Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle

TY - JOUR

T1 - Acute systemic insulin intolerance does not alter the response of the Akt/GSK-3 pathway to environmental hypoxia in human skeletal muscle

AU - D'Hulst, Gommaar

AU - Sylow, Lykke

AU - Hespel, Peter

AU - Deldicque, Louise

N1 - CURIS 2015 NEXS 034

PY - 2015/6/1

Y1 - 2015/6/1

N2 - 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.Purpose: To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans.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.Conclusion: 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.

AB - 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.Purpose: To investigate how acute environmental hypoxia regulates blood glucose and downstream intramuscular insulin signaling after a meal in healthy humans.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.Conclusion: 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.

U2 - 10.1007/s00421-015-3103-2

DO - 10.1007/s00421-015-3103-2

M3 - Journal article

C2 - 25577409

SN - 1439-6319

VL - 115

SP - 1219

EP - 1231

JO - European Journal of Applied Physiology

JF - European Journal of Applied Physiology

IS - 6

ER -