Increased muscle fatigability in GLUT-4-deficient mice.
GLUT-4 plays a predominant role in glucose uptake during muscle contraction. In the present study, we have investigated in mice whether disruption of the GLUT-4 gene affects isometric and shortening contractile performance of the dorsal flexor muscle complex in situ. Moreover, we have explored the hypothesis that lack of GLUT-4 enhances muscle fatigability. Isometric performance normalized to muscle mass during a single tetanic contraction did not differ between wild-type (WT) and GLUT-4-deficient [GLUT-4(-/-)] mice. Shortening contractions, however, revealed a significant 1.4-fold decrease in peak power per unit mass, most likely caused by the fiber-type transition from fast-glycolytic fibers (IIB) to fast-oxidative fibers (IIA) in GLUT-4(-/-) dorsal flexors. In addition, the resting glycogen content was significantly lower (34%) in the dorsal flexor complex of GLUT-4(-/-) mice than in WT mice. Moreover, the muscle complex of GLUT-4(-/-) mice showed enhanced susceptibility to fatigue, which may be related to the decline in the muscle carbohydrate store. The significant decrease in relative work output during the steady-state phase of the fatigue protocol suggests that energy supply via alternative routes is not capable to compensate fully for the lack of GLUT-4.
Gorselink
M
M
Department of Physiology, University of Maastricht, 6200 MD Maastricht, The Netherlands.
Drost
M R
MR
de Brouwer
K F J
KF
Schaart
G
G
van Kranenburg
G P J
GP
Roemen
T H M
TH
van Bilsen
M
M
Charron
M J
MJ
van der Vusse
G J
GJ
D000818:Animals; D004558:Electric Stimulation; D004734:Energy Metabolism; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics; D009004:Monosaccharide Transport Proteins / Q000172:deficiency* / Q000235:genetics; D009119:Muscle Contraction / Q000502:physiology; D018763:Muscle Fatigue / Q000502:physiology*; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000378:metabolism / Q000648:ultrastructure; D010710:Phosphates / Q000378:metabolism; D012016:Reference Values
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010710:Phosphates; C495693:Slc2a4 protein, mouse; D006003:Glycogen