Purpose: This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and pre-diabetic subjects exercising in normobaric hypoxia.

Methods: Seventeen healthy (H; 28.8±2.4y; VO2max: 45.1±1.8mL·kg-1·min-1) and fifteen pre-diabetic (P; 44.6±3.9y; VO2max: 30.8±2.5mL·kg-1·min-1) men were randomly assigned to two groups performing an acute exercise bout (heart rate corresponding to 55% VO2max) either in normoxic (NE) or in hypoxic (HE; FiO2 14.0%) conditions. An oral glucose tolerance test (OGTT) was performed in a basal state and after an acute exercise bout. Muscle biopsies from m. vastus lateralis were taken before and after exercise. Venous blood samples were taken at regular intervals before, during and after exercise.

Results: The two groups exercising in hypoxia had a larger area under the curve of blood glucose levels during the OGTT after exercise compared to baseline (H: +4%; P: +11%). Compared to pre-exercise, an increase in p-TBC1D1 Ser237 and in p-AMPK Thr172 was observed post-exercise in P NE (+95%; +55%, respectively) and H HE (+91%; +43%, respectively). An increase in p-ACC Ser212 was measured after exercise in all groups (H NE: +228%; P NE: +252%; H HE: +252%; P HE: +208%).

Conclusions: Our results show that an acute bout of exercise in hypoxia reduces glucose tolerance in healthy and pre-diabetic subjects. At a molecular level, some adaptations regulating glucose transport in muscle were found in all groups without associations with glucose tolerance after exercise. The results suggest that hypoxia negatively affects glucose tolerance post-exercise through unidentified mechanisms.