Department of Molecular Physiology and Biophysics, Vanderbilt University, 7415 MRB4 (Langford), 2213 Garland Avenue, Nashville, TN 37232, USA.
Department of Biochemistry and Molecular Biology, Oregon Health & Science University, L224, MRB 624, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
J Mol Biol. 2020 Mar 6;432(5):1326-1346. doi: 10.1016/j.jmb.2019.08.014. Epub 2019 Aug 30.
Ca is an essential signal for pancreatic β-cell function. Ca plays critical roles in numerous β-cell pathways such as insulin secretion, transcription, metabolism, endoplasmic reticulum function, and the stress response. Therefore, β-cell Ca handling is tightly controlled. At the plasma membrane, Ca entry primarily occurs through voltage-dependent Ca channels. Voltage-dependent Ca channel activity is dependent on orchestrated fluctuations in the plasma membrane potential or voltage, which are mediated via the activity of many ion channels. During the pathogenesis of type 2 diabetes the β-cell is exposed to stressful conditions, which result in alterations of Ca handling. Some of the changes in β-cell Ca handling that occur under stress result from perturbations in ion channel activity, expression or localization. Defective Ca signaling in the diabetic β-cell alters function, limits insulin secretion and exacerbates hyperglycemia. In this review, we focus on the β-cell ion channels that control Ca handling and how they impact β-cell dysfunction in type 2 diabetes.
钙是胰腺β细胞功能的必需信号。钙在胰岛素分泌、转录、代谢、内质网功能和应激反应等众多β细胞途径中发挥关键作用。因此,β细胞的钙处理受到严格控制。在质膜上,钙主要通过电压依赖性钙通道进入。电压依赖性钙通道的活性取决于质膜电位或电压的协调波动,这是通过许多离子通道的活性来介导的。在 2 型糖尿病的发病机制中,β细胞暴露于应激条件下,导致钙处理发生改变。β细胞钙处理中的一些应激下发生的变化是由于离子通道活性、表达或定位的改变。糖尿病β细胞中钙信号的缺陷改变了功能,限制了胰岛素的分泌,并加重了高血糖。在这篇综述中,我们重点介绍了控制钙处理的β细胞离子通道,以及它们如何影响 2 型糖尿病中的β细胞功能障碍。