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Gi/o protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na+/K+ ATPase activation

Author

Listed:
  • Matthew T. Dickerson

    (Vanderbilt University)

  • Prasanna K. Dadi

    (Vanderbilt University)

  • Karolina E. Zaborska

    (Vanderbilt University)

  • Arya Y. Nakhe

    (Vanderbilt University)

  • Charles M. Schaub

    (Vanderbilt University)

  • Jordyn R. Dobson

    (Vanderbilt University)

  • Nicole M. Wright

    (Vanderbilt University)

  • Joshua C. Lynch

    (Vanderbilt University)

  • Claire F. Scott

    (Vanderbilt University)

  • Logan D. Robinson

    (Vanderbilt University)

  • David A. Jacobson

    (Vanderbilt University)

Abstract

Gi/o-coupled somatostatin or α2-adrenergic receptor activation stimulated β-cell NKA activity, resulting in islet Ca2+ fluctuations. Furthermore, intra-islet paracrine activation of β-cell Gi/o-GPCRs and NKAs by δ-cell somatostatin secretion slowed Ca2+ oscillations, which decreased insulin secretion. β-cell membrane potential hyperpolarization resulting from Gi/o-GPCR activation was dependent on NKA phosphorylation by Src tyrosine kinases. Whereas, β-cell NKA function was inhibited by cAMP-dependent PKA activity. These data reveal that NKA-mediated β-cell membrane potential hyperpolarization is the primary and conserved mechanism for Gi/o-GPCR control of electrical excitability, Ca2+ handling, and insulin secretion.

Suggested Citation

  • Matthew T. Dickerson & Prasanna K. Dadi & Karolina E. Zaborska & Arya Y. Nakhe & Charles M. Schaub & Jordyn R. Dobson & Nicole M. Wright & Joshua C. Lynch & Claire F. Scott & Logan D. Robinson & David, 2022. "Gi/o protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na+/K+ ATPase activation," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34166-z
    DOI: 10.1038/s41467-022-34166-z
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    References listed on IDEAS

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    1. Huan Wang & Aaron Bender & Peng Wang & Esra Karakose & William B. Inabnet & Steven K. Libutti & Andrew Arnold & Luca Lambertini & Micheal Stang & Herbert Chen & Yumi Kasai & Milind Mahajan & Yayoi Kin, 2017. "Insights into beta cell regeneration for diabetes via integration of molecular landscapes in human insulinomas," Nature Communications, Nature, vol. 8(1), pages 1-15, December.
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