male ; Membrane Potentials/drug effects ; Mice
    • 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 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 (Δ V m ~ 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.
      Competing Interests: The authors declare that they have no competing interests.
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    • Accession Number:
      0 (Insulin)
      0 (Peptides)
      0 (Potassium Channels, Tandem Pore Domain)
      0 (potassium channel protein TREK-1)
      0 (spadin peptide)
      IY9XDZ35W2 (Glucose)
      SY7Q814VUP (Calcium)
    • Publication Date:
      Date Created: 20170121 Date Completed: 20170518 Latest Revision: 20190723
    • Publication Date:
      20240829
    • Accession Number:
      PMC5220496
    • Accession Number:
      10.1155/2016/3142175
    • Accession Number:
      28105440