Insulin also upregulates angiotensin II type 1 receptors in mesangial cells, thereby intensifying the adverse effects of angiotensin II on the kidneys.21 Moreover, insulin resistance and hyperinsulinemia are associated with excessive local production of endothelin-1, decreased endothelial production of nitric oxide and increased oxidative stress.22 This evidence concerns the gene EDN1 and hyperinsulinism.