Glucose-induced electrical activities and insulin secretion in pancreatic islet β-cells are modulated by CFTR.

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  • Additional Information
    • Source:
      Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
    • Publication Information:
      Original Publication: [London] : Nature Pub. Group
    • Subject Terms:
      Cystic Fibrosis Transmembrane Conductance Regulator/*metabolism ; Glucose/*pharmacology ; Insulin/*metabolism ; Insulin-Secreting Cells/*metabolism; Animals ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; Enzyme-Linked Immunosorbent Assay ; Insulin Secretion ; Insulin-Secreting Cells/drug effects ; Male ; Membrane Potentials/drug effects ; Mice ; Mice, Inbred C57BL ; Patch-Clamp Techniques
    • Abstract:
      The cause of insulin insufficiency remains unknown in many diabetic cases. Up to 50% adult patients with cystic fibrosis (CF), a disease caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR), develop CF-related diabetes (CFRD) with most patients exhibiting insulin insufficiency. Here we show that CFTR is a regulator of glucose-dependent electrical acitivities and insulin secretion in β-cells. We demonstrate that glucose elicited whole-cell currents, membrane depolarization, electrical bursts or action potentials, Ca(2+) oscillations and insulin secretion are abolished or reduced by inhibitors or knockdown of CFTR in primary mouse β-cells or RINm5F β-cell line, or significantly attenuated in CFTR mutant (DF508) mice compared with wild-type mice. VX-809, a newly discovered corrector of DF508 mutation, successfully rescues the defects in DF508 β-cells. Our results reveal a role of CFTR in glucose-induced electrical activities and insulin secretion in β-cells, shed light on the pathogenesis of CFRD and possibly other idiopathic diabetes, and present a potential treatment strategy.
    • Comments:
      Comment in: Nat Rev Endocrinol. 2014 Oct;10(10):577. (PMID: 25069468)
      Comment in: Sci China Life Sci. 2014 Oct;57(10):1044-5. (PMID: 25216709)
      Comment in: Sci China Life Sci. 2014 Oct;57(10):1046. (PMID: 25216710)
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    • Accession Number:
      0 (Insulin)
      126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
      IY9XDZ35W2 (Glucose)
    • Publication Date:
      Date Created: 20140716 Date Completed: 20151214 Latest Revision: 20211021
    • Publication Date:
      20231215
    • Accession Number:
      PMC4104438
    • Accession Number:
      10.1038/ncomms5420
    • Accession Number:
      25025956