IGF1 and Hyperinsulinemia: Indeed, the insulin resistance and hyperinsulinemia can increase cellular proliferation by different mechanisms: activation of the mitogen-activated protein kinase (MAPK) pathway (to overcome the inhibition and restore the PI3K pathway), higher synthesis of bioactive IGF-I, and the binding of insulin to IGF-binding proteins (IGFBPs), with the displacement and augmented levels of free IGF14,32.