INSR and fibrosarcoma: Insulin increases eNOS activity and NO production through the insulin receptor (IR)/insulin receptor substrate 1 (IRS-1)/PI3K/phosphoinositide-dependent kinase-1 (PDK-1)/Ak strain transforming (AKT) pathway [54], while insulin stimulates ET-1 secretion through the IR/growth factor receptor-bound protein 1(GRB-1)/rat sarcoma (RAS)/rapidly accelerated fibrosarcoma (RAF)/MAPK pathway [54].