锌转运蛋白8与1型和2型糖尿病的研究进展

ZnT8(zinc transporter,member8)是锌离子转运蛋白,主要定位于胰岛β细胞,能将胞浆锌离子转运至胰岛素储存/分泌性囊泡内,其转运功能降低会影响胰岛素合成、储存和分泌,能增加2型糖尿病(T2DM)的发病风险。ZnT8蛋白也可作为抗原引起β细胞自身免疫损伤,诱发1型糖尿病(T1DM)。ZnT8基因多态性是引起其锌离子转运功能和免疫原性变化的重要因素,与糖尿病的发生、发展密切相关。该文综述了ZnT8与T1DM和T2DM的研究进展,提示ZnT8可作为糖尿病防治的新药物靶点。

Development of the association of ZnT8 with type 1 diabetes and type 2 diabetes

ZnT8 （zinc transporter,member 8） has recently emerged as a major autoantigenic target of type 1 diabetes and the encoding gene also acts as a genetic marker for type 2 diabetes. This transporter,localized in secretion/storage vesicles membrane,facilitates the cellular efflux of zinc from the cytoplasm into intracellular insulincontaining vesicles and provision of zinc for insulin maturation and storage processes. Altered function of ZnT8 in pancreatic β cells of subjects carrying the risk allele might produce zinc imbalance between secretory/storage vesicles and cytoplasm,with subsequent cell death and loss of β cell mass. Therefore,it may serve as a mediator of insulin synthesizes,storage and secretion. The common polymorphism at aa 325 of the protein has been implicated in type 1 diabetes by determining the autoantibody epitope specificity. The polymorphism of the gene has been suggested for a dual role,which is in modulating anti-ZnT8 self-antibody specificity and conferring genetic susceptibility to type 2 diabetes. In this review,recent progresses of the study in ZnT8 structure,function and the association with type 1 diabetes and type 2 diabetes will be summarized.