Figure 1.

Schematic representation of the insulin-IGF network. The insulin-IGF family includes three ligands, three receptors and at least six IGFBPs. Experimental analyses provided evidence of cross-reactivity between ligands and receptors. Hence, IGF2 binds with high affinity to the InsR. In addition, both IGF1 and IGF2 activate hybrid receptors, formed by an IGF1R hemireceptor in association with an InsR hemireceptor (not shown). The IGF2/mannose 6-phosphate receptor is responsible for IGF2 recycling and is not involved in signaling. Most IGF1 in the circulation is bound to IGFBP3, which forms a multi-complex with an acid-labile subunit (ALS) and protects IGF1 from proteolytic degradation.