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Updated: May 9, 2026
08:01
Measurement of Insulin- and Contraction-Stimulated Glucose Uptake in Isolated and Incubated Mature Skeletal Muscle from Mice
Published on: May 16, 2021
Exercise, GLUT4, and skeletal muscle glucose uptake
Erik A Richter1, Mark Hargreaves
1Molecular Physiology Group, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark. erichter@ifi.ku.dk
Physiological Reviews
|August 1, 2013
Summary
Exercise stimulates muscle glucose uptake by regulating the GLUT4 transporter. Signaling pathways involving AMPK and CaMKII enhance GLUT4 expression, improving glucose metabolism and storage.
Area of Science:
- Exercise Physiology
- Molecular Biology
- Metabolic Regulation
Background:
- Normal glucose metabolism is crucial for health, with muscle cells relying on the GLUT4 transporter for glucose uptake.
- Muscle contraction triggers GLUT4 translocation to the cell membrane, facilitating glucose entry.
Purpose of the Study:
- To elucidate the regulatory mechanisms of exercise-induced muscle glucose uptake.
- To detail the molecular signaling pathways governing GLUT4 translocation and expression.
Main Methods:
- Review of current literature on molecular signaling in muscle contraction.
- Analysis of signaling cascades involving AMPK, Ca(2+), NOS, GTPases, Rab, SNARE proteins, and cytoskeletal components.
- Examination of signaling pathways regulating GLUT4 expression, including the HDAC4/5-MEF2 axis.
Main Results:
- Exercise-induced muscle glucose uptake is primarily regulated by GLUT4 translocation and expression.
- Complex signaling cascades involving proximal (AMPK, Ca(2+), NOS) and distal (GTPases, Rab, SNAREs, cytoskeleton) components mediate GLUT4 translocation.
- Key kinases AMPK and CaMKII regulate GLUT4 expression via the HDAC4/5-MEF2 pathway, increasing GLUT4 transcription.
Conclusions:
- Exercise training is a potent stimulus for increasing skeletal muscle GLUT4 expression.
- Enhanced GLUT4 expression contributes to improved insulin sensitivity, glucose disposal, and glycogen storage.
- Understanding these mechanisms is vital for managing metabolic health in both healthy individuals and those with disease.
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