Transcriptional activation of the IL-6 gene in human contracting skeletal muscle: influence of muscle glycogen content.
In humans, the plasma interleukin 6 (IL-6) concentration increases dramatically during low-intensity exercise. Measurements across the working limb indicate that skeletal muscle is the source of IL-6 production. To determine whether energy availability influences the regulation of IL-6 expression during prolonged exercise, six male subjects completed two trials consisting of 180 min of two-legged dynamic knee extensor with either normal or low (~60% of control) pre-exercise muscle glycogen levels. Increases in plasma IL-6 during exercise were significantly higher (P<0.05) in the low-glycogen (16-fold) trial verses the control (10-fold) trial. Transcriptional activation of the IL-6 gene in skeletal muscle was also higher in the low-glycogen trial; it increased by about 40-fold after 90 min of exercise and about 60-fold after 180 min of exercise. Muscle IL-6 mRNA followed a similar but delayed pattern, increasing by more than 100-fold in the low-glycogen trial and by about 30-fold in the control trial. These data demonstrate that exercise activates transcription of the IL-6 gene in working skeletal muscle, a response that is dramatically enhanced when glycogen levels are low. These findings also support the hypothesis that IL-6 may be produced by contracting myofibers when glycogen levels become critically low as a means of signaling the liver to increase glucose production.
Keller
C
C
The Copenhagen Muscle Research Centre, Department of Infectious Diseases, University of Copenhagen, Denmark.
Steensberg
A
A
Pilegaard
H
H
Osada
T
T
Saltin
B
B
Pedersen
B K
BK
Neufer
P D
PD
D015444:Exercise / Q000502:physiology; D006003:Glycogen / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D009119:Muscle Contraction / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D015850:Interleukin-6; D012333:RNA, Messenger; D006003:Glycogen