Napoli R, Hirshman M F, Horton E S
Metabolism Section, Joslin Diabetes Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
J Clin Invest. 1995 Jul;96(1):427-37. doi: 10.1172/JCI118053.
Skeletal muscle glucose transport is altered in diabetes in humans, as well as in rats. To investigate the mechanisms of this abnormality, we measured glucose transport Vmax, the total transporter number, their average intrinsic activity, GLUT4 and GLUT1 contents in skeletal muscle plasma membrane vesicles from basal or insulin-stimulated streptozocin diabetic rats with different duration of diabetes, treated or not with phlorizin. The glucose transport Vmax progressively decreased with the duration of diabetes. In the basal state, this decrease was primarily associated with the reduction of transporter intrinsic activity, which appeared earlier than any change in transporter number or GLUT4 and GLUT1 content. In the insulin-stimulated state, the decrease of transport was mainly associated with severe defects in transporter translocation. Phlorizin treatment partially increased the insulin-stimulated glucose transport by improving the transporter translocation defects. In conclusion, in streptozocin diabetes (a) reduction of intrinsic activity plays a major and early role in the impairment of basal glucose transport; (b) a defect in transporter translocation is the mechanism responsible for the decrease in insulin-stimulated glucose transport; and (c) hyperglycemia per se affects the insulin-stimulated glucose transport by altering the transporter translocation.
在人类糖尿病以及大鼠糖尿病中，骨骼肌葡萄糖转运均发生改变。为了探究这种异常的机制，我们测量了不同糖尿病病程的基础状态或胰岛素刺激状态下的链脲佐菌素糖尿病大鼠（无论是否用根皮苷治疗）骨骼肌质膜囊泡中的葡萄糖转运最大速率（Vmax）、转运体总数、它们的平均内在活性、葡萄糖转运蛋白4（GLUT4）和葡萄糖转运蛋白1（GLUT1）含量。葡萄糖转运Vmax随糖尿病病程逐渐降低。在基础状态下，这种降低主要与转运体内在活性的降低有关，这一现象比转运体数量或GLUT4和GLUT1含量的任何变化出现得都早。在胰岛素刺激状态下，转运的降低主要与转运体转位的严重缺陷有关。根皮苷治疗通过改善转运体转位缺陷部分增加了胰岛素刺激的葡萄糖转运。总之，在链脲佐菌素糖尿病中：（a）内在活性的降低在基础葡萄糖转运受损中起主要且早期的作用；（b）转运体转位缺陷是胰岛素刺激的葡萄糖转运降低的机制；（c）高血糖本身通过改变转运体转位影响胰岛素刺激的葡萄糖转运。
