Insulin elicits a redistribution of transferrin receptors in 3T3-L1 adipocytes through an increase in the rate constant for receptor externalization.
Insulin elicits a redistribution of transferrin receptors in 3T3-L1 adipocytes through an increase in the rate constant for receptor externalization.
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DOI：
10.1016/s0021-9258(18)48032-5
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发表时间：
1987-05
期刊：
影响因子：
--
通讯作者：
L. Tanner;G. Lienhard
中科院分区：
文献类型：
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作者：
L. Tanner;G. Lienhard
3 T3-L1脂肪细胞与胰岛素在37 ℃孵育导致转铁蛋白与细胞表面受体的特异性结合增加2倍，如通过随后在4 ℃与125 I-转铁蛋白孵育细胞所测量的。半数最大效应所需的胰岛素浓度为10 nM，胰岛素作用的半衰期为40 s。相比之下，胰岛素刺激3 T3-L1脂肪细胞中的己糖转运，半最大效应为8 nM，半衰期为105 s。Scatchard分析125 I-转铁蛋白结合细胞在4摄氏度表明，胰岛素诱导的转铁蛋白受体结合的增加是由于表面转铁蛋白受体的数量增加。当细胞孵育2小时，在37摄氏度与125 I-转铁蛋白，以实现稳态结合，然后暴露于胰岛素，有一个1.7倍的增加，表面结合转铁蛋白（酸敏感）和相应的减少细胞内结合转铁蛋白（酸不敏感）。因此，胰岛素促进细胞内转铁蛋白受体向质膜的移位。伴随着响应胰岛素的表面受体的2倍增加，从59 Fe 3+负载的转铁蛋白的59 Fe 3+摄取速率增加了2倍。在37摄氏度的细胞内125 I-转铁蛋白受体复合物的外化率进行了测定的基础和胰岛素处理的细胞。胰岛素使该过程的一级速率常数增加了1.7倍。胰岛素对外化速率的影响足以解释表面转铁蛋白受体的增加。
Incubation of 3T3-L1 adipocytes with insulin at 37 degrees C resulted in a 2-fold increase in specific binding of transferrin to cell-surface receptors, as measured by a subsequent incubation of cells at 4 degrees C with 125I-transferrin. The insulin concentration required for half-maximal effect was 10 nM, and the half-time for insulin action was 40 s. By comparison, insulin stimulated hexose transport in 3T3-L1 adipocytes with a half-maximal effect at 8 nM and a half-time of 105 s. Scatchard analysis of 125I-transferrin binding to cells at 4 degrees C showed that the insulin-induced increase in transferrin receptor binding was due to an increase in the number of surface transferrin receptors. When cells were incubated for 2 h at 37 degrees C with 125I-transferrin to achieve steady-state binding and then exposed to insulin, there was a 1.7-fold increase in surface-bound transferrin (acid-sensitive) and a corresponding decrease in intracellularly bound transferrin (acid-insensitive). Thus, insulin elicits translocation of intracellular transferrin receptors to the plasma membrane. Concomitant with the 2-fold increase in surface receptors in response to insulin, there was a 2-fold increase in the rate of 59Fe3+ uptake from 59Fe3+-loaded transferrin. The rate of externalization of the intracellular 125I-transferrin-receptor complex at 37 degrees C was determined for basal and insulin-treated cells. Insulin increased the first-order rate constant for this process 1.7-fold. The effect of insulin on the rate of externalization is sufficient to account for the increase in surface transferrin receptors.