GHR and Hyperinsulinemia: In addition, hyperinsulinemia increases insulin-like growth factor 1 (IGF-1) bioavailability by increasing hepatic growth hormone receptor expression and repressing hepatic production of IGF-binding proteins (IGFBP) (39), resulting in hyperactivation of the Ras-MAPK and PI3K/Akt pathways in malignant cells to promote cell proliferation (40).