IGF1R and Hyperinsulinemia: Additionally, hyperinsulinemia also promoted increased production of IGF-1 by the liver which in turn further amplified IGF1R signaling through the PI3K–AKT–mTOR and RAS–MAPK pathways, which stimulate expression of the MYC proto-oncogene, cell proliferation, anti-apoptotic, and anabolic effects in tumor cells [104,190,209–212].