title: Downregulation of ZnT8 expression in pancreatic β-cells of diabetic mice.
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.
authors.affiliation: Department of Medicine, Metabolism and Endocrinology, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo, Japan.
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tamaki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujitani
authors.forename: Toyoyoshi
authors.initials: T
authors.lastname: Uchida
authors.forename: Takahisa
authors.initials: T
authors.lastname: Hirose
authors.forename: Ryuzo
authors.initials: R
authors.lastname: Kawamori
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Watada
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000378:metabolism; D000918:Antibody Specificity; D027682:Cation Transport Proteins / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011817:Rabbits; D051381:Rats; D000075703:Zinc Transporter 8
chemical_list: D000906:Antibodies; D027682:Cation Transport Proteins; C516348:Slc30a8 protein, mouse; D000075703:Zinc Transporter 8