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Effect of exercise intensity and hypoxia on skeletal muscle AMPK signaling and substrate metabolism in humans

Departments of Physiology, ¹The University of Melbourne, Parkville, Victoria; ²Monash University, Clayton, Victoria; ³Naresuan University, Phitsanulok, Thailand; and ⁴St. Vincent's Institute and Commonwealth Scientific and Industrial Research Organisation Molecular and Health Sciences, Fitzroy, Victoria, Australia

Submitted 23 September 2005 ; accepted in final form 26 October 2005

We compared in human skeletal muscle the effect of absolute vs. relative exercise intensity on AMP-activated protein kinase (AMPK) signaling and substrate metabolism under normoxic and hypoxic conditions. Eight untrained males cycled for 30 min under hypoxic conditions (11.5% O₂, 111 ± 12 W, 72 ± 3% hypoxia O_{2 peak}; 72% Hypoxia) or under normoxic conditions (20.9% O₂) matched to the same absolute (111 ± 12 W, 51 ± 1% normoxia O_{2 peak}; 51% Normoxia) or relative (to O_{2 peak}) intensity (171 ± 18 W, 73 ± 1% normoxia O_{2 peak}; 73% Normoxia). Increases (P < 0.05) in AMPK activity, AMPK Thr¹⁷² phosphorylation, ACC Ser²²¹ phosphorylation, free AMP content, and glucose clearance were more influenced by the absolute than by the relative exercise intensity, being greatest in 73% Normoxia with no difference between 51% Normoxia and 72% Hypoxia. In contrast to this, increases in muscle glycogen use, muscle lactate content, and plasma catecholamine concentration were more influenced by the relative than by the absolute exercise intensity, being similar in 72% Hypoxia and 73% Normoxia, with both trials higher than in 51% Normoxia. In conclusion, increases in muscle AMPK signaling, free AMP content, and glucose disposal during exercise are largely determined by the absolute exercise intensity, whereas increases in plasma catecholamine levels, muscle glycogen use, and muscle lactate levels are more closely associated with the relative exercise intensity.

metabolic regulation; glucose kinetics; contraction

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