Weinstein S P, Wilson C M, Pritsker A, Cushman S W
Department of Medicine, The Mount Sinai School of Medicine, New York, NY, USA.
Metabolism. 1998 Jan;47(1):3-6. doi: 10.1016/s0026-0495(98)90184-6.
To test the hypothesis that glucocorticoids reduce insulin-stimulated skeletal muscle glucose transport by inhibiting the recruitment of GLUT4 glucose transporters to the cell surface, we determined the effect of glucocorticoid treatment on cell-surface GLUT4 using the impermeant glucose transporter photolabel, 2-N-4-(1-azi-2,2,2-trifluoroethyl)benzoyl-[2-3H]1,3-bis-(D-mann os-4-yloxy)-2-propylamine (ATB-[2-3H]BMPA), and GLUT4 immunoprecipitation. Male Sprague-Dawley rats were treated with dexamethasone ([Dex] 0.9 mg/kg for 2 days) and compared against pair-fed controls. 2-[3H]deoxyglucose (2-[3H]DG) uptake in isolated soleus muscles was measured under conditions in which uptake reflects glucose transport activity. In control muscles, 2-[3H]DG uptake was stimulated eightfold by insulin (20 nmol/L). Dex treatment reduced maximal insulin-stimulated 2-[3H]DG uptake by 48% +/- 4% (mean +/- SEM) and decreased cell-surface (ATB-[2-3H]BMPA-photolabeled) GLUT4 by 48% +/- 3%, despite an increase in total muscle GLUT4 content of 26% +/- 7%. These findings indicate that glucocorticoid-induced inhibition of insulin-stimulated glucose transport in muscle is due to impaired recruitment of GLUT4 to the cell surface.
为了验证糖皮质激素通过抑制GLUT4葡萄糖转运体向细胞表面募集来降低胰岛素刺激的骨骼肌葡萄糖转运这一假说，我们使用非渗透性葡萄糖转运体光标记物2-N-4-(1-叠氮基-2,2,2-三氟乙基)苯甲酰-[2-³H]1,3-双-(D-甘露糖-4-氧基)-2-丙胺（ATB-[2-³H]BMPA）以及GLUT4免疫沉淀法，确定了糖皮质激素处理对细胞表面GLUT4的影响。将雄性Sprague-Dawley大鼠用 dexamethasone（[地塞米松]0.9mg/kg，持续2天）处理，并与配对喂养的对照组进行比较。在摄取反映葡萄糖转运活性的条件下，测量分离的比目鱼肌中2-[³H]脱氧葡萄糖（2-[³H]DG）的摄取。在对照肌肉中，胰岛素（20nmol/L）使2-[³H]DG摄取增加了8倍。地塞米松处理使胰岛素刺激的最大2-[³H]DG摄取降低了48%±4%（平均值±标准误），并使细胞表面（ATB-[2-³H]BMPA光标记的）GLUT4减少了48%±3%，尽管总肌肉GLUT4含量增加了26%±7%。这些发现表明，糖皮质激素诱导的肌肉中胰岛素刺激的葡萄糖转运抑制是由于GLUT4向细胞表面的募集受损所致。
