Deletion of the mouse Slc30a8 gene encoding zinc transporter-8 results in impaired insulin secretion

• DOI: 10.1042/bj20090530
• Publication Date: 2009-05-19T10:37:57Z
• Authors: Lynley D. Pound; Suparna A. Sarkar; Richard K. P. Ben...; Yingda Wang; Adisak Suwanichkul; Melanie K. Shadoan; Richard L. Printz; James K. Oeser; Catherine E. Lee; David W. Piston; Owen P. McGuinness; John C. Hutton; David R. Powell; Richard M. O'Brien
• Keywords: Pancreatic Islets; Carbohydrate Metabolism

The Slc30a8 gene encodes the islet-specific zinc transporter ZnT-8, which provides for insulin-hexamer formation. Polymorphic variants in amino acid residue 325 of human ZnT-8 are associated with altered susceptibility to Type 2 diabetes and autoantibody epitope specificity changes 1 diabetes. To assess physiological importance mice carrying a exon 3 deletion were analysed histologically phenotyped energy metabolism pancreatic hormone secretion. No gross anatomical or behavioural differences body weight observed between wild-type ZnT-8−/− mice, mouse islets indistinguishable from terms their numbers, size cellular composition. However, total content was markedly reduced islets, as evaluated both by Timm's histochemical staining sections direct measurements isolated islets. Blood glucose levels unchanged 16-week-old, 6 h fasted animals either gender; however, plasma insulin concentrations female (∼31%) male (∼47%) mice. Intraperitoneal tolerance tests demonstrated no impairment clearance but glucose-stimulated secretion ∼33% relative littermates. In summary, is accompanied modest without major alterations metabolism.