D'Hulst Gommaar, Sylow Lykke, Hespel Peter, Deldicque Louise
Department of Kinesiology, Exercise Physiology Research Group, FaBeR, KU Leuven, Tervuursevest 101, 3001, Leuven, Belgium.
Eur J Appl Physiol. 2015 Jun;115(6):1219-31. doi: 10.1007/s00421-015-3103-2. Epub 2015 Jan 11.
To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans.
Fifteen subjects were exposed for 4 h to normoxia (NOR) or to normobaric hypoxia (HYP, FiO2 = 0.11) in a randomized order 40 min after consumption of a high glycemic meal. A muscle biopsy from m. vastus lateralis and a blood sample were taken before (T0), after 1 h (T60) and 4 h (T240) in NOR or HYP and blood glucose levels were measured before exposure and every 30 min.
In HYP, blood glucose was reduced 100 min (110.1 ± 5.4 in NOR vs 89.5 ± 4.7 mg dl(-1) in HYP) and 130 min (98.7 ± 3.8 in NOR vs 85.6 ± 4.9 mg dl(-1) in HYP) after completion of a meal, which resulted in an 83 % lower AUC in HYP compared to NOR (p = 0.006). This coincided with 40 % lower GLUT4 protein in the cytosolic fraction (p = 0.013) and a tendency to increase in the crude membrane fraction (p = 0.070) in HYP compared to NOR. At T240, blood glucose concentration was similar between HYP and NOR, whereas plasma insulin as well as phosphorylation of muscle Akt and GSK-3 was ~2-fold higher in HYP compared to NOR (p < 0.05). In contrast, Rac1 protein was less abundant in the membrane fraction in HYP compared to NOR (p = 0.003), reflecting lower activation.
Acute environmental hypoxia initially reduced blood glucose response to a meal, possibly via an increase in GLUT4 abundance at the sarcolemmal membrane. Later on, whole body insulin intolerance developed independently of defects in conventional insulin signaling in skeletal muscle.
研究急性环境性低氧如何调节健康人餐后血糖及下游肌肉内胰岛素信号传导。
15名受试者在食用高糖餐后40分钟，以随机顺序暴露于常氧（NOR）或常压低氧（HYP，FiO2 = 0.11）环境4小时。在NOR或HYP环境下，于暴露前（T0）、1小时后（T60）和4小时后（T240）采集股外侧肌肌肉活检样本和血样，并在暴露前及每隔30分钟测量血糖水平。
在HYP环境下，餐后100分钟（NOR组为110.1±5.4，HYP组为89.5±4.7mg dl(-1)）和130分钟（NOR组为98.7±3.8，HYP组为85.6±4.9mg dl(-1)）血糖降低，导致HYP组的曲线下面积（AUC）比NOR组低83%（p = 0.006）。这与HYP组胞质部分GLUT4蛋白降低40%（p = 0.013）以及粗膜部分有增加趋势（p = 0.070）相吻合，与NOR组相比。在T240时，HYP组和NOR组的血糖浓度相似，而HYP组的血浆胰岛素以及肌肉Akt和GSK-3的磷酸化水平比NOR组高约2倍（p < 0.05）。相反，与NOR组相比，HYP组膜部分的Rac1蛋白含量较少（p = 0.003），反映出激活程度较低。
急性环境性低氧最初降低了餐后血糖反应，可能是通过增加肌膜上GLUT4的丰度。随后，全身胰岛素抵抗的发生独立于骨骼肌中传统胰岛素信号传导的缺陷。
