Sinha M K, Jenquin M
Section of Endocrinology and Metabolism, School of Medicine, East Carolina University, Greenville, North Carolina 27858-4354.
Diabetes. 1987 Oct;36(10):1161-6. doi: 10.2337/diab.36.10.1161.
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.
通过检测来自胎儿（约受孕后21天）、新生（1日龄和7日龄）及成年大鼠的部分纯化的可溶性肝受体中的胰岛素结合、亚基结构、自身磷酸化及酪氨酸特异性蛋白激酶活性，来确定胰岛素受体结构和功能特征的个体发生情况。在不同胰岛素浓度存在下，这些受体制剂与特异性125I标记胰岛素的结合在胎儿和新生大鼠中高于成年大鼠。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳放射自显影上，α和β亚基的电泳迁移率在不同发育阶段相似。胰岛素刺激的胰岛素受体自身磷酸化在不同组中相似。在固定蛋白量时，在不同胰岛素浓度（1×10⁻⁸至1×10⁻⁶M）存在下，胎儿和新生大鼠中的酪氨酸特异性蛋白激酶活性显著高于成年大鼠。然而，当以胰岛素结合活性的函数表示时，由于成年大鼠组中胰岛素结合减少，胎儿和新生大鼠中胰岛素刺激的酪氨酸特异性蛋白激酶活性似乎与成年大鼠相似。这些结果证明了胎儿、新生和成年大鼠肝胰岛素受体的结构和功能相似性。先前报道的胎儿和成年大鼠肝脏中胰岛素介导的生物学功能的相对差异是由于胰岛素受体激酶激活后远端步骤的改变。
