Figure 1. Insulin and IGF-1 signaling pathways intersect.

Insulin receptor and IGF-1 receptor activation initiates a cascade of phosphorylation events. At the time of ligand binding the receptors change conformation and autophosphorylate, leading to the recruitment and phosphorylation of receptor substrates, such as IRS and Shc proteins. Shc activates the Ras/MAPK pathway, whereas IRS protein recruits PI3K to activate the PI3K/AKT pathway, leading to the generation of the second messenger PIP₃. Membrane-bound PIP₃ then recruits and activates PDK1, which phosphorylates and activates AKT and atypical PKCs (aPKC). AKT mediates most of insulin’s metabolic effects and regulates the cell cycle and cell survival. The Shc/Grb2/SOS/Ras/Raf/MAPK pathway controls cellular proliferation and gene transcription.