Siques Patricia, Brito Julio, Flores Karen, Ordenes Stefany, Arriaza Karem, Pena Eduardo, León-Velarde Fabiola, López de Pablo Ángel L, Gonzalez M C, Arribas Silvia
Institute of Health Studies, University Arturo Prat, Iquique, Chile.
Department of Biological and Physiological Sciences, Facultad de Ciencias y Filosofía/IIA, Cayetano Heredia University, Lima, Peru.
Front Physiol. 2018 Jun 28;9:799. doi: 10.3389/fphys.2018.00799. eCollection 2018.
In chronic hypoxia (CH) and short-term chronic intermittent hypoxia (CIH) exposure, glycemia and insulin levels decrease and insulin sensitivity increases, which can be explained by changes in glucose transport at skeletal muscles involving GLUT1, GLUT4, Akt, and AMPK, as well as GLUT4 translocation to cell membranes. However, during long-term CIH, there is no information regarding whether these changes occur similarly or differently than in other types of hypoxia exposure. This study evaluated the levels of AMPK and Akt and the location of GLUT4 in the soleus muscles of lean rats exposed to long-term CIH, CH, and normoxia (NX) and compared the findings. Thirty male adult rats were randomly assigned to three groups: a NX (760 Torr) group ( = 10), a CIH group (2 days hypoxia/2 days NX; = 10) and a CH group ( = 10). Rats were exposed to hypoxia for 30 days in a hypobaric chamber set at 428 Torr (4,600 m). Feeding (10 g daily) and fasting times were accurately controlled. Measurements included food intake (every 4 days), weight, hematocrit, hemoglobin, glycemia, serum insulin (by ELISA), and insulin sensitivity at days 0 and 30. GLUT1, GLUT4, AMPK levels and Akt activation in rat soleus muscles were determined by western blot. GLUT4 translocation was measured with confocal microscopy at day 30. (1) Weight loss and increases in hematocrit and hemoglobin were found in both hypoxic groups ( < 0.05). (2) A moderate decrease in glycemia and plasma insulin was found. (3) Insulin sensitivity was greater in the CIH group ( < 0.05). (4) There were no changes in GLUT1, GLUT4 levels or in Akt activation. (5) The level of activated AMPK was increased only in the CIH group ( < 0.05). (6) Increased GLUT4 translocation to the plasma membrane of soleus muscle cells was observed in the CIH group ( < 0.05). In lean rats experiencing long-term CIH, glycemia and insulin levels decrease and insulin sensitivity increases. Interestingly, there is no increase of GLUT1 or GLUT4 levels or in Akt activation. Therefore, cellular regulation of glucose seems to primarily involve GLUT4 translocation to the cell membrane in response to hypoxia-mediated AMPK activation.
在慢性缺氧（CH）和短期慢性间歇性缺氧（CIH）暴露过程中，血糖和胰岛素水平降低，胰岛素敏感性增加，这可以通过骨骼肌中涉及葡萄糖转运蛋白1（GLUT1）、葡萄糖转运蛋白4（GLUT4）、蛋白激酶B（Akt）和腺苷酸活化蛋白激酶（AMPK）的葡萄糖转运变化以及GLUT4向细胞膜的转位来解释。然而，在长期CIH过程中，关于这些变化与其他类型缺氧暴露中是否相似或不同，尚无相关信息。本研究评估了长期暴露于CIH、CH和常氧（NX）的瘦大鼠比目鱼肌中AMPK和Akt的水平以及GLUT4的定位，并比较了研究结果。30只成年雄性大鼠随机分为三组：NX（760托）组（n = 10）、CIH组（2天缺氧/2天常氧；n = 10）和CH组（n = 10）。大鼠在设置为428托（海拔4600米）的低压舱中暴露于缺氧环境30天。精确控制喂食（每天10克）和禁食时间。测量指标包括第0天和第30天的食物摄入量（每4天一次）、体重、血细胞比容、血红蛋白、血糖、血清胰岛素（通过酶联免疫吸附测定法）和胰岛素敏感性。通过蛋白质免疫印迹法测定大鼠比目鱼肌中GLUT1、GLUT4、AMPK水平和Akt激活情况。在第30天用共聚焦显微镜测量GLUT4转位。（1）两个缺氧组均出现体重减轻以及血细胞比容和血红蛋白升高（P < 0.05）。（2）血糖和血浆胰岛素出现中度降低。（3）CIH组胰岛素敏感性更高（P < 0.05）。（4）GLUT1、GLUT4水平或Akt激活无变化。（5）仅CIH组激活的AMPK水平升高（P < 0.05）。（6）在CIH组观察到比目鱼肌细胞质膜上GLUT4转位增加（P < 0.05）。在经历长期CIH的瘦大鼠中，血糖和胰岛素水平降低，胰岛素敏感性增加。有趣的是，GLUT1或GLUT4水平以及Akt激活并未增加。因此，葡萄糖的细胞调节似乎主要涉及响应缺氧介导的AMPK激活时GLUT4向细胞膜的转位。
