Interestingly, in spite of a general reduction in IR levels in insulin-resistant states [19], the IR-A/IR-B ratio is increased in several tissues [20], supporting the scenario proposed in Figure 1 for the role of the IGF-II-IR-A axis in linking obesity/type 2 diabetes and cancer development. The gene discussed is IGF2; the disease is obesity due to melanocortin 4 receptor deficiency.