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Review
. 2016 Jul;7(4):459-65.
doi: 10.1111/jdi.12441. Epub 2016 Jan 9.

Different role of zinc transporter 8 between type 1 diabetes mellitus and type 2 diabetes mellitus

Bo Yi  1 , Gan Huang  1 , Zhiguang Zhou  1
Affiliations
Review

Different role of zinc transporter 8 between type 1 diabetes mellitus and type 2 diabetes mellitus

Bo Yi et al. J Diabetes Investig. 2016 Jul.

Abstract

Diabetes can be simply classified into type 1 diabetes mellitus and type 2 diabetes mellitus. Zinc transporter 8 (ZnT8), a novel islet autoantigen, is specifically expressed in insulin-containing secretory granules of β-cells. Genetic studies show that the genotypes of SLC30A8 can determine either protective or diabetogenic response depending on environmental and lifestyle factors. The ZnT8 protein expression, as well as zinc content in β-cells, was decreased in diabetic mice. Thus, ZnT8 might participate in insulin biosynthesis and release, and subsequently involved deteriorated β-cell function through direct or indirect mechanisms in type 1 diabetes mellitus and type 2 diabetes mellitus. From a clinical feature standpoint, the prevalence of ZnT8A is gradiently increased in type 2 diabetes mellitus, latent autoimmune diabetes in adults and type 1 diabetes mellitus. The frequency and epitopes of ZnT8-specific T cells and cytokine release by ZnT8-specific T cells are also different in diabetic patients and healthy controls. Additionally, the response to ZnT8 administration is also different in type 1 diabetes mellitus and type 2 diabetes mellitus. In the present review, we summarize the literature about clinical aspects of ZnT8 in the pathogenesis of diabetes, and suggest that ZnT8 might play a different role between type 1 diabetes mellitus and type 2 diabetes mellitus.

Keywords: Type 1 diabetes mellitus; Type 2 diabetes mellitus; Zinc transporter 8.

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Figures

Figure 1
Figure 1
The clinical features (below the dotted line) and potential pathway (above the dotted line) of zinc transporter 8 (ZnT8)in diabetes. The initial phase of diabetes might be the interaction between genetic and environmental factors. One or more of the 12 rare mutations of SLC30A8 might be dominant to environmental factors and reduce the risk of diabetes (protect effect). In contrast, the C allele of rs13266634 single nucleotide polymorphism might downregulate ZnT8 protein expression and transporter activity causing decreased zinc concentration (indirect biological effect), and subsequently impaired β‐cell function (direct biological effect). In addition, during the biosynthesis and secretion of insulin, exocytosis of insulin granules can increase the chance of ZnT8 exposed to the cell surface, which initiates ZnT8 epitope‐specific T cells‐mediated β‐cell destruction, and cause type 1 diabetes mellitus (T1DM; autoimmune injury), or cause type 2 diabetes mellitus (T2DM) and latent autoimmune diabetes in adults (LADA; combined with insulin resistance). The prevalence of ZnT8A and ZnT8‐specific T cells is gradiently decreased from T1DM, through T2DM, then to healthy controls clinically. The cytokine secretion and T cell epitopes of ZnT8‐specific T cells are different in T1DM and T2DM. The solid lines represent certain effect. The dashed line represents the possible effect. The symbol ‘?’ represents the lack of relevant data. IL‐10, interleukin‐10; Th1, type 1 T helper; Th2, type 2 T helper.
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