Lise Wogensen

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

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Standard

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. / Smidt, Kamille; Jessen, Niels; Petersen, Andreas Brønden; Larsen, Agnete; Magnusson, Nils; Jeppesen, Johanne Bruun; Stoltenberg, Meredin; Culvenor, Janetta G; Tsatsanis, Andrew; Brock, Birgitte; Schmitz, Ole; Wogensen, Lise; Bush, Ashley I; Rungby, Jørgen.

I: P L o S One, Bind 4, Nr. 5, 2009, s. e5684.

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

Harvard

APA

CBE

MLA

Vancouver

Author

Smidt, Kamille ; Jessen, Niels ; Petersen, Andreas Brønden ; Larsen, Agnete ; Magnusson, Nils ; Jeppesen, Johanne Bruun ; Stoltenberg, Meredin ; Culvenor, Janetta G ; Tsatsanis, Andrew ; Brock, Birgitte ; Schmitz, Ole ; Wogensen, Lise ; Bush, Ashley I ; Rungby, Jørgen. / 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. I: P L o S One. 2009 ; Bind 4, Nr. 5. s. e5684.

Bibtex

@article{daf2cda0212b11dfb95d000ea68e967b,
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",
abstract = "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.",
keywords = "Animals, Blood Glucose, Carrier Proteins, Cation Transport Proteins, Cell Death, Cell Line, Chelating Agents, Dose-Response Relationship, Drug, Fasting, Gene Expression Regulation, Gene Knockdown Techniques, Glucose, Hyperglycemia, Insulin, Insulin-Secreting Cells, Membrane Proteins, Mice, Mice, Knockout, Rats, Streptozocin, Stress, Physiological, Zinc",
author = "Kamille Smidt and Niels Jessen and Petersen, {Andreas Br{\o}nden} and Agnete Larsen and Nils Magnusson and Jeppesen, {Johanne Bruun} and Meredin Stoltenberg and Culvenor, {Janetta G} and Andrew Tsatsanis and Birgitte Brock and Ole Schmitz and Lise Wogensen and Bush, {Ashley I} and J{\o}rgen Rungby",
year = "2009",
doi = "10.1371/journal.pone.0005684",
language = "English",
volume = "4",
pages = "e5684",
journal = "P L o S One",
issn = "1932-6203",
publisher = "public library of science",
number = "5",

}

RIS

TY - JOUR

T1 - 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

AU - Smidt, Kamille

AU - Jessen, Niels

AU - Petersen, Andreas Brønden

AU - Larsen, Agnete

AU - Magnusson, Nils

AU - Jeppesen, Johanne Bruun

AU - Stoltenberg, Meredin

AU - Culvenor, Janetta G

AU - Tsatsanis, Andrew

AU - Brock, Birgitte

AU - Schmitz, Ole

AU - Wogensen, Lise

AU - Bush, Ashley I

AU - Rungby, Jørgen

PY - 2009

Y1 - 2009

N2 - 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.

AB - 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.

KW - Animals

KW - Blood Glucose

KW - Carrier Proteins

KW - Cation Transport Proteins

KW - Cell Death

KW - Cell Line

KW - Chelating Agents

KW - Dose-Response Relationship, Drug

KW - Fasting

KW - Gene Expression Regulation

KW - Gene Knockdown Techniques

KW - Glucose

KW - Hyperglycemia

KW - Insulin

KW - Insulin-Secreting Cells

KW - Membrane Proteins

KW - Mice

KW - Mice, Knockout

KW - Rats

KW - Streptozocin

KW - Stress, Physiological

KW - Zinc

U2 - 10.1371/journal.pone.0005684

DO - 10.1371/journal.pone.0005684

M3 - Journal article

C2 - 19492079

VL - 4

SP - e5684

JO - P L o S One

JF - P L o S One

SN - 1932-6203

IS - 5

ER -