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

LD Pound, SA Sarkar, RKP Benninger… - Biochemical …, 2009 - portlandpress.com
LD Pound, SA Sarkar, RKP Benninger, Y Wang, A Suwanichkul, MK Shadoan, RL Printz…
Biochemical Journal, 2009portlandpress.com
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 …
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, as 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 (∼31%) and male (∼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 ∼33% relative to wild-type littermates. In summary, Slc30a8 gene deletion is accompanied by a modest impairment in insulin secretion without major alterations in glucose metabolism.
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