Format

Send to

Choose Destination

See 1 citation found by title matching your search:

Cell Metab. 2012 Oct 3;16(4):449-61. doi: 10.1016/j.cmet.2012.09.001. Epub 2012 Sep 20.

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

Author information

1
Center for Medical Research Methodology, Department of Biomedical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

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-1β induces divalent metal transporter 1 (DMT1) expression correlating with increased β 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, β cells become prone to ROS-mediated inflammatory damage via aberrant cellular iron metabolism, a finding with potential general cellular implications.

PMID:
23000401
DOI:
10.1016/j.cmet.2012.09.001
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center