Prior exercise in humans redistributes intramuscular GLUT4 and enhances insulin-stimulated sarcolemmal and endosomal GLUT4 translocation
Jonas R.Knudsen Molecular Metabolism 17 April 2020, 100998
Highlights
• Intramyocellular GLUT4 is redistributed 4h after exercise in humans.
• GLUT4 content is increased in GLUT4 storage vesicles and T-tubuli post-exercise.
• Prior exercise + insulin increases sarcolemmal and endosomal GLUT4.
• GLUT4 redistribution may thus contribute to post-exercise muscle insulin-sensitization.
Objective
Exercise is a cornerstone in the management of skeletal muscle insulin-resistance. A well-established benefit of a single bout of exercise is increased insulin sensitivity for hours post-exercise in the previously exercised musculature. Although rodent studies suggest that the insulin-sensitization phenomenon involves enhanced insulin-stimulated GLUT4 cell surface translocation and might involve intramuscular redistribution of GLUT4, the conservation to humans is unknown.
Methods
Healthy young males underwent an insulin-sensitizing one-legged kicking exercise bout for 1 hour followed by fatigue bouts to exhaustion. Muscle biopsies were obtained 4h post-exercise before and after a 2h hyperinsulinemic-euglycemic clamp.
Results
A detailed microscopy-based analysis of GLUT4 distribution muscle specimen in 7 different myocellular compartments revealed that prior exercise increased GLUT4 localization in insulin-responsive storage vesicles and T-tubuli. Furthermore, insulin-stimulated GLUT4 localization was augmented at the sarcolemma and in the endosomal compartments.
Conclusion
An intracellular redistribution of GLUT4 post-exercise is proposed as a molecular mechanism contributing to the insulin-sensitizing effect of prior exercise in human skeletal muscle.