| First Author | Hansen JB | Year | 2012 |
| Journal | Cell Metab | Volume | 16 |
| Issue | 4 | Pages | 449-61 |
| PubMed ID | 23000401 | Mgi Jnum | J:191004 |
| Mgi Id | MGI:5451144 | Doi | 10.1016/j.cmet.2012.09.001 |
| Citation | Hansen JB, et al. (2012) Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic beta cell fate in response to cytokines. Cell Metab 16(4):449-61 |
| abstractText | 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-1beta induces divalent metal transporter 1 (DMT1) expression correlating with increased beta 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, beta cells become prone to ROS-mediated inflammatory damage via aberrant cellular iron metabolism, a finding with potential general cellular implications. |
