Figure 1: The “big picture” between DM2 and cancer. (a) The shared metabolic factors underlying both DM2 and cancer, including visceral adiposity, inflammation, hyperglycemia, and hyperinsulinemia lead to (b) increased insulin receptor substrate (IRS) stimulating the phosphorylation of Ras signaling proteins and potentially increasing tumor cell growth and proliferation. IRS-associated PI3K signaling is compromised by insulin resistant states, such as in DM2, and downstream GLUT4 translocation is disrupted. This disruption drives PI3K signaling towards AKT/mTOR. AKT and mTOR can affect both the metabolic and mitogenic pathway, but because of the signaling dysfunction, AKT and mTOR are driven towards the mitogenic pathway.