RESUMEN
Nitric oxide (NO) has been implicated in pancreatic ß-cell death in the development of diabetes. The mechanisms underlying NO-induced ß-cell death have not been clearly defined. Recently, receptor-interacting protein-1 (RIP1)-dependent necrosis, which is inhibited by necrostatin-1, an inhibitor of RIP1, has emerged as a form of regulated necrosis. Here, we show that NO donor-induced ß-cell death was inhibited by necrostatin-1. Unexpectedly, however, RIP1 knockdown neither inhibited cell death nor altered the protective effects of necrostatin-1 in NO donor-treated ß-cells. These results indicate that NO donor induces necrostatin-1-inhibitable necrotic ß-cell death independent of RIP1. Our findings raise the possibility that NO-mediated ß-cell necrosis may be a novel form of signal-regulated necrosis, which play a role in the progression of diabetes.