AMP–Activated Protein Kinase Activation Causes GLUT4 Translocation in Skeletal Muscle
AMP–Activated Protein Kinase Activation Causes GLUT4 Translocation in Skeletal Muscle
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发表时间：
1999
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通讯作者：
E. J. Kurth-Kraczek;M. Hirshman;L. Goodyear;William W. Wi
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作者：
E. J. Kurth-Kraczek;M. Hirshman;L. Goodyear;William W. Wi
先前已经报道，运动引起骨骼肌中葡萄糖摄取的增加以及5-AMP-活化蛋白激酶（AMPK）活性的增加。腺苷类似物5-氨基咪唑-4-甲酰胺-1-（cid：98）- D -吡喃B-糖苷（AICA-核苷）被细胞吸收并磷酸化形成AICA-核苷单磷酸（ZMP），其也可激活AMPK。本研究旨在确定通过AICA-核苷激活AMPK观察到的葡萄糖摄取增加是否是由于GLUT 4从细胞内位置易位到质膜，类似于响应收缩所见。大鼠后肢灌注Krebs-Henseleit碳酸氢盐，含4%牛血清白蛋白、洗涤的牛红细胞、8 mmol/l葡萄糖和±2 mmol/l AICA-核苷或±60 nmol/l胰岛素。灌注培养基中含有AICA核苷被发现显着增加AMPK活性，葡萄糖摄取，和GLUT 4易位在骨骼肌高于基础水平。胰岛素灌注的肌肉显示葡萄糖摄取和GLUT 4易位显著增加，但AMPK活化与基础水平相比无显著变化。这些结果提供的证据表明，在灌流大鼠后肢肌肉中观察到的由AICA-核糖苷激活AMPK的葡萄糖摄取增加是由于GLUT 4向表面膜的易位增加。1999
It has previously been reported that exercise causes an increase in glucose uptake in skeletal muscle and also an increase in 5 (cid:57) AMP–activated protein kinase (AMPK) a c t i v i t y. 5-Aminoimidazole-4-carboxamide-1- (cid:98) - D - r i b o f u-ranoside (AICA-riboside), an analog of adenosine, is taken up into cells and phosphorylated to form AICA-riboside monophosphate (ZMP), which can also activate AMPK. This study was designed to determine whether the increase in glucose uptake observed with AMPK activation by AICA-riboside is due to GLUT4 translocation from an intracellular location to the plasma membranes, similar to that seen in response to contraction. Rat hindlimbs were perfused with Krebs-Henseleit bicar-bonate containing 4% bovine serum albumin, washed bovine erythrocytes, 8 mmol/l glucose, and ±2 mmol/l AICA-riboside or ±60 nmol/l insulin. Perfusion medium containing AICA-riboside was found to significantly increase AMPK activity, glucose uptake, and GLUT4 translocation in skeletal muscle above basal levels. Insulin-perfused muscles showed significant increases in glucose uptake and GLUT4 translocation, but AMPK activation was not significantly changed from basal lev- els. These results provide evidence that the increased glucose uptake observed with AMPK activation by AICA-riboside in perfused rat hindlimb muscles is due to an increase in the translocation of GLUT4 to surface membranes. 1999