INS and Insulin resistance: Insulin, either from exogenous injection or from endogenous hyperinsulinemia as a result of insulin resistance, together with the overexpressed IGF-1 and IGF-2 (more remarkably expressed) from occult cancer cells or the local production of IGF-2 in response to hypoxia in the tissue [136], can theoretically promote the growth of GCa cells via their activation of mitogenic pathways.