The insulin receptor (IR) with its two subtypes IR-A and IR-B, the insulin growth factor 1 receptor (IGF-1R) and the hybrid receptors (IGF-1R/IR-A and IGF-1R/IR-B). Structurally, IR and the IGF-1R have two extracellular α-subunits and two transmembrane β-subunits that are joined to each other by disulfide bonds. Affinity, insulin binds with high affinity to IR-A or IR-B but has low affinity for IGF-1R, while insulin has no binding to the hybrid receptors. IGF-1 binds to the IGF-1R and to the hybrid receptors IGF-1R/IR-A or IGF-1R/IR-B. IGF-2 binds to IR-A, IGF-1R, or to IGF-1R/IR-A hybrid receptor. Signaling, ligand binding to insulin receptor-A or to IGF-1 receptor mediates the mitogenic signaling pathway, while ligand binding to insulin receptor-B activates metabolic signaling. Binding to the hybrid receptors, leading to mitogenic or metabolic signaling, is determined by the IR isoform that formed the hybrid receptors.