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 (approximately 21 days postconception), neonatal (1- and 7-day-old), and adult rats. Specific 125I-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 alpha- and beta-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 X 10(-8) to 1 X 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 in a step(s) distal to activation of insulin-receptor kinase.
Sinha
M K
MK
Section of Endocrinology and Metabolism, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Jenquin
M
M
D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism*; D001667:Binding, Competitive; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D005333:Fetus / Q000378:metabolism*; D007163:Immunosorbent Techniques; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D008970:Molecular Weight; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000378:metabolism*
D007328:Insulin; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin