title: siRNA-mediated knock-down of ZnT3 and ZnT8 affects production and secretion of insulin and apoptosis in INS-1E cells.
abstract: Zinc is essential for the crystallization of insulin in pancreatic β-cells and is thought to induce apoptosis in a dose-dependent manner, thereby regulating β-cell mass. Therefore, a tight intracellular regulation of Zn²(+) is required. The zinc-transporter family SLC30A is an important factor in the regulation of zinc homeostasis. The aim of this study was to examine the effect of the zinc transporters ZnT3 and ZnT8 on insulin metabolism and apoptosis. Both these proteins are present in pancreatic β-cells and have been linked to diabetes. The objective of our study was to perform a considerable siRNA-mediated knock-down of ZnT3 and ZnT8 in INS-1E cells, a pancreatic β-cell model, and afterwards examine the impact on cell viability and insulin metabolism. Increased levels of apoptosis were observed after knock-down of both ZnT3 and ZnT8. Insulin secretion was significantly reduced by ZnT3 knock-down, whereas knock-down of ZnT8 resulted in increased intracellular content of insulin accompanied by a relatively lowered secretion. Both zinc transporters in this way seem to play a role in β-cell survival and the ability of these cells to react appropriately to surrounding glucose concentrations.
authors.affiliation: Department of Pharmacology, University of Aarhus, Denmark. andreas.petersen@farm.au.dk
authors.forename: Andreas B
authors.initials: AB
authors.lastname: Petersen
authors.forename: Kamille
authors.initials: K
authors.lastname: Smidt
authors.forename: Nils E
authors.initials: NE
authors.lastname: Magnusson
authors.forename: Fabrice
authors.initials: F
authors.lastname: Moore
authors.forename: Laerke
authors.initials: L
authors.lastname: Egefjord
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
mesh_terms: D000818:Animals; D017209:Apoptosis; D027682:Cation Transport Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D007328:Insulin / Q000096:biosynthesis* / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D000075703:Zinc Transporter 8
chemical_list: D027682:Cation Transport Proteins; D007328:Insulin; D034741:RNA, Small Interfering; C542071:Slc30a8 protein, rat; D000075703:Zinc Transporter 8; C503697:zinc transporter 3, rat