Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki 852-8501, Japan.
Endocr J. 2012;59(7):531-7. doi: 10.1507/endocrj.ej12-0069. Epub 2012 Mar 8.
Zinc is essential for the proper storage, secretion, and the action of insulin and is transported from cytoplasm to insulin secretory granules in the pancreatic β-cells by SLC30A zinc transporters (ZnT). ZnT8 is specifically expressed in the pancreatic β-cells and has been identified as a novel target autoantigen in patients with type 1 diabetes. Autoantibodies to ZnT8 (ZnT8A) are detected in 50-60% of Japanese patients with acute-onset and 20% with slow-onset type 1 diabetes. Furthermore, humoral autoreactivity to ZnT8 is unique in terms of a key determinant, which is not reported on other islet autoantigens such as insulin, glutamic acid decarboxylase, or the protein tyrosine phosphatase-related molecules IA-2. Type 2 diabetes-associated nonsynonymous single nucleotide polymorphism in SLC30A8 (the gene of ZnT8), rs13266634 (Arg325Trp), modulates ZnT8A specificities thereby indicating that this amino acid substitution has the critical role in antibody binding. The humoral autoreactivity to ZnT8 depends on the clinical phenotype, which may provide clues to understand the role of this protein in the pathogenesis of type 1 diabetes.
锌对于胰岛素的正确储存、分泌和作用是必不可少的，并且通过 SLC30A 锌转运体（ZnT）从细胞质转运到胰腺β细胞的胰岛素分泌颗粒中。ZnT8 特异性表达于胰腺β细胞，已被鉴定为 1 型糖尿病患者的新型自身抗原靶标。在急性起病的 50-60%的日本 1 型糖尿病患者和 20%的缓起病的患者中检测到针对 ZnT8（ZnT8A）的自身抗体。此外，ZnT8 的体液自身反应性在关键决定因素方面是独特的，在其他胰岛自身抗原（如胰岛素、谷氨酸脱羧酶或蛋白酪氨酸磷酸酶相关分子 IA-2）上未报道。SLC30A8（ZnT8 基因）中的与 2 型糖尿病相关的非同义单核苷酸多态性 rs13266634（Arg325Trp）调节 ZnT8A 的特异性，从而表明该氨基酸取代在抗体结合中具有关键作用。对 ZnT8 的体液自身反应性取决于临床表型，这可能为了解该蛋白在 1 型糖尿病发病机制中的作用提供线索。
