Lund S, Holman G D, Schmitz O, Pedersen O
Medical Research Laboratory, Aarhus Kommunehospital, Aarhus University Hospital, Denmark.
Proc Natl Acad Sci U S A. 1995 Jun 20;92(13):5817-21. doi: 10.1073/pnas.92.13.5817.
The acute effects of contraction and insulin on the glucose transport and GLUT4 glucose transporter translocation were investigated in rat soleus muscles by using a 3-O-methylglucose transport assay and the sensitive exofacial labeling technique with the impermeant photoaffinity reagent 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-1,3-bis(D-mannose-4-y loxy)-2- propylamine (ATB-BMPA), respectively. Addition of wortmannin, which inhibits phosphatidylinositol 3-kinase, reduced insulin-stimulated glucose transport (8.8 +/- 0.5 mumol per ml per h vs. 1.4 +/- 0.1 mumol per ml per h) and GLUT4 translocation [2.79 +/- 0.20 pmol/g (wet muscle weight) vs. 0.49 +/- 0.05 pmol/g (wet muscle weight)]. In contrast, even at a high concentration (1 microM), wortmannin had no effect on contraction-mediated glucose uptake (4.4 +/- 0.1 mumol per ml per h vs. 4.1 +/- 0.2 mumol per ml per h) and GLUT4 cell surface content [1.75 +/- 0.16 pmol/g (wet muscle weight) vs. 1.52 +/- 0.16 pmol/g (wet muscle weight)]. Contraction-mediated translocation of the GLUT4 transporters to the cell surface was closely correlated with the glucose transport activity and could account fully for the increment in glucose uptake after contraction. The combined effects of contraction and maximal insulin stimulation were greater than either stimulation alone on glucose transport activity (11.5 +/- 0.4 mumol per ml per h vs. 5.6 +/- 0.2 mumol per ml per h and 9.0 +/- 0.2 mumol per ml per h) and on GLUT4 translocation [4.10 +/- 0.20 pmol/g (wet muscle weight) vs. 1.75 +/- 0.25 pmol/g (wet muscle weight) and 3.15 +/- 0.18 pmol/g (wet muscle weight)]. The results provide evidence that contraction stimulates translocation of GLUT4 in skeletal muscle through a mechanism distinct from that of insulin.
通过使用3 - O - 甲基葡萄糖转运试验以及用不渗透的光亲和试剂2 - N - 4 -（1 - 叠氮基 - 2,2,2 - 三氟乙基）苯甲酰基 - 1,3 - 双（D - 甘露糖 - 4 - 氧基）- 2 - 丙胺（ATB - BMPA）的敏感外表面标记技术，研究了收缩和胰岛素对大鼠比目鱼肌葡萄糖转运和GLUT4葡萄糖转运体转位的急性影响。加入抑制磷脂酰肌醇3 - 激酶的渥曼青霉素后，胰岛素刺激的葡萄糖转运减少（8.8±0.5 μmol/ml·h对1.4±0.1 μmol/ml·h），GLUT4转位也减少[2.79±0.20 pmol/g（湿肌肉重量）对0.49±0.05 pmol/g（湿肌肉重量）]。相比之下，即使在高浓度（1 μM）下，渥曼青霉素对收缩介导的葡萄糖摄取（4.4±0.1 μmol/ml·h对4.1±0.2 μmol/ml·h）和GLUT4细胞表面含量[1.75±0.16 pmol/g（湿肌肉重量）对1.52±0.16 pmol/g（湿肌肉重量）]没有影响。收缩介导的GLUT4转运体向细胞表面的转位与葡萄糖转运活性密切相关，并且可以完全解释收缩后葡萄糖摄取的增加。收缩和最大胰岛素刺激的联合作用对葡萄糖转运活性（11.5±0.4 μmol/ml·h对5.6±0.2 μmol/ml·h和9.0±0.2 μmol/ml·h）和GLUT4转位[4.10±0.20 pmol/g（湿肌肉重量）对1.75±0.25 pmol/g（湿肌肉重量）和3.15±0.18 pmol/g（湿肌肉重量）]的影响大于单独任何一种刺激。结果提供了证据，表明收缩通过一种不同于胰岛素的机制刺激骨骼肌中GLUT4的转位。
