Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines. / Hansen, Jakob Bondo; Tonnesen, Morten Fog; Madsen, Andreas Nygaard; Hagedorn, Peter; Friberg, Josefine; Grunnet, Lars Groth; Heller, R Scott; Nielsen, Anja Østergren; Størling, Joachim; Baeyens, Luc; Anker-Kitai, Leeat; Qvortrup, Klaus; Bouwens, Luc; Efrat, Shimon; Aalund, Mogens; Andrews, Nancy C; Billestrup, Nils; Karlsen, Allan E; Holst, Birgitte; Pociot, Flemming; Mandrup-Poulsen, Thomas.

In: Cell Metabolism, Vol. 16, No. 4, 2012, p. 449-61.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Hansen, JB, Tonnesen, MF, Madsen, AN, Hagedorn, P, Friberg, J, Grunnet, LG, Heller, RS, Nielsen, AØ, Størling, J, Baeyens, L, Anker-Kitai, L, Qvortrup, K, Bouwens, L, Efrat, S, Aalund, M, Andrews, NC, Billestrup, N, Karlsen, AE, Holst, B, Pociot, F & Mandrup-Poulsen, T 2012, 'Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines', Cell Metabolism, vol. 16, no. 4, pp. 449-61. https://doi.org/10.1016/j.cmet.2012.09.001

APA

Hansen, J. B., Tonnesen, M. F., Madsen, A. N., Hagedorn, P., Friberg, J., Grunnet, L. G., Heller, R. S., Nielsen, A. Ø., Størling, J., Baeyens, L., Anker-Kitai, L., Qvortrup, K., Bouwens, L., Efrat, S., Aalund, M., Andrews, N. C., Billestrup, N., Karlsen, A. E., Holst, B., ... Mandrup-Poulsen, T. (2012). Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines. Cell Metabolism, 16(4), 449-61. https://doi.org/10.1016/j.cmet.2012.09.001

Vancouver

Hansen JB, Tonnesen MF, Madsen AN, Hagedorn P, Friberg J, Grunnet LG et al. Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines. Cell Metabolism. 2012;16(4):449-61. https://doi.org/10.1016/j.cmet.2012.09.001

Author

Hansen, Jakob Bondo ; Tonnesen, Morten Fog ; Madsen, Andreas Nygaard ; Hagedorn, Peter ; Friberg, Josefine ; Grunnet, Lars Groth ; Heller, R Scott ; Nielsen, Anja Østergren ; Størling, Joachim ; Baeyens, Luc ; Anker-Kitai, Leeat ; Qvortrup, Klaus ; Bouwens, Luc ; Efrat, Shimon ; Aalund, Mogens ; Andrews, Nancy C ; Billestrup, Nils ; Karlsen, Allan E ; Holst, Birgitte ; Pociot, Flemming ; Mandrup-Poulsen, Thomas. / Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines. In: Cell Metabolism. 2012 ; Vol. 16, No. 4. pp. 449-61.

Bibtex

@article{3458d13c7603431b8b920c9d3acc2023,

title = "Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic {\ss} cell fate in response to cytokines",

abstract = "Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Little is known about iron transport regulation during inflammatory attack. Through a combination of in vitro and in vivo studies, we show that the proinflammatory cytokine IL-1{\ss} induces divalent metal transporter 1 (DMT1) expression correlating with increased {\ss} cell iron content and ROS production. Iron chelation and siRNA and genetic knockdown of DMT1 expression reduce cytokine-induced ROS formation and cell death. Glucose-stimulated insulin secretion in the absence of cytokines in Dmt1 knockout islets is defective, highlighting a physiological role of iron and ROS in the regulation of insulin secretion. Dmt1 knockout mice are protected against multiple low-dose streptozotocin and high-fat diet-induced glucose intolerance, models of type 1 and type 2 diabetes, respectively. Thus, {\ss} cells become prone to ROS-mediated inflammatory damage via aberrant cellular iron metabolism, a finding with potential general cellular implications.",

author = "Hansen, {Jakob Bondo} and Tonnesen, {Morten Fog} and Madsen, {Andreas Nygaard} and Peter Hagedorn and Josefine Friberg and Grunnet, {Lars Groth} and Heller, {R Scott} and Nielsen, {Anja {\O}stergren} and Joachim St{\o}rling and Luc Baeyens and Leeat Anker-Kitai and Klaus Qvortrup and Luc Bouwens and Shimon Efrat and Mogens Aalund and Andrews, {Nancy C} and Nils Billestrup and Karlsen, {Allan E} and Birgitte Holst and Flemming Pociot and Thomas Mandrup-Poulsen",

year = "2012",

doi = "10.1016/j.cmet.2012.09.001",

language = "English",

volume = "16",

pages = "449--61",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "4",

}

RIS

TY - JOUR

T1 - Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic ß cell fate in response to cytokines

AU - Hansen, Jakob Bondo

AU - Tonnesen, Morten Fog

AU - Madsen, Andreas Nygaard

AU - Hagedorn, Peter

AU - Friberg, Josefine

AU - Grunnet, Lars Groth

AU - Heller, R Scott

AU - Nielsen, Anja Østergren

AU - Størling, Joachim

AU - Baeyens, Luc

AU - Anker-Kitai, Leeat

AU - Qvortrup, Klaus

AU - Bouwens, Luc

AU - Efrat, Shimon

AU - Aalund, Mogens

AU - Andrews, Nancy C

AU - Billestrup, Nils

AU - Karlsen, Allan E

AU - Holst, Birgitte

AU - Pociot, Flemming

AU - Mandrup-Poulsen, Thomas

PY - 2012

Y1 - 2012

N2 - Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Little is known about iron transport regulation during inflammatory attack. Through a combination of in vitro and in vivo studies, we show that the proinflammatory cytokine IL-1ß induces divalent metal transporter 1 (DMT1) expression correlating with increased ß cell iron content and ROS production. Iron chelation and siRNA and genetic knockdown of DMT1 expression reduce cytokine-induced ROS formation and cell death. Glucose-stimulated insulin secretion in the absence of cytokines in Dmt1 knockout islets is defective, highlighting a physiological role of iron and ROS in the regulation of insulin secretion. Dmt1 knockout mice are protected against multiple low-dose streptozotocin and high-fat diet-induced glucose intolerance, models of type 1 and type 2 diabetes, respectively. Thus, ß cells become prone to ROS-mediated inflammatory damage via aberrant cellular iron metabolism, a finding with potential general cellular implications.

AB - Reactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Little is known about iron transport regulation during inflammatory attack. Through a combination of in vitro and in vivo studies, we show that the proinflammatory cytokine IL-1ß induces divalent metal transporter 1 (DMT1) expression correlating with increased ß cell iron content and ROS production. Iron chelation and siRNA and genetic knockdown of DMT1 expression reduce cytokine-induced ROS formation and cell death. Glucose-stimulated insulin secretion in the absence of cytokines in Dmt1 knockout islets is defective, highlighting a physiological role of iron and ROS in the regulation of insulin secretion. Dmt1 knockout mice are protected against multiple low-dose streptozotocin and high-fat diet-induced glucose intolerance, models of type 1 and type 2 diabetes, respectively. Thus, ß cells become prone to ROS-mediated inflammatory damage via aberrant cellular iron metabolism, a finding with potential general cellular implications.

U2 - 10.1016/j.cmet.2012.09.001

DO - 10.1016/j.cmet.2012.09.001

M3 - Journal article

C2 - 23000401

VL - 16

SP - 449

EP - 461

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -

ID: 43223237

Department of Biomedical Sciences