Departments of Surgery and Medicine, University of California Irvine, CA, USA.
Am J Transl Res. 2013 Dec 1;6(1):64-70. eCollection 2013.
Overt and subtle iron overload cause diabetes by lowering insulin production and promoting insulin resistance. Via divalent metal transporters pancreatic beta cells take up non-transferrin-bound iron which by catalyzing Fenton reaction can cause oxidative stress. Due to their strict dependence on mitochondrial glucose metabolism and limited antioxidant capacity, beta cells are exquisitely vulnerable to oxidative stress and hence catalytically active iron. Intravenous (IV) iron preparations are routinely used in the management of anemia in patients with end stage renal disease. This has led to an epidemic of iron overload in this population. This study explored the effect of pharmacologically-relevant concentrations of a commonly used IV iron preparation on the beta cells in isolated pancreatic islets.
Isolated rat pancreatic islets were incubated for 24 hours in culture media containing vehicle or pharmacologically-relevant concentration of ferric sucrose and examined for the extent of cell death and oxidative stress.
Exposure to iron sucrose resulted in a concentration-dependent oxidative stress and pancreatic islet cell death predominantly affecting beta cells.
At pharmacologically-relevant concentrations a commonly used IV iron preparation causes oxidative stress and beta cell death. These findings suggest that indiscriminate use of IV iron may impair insulin production capacity in ESRD patients the majority of whom have Type-2 diabetes.
显性和隐性铁过载通过降低胰岛素分泌和促进胰岛素抵抗导致糖尿病。通过二价金属转运蛋白，胰岛β细胞摄取非转铁蛋白结合铁，铁通过芬顿反应可以引起氧化应激。由于β细胞严格依赖于线粒体葡萄糖代谢和有限的抗氧化能力，因此对氧化应激和催化活性铁非常敏感。静脉内（IV）铁制剂常规用于治疗终末期肾病患者的贫血。这导致该人群中铁过载的流行。本研究探讨了常用 IV 铁制剂的药理相关浓度对分离胰岛中β细胞的影响。
将分离的大鼠胰岛在含有载体或药理相关浓度的蔗糖铁的培养基中孵育 24 小时，并检查细胞死亡和氧化应激的程度。
暴露于蔗糖铁导致浓度依赖性氧化应激和胰岛细胞死亡，主要影响β细胞。
在药理相关浓度下，常用的 IV 铁制剂会引起氧化应激和β细胞死亡。这些发现表明，在 ESRD 患者中，大量患有 2 型糖尿病的患者中，IV 铁的滥用可能会损害胰岛素的产生能力。
