Figure 2

A simplified view of insulin/IGF1 signaling. Insulin/IGF1 signaling is mediated by a complex, highly integrated network that controls several processes. Two major pathways are activated by insulin/IGF1 signaling, the ATK/PI3K pathway and the ERK/MAPK pathway, which are involved in several cellular processes such as metabolism, cell growth, proliferation, and apoptosis. Activation of the INSR/IGF1R by insulin/IGF1 binding leads to autophosphorylation of the β subunits and the receptor tyrosine kinase subsequently phosphorylates IRS proteins on their tyrosine residues. This creates recognition sites for additional effector molecules containing SH2 domains, such the p85 regulatory subunit of PI3K (which activates the AKT/PI3K pathway and is mainly responsible for the metabolic actions of insulin/IGF1) and GRB2 (which activates the ERK/MAPK pathway and primarily regulates cell growth and differentiation). Additionally, the INSR and IGF1R can phosphorylate other substrates, such as SHC and GAB1, which link multiple pathways. Together, these signals stimulate a variety of different downstream biological effects including mitogenesis, gene expression, glucose transport, and glycogen synthesis.