Results

RDF/XMLNTriplesTurtleShow queryShare ▶
SubjectPredicateObject
http://purl.uniprot.org/citations/19492079http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19492079http://www.w3.org/2000/01/rdf-schema#comment"

Background

Ion transporters of the Slc30A-(ZnT-) family regulate zinc fluxes into sub-cellular compartments. beta-cells depend on zinc for both insulin crystallization and regulation of cell mass.

Methodology/principal findings

This study examined: the effect of glucose and zinc chelation on ZnT gene and protein levels and apoptosis in beta-cells and pancreatic islets, the effects of ZnT-3 knock-down on insulin secretion in a beta-cell line and ZnT-3 knock-out on glucose metabolism in mice during streptozotocin-induced beta-cell stress. In INS-1E cells 2 mM glucose down-regulated ZnT-3 and up-regulated ZnT-5 expression relative to 5 mM. 16 mM glucose increased ZnT-3 and decreased ZnT-8 expression. Zinc chelation by DEDTC lowered INS-1E insulin content and insulin expression. Furthermore, zinc depletion increased ZnT-3- and decreased ZnT-8 gene expression whereas the amount of ZnT-3 protein in the cells was decreased. Zinc depletion and high glucose induced apoptosis and necrosis in INS-1E cells. The most responsive zinc transporter, ZnT-3, was investigated further; by immunohistochemistry and western blotting ZnT-3 was demonstrated in INS-1E cells. 44% knock-down of ZnT-3 by siRNA transfection in INS-1E cells decreased insulin expression and secretion. Streptozotocin-treated mice had higher glucose levels after ZnT-3 knock-out, particularly in overt diabetic animals.

Conclusion/significance

Zinc transporting proteins in beta-cells respond to variations in glucose and zinc levels. ZnT-3, which is pivotal in the development of cellular changes as also seen in type 2 diabetes (e.g. amyloidosis in Alzheimer's disease) but not previously described in beta-cells, is present in this cell type, up-regulated by glucose in a concentration dependent manner and up-regulated by zinc depletion which by contrast decreased ZnT-3 protein levels. Knock-down of the ZnT-3 gene lowers insulin secretion in vitro and affects in vivo glucose metabolism after streptozotocin treatment."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.org/dc/terms/identifier"doi:10.1371/journal.pone.0005684"xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Culvenor J.G."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Larsen A."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Bush A.I."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Jessen N."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Schmitz O."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Brock B."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Petersen A.B."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Rungby J."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Smidt K."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Wogensen L."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Stoltenberg M."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Tsatsanis A."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Jeppesen J.B."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/author"Magnusson N."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/date"2009"xsd:gYear
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/name"PLoS One"xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/pages"e5684"xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/title"SLC30A3 responds to glucose- and zinc variations in beta-cells and is critical for insulin production and in vivo glucose-metabolism during beta-cell stress."xsd:string
http://purl.uniprot.org/citations/19492079http://purl.uniprot.org/core/volume"4"xsd:string
http://purl.uniprot.org/citations/19492079http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/19492079
http://purl.uniprot.org/citations/19492079http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/19492079
http://purl.uniprot.org/uniprot/#_P97441-mappedCitation-19492079http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/19492079
▶