Subunit Structure, Autophosphorylation, and Tyrosine-Specific Protein Kinase Activity of Hepatic Insulin Receptors in Fetal, Neonatal, and Adult Rats

The ontogeny of the structural and functional characteristics of insulin receptors is determined by examining insulin binding, subunit structure, autophosphorylation, and tyrosine-specific protein kinase activity in partially purified solubilized liver receptors from fetal (∼21 days postconception), neonatal (1- and 7-day-old), and adult rats. Specific ¹²⁵l-labeled insulin binding to these receptor preparations in the presence of different insulin concentrations was higher in fetal and neonatal rats compared with that in the adult rats. The electrophoretic mobilities of the α- and β-subunits on sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography were similar at different stages of development. Insulin-stimulated autophosphorylation of insulin receptors was similar in the different groups. With fixed amounts of protein, the tyrosine-specific protein kinase activity in the presence of different insulin concentrations (1 × 10⁻⁸ to 1 × 10⁻⁶ M) was significantly higher in the fetal and neonatal rats than in adult rats. However, when expressed as a function of insulin-binding activity, the insulin-stimulated tyrosine-specific protein kinase activity in fetal and neonatal rats appears to be similar to that in adult rats because of decreased insulin binding in the latter group. These results demonstrate the structural and functional similarities of hepatic insulin receptors in fetal, neonatal, and adult rats. The relative differences in insulin-mediated biological functions in fetal and adult rat livers as reported previously are due to alterations ina step(s) distal to activation of insulin-receptor kinase.