Bassas L, de Pablo F, Lesniak M A, Roth J
Diabetes Branch, National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, Maryland 20892.
Endocrinology. 1987 Oct;121(4):1468-76. doi: 10.1210/endo-121-4-1468.
Since specific binding to receptors and biological effects of insulin and insulin-like growth factors (IGFs) are demonstrable soon after the neural tube closes and organogenesis begins in the chick embryo, in the present study we have analyzed the structural characteristics and specificity of the receptors for insulin and IGFs at this early stage of development. We show that membranes from newly differentiated chick embryo tissues (day 6 brain, day 6 heart, day 8 liver, day 12 skeletal muscle) as well as whole embryos postneurulation (day 2, stage of 27-30 somites) have two populations of receptors with distinct specificity: insulin and type I IGF (IGF-I) receptors. Both insulin and IGF-I alpha-subunits, as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, had tissue-dependent heterogeneity in Mr (liver greater than heart = skeletal muscle greater than brain) ranging from 138 kilodaltons (kDa) to 129 kDa. Desialylation of the receptors by treatment with neuraminidase produced a significant change in the Mr of the alpha-subunits in liver and heart but not in brain or the whole day 2 embryo. In each tissue the pattern for insulin receptors and IGF-I receptors was strikingly similar. Our studies raise the possibility that postranslational modifications of the insulin and IGF-I receptors, characteristic of terminally differentiated tissues, are already present in early organogenesis. Further, structural heterogeneity of the binding subunit of these receptors among tissues appears to be widespread and not exclusive to the brain receptor. An insulin receptor with features similar to the neural type is the only one detected in embryos at the beginning of organogenesis (day 2). The functional implication of this developmental tissue-specific regulation of insulin and IGF-I receptors, is still speculative. Its possible importance is suggested by the fact that it occurs embryologically early and affects both insulin and IGF-I receptors in parallel.
由于在鸡胚神经管闭合和器官发生开始后不久就能证明胰岛素和胰岛素样生长因子（IGFs）与受体的特异性结合及生物学效应，在本研究中，我们分析了发育早期阶段胰岛素和IGFs受体的结构特征及特异性。我们发现，新分化的鸡胚组织（第6天的脑、第6天的心脏、第8天的肝脏、第12天的骨骼肌）以及神经胚形成后的全胚（第2天，27 - 30体节阶段）具有两种特异性不同的受体群体：胰岛素受体和I型IGF（IGF - I）受体。通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳估计，胰岛素和IGF - I的α亚基在Mr上具有组织依赖性异质性（肝脏＞心脏 = 骨骼肌＞脑），范围从138千道尔顿（kDa）到129 kDa。用神经氨酸酶处理使受体去唾液酸化后，肝脏和心脏中α亚基的Mr发生了显著变化，但脑或第2天的全胚中未发生变化。在每个组织中，胰岛素受体和IGF - I受体的模式都极为相似。我们的研究提出了一种可能性，即终末分化组织特有的胰岛素和IGF - I受体的翻译后修饰在早期器官发生时就已存在。此外，这些受体结合亚基在组织间的结构异质性似乎很普遍，并非脑受体所特有。在器官发生开始时（第2天）的胚胎中检测到的唯一一种具有类似于神经型特征的胰岛素受体。胰岛素和IGF - I受体这种发育过程中组织特异性调节的功能意义仍具有推测性。其可能的重要性体现在它在胚胎发育早期就出现并且同时影响胰岛素和IGF - I受体。
