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健康及2型糖尿病状态下胰腺β细胞中的钙信号传导

Calcium signaling in pancreatic β-cells in health and in Type 2 diabetes.

作者信息

Gilon Patrick, Chae Hee-Young, Rutter Guy A, Ravier Magalie A

机构信息

Pole d'endocrinologie, diabète et nutrition, Institut de recherche expérimentale et clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.

Pole d'endocrinologie, diabète et nutrition, Institut de recherche expérimentale et clinique, Université Catholique de Louvain, B-1200 Brussels, Belgium.

出版信息

Cell Calcium. 2014 Nov;56(5):340-61. doi: 10.1016/j.ceca.2014.09.001. Epub 2014 Sep 8.

DOI:10.1016/j.ceca.2014.09.001
PMID:25239387
Abstract

Changes in cytosolic free Ca(2+) concentration ([Ca(2+)]c) play a crucial role in the control of insulin secretion from the electrically excitable pancreatic β-cell. Secretion is controlled by the finely tuned balance between Ca(2+) influx (mainly through voltage-dependent Ca(2+) channels, but also through voltage-independent Ca(2+) channels like store-operated channels) and efflux pathways. Changes in [Ca(2+)]c directly affect [Ca(2+)] in various organelles including the endoplasmic reticulum (ER), mitochondria, the Golgi apparatus, secretory granules and lysosomes, as imaged using recombinant targeted probes. Because most of these organelles have specific Ca(2+) influx and efflux pathways, they mutually influence free [Ca(2+)] in the others. In this article, we review the mechanisms of control of [Ca(2+)] in various compartments and particularly the cytosol, the endoplasmic reticulum ([Ca(2+)]ER), acidic stores and mitochondrial matrix ([Ca(2+)]mito), focusing chiefly on the most important physiological stimulus of β-cells, glucose. We also briefly review some alterations of β-cell Ca(2+) homeostasis in Type 2 diabetes.

摘要

胞质游离钙离子浓度([Ca(2+)]c)的变化在电兴奋性胰腺β细胞胰岛素分泌的调控中起着关键作用。分泌受Ca(2+)内流(主要通过电压依赖性Ca(2+)通道,但也通过如储存-操作性通道等电压非依赖性Ca(2+)通道)与外流途径之间精确调节的平衡所控制。如使用重组靶向探针成像所示,[Ca(2+)]c的变化直接影响包括内质网(ER)、线粒体、高尔基体、分泌颗粒和溶酶体在内的各种细胞器中的[Ca(2+)]。由于这些细胞器中的大多数都有特定的Ca(2+)内流和外流途径,它们相互影响其他细胞器中的游离[Ca(2+)]。在本文中,我们综述了各种区室特别是胞质溶胶、内质网([Ca(2+)]ER)、酸性储存库和线粒体基质([Ca(2+)]mito)中[Ca(2+)]的调控机制,主要聚焦于β细胞最重要的生理刺激物——葡萄糖。我们还简要综述了2型糖尿病中β细胞Ca(2+)稳态的一些改变。

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