Modulation of the caveolin-3 and Akt status in daveolae by insulin resistance in H9c2 cardiomyoblasts
Modulation of the caveolin-3 and Akt status in daveolae by insulin resistance in H9c2 cardiomyoblasts
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DOI：
10.1038/emm.2005.23
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发表时间：
2005-06-30
影响因子：
12.8
通讯作者：
Pak, Y
中科院分区：
文献类型：
--
作者：
Ha, H;Pak, Y
我们研究了H9c2心肌细胞对胰岛素的葡萄糖摄取和Akt和caveolin-3的易位对胰岛素的响应，H9c2心肌细胞在25 mM葡萄糖培养基中暴露于100 nM胰岛素的实验性胰岛素抵抗条件下24小时。与在5 mM葡萄糖培养基中生长的对照细胞相比，胰岛素抵抗条件下的细胞表现出胰岛素刺激的2-deoxy[h -3]葡萄糖摄取减少。除了胰岛素诱导的Akt转运到膜上的减少外，我们还观察到胰岛素刺激的磷酸化Akt的膜关联显著减少，从而导致细胞质池的增加。细胞中对胰岛素反应的肌动蛋白重塑也被大大延缓。当检测Akt和caveolin-3向小窝的易位时，胰岛素抵抗条件减弱了Akt和caveolin-3从细胞质中向小窝的定位。结果，胰岛素刺激的小泡中Akt活性显著降低。综上所述，我们的数据表明，细胞中葡萄糖摄取的减少与小窝蛋白-3、AM和磷酸化Akt水平的降低有关。我们得出结论，胰岛素抵抗状态导致它们向小泡转运的延迟，进而导致胰岛素信号的衰减，即激活Akt在小泡中使葡萄糖摄取到H9c2心肌细胞。
We investigated glucose uptake and the translocation of Akt and caveolin-3 in response to insulin in H9c2 cardiomyoblasts exposed to an experimental insulin resistance condition of 100 nM insulin in a 25 mM glucose containing media for 24 h. The cells under the insulin resistance condition exhibited a decrease in insulin-stimulated 2-deoxy[H-3]glucose uptake as compared to control cells grown in 5 mM glucose media. In addition to a reduction in insulin-induced Akt translocation to membranes, we observed a significant decrease in insulin-stimulated membrane association of phosphorylated Akt with a consequent increase of the cytosolic pool. Actin remodeling in response to insulin was also greatly retarded in the cells. When translocation of Akt and caveolin-3 to caveolae was examined, the insulin resistance condition attenuated localization of Akt and caveolin-3 to caveolae from cytosol. As a result, insulin-stimulated Akt activation in caveolae was significantly decreased. Taken together, our data indicate that the decrease of glucose uptake into the cells is related to their reduced levels of caveolin-3, AM and phosphorylated Akt in, caveolae. We conclude that the insulin resistance condition induced the retardation of their translocation to caveolae and in turn caused an attenuation in insulin signaling, namely activation of Akt in caveolae for glucose uptake into H9c2 cardiomyoblasts.