Appell K C, Simpson I A, Cushman S W
Experimental Diabetes, Metabolism and Nutrition Section, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892.
J Biol Chem. 1988 Aug 5;263(22):10824-9.
Insulin is known to increase the number of cell surface insulin-like growth factor II (IGF-II) receptors in isolated rat adipose cells through a subcellular redistribution mechanism similar to that for the glucose transporter. The effects of insulin on these two processes, therefore, have now been directly compared in the same cell preparations. 1) Insulin increases the steady state number of cell surface IGF-II receptors by 7-13-fold without affecting receptor affinity; however, insulin stimulates glucose transport activity by 25-40-fold. 2) The insulin concentration required for half-maximal stimulation of cell surface IGF-II receptor number is approximately 30% lower than that for the stimulation of glucose transport activity. 3) The half-time for the achievement of insulin's maximal effect at 37 degrees C is much shorter for IGF-II receptor number (approximately 0.8 min) than for glucose transport activity (approximately 2.6 min). 4) Reversal of insulin's action at 37 degrees C occurs more rapidly for cell surface IGF-II receptors (t1/2 congruent to 2.9 min) than for glucose transport activity (t1/2 congruent to 4.9 min). 5) When the relative subcellular distribution of IGF-II receptors is examined in basal cells, less than 10% of the receptors are localized to the plasma membrane fraction indicating that most of the receptors, like glucose transporters, are localized to an intracellular compartment. However, in response to insulin, the number of plasma membrane IGF-II receptors increases only approximately 1.4-fold while the number of glucose transporters increases approximately 4.5-fold. Thus, while the stimulatory actions of insulin on cell surface IGF-II receptors and glucose transport activity are qualitatively similar, marked quantitative differences suggest that the subcellular cycling of these two integral membrane proteins occurs by distinct processes.
已知胰岛素可通过一种类似于葡萄糖转运蛋白的亚细胞再分布机制，增加分离的大鼠脂肪细胞表面胰岛素样生长因子II（IGF-II）受体的数量。因此，现在已在相同的细胞制剂中直接比较了胰岛素对这两个过程的影响。1）胰岛素可使细胞表面IGF-II受体的稳态数量增加7至13倍，而不影响受体亲和力；然而，胰岛素可使葡萄糖转运活性提高25至40倍。2）刺激细胞表面IGF-II受体数量达到最大值一半时所需的胰岛素浓度，比刺激葡萄糖转运活性所需的浓度低约30%。3）在37℃时，胰岛素对IGF-II受体数量达到最大效应的半衰期（约0.8分钟）比对葡萄糖转运活性的半衰期（约2.6分钟）短得多。4）在37℃时，胰岛素作用的逆转对于细胞表面IGF-II受体来说更快（t1/2约为2.9分钟），而对于葡萄糖转运活性则较慢（t1/2约为4.9分钟）。5）当在基础细胞中检查IGF-II受体的相对亚细胞分布时，不到10%的受体定位于质膜部分，这表明大多数受体与葡萄糖转运蛋白一样，定位于细胞内区室。然而，在胰岛素作用下，质膜IGF-II受体的数量仅增加约1.4倍，而葡萄糖转运蛋白的数量增加约4.5倍。因此，虽然胰岛素对细胞表面IGF-II受体和葡萄糖转运活性的刺激作用在性质上相似，但明显的数量差异表明，这两种整合膜蛋白的亚细胞循环是通过不同的过程发生的。
