Several lines of evidence suggest that estrogen (17-β estradiol; E2) protects against diabetes mellitus and plays important roles in pancreatic β-cell survival and function. Mounting clinical and experimental evidence also suggest that E2 modulates cellular iron metabolism by regulating the expression of several iron regulatory genes, including hepcidin (HAMP), hypoxia-inducible factor 1-α, ferroportin (SLC40A1), and lipocalin (LCN2). However, whether E2 regulates cellular iron metabolism in pancreatic β cells and whether the antidiabetic effects of E2 can be, at least partially, attributed to its role in iron metabolism is not known. In this context, pancreatic β cells express considerable levels of conventional E2 receptors (ERs; mainly ER-α) and nonconventional G protein-coupled estrogen receptors and hence responsive to E2 signals. Moreover, pancreatic islet cells require significant amounts of iron for proper functioning, replication and survival and, hence, well equipped to manage cellular iron metabolism (acquisition, utilization, storage, and release). In this review, we examine the link between E2 and cellular iron metabolism in pancreatic β cells and discuss the bearing of such a link on β-cell survival and function.
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