Is GLUT4 translocation the answer to exercise-stimulated muscle glucose uptake?

Exercise in humans increases muscle glucose uptake up to 100-fold compared with rest. The magnitude of increase depends on exercise intensity and duration. Although knockout of glucose transporter type 4 (GLUT4) convincingly has shown that GLUT4 is necessary for exercise to increase muscle glucose uptake, studies only show an approximate twofold increase in GLUT4 translocation to the muscle cell membrane when transitioning from rest to exercise. Therefore, there is a big discrepancy between the increase in glucose uptake and GLUT4 translocation. It is suggested that either the methods for measurements of GLUT4 translocation in muscle grossly underestimate the real translocation of GLUT4 or, alternatively, GLUT4 intrinsic activity increases in muscle during exercise, perhaps due to increased muscle temperature and/or mechanical effects during contraction/relaxation cycles.