Previous studies from our group have shown excess superoxide production in mice with whole body haploinsufficiency of the insulin receptor (6, 30) in mice with endothelial cell-specific insulin resistance due to expression of a dominant negative human insulin receptor (5, 30) and in mice with excessive insulin signaling in the endothelium, a model of hyperinsulinemia induced insulin resistance (32). Here, INSR is linked to hyperinsulinism.