Role of insulin receptors and IGF receptors in growth and development

Observations in targeted mouse mutants and patients with genetic abnormalit ies grant insight into the various and distinct roles of insulin-like growt h factor receptors (IGF-Rs) and insulin receptors (IRs) during early develo pment. While IGF-1Rs (mediating both IGF-1 and IGF-2 actions) are important for embryonic and fetal growth, IRs (mediating IGF-2 rather than insulin a ction) play a minor role. However, it is an oversimplification to conclude that IGF-1Rs mediate growth and IRs mediate metabolic responses. Mice lacki ng both IRs and IGF-1Rs are more severely growth retarded than mice lacking either receptor alone. The phenotype of combined deficiency of IRs and IGF -1Rs is similar to the phenotype caused by the absence of IGF-1 and IGF-2. This provides genetic proof that these two receptors account for the entire ty of the growth promoting effects of IGF-1 and IGF-2. There is little evid ence that hybrid insulin/IGF-1 receptors promote embryonic growth to a sign ificant degree. The clinical presentation regarding severity of growth reta rdation and metabolic disturbances observed in animal models versus in huma ns may differ greatly and the reasons will be reviewed in detail.