Effect of prolonged intermittent hypoxia and exercise trainingg on glucose tolerance and musclke glut4 expression

Por: C. H. Kuo, J. L. Ivy, L. L. Chiu e Y. M. Cho.

Athens 2004: Pre-olympic Congress

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We previously demonstrated that high altitude living condition improves glucose tolerance (Lee et al., 2003). It is not known whether this adaptation was associated with increase in GLUT4 protein expression. Therefore, we investigated the interactive effect of hypoxia and endurance training on glucose tolerance and muscle GLUT4 protein expression in Sprague-Dawley rats.


Thirty-two rats were weight-matched and assigned to one of the following four groups: control, endurance training, hypoxia, or hypoxia followed by endurance training. Hypoxia treatment consisted of breathing 14% O2 for 12 hr/d under normobaric conditions, and the training protocol consisted of swimming animals for 2X3 h/d. At the end of the 3rd week of treatment, an oral glucose tolerance test (OGTT) was administered 16-hr post treatment. At the end of the 4th week, GLUT4 protein, mRNA, and glycogen storage was determined in skeletal muscle.


Endurance training significantly improved OGTT and elevated GLUT4 protein expression in the plantaris and red gastrocnemius, but not in the white gastrocnemius muscle. Hypoxia improved OGTT to a greater extent than endurance training, but did not alter GLUT4 protein expression. Additionally, hypoxia followed by endurance training produced a greater increase in GLUT4 protein and mRNA when compared to endurance training alone.

Hypoxia improves glucose tolerance in the absence of increased GLUT4 protein expression and appears to sensitize the endurance training effect on muscle GLUT4 expression and glycogen storage. The current result opens the possibility of utilizing intermittent hypoxia for the clinical treatment of type II diabetes or insulin resistance.


  1. Lee WC, Chen JJ, Hou CW, Ho HY, Liang MP, Sen YW, Kuo CH (2003). Short-term altitude mountain living improves glucose tolerance. High Altitude Medicine & Biology, 4(1): 81-91.



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