Insulin increases cell surface GLUT4 levels by dose dependently discharging GLUT4 into a cell surface recycling pathway
Insulin increases cell surface GLUT4 levels by dose dependently discharging GLUT4 into a cell surface recycling pathway
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DOI：
10.1128/mcb.24.14.6456-6466.2004
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发表时间：
2004-07-01
影响因子：
5.3
通讯作者：
James, DE
中科院分区：
文献类型：
--
作者：
Govers, R;Coster, ACF;James, DE
胰岛素响应性葡萄糖转运蛋白 GLUT4 在葡萄糖稳态中发挥着重要作用。使用一种新的测定方法来研究 3T3-L1 成纤维细胞/前脂肪细胞和脂肪细胞中的 GLUT4 运输。虽然胰岛素刺激两种细胞类型中的 GLUT4 易位至质膜，但在未刺激的成纤维细胞中，GLUT4 容易在内体和质膜之间循环，而脂肪细胞中的情况并非如此。这种在基底脂肪细胞中的有效保留部分是由 GLUT4 中的 C 端靶向基序介导的。胰岛素导致包括质膜在内的运输周期中存在的 GLUT4 分子数量增加七倍。引人注目的是，这种增加的幅度与胰岛素剂量相关，表明胰岛素诱导的 GLUT4 在质膜上的出现不能仅仅用固定细胞内 GLUT4 池再循环的动力学变化来解释。这些数据与模型一致，其中GLUT4存在于储存室中，在胰岛素刺激下从储存室中以分级或量子方式释放，并且其中释放的GLUT4独立于未释放池在细胞内室和细胞表面之间连续循环。
The insulin-responsive glucose transporter GLUT4 plays an essential role in glucose homeostasis. A novel assay was used to study GLUT4 trafficking in 3T3-L1 fibroblasts/preadipocytes and adipocytes. Whereas insulin stimulated GLUT4 translocation to the plasma membrane in both cell types, in nonstimulated fibroblasts GLUT4 readily cycled between endosomes and the plasma membrane, while this was not the case in adipocytes. This efficient retention in basal adipocytes was mediated in part by a C-terminal targeting motif in GLUT4. Insulin caused a sevenfold increase in the amount of GLUT4 molecules present in a trafficking cycle that included the plasma membrane. Strikingly, the magnitude of this increase correlated with the insulin dose, indicating that the insulin-induced appearance of GLUT4 at the plasma membrane cannot be explained solely by a kinetic change in the recycling of a fixed intracellular GLUT4 pool. These data are consistent with a model in which GLUT4 is present in a storage compartment, from where it is released in a graded or quantal manner upon insulin stimulation and in which released GLUT4 continuously cycles between intracellular compartments and the cell surface independently of the nonreleased pool.