期刊
BIOCHEMICAL JOURNAL
卷 421, 期 -, 页码 371-376出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20090530
关键词
autoantigen; glucose; insulin; islet; Mouse; zinc transporter
资金
- National Institutes of Health [DK076027, DK064877, DK53434, GM72048, P60 DK20593, DK59637]
- Juvenile Diabetes Research Foundation Autoimmunity Prevention Center
- Barbara Davis Center Diabetes and Endocrinology Research Center [P30 DK57516]
- Department of Defence Medical Free-Electron Laser Program
- Vanderbilt Hormone Assay and Analytical Services Core
The Slc30a8 gene encodes the islet-specific zinc transporter ZnT-8, which provides zinc 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 ZnT-8 autoantibody epitope specificity changes in Type 1 diabetes. To assess the physiological importance of ZnT-8, mice carrying a Slc30a8 exon 3 deletion were analysed histologically and phenotyped for energy metabolism and pancreatic hormone secretion. No gross anatomical or behavioural changes or differences in body weight were observed between wild-type and ZnT-8(-/-) mice, and ZnT-8(-/-) mouse islets were indistinguishable from wild-type in terms of their numbers, size and cellular composition. However, total zinc content was markedly reduced in ZnT-8(-/-) Mouse islets, its evaluated both by Timm's histochemical staining of pancreatic sections and direct measurements in isolated islets. Blood glucose levels were unchanged in 16-week-old, 6 h fasted animals of either gender: however. plasma insulin concentrations were reduced in both female (similar to 31%) and male (similar to 47%) ZnT-8(-/-) mice. Intraperitoneal glucose tolerance tests demonstrated no impairment in glucose clearance in male ZnT-8(-/-) mice, but glucose-stimulated insulin secretion from isolated islets was reduced similar to 33% relative to wild-type littermates. In summary Slc30a8 gene deletion is accompanied by it modest impairment in insulin secretion without major alterations in glucose metabolism.
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