Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
Islets. 2009 Sep-Oct;1(2):124-8. doi: 10.4161/isl.1.2.9433.
Zinc transporter 8 (ZnT8) has been identified as a β-cell-specific Zinc transporter expressed in insulin-secretory granules. Recent genome wide association studies indicated that Arg325Trp polymorphism of Slc30a8 encoding ZnT8 is associated with susceptibility to type 2 diabetes. As a first step towards understanding the pathogenic role of ZnT8 in diabetes, we evaluated the expression of ZnT8 in mouse pancreas. A rabbit polyclonal antibody specific to ZnT8 was raised. The raised ZnT8 antibody reacted with mouse, rat and human ZnT8 expressed in β-cells without cross-reacting with other ZnTs. ZnT8 was expressed in α-, β- and PP-cells, but not in δ-cells, in adult mouse islets. During mouse pancreas development, ZnT8 expression was detected as early as embryonic day 15.5 when β-cells started to appear in large numbers. Finally, the expression level of ZnT8 was compared with pancreas of two diabetic model mice, db/db mice and Akita mice. In both animal models of diabetes, ZnT8 expression was remarkably downregulated in the early stage of diabetes. As a conclusion, ZnT8 is expressed in multiple lineages of endocrine cells in the pancreas. Our findings suggest that downregulation of ZnT8 may be associated with impaired function of β-cells in diabetes.
锌转运蛋白 8（ZnT8）已被鉴定为一种在胰岛素分泌颗粒中表达的β细胞特异性锌转运蛋白。最近的全基因组关联研究表明，Slc30a8 编码 ZnT8 的 Arg325Trp 多态性与 2 型糖尿病的易感性有关。作为了解 ZnT8 在糖尿病中致病作用的第一步，我们评估了 ZnT8 在小鼠胰腺中的表达。我们制备了一种针对 ZnT8 的兔多克隆抗体。该 ZnT8 抗体与在β细胞中表达的小鼠、大鼠和人 ZnT8 反应，而不与其他 ZnTs 发生交叉反应。ZnT8 在α-、β-和 PP-细胞中表达，但在δ-细胞中不表达，在成年小鼠胰岛中。在小鼠胰腺发育过程中，ZnT8 的表达早在胚胎第 15.5 天β细胞大量出现时就被检测到。最后，我们比较了两种糖尿病模型小鼠（db/db 小鼠和 Akita 小鼠）的胰腺中 ZnT8 的表达水平。在这两种糖尿病动物模型中，ZnT8 的表达在糖尿病的早期阶段显著下调。总之，ZnT8 在胰腺的多个内分泌细胞谱系中表达。我们的研究结果表明，ZnT8 的下调可能与糖尿病中β细胞功能障碍有关。
