Zinc transporters and their role in the pancreatic β-cell.

Zinc transporters and their role in the pancreatic β-cell.
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DOI:
10.1111/j.2040-1124.2012.00199.x
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发表时间:
2012-06-06
影响因子:
3.2
通讯作者:
Schuit F
Schuit F
中科院分区:
医学3区
文献类型:
--
作者:
Lemaire K;Chimienti F;Schuit F

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锌是一种对人类健康极其重要的必需营养素,缺锌是增加死亡率和发病率的严重危险因素。由于锌稳态异常会导致糖尿病,并且由于胰腺β细胞含有任何已知细胞类型中最高的锌含量,因此了解β细胞中锌通量是如何控制的很有意义。锌转运蛋白多蛋白家族的发现促进了对锌稳态的理解,其中之一-锌转运蛋白8(ZnT 8)-在胰岛中大量特异性表达。在这篇综述中,我们讨论了ZnT 8在锌-胰岛素晶体形成中的生理作用的证据,锌-胰岛素晶体是大多数胰岛素储存在分泌颗粒中的物理形式。此外,我们交叉检查了在转基因小鼠品系中收集的这些信息,以了解人类ZnT 8基因的遗传变异易患2型糖尿病,并且ZnT 8蛋白上的表位触发1型糖尿病患者的自身免疫。总的结论是,我们仍然处于完全理解锌稳态如何在正常β细胞中运作以及异常如何导致β细胞功能障碍和糖尿病的黎明。(J Diabetes Invest,doi:10.1111/j.2040 - 1124.2012.00199.x,2012)
Zinc is an essential nutrient with tremendous importance for human health, and zinc deficiency is a severe risk factor for increased mortality and morbidity. As abnormal zinc homeostasis causes diabetes, and because the pancreatic β‐cell contains the highest zinc content of any known cell type, it is of interest to know how zinc fluxes are controlled in β‐cells. The understanding of zinc homeostasis has been boosted by the discovery of multiprotein families of zinc transporters, and one of them – zinc transporter 8 (ZnT8) – is abundantly and specifically expressed in the pancreatic islets of Langerhans. In this review, we discuss the evidence for a physiological role of ZnT8 in the formation of zinc‐insulin crystals, the physical form in which most insulin is stored in secretory granules. In addition, we cross‐examine this information, collected in genetically modified mouse strains, to the knowledge that genetic variants of the human ZnT8 gene predispose to the onset of type 2 diabetes and that epitopes on the ZnT8 protein trigger autoimmunity in patients with type 1 diabetes. The overall conclusion is that we are still at the dawn of a complete understanding of how zinc homeostasis operates in normal β‐cells and how abnormalities lead to β‐cell dysfunction and diabetes. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2012.00199.x, 2012)
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