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

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.

SUBMITTER: Dickerson MT 

PROVIDER: S-EPMC9617941 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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G<sub>i/o</sub> protein-coupled receptor inhibition of beta-cell electrical excitability and insulin secretion depends on Na<sup>+</sup>/K<sup>+</sup> ATPase activation.

Dickerson Matthew T MT   Dadi Prasanna K PK   Zaborska Karolina E KE   Nakhe Arya Y AY   Schaub Charles M CM   Dobson Jordyn R JR   Wright Nicole M NM   Lynch Joshua C JC   Scott Claire F CF   Robinson Logan D LD   Jacobson David A DA  

Nature communications 20221029 1

G<sub>i/o</sub>-coupled somatostatin or α2-adrenergic receptor activation stimulated β-cell NKA activity, resulting in islet Ca<sup>2+</sup> fluctuations. Furthermore, intra-islet paracrine activation of β-cell G<sub>i/o</sub>-GPCRs and NKAs by δ-cell somatostatin secretion slowed Ca<sup>2+</sup> oscillations, which decreased insulin secretion. β-cell membrane potential hyperpolarization resulting from G<sub>i/o</sub>-GPCR activation was dependent on NKA phosphorylation by Src tyrosine kinases.  ...[more]

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