دورية أكاديمية
أعرض في EDS

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.

التفاصيل البيبلوغرافية
العنوان: 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.
المؤلفون: Smidt K; Department of Pharmacology, University of Aarhus, Arhus, Denmark., Jessen N, Petersen AB, Larsen A, Magnusson N, Jeppesen JB, Stoltenberg M, Culvenor JG, Tsatsanis A, Brock B, Schmitz O, Wogensen L, Bush AI, Rungby J
المصدر: PloS one [PLoS One] 2009 May 25; Vol. 4 (5), pp. e5684. Date of Electronic Publication: 2009 May 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Carrier Proteins/*metabolism , Glucose/*pharmacology , Insulin/*metabolism , Insulin-Secreting Cells/*drug effects , Insulin-Secreting Cells/*metabolism , Membrane Proteins/*metabolism , Stress, Physiological/*drug effects , Zinc/*pharmacology, Animals ; Blood Glucose/drug effects ; Carrier Proteins/genetics ; Cation Transport Proteins/genetics ; Cation Transport Proteins/metabolism ; Cell Death/drug effects ; Cell Line ; Chelating Agents/pharmacology ; Dose-Response Relationship, Drug ; Fasting/blood ; Gene Expression Regulation/drug effects ; Gene Knockdown Techniques ; Glucose/metabolism ; Hyperglycemia/metabolism ; Insulin/genetics ; Insulin Secretion ; Insulin-Secreting Cells/cytology ; Membrane Proteins/genetics ; Membrane Transport Proteins ; Mice ; Mice, Knockout ; Rats ; Streptozocin ; Zinc Transporter 8
مستخلص: 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.
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المشرفين على المادة: 0 (Blood Glucose)
0 (Carrier Proteins)
0 (Cation Transport Proteins)
0 (Chelating Agents)
0 (Insulin)
0 (Membrane Proteins)
0 (Membrane Transport Proteins)
0 (Slc30a3 protein, mouse)
0 (Slc30a8 protein, mouse)
0 (Zinc Transporter 8)
5W494URQ81 (Streptozocin)
IY9XDZ35W2 (Glucose)
J41CSQ7QDS (Zinc)
تواريخ الأحداث: Date Created: 20090604 Date Completed: 20090720 Latest Revision: 20211020
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC2683566
DOI: 10.1371/journal.pone.0005684
PMID: 19492079
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0005684