Role of High Voltage-Gated Ca(2+) Channel Subunits in Pancreatic β-Cell Insulin Release. From Structure to Function.
Role of High Voltage-Gated Ca(2+) Channel Subunits in Pancreatic β-Cell Insulin Release. From Structure to Function.
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高压门控 Ca(2+) 通道亚基在胰腺 β 细胞胰岛素释放中的作用。从结构到功能。
DOI：
10.3390/cells10082004
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发表时间：
2021-08-06
期刊：
影响因子：
6
通讯作者：
Geisler SM
中科院分区：
文献类型：
--
作者：
Tuluc P;Theiner T;Jacobo-Piqueras N;Geisler SM
朗格汉斯胰岛分泌多种对葡萄糖稳态至关重要的激素。 β细胞是胰岛的主要细胞成分，分泌胰岛素，这是唯一能够降低血浆葡萄糖浓度的激素。反调节激素胰高血糖素由 α 细胞分泌，而 δ 细胞则分泌生长抑素，通过旁分泌机制调节 α 和 β 细胞的活性。这三种肽激素被包装成分泌颗粒，在细胞内 Ca2+ 浓度局部增加后通过胞吐作用释放。高压门控 Ca2+ 通道 (HVCC) 在胰腺激素释放中发挥着核心作用，既是兴奋-分泌耦合所需的 Ca2+ 来源，又是释放机制的支架。 HVCC 是由主要成孔跨膜 α1 和辅助细胞内 β、细胞外 α2δ 和跨膜 γ 亚基组成的多蛋白复合物。在这里，我们回顾了目前关于胰腺 β 细胞中表达的所有 HVCC 亚基对电活动、兴奋-分泌耦合和 β 细胞质量的作用的理解。我们审查的证据来自许多采用药理学方法以及转基因小鼠模型的开创性研究。在编码 HVCC 亚基的基因的遗传变异的背景下讨论了对人类糖尿病的重要性。
The pancreatic islets of Langerhans secrete several hormones critical for glucose homeostasis. The β-cells, the major cellular component of the pancreatic islets, secrete insulin, the only hormone capable of lowering the plasma glucose concentration. The counter-regulatory hormone glucagon is secreted by the α-cells while δ-cells secrete somatostatin that via paracrine mechanisms regulates the α- and β-cell activity. These three peptide hormones are packed into secretory granules that are released through exocytosis following a local increase in intracellular Ca2+ concentration. The high voltage-gated Ca2+ channels (HVCCs) occupy a central role in pancreatic hormone release both as a source of Ca2+ required for excitation-secretion coupling as well as a scaffold for the release machinery. HVCCs are multi-protein complexes composed of the main pore-forming transmembrane α1 and the auxiliary intracellular β, extracellular α2δ, and transmembrane γ subunits. Here, we review the current understanding regarding the role of all HVCC subunits expressed in pancreatic β-cell on electrical activity, excitation-secretion coupling, and β-cell mass. The evidence we review was obtained from many seminal studies employing pharmacological approaches as well as genetically modified mouse models. The significance for diabetes in humans is discussed in the context of genetic variations in the genes encoding for the HVCC subunits.
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