| First Author | Accili D | Year | 1999 |
| Journal | J Pediatr Endocrinol Metab | Volume | 12 |
| Issue | 4 | Pages | 475-85 |
| PubMed ID | 10417963 | Mgi Jnum | J:57354 |
| Mgi Id | MGI:1344491 | Doi | 10.1515/jpem.1999.12.4.475 |
| Citation | Accili D, et al. (1999) Targeted gene mutations define the roles of insulin and IGF-I receptors in mouse embryonic development. J Pediatr Endocrinol Metab 12(4):475-85 |
| abstractText | Insulin-like growth factors (IGFs) and their receptors regulate embryonic and post-natal growth. Genetic evidence derived from targeted mouse mutants indicates that both the insulin receptor (IR) and IGF-I receptors (IGF-IRs) are required for mouse embryonic growth. However, the roles of IRs and IGF-IRs are functionally distinct, with IGF-IRs mediating both IGF-I and IGF-II actions, and IRs mediating IGF-II, rather than insulin, action. The combined interactions of IGF-IRs and IRs with IGF-I and IGF-II account for the entirety of the growth effects of these two ligands, and provide the molecular basis for IGFs-mediated intrauterine growth and differentiation. Genetic ablation experiments of insulin receptor substrate-1 (IRS-1) and -2 (IRS-2), two important molecules in the IR and IGF-IR signaling pathways, are also beginning to shed light onto the mechanisms accounting for the specificity of IR and IGF-IR signaling. IRS-1-deficient mice are growth retarded, while IRS-2-deficient mice develop diabetes, indicating that the two molecules play a more specific role than previously recognized in IGF-IR and IR signaling. |
