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," "ß 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.

Modulation of monocyte hyperresponsiveness to TLR ligands by 1,25-dihydroxy-vitamin D3 from LADA and T2DM.

To investigate the differences of Toll-like receptors (TLRs) expression and response of monocyte and modulation of 1,25-dihydroxy-vitamin D3 on monocyte activity. Peripheral blood monocytes were collected from 23 healthy controls, 18 latent autoimmune diabetes in adults (LADA), and 22 type 2 diabetes mellitus (T2DM), respectively. CD14, TLR2 and TLR4 expression were analyzed. Moreover, the effect of 1,25-dihydroxy-vitamin D3 (1,25(OH)(2)D3) on monocyte response to lipoteichoic acid (LTA) and lipopolysaccharide (LPS) was evaluated in vitro by measuring phosphorylation level of NF-kappaB-p65 and associated cytokine production. Monocytes showed significantly higher surface CD14 expression from LADA compared with that from T2DM and controls, and high expression of TLR4 from LADA and T2DM than controls. After incubation with LPS or LTA, decreased surface expressions of CD14 were observed on monocytes from T2DM and controls, in contrast to the increased on monocytes from LADA. Activation of NF-kappaB and amounts of IL-1beta and TNF-alpha production by stimulation with ligands significantly increased in LADA and T2DM, which was modulated by 1,25(OH)(2)D3 to similar level, as compared to controls. The modulation of 1,25(OH)(2)D3 on monocytes makes us to consider more potency of vitamin D3 as therapy in LADA and T2DM.

[Complete Freund's adjuvant-induced splenic T cell apoptosis in the prevention of diabetes in non-obese diabetic mice].

OBJECTIVE: To study the apoptosis of T lymphocytes in the spleen and its role in complete Freund's adjuvant (CFA) preventing diabetes in non-obese diabetic (NOD) mice. METHODS: Forty-two NOD mice were divided into two groups randomly: CFA-treated NOD female mice (6w, 12w and 30w) and PBS-treated NOD female mice (6w, 12w and 30w). The apoptosis of splenic T lymphocytes was observed with the TDT-mediated fluorescein-dUTP nick-end labelling (TUNEL) technique and avidin-biotin complex method. RESULTS: CFA induced the apoptosis of CD4+ T lymphocytes in the mouse spleen and could prevent the development of Type 1 diabetes (T1DM) in NOD female mice. CONCLUSION: CFA preventing Type 1 diabetes in NOD mice may be related to the apoptosis of T lymphocytes in the spleen, which downregulates mature CD4+ T lymphocytes in the periphery.