title: Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle.
abstract: OBJECTIVE
  To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Kinesiology, Exercise Physiology Research Group, FaBeR, KU Leuven, Tervuursevest 101, 3001, Leuven, Belgium.
authors.forename: Gommaar
authors.initials: G
authors.lastname: D'Hulst
authors.forename: Lykke
authors.initials: L
authors.lastname: Sylow
authors.forename: Peter
authors.initials: P
authors.lastname: Hespel
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
mesh_terms: D001786:Blood Glucose / Q000378:metabolism*; D004040:Dietary Carbohydrates / Q000378:metabolism; D004041:Dietary Fats / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D051275:Glucose Transporter Type 4; D007328:Insulin; C495692:SLC2A4 protein, human; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D010100:Oxygen