Molecular Physiology and Biophysics Department, Vanderbilt University, 7425B MRB IV, 2213 Garland Ave., Nashville, TN, USA.
Nat Commun. 2022 Oct 29;13(1):6461. doi: 10.1038/s41467-022-34166-z.
G-coupled somatostatin or α2-adrenergic receptor activation stimulated β-cell NKA activity, resulting in islet Ca fluctuations. Furthermore, intra-islet paracrine activation of β-cell G-GPCRs and NKAs by δ-cell somatostatin secretion slowed Ca oscillations, which decreased insulin secretion. β-cell membrane potential hyperpolarization resulting from G-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-GPCR control of electrical excitability, Ca handling, and insulin secretion.
G 蛋白偶联生长抑素或 α2-肾上腺素能受体的激活刺激β细胞 NKA 活性，导致胰岛 Ca 波动。此外，δ细胞分泌的生长抑素通过胰岛内旁分泌激活β细胞 G-GPCR 和 NKA，减缓 Ca 振荡，从而减少胰岛素分泌。G-GPCR 激活引起的β细胞膜电位超极化依赖于Src 酪氨酸激酶对 NKA 的磷酸化。然而，β细胞 NKA 功能受到 cAMP 依赖性 PKA 活性的抑制。这些数据表明，NKA 介导的β细胞膜电位超极化是 G-GPCR 控制电兴奋性、Ca 处理和胰岛素分泌的主要和保守机制。
