GLUT4 translocation and dispersal operate in multiple cell types and are negatively correlated with cell size in adipocytes.
GLUT4 translocation and dispersal operate in multiple cell types and are negatively correlated with cell size in adipocytes.
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GLUT4易位和分散在多种细胞类型中起作用，并且与脂肪细胞中的细胞大小呈负相关。
DOI：
10.1038/s41598-022-24736-y
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发表时间：
2022-11-29
影响因子：
4.6
通讯作者：
Gould, Gwyn W.
中科院分区：
文献类型：
--
作者：
Koester, Anna M.;Geiser, Angeline;Bowman, Peter R. T.;van de Linde, Sebastian;Gadegaard, Nikolaj;Bryant, Nia J.;Gould, Gwyn W.
葡萄糖转运蛋白GLUT 4向脂肪细胞和肌肉表面的调节转运是胰岛素的关键作用。这是由含GLUT 4的囊泡与质膜的递送和融合所支持的。最近的研究表明，胰岛素的进一步作用是介导GLUT 4分子从GLUT 4囊泡与质膜融合的位点分散。虽然在脂肪细胞中显示，胰岛素刺激的分散是否发生在其他细胞和/或由其他蛋白质表现仍然是一个争论的问题。在这里，我们表明，胰岛素刺激GLUT 4分散在质膜的脂肪细胞，诱导多能干细胞衍生的心肌细胞和HeLa细胞，这表明这种现象是特定的GLUT 4在所有类型的细胞中表达。相比之下，胰岛素刺激的TfR的分散在HeLa细胞中没有观察到，这表明该机制可能是GLUT 4所独有的。与分散是一个重要的生理机制相一致，我们观察到胰岛素刺激的GLUT 4分散在胰岛素抵抗的条件下减少。不同大小的脂肪细胞显示出不同的代谢特性：与较小的细胞相比，较大的脂肪细胞显示出胰岛素刺激的葡萄糖转运减少。在这里，我们表明，GLUT 4传递到质膜和GLUT 4分散减少较大的脂肪细胞，支持的假设，即较大的脂肪细胞是难治性胰岛素挑战相比，他们较小的同行，即使在一个假定的同质群体的细胞。
The regulated translocation of the glucose transporter, GLUT4, to the surface of adipocytes and muscle is a key action of insulin. This is underpinned by the delivery and fusion of GLUT4-containing vesicles with the plasma membrane. Recent studies have revealed that a further action of insulin is to mediate the dispersal of GLUT4 molecules away from the site of GLUT4 vesicle fusion with the plasma membrane. Although shown in adipocytes, whether insulin-stimulated dispersal occurs in other cells and/or is exhibited by other proteins remains a matter of debate. Here we show that insulin stimulates GLUT4 dispersal in the plasma membrane of adipocytes, induced pluripotent stem cell-derived cardiomyocytes and HeLa cells, suggesting that this phenomenon is specific to GLUT4 expressed in all cell types. By contrast, insulin-stimulated dispersal of TfR was not observed in HeLa cells, suggesting that the mechanism may be unique to GLUT4. Consistent with dispersal being an important physiological mechanism, we observed that insulin-stimulated GLUT4 dispersal is reduced under conditions of insulin resistance. Adipocytes of different sizes have been shown to exhibit distinct metabolic properties: larger adipocytes exhibit reduced insulin-stimulated glucose transport compared to smaller cells. Here we show that both GLUT4 delivery to the plasma membrane and GLUT4 dispersal are reduced in larger adipocytes, supporting the hypothesis that larger adipocytes are refractory to insulin challenge compared to their smaller counterparts, even within a supposedly homogeneous population of cells.
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影响因子：
3.7
作者：
Bowman, Peter R. T.;Smith, Godfrey L.;Gould, Gwyn W.
通讯作者：
Gould, Gwyn W.
影响因子：
8.2
作者：
Franck, N.;Stenkula, K. G.;Nystrom, F. H.
通讯作者：
Nystrom, F. H.
影响因子：
4.1
作者：
Brewer, Paul Duffield;Habtemichael, Estifanos N.;Mastick, Cynthia Corley
通讯作者：
Mastick, Cynthia Corley
影响因子：
4.6
作者：
Hansson, Bjorn;Moren, Bjorn;Stenkula, Karin G.
通讯作者：
Stenkula, Karin G.
影响因子：
4.8
作者：
Blüher, M;Patti, ME;Kahn, CR
通讯作者：
Kahn, CR