In the case of cancer-secreted (autocrine) IGF-II, even at lower tissue concentrations than those found in the blood of patients with paraneoplastic hypoglycemia, is able to activate the IGF-IR, the fetal IR isoform (IRA) which is over-expressed in cancers [16,48], as well as the IGF-IR/IRA hybrids [25]. The gene discussed is INSR; the disease is cancer.