Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.
Low-flow ischemia leads to translocation of canine heart GLUT-4 and GLUT-1 glucose transporters to the sarcolemma in vivo.
复制标题
DOI：
10.1161/01.cir.95.2.415
复制
发表时间：
1997-01
期刊：
影响因子：
37.8
通讯作者：
L. Young;Yin Renfu;R. Russell;Xiaoyue Hu;Michael J. Caplan;Jian-Ming Ren;Gerald I. Shulman;A. Sinusas
中科院分区：
文献类型：
--
作者：
L. Young;Yin Renfu;R. Russell;Xiaoyue Hu;Michael J. Caplan;Jian-Ming Ren;Gerald I. Shulman;A. Sinusas
心肌缺血增加体内心脏葡萄糖利用。然而，低血流缺血是否导致葡萄糖转运蛋白（GLUT）-4和/或GLUT-1易位到体内肌膜是未知的。方法和结果在犬心肌模型中，我们通过使用肌膜和细胞内膜的免疫印迹和共聚焦显微镜的免疫荧光定位来评估在体心肌葡萄糖代谢和GLUT-4和GLUT-1的分布。体内葡萄糖提取增加了5倍（P <0.001），并与缺血区域的净乳酸释放相关。与非缺血区域相比，缺血导致GLUT-4（15 +/- 2%至30 +/-3%，P <0.02）和GLUT-1（41 +/- 4%至58 +/-3%，P <0.03）的肌膜含量增加，并且其细胞内含量平行减少。免疫荧光显示心肌细胞上存在GLUT-4和GLUT-1。GLUT-1有一个更突出的细胞表面图案比GLUT-4，这主要是在非缺血区域的细胞内。然而，在缺血区域发现显著的GLUT-4表面标记。结论：在急性低血流缺血时，胰岛素敏感性GLUT-4转运蛋白从细胞内储存池向肌膜的转位发生在体内。GLUT-1也存在于细胞内储存池中，在缺血时，GLUT-1从细胞内储存池移位至肌膜。这些结果表明，GLUT-1和GLUT-4在体内缺血介导的心肌葡萄糖摄取中是重要的。
BACKGROUND Myocardial ischemia increases heart glucose utilization in vivo. However, whether low-flow ischemia leads to the translocation of glucose transporter (GLUT)-4 and/or GLUT-1 to the sarcolemma in vivo is unknown. METHODS AND RESULTS In a canine model, we evaluated myocardial glucose metabolism in vivo and the distribution of GLUT-4 and GLUT-1 by use of immunoblotting of sarcolemma and intracellular membranes and immunofluorescence localization with confocal microscopy. In vivo glucose extraction increased fivefold (P < .001) and was associated with net lactate release in the ischemic region. Ischemia led to an increase in the sarcolemma content of both GLUT-4 (15 +/- 2% to 30 +/- 3%, P < .02) and GLUT-1 (41 +/- 4% to 58 +/- 3%, P < .03) compared with the nonischemic region and to a parallel decrease in their intracellular contents. Immunofluorescence demonstrated the presence of both GLUT-4 and GLUT-1 on cardiac myocytes. GLUT-1 had a more prominent cell surface pattern than GLUT-4, which was primarily intracellular in the nonischemic region. However, significant GLUT-4 surface labeling was found in the ischemic region. CONCLUSIONS Translocation of the insulin-responsive GLUT-4 transporter from an intracellular storage pool to the sarcolemma occurs in vivo during acute low-flow ischemia. GLUT-1 is also present in an intracellular storage pool from which it undergoes translocation to the sarcolemma in response to ischemia. These results indicate that both GLUT-1 and GLUT-4 are important in ischemia-mediated myocardial glucose uptake in vivo.