Downregulation of ZnT8 expression in pancreatic β-cells of diabetic mice.

Zinc transporter 8 (ZnT8) has been identified as a β-cell-specific Zinc transporter expressed in insulin-secretory granules. Recent genome wide association studies indicated that Arg325Trp polymorphism of Slc30a8 encoding ZnT8 is associated with susceptibility to type 2 diabetes. As a first step towards understanding the pathogenic role of ZnT8 in diabetes, we evaluated the expression of ZnT8 in mouse pancreas. A rabbit polyclonal antibody specific to ZnT8 was raised. The raised ZnT8 antibody reacted with mouse, rat and human ZnT8 expressed in β-cells without cross-reacting with other ZnTs. ZnT8 was expressed in α-, β- and PP-cells, but not in δ-cells, in adult mouse islets. During mouse pancreas development, ZnT8 expression was detected as early as embryonic day 15.5 when β-cells started to appear in large numbers. Finally, the expression level of ZnT8 was compared with pancreas of two diabetic model mice, db/db mice and Akita mice. In both animal models of diabetes, ZnT8 expression was remarkably downregulated in the early stage of diabetes. As a conclusion, ZnT8 is expressed in multiple lineages of endocrine cells in the pancreas. Our findings suggest that downregulation of ZnT8 may be associated with impaired function of β-cells in diabetes.