Human disease states that result in excess iron accumulation, e.g., hereditary hemochromatosis and beta thalassemia major, are associated with an increased incidence of diabetes. In these disorders surplus iron overwhelms normal transport and storage mechanisms leading to the appearance of excess free iron in circulation and the subsequent deposition of iron in tissues such as the pancreas. Excess iron in tissues can lead to the formation of free radicals, which can damage beta cells and lead to cell death or dysfunction. Despite the long-established connection between iron overload and diabetes, exactly how iron is transported into pancreatic beta cells is not yet known. Currently only three mammalian proteins are known to be able to transport free iron: Divalent Metal-Ion Transporter-1 (DMT1), ZRT/IRT-Like Protein 14 (ZIP14), and ZRT/IRT-Like Protein 8 (ZIP8). The aim of our project is to determine the expression and subcellular localization of these established iron transporters in the cell types of the human pancreas, focusing primarily on beta cells. Identification of potential routes for beta cell iron uptake will provide targets for future mechanistic studies concerning the relationship between beta cell iron loading and function.