Insulin release from beta cells depends on ATP energy generated by mitochondrial. The electron transport chain is the primary group of proteins that make ATP energy and they require iron to do so. Consequently, iron is essential for insulin release, and iron deficiency inhibits beta cell function. Conversely, excess cellular iron leads to an increase in reactive oxygen species (ROS), which can damage cells and cause dysfunction. Evidence indicates that both ROS and mitochondrial dysfunction occur during diabetes progression. Beta cells have low antioxidant capacity making them susceptible to ROS from iron overload. Iron overload can cause mitochondrial fragmentation and dysfunction. Indeed, diseases of iron overload such as hereditary hemochromatosis and Friedreich’s ataxia have an associated risk of diabetes in the absence of autoimmunity. Inflammation alters iron metabolism by promoting sequestration within cells. Prolonged inflammation can cause anemia of inflammation, which has been reported in patients with T1D, where serum iron levels are too low to promote the differentiation of red blood cells. An inflammatory signaling molecule called interferon gamma (IFNy) is increased in individuals who develop diabetes long before the onset of disease. IFNy has been shown to increase cellular iron. Taken together, these data demonstrate the importance of understanding iron metabolism under basal conditions and during T1D disease progression in beta cells. Importantly, iron metabolism pathways may serve as targets for intervention for the treatment of diabetes.
