Insulin signaling via phosphorylation of the Src homology 2 domain-containing transforming proteins (SHC) and subsequent activation of the mitogen-activated kinase protein kinase kinase (MEK) - extracellular signal-regulated kinase (ERK) is not affected by insulin resistance and contributes to these effects of hyperinsulinemia (Figure 2) (101, 102). This evidence concerns the gene INS and Insulin resistance.