Current and Future Clinical Applications of Zinc Transporter-8 in Type 1 Diabetes Mellitus

OBJECTIVE: To evaluate the utility of zinc transporter-8 (ZnT8) in the improvement of type 1 diabetes mellitus (T1DM) diagnosis and prediction, and to explore whether ZnT8 is a potential therapeutic target in T1DM. DATA SOURCES: A search was conducted within the medical database PubMed for relevant articles published from 2001 to 2015. The search terms are as follows: “ZnT8,” “type 1 diabetes,” “latent autoimmune diabetes in adults,” “type 2 diabetes,” “islet autoantibodies,” “zinc supplement,” “T cells,” “β cell,” “immune therapy.” We also searched the reference lists of selected articles. STUDY SELECTION: English-language original articles and critical reviews concerning ZnT8 and the clinical applications of islet autoantibodies in diabetes were reviewed. RESULTS: The basic function of ZnT8 is maintaining intracellular zinc homeostasis, which modulates the process of insulin biosynthesis, storage, and secretion. Autoantibodies against ZnT8 (ZnT8A) and ZnT8-specific T cells are the reliable biomarkers for the identification, stratification, and characterization of T1DM. Additionally, the results from the animal models and clinical trials have shown that ZnT8 is a diabetogenic antigen, suggesting the possibility of ZnT8-specific immunotherapy as an alternative for T1DM therapy. CONCLUSIONS: ZnT8 is a novel islet autoantigen with a widely potential for clinical applications in T1DM. However, before the large-scale clinical applications, there are still many problems to be solved.