Multiple roles of phosphatidylinositol 3-kinase in regulation of glucose transport, amino acid transport, and glucose transporters in L6 skeletal muscle cells.
Multiple roles of phosphatidylinositol 3-kinase in regulation of glucose transport, amino acid transport, and glucose transporters in L6 skeletal muscle cells.
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磷脂酰肌醇 3-激酶在 L6 骨骼肌细胞中葡萄糖转运、氨基酸转运和葡萄糖转运蛋白调节中的多重作用。
作者：
T. Tsakiridis;H. Mcdowell;Trevor R. Walker;C. Downes;H. Hundal;Mladen Vranic;Amira Klip
磷脂酰肌醇3-激酶（PI 3 k）活性是胰岛素刺激脂肪细胞和中国仓鼠卵巢细胞葡萄糖转运所必需的。渥曼青霉素（Wortmannin，WM）是一种PI 3 k抑制剂，可抑制胰岛素对葡萄糖转运的刺激作用，抑制细胞表面葡萄糖转运蛋白的增加。然而，抑制PI 3 k对维持基础和胰岛素刺激的葡萄糖转运以及对葡萄糖转运蛋白的细胞内供体库的影响尚未阐明。在这里，我们表明，在L 6骨骼肌细胞中的文化WM显着抑制基础PI 3 K活性（40%），降低磷脂酰肌醇3，4-磷酸和3，4，5-磷酸（约50%）的水平，并取消激活酶的胰岛素。WM抑制葡萄糖（45%）和氨基酸通过系统A（25%）的运输基础率，并取消胰岛素的刺激。胰岛素引起PI 3 k活性和PI 3 k产物的短暂增加，在40分钟内恢复到基础水平，而葡萄糖和氨基酸转运仍然升高。在这些条件下，WM降低葡萄糖和氨基酸转运的速率回到基础水平。在未受刺激的细胞中，WM显著降低了质膜上GLUT 4葡萄糖转运蛋白的含量，并阻止了胰岛素将转运蛋白招募到质膜上的能力。有趣的是，GLUT 3和GLUT 4葡萄糖转运蛋白的细胞内池在单独WM处理时显著减少。我们的结论是，在肌肉细胞中，PI 3 K活性是必需的，以维持基础和胰岛素刺激的葡萄糖和氨基酸的运输，以及开发刺激的两个运输过程中响应激素。我们推测，PI 3 k，可能通过生产磷脂酰肌醇3，4-磷酸和3，4，5-磷酸，调节基底质膜葡萄糖转运蛋白再循环和转运蛋白细胞内池的组织，除了是胰岛素信号。
Phosphatidylinositol 3-kinase (PI3k) activity is required for the insulin stimulation of glucose transport in adipocytes and Chinese hamster ovary cells. Wortmannin (WM), an inhibitor of PI3k, inhibits the stimulation of glucose transport by insulin and the gain of glucose transporters at the cell surface. However, the effect of inhibition of PI3k on the maintenance of the basal and the insulin-stimulated glucose transport and on the intracellular donor pool of glucose transporters has not been clarified. Here we show that in L6 skeletal muscle cells in culture WM significantly inhibits the basal PI3k activity (by 40%), decreases the levels of phosphatidylinositol 3,4-phosphate and 3,4,5-phosphate (by about 50%) and abolishes the activation of the enzyme by insulin. WM inhibited the basal rate of transport of glucose (by 45%) and of amino acids through system A (by 25%) and abolished their stimulation by insulin. Insulin caused a transient increase in PI3k activity and PI3k products that returned to basal levels within 40 min, whereas glucose and amino acid transport remained elevated. Under these conditions, WM reduced the rate of glucose and amino acid transport back to basal levels. In unstimulated cells, WM decreased significantly the GLUT4 glucose transporter content at the plasma membrane and prevented the ability of insulin to recruit transporters to this membrane. Interestingly, the intracellular pools of the GLUT3 and GLUT4 glucose transporters were significantly reduced in response to WM treatment alone. We conclude that in muscle cells PI3k activity is required to maintain basal and insulin-stimulated glucose and amino acid transport, as well as to develop the stimulation of the two transport processes in response to the hormone. We hypothesize that PI3k, likely through production of phosphatidylinositol 3,4-phosphate and 3,4,5-phosphate, regulates the basal plasma membrane glucose transporter recycling and the organization of the transporter intracellular pool, in addition to being an insulin signal.
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DOI：
10.1016/s0021-9258(19)49748-2
发表时间：
1992-06
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Cynthia A. Corley;Cain;William S Trimblez;Gustav E Lienhardq
通讯作者：
Cynthia A. Corley;Cain;William S Trimblez;Gustav E Lienhardq
血小板衍生生长因子刺激产生的多磷酸肌醇的鉴定和定量。
影响因子：
--
作者：
Serunian,LA;Auger,KR;Cantley,LC
通讯作者：
Cantley,LC
DOI：
10.1016/s0021-9258(17)42297-6
发表时间：
1994-01
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
M. White;C. Kahn
通讯作者：
M. White;C. Kahn
胰岛素对大鼠脂肪细胞中 GLUT4 亚细胞分布稳态动力学的影响。
DOI：
--
发表时间：
1992
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Jhun,BH;Rampal,AL;Liu,H;Lachaal,M;Jung,CY
通讯作者：
Jung,CY