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.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36309517.
- Also identified by DOI 10.1038/s41467-022-34166-z and PMC identifier 9617941.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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. 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 G<sub>i/o</sub>-GPCR control of electrical excitability, Ca<sup>2+</sup> handling, and insulin secretion.
Medical subject headings
- Insulin-Secreting Cells