INS and Hyperinsulinemia: Insulin and IGF1 stimulate glucose uptake, activate the PI3K/AKT/mTOR pathway,272 potentiate crosstalk with GPCR agonists196 and increase YAP function in human PDAC cells.197 Accordingly, a recent study demonstrated that insulin receptors expressed in the pancreatic acinar cells of KC mice subjected to DIO play critical roles in mediating hyperinsulinemia-driven PanIN development.273