Kinetics of GLUT4 trafficking in rat and human skeletal muscle.
Kinetics of GLUT4 trafficking in rat and human skeletal muscle.
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作者：
Karlsson HK;Chibalin AV;Koistinen HA;Yang J;Koumanov F;Wallberg-Henriksson H;Zierath JR;Holman GD
在骨骼肌中，胰岛素刺激葡萄糖转运活性三到四倍，这种刺激的很大一部分与GLUT4从细胞内腔室到细胞表面的净易位有关。我们研究了胰岛素或amp激活的蛋白激酶激活剂AICAR在多大程度上可以导致GLUT4易位途径的胞吐肢体的刺激，从而解释了葡萄糖运输活性的净增加。利用生物素化的光亲和标记，我们标记了内源性GLUT4，并研究了大鼠和人类骨骼肌对胰岛素或AICAR反应的胞外分泌动力学。从雄性Wistar大鼠获得离体耳蜗上睑肌。对6名健康男性（年龄39±11岁，BMI 25.8±0.8 kg/m2）进行开放性肌肉活检，制备股外侧骨骼肌条。在大鼠上耳廓肌中，胰岛素暴露导致GLUT4的胞吐率增加6倍（基础和胰岛素刺激的速率常数分别为0.010和0.067 min−1）。在人股外侧肌中，胰岛素刺激GLUT4易位的方式是使胞吐速率常数增加6倍（基础速率常数和胰岛素刺激速率常数分别为0.011和0.075 min - 1）。相比之下，AICAR治疗并没有显著增加大鼠或人肌肉的胞吐。胰岛素刺激GLUT4的胞吐速率常数足以解释大部分观察到的大鼠和人类肌肉中葡萄糖转运活性的增加。
In skeletal muscle, insulin stimulates glucose transport activity three- to fourfold, and a large part of this stimulation is associated with a net translocation of GLUT4 from an intracellular compartment to the cell surface. We examined the extent to which insulin or the AMP-activated protein kinase activator AICAR can lead to a stimulation of the exocytosis limb of the GLUT4 translocation pathway and thereby account for the net increase in glucose transport activity. Using a biotinylated photoaffinity label, we tagged endogenous GLUT4 and studied the kinetics of exocytosis of the tagged protein in rat and human skeletal muscle in response to insulin or AICAR. Isolated epitrochlearis muscles were obtained from male Wistar rats. Vastus lateralis skeletal muscle strips were prepared from open muscle biopsies obtained from six healthy men (age 39 ± 11 years and BMI 25.8 ± 0.8 kg/m2). In rat epitrochlearis muscle, insulin exposure leads to a sixfold stimulation of the GLUT4 exocytosis rate (with basal and insulin-stimulated rate constants of 0.010 and 0.067 min−1, respectively). In human vastus lateralis muscle, insulin stimulates GLUT4 translocation by a similar sixfold increase in the exocytosis rate constant (with basal and insulin-stimulated rate constants of 0.011 and 0.075 min−1, respectively). In contrast, AICAR treatment does not markedly increase exocytosis in either rat or human muscle. Insulin stimulation of the GLUT4 exocytosis rate constant is sufficient to account for most of the observed increase in glucose transport activity in rat and human muscle.
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影响因子：
3.5
作者：
DUDEK, RW;DOHM, GL;WILSON, CM
通讯作者：
WILSON, CM
影响因子：
7.7
作者：
Karlsson, HKR;Zierath, JR;Wallberg-Henriksson, H
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5.3
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Govers, R;Coster, ACF;James, DE
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影响因子：
158.5
作者：
Cline, GW;Petersen, KF;Shulman, GI
通讯作者：
Shulman, GI
影响因子：
7.7
作者：
Koistinen, HA;Galuska, D;Wallberg-Henriksson, H
通讯作者：
Wallberg-Henriksson, H