Heaton J H, Krett N L, Gelehrter T D
Endocrinology. 1986 Jun;118(6):2555-60. doi: 10.1210/endo-118-6-2555.
We have previously reported that insulin induces a complete and reversible desensitization to the induction of tyrosine aminotransferase by insulin and insulin-like growth factors (IGFs) in HTC rat hepatoma cells. This loss of responsiveness cannot be accounted for by down-regulation of cell surface receptors, but occurs at a postbinding step in hormone action. Here we present evidence that IGF-I and IGF-II also induce desensitization to the actions of both IGFs and insulin and that this effect is mediated by IGF receptors. First, the concentration dependence for this effect is similar to that for the IGF-I and IGF-II induction of tyrosine aminotransferase, which has been shown to be mediated by IGF receptors. Second, antibody to the insulin receptor, which blocks insulin, but not IGF-II, binding to HTC cells, causes a rightward shift in the concentration dependence for insulin induction of desensitization, but does not significantly change the concentration dependence for IGF-II. These results indicate that IGF-II-induced desensitization to IGF-II is not mediated by the insulin receptor, but presumably by an IGF receptor. Although the IGFs do cause a moderate decrease in the binding of IGFs and insulin (to approximately 50-75% of the control value), this cannot account for the virtually complete desensitization to their actions. We conclude that IGFs, like insulin, induce a nearly complete loss of responsiveness to insulin and IGFs, that this effect is mediated via IGF receptors, and that desensitization occurs at a step distal to hormone binding which may be common to the actions of insulin and the IGFs.
我们之前曾报道，胰岛素可诱导HTC大鼠肝癌细胞对胰岛素和胰岛素样生长因子（IGFs）诱导的酪氨酸转氨酶产生完全且可逆的脱敏作用。这种反应性的丧失不能用细胞表面受体的下调来解释，而是发生在激素作用的结合后步骤。在此，我们提供证据表明，IGF-I和IGF-II也会诱导对IGFs和胰岛素作用的脱敏，且这种效应是由IGF受体介导的。首先，这种效应的浓度依赖性与IGF-I和IGF-II诱导酪氨酸转氨酶的浓度依赖性相似，而后者已被证明是由IGF受体介导的。其次，胰岛素受体抗体可阻断胰岛素与HTC细胞的结合，但不阻断IGF-II与HTC细胞的结合，它会使胰岛素诱导脱敏的浓度依赖性向右移动，但不会显著改变IGF-II的浓度依赖性。这些结果表明，IGF-II诱导的对IGF-II的脱敏不是由胰岛素受体介导的，而是可能由IGF受体介导。尽管IGFs确实会使IGFs和胰岛素的结合适度减少（降至对照值的约50 - 75%），但这无法解释对它们作用的几乎完全脱敏。我们得出结论，IGFs与胰岛素一样，会诱导对胰岛素和IGFs的反应性几乎完全丧失，这种效应是通过IGF受体介导的，且脱敏发生在激素结合的远端步骤，这可能是胰岛素和IGFs作用的共同之处。
