Egefjord Laerke, Petersen Andreas B, Rungby Jørgen
Department of Pharmacology, University of Aarhus, Aarhus, Denmark.
Curr Diabetes Rev. 2010 Jan;6(1):52-7. doi: 10.2174/157339910790442655.
Zinc concentrates in islet cells and is related to insulin secretion. Islet cells act as a unit within islets and hormone secretion in the islets is profoundly influenced by paracrine and autocrine regulation. Zinc has been recognised as a candidate paracrine inhibitor of glucagon secretion in alpha-cells. Further zinc fluxes may contribute to regulation of cell mass, Zn2+ may be cytotoxic and Zn2+ depletion by itself can cause cell death induced by oxidative stress. Recently, both free zinc ions and a number of zinc transporters have been localized in alpha-cells. These include zinc importers, ZIP1, ZIP10, and ZIP14 of the SLC39A family and zinc exporters, ZnT1, and ZnT4-8 of the SLC30A family. Furthermore, the redox state of thiol groups and Voltage Gated Ca2+ Channels (VGCC) add to the maintenance of a tight cytoplasmatic zinc homeostasis in the alpha-cells. The ZnT8 protein has emerged as particularly interesting since this zinc transporter has been identified as a genetic risk factor for the development of both type 1 and type 2 diabetes in which both alpha- and beta-cell functions are affected. Recent data discussed here suggest specific effects of Zn2+ on glucagon secretion and other alpha-cell functions.
锌在胰岛细胞中富集并与胰岛素分泌相关。胰岛细胞作为胰岛内的一个单位，胰岛中的激素分泌受到旁分泌和自分泌调节的深刻影响。锌已被认为是α细胞中胰高血糖素分泌的候选旁分泌抑制剂。进一步的锌通量可能有助于调节细胞数量，锌离子可能具有细胞毒性，而锌离子自身的耗竭可导致氧化应激诱导的细胞死亡。最近，游离锌离子和一些锌转运体已在α细胞中定位。这些包括SLC39A家族的锌导入体ZIP1、ZIP10和ZIP14以及SLC30A家族的锌输出体ZnT1和ZnT4 - 8。此外，硫醇基团的氧化还原状态和电压门控钙通道（VGCC）有助于维持α细胞内严格的细胞质锌稳态。ZnT8蛋白显得尤为有趣，因为这种锌转运体已被确定为1型和2型糖尿病发生发展的遗传风险因素，在这两种糖尿病中α细胞和β细胞的功能均受到影响。此处讨论的最新数据表明锌离子对胰高血糖素分泌和其他α细胞功能具有特定作用。
