ZnT8 and type 1 diabetes [Review]

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  • Kawasaki Eiji
    Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki 852-8501, Japan Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki 852-8501, Japan

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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.

収録刊行物

  • Endocrine Journal

    Endocrine Journal 59 (7), 531-537, 2012

    一般社団法人 日本内分泌学会

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