Glucose is an important energy-rich molecule that is taken up into cells upon stimulation by insulin. Muscle glucose uptake is composed of primarily three steps that can be regulated: glucose delivery, glucose transport, and phosphorylation (Howlett et al. 2013).
The transport of glucose into the muscle cell must be facilitated by the intermembrane transport protein, GLUT4 (Howlett et al. 2013). It follows that insulin regulates the presence of GLUT4 on the plasma membrane. Studies show that the exocytosis of the intracellular glucose storage vesicles, GSVs, to the membrane is in fact increased following insulin stimulation (Howlett et al. 2013; Richter and Hargreaves 2013).
It is believed that this glucose transport is the potentially limiting step for muscle glucose uptake under resting conditions (Richter and Hargreaves 2013). This is because, in absence of insulin, approximately 99% of GLUT4 resides in storage vesicles and other intracellular organelles (Sadler et al. 2013). Very little is actually present on the plasma membrane.
However, one of the primary sources of energy for exercise comes from blood glucose. During exercise, skeletal muscle glucose uptake increases by up to 40-50 times, depending upon the exercise intensity and duration (Howlett et al. 2013). Consequently, the availability of GLUT4 on muscle cells is important for the sufficient uptake of glucose. This fundamental importance has been demonstrated, where muscle contractions had a negligible effect on glucose uptake in mice that were deficient in GLUT4 (Richter and Hargreaves 2013). In another experiment, a 90% reduction in skeletal muscle GLUT4 also completely abolished muscle glucose uptake during exercise (Howlett et al. 2013).
Despite its major role, it has been shown that GLUT4 translocation is no longer a major barrier to glucose uptake while exercising, with glucose phosphorylation potentially becoming the...