At pharmacologically relevant concentrations intravenous iron preparations cause pancreatic beta cell death.

BACK GROUND 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. METHODS 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. RESULTS Exposure to iron sucrose resulted in a concentration-dependent oxidative stress and pancreatic islet cell death predominantly affecting beta cells. CONCLUSIONS 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.