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

Islets. 2009 Sep-Oct;1(2):124-8. doi: 10.4161/isl.1.2.9433.

Abstract

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.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / metabolism
  • Antibody Specificity
  • Cation Transport Proteins / genetics*
  • Cation Transport Proteins / immunology
  • Cation Transport Proteins / metabolism
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / genetics*
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / pathology*
  • Down-Regulation / genetics
  • Female
  • Gene Expression
  • Humans
  • Insulin-Secreting Cells / metabolism*
  • Insulin-Secreting Cells / pathology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Rabbits
  • Rats
  • Zinc Transporter 8

Substances

  • Antibodies
  • Cation Transport Proteins
  • Slc30a8 protein, mouse
  • Zinc Transporter 8