The Zinc Transporter Slc30a8/ZnT8 Is Required in a Subpopulation of Pancreatic α-Cells for Hypoglycemia-induced Glucagon Secretion.

ABSTRACT: SLC30A8 encodes a zinc transporter ZnT8 largely restricted to pancreatic islet β- and α-cells, and responsible for zinc accumulation into secretory granules. Although common SLC30A8 variants, believed to reduce ZnT8 activity, increase type 2 diabetes risk in humans, rare inactivating mutations are protective. To investigate the role of Slc30a8 in the control of glucagon secretion, Slc30a8 was inactivated selectively in α-cells by crossing mice with alleles floxed at exon 1 to animals expressing Cre recombinase under the pre-proglucagon promoter. Further crossing to Rosa26:tdRFP mice, and sorting of RFP(+): glucagon(+) cells from KO mice, revealed recombination in ∼ 30% of α-cells, of which ∼ 50% were ZnT8-negative (14 ± 1.8% of all α-cells). Although glucose and insulin tolerance were norm

SUBMITTER: Solomou A 

PROVIDER: S-EPMC4571871 | biostudies-literature | 2015 Aug

REPOSITORIES: biostudies-literature