Exercise & Glucose Uptake

According to research, there are two pathways that stimulates glucose uptake via the GLUT-4 transporter protein.  Even if the insulin-signaling pathway is inhibited, the other pathway that activates AMPK can promote glucose uptake, shown in the Figure above.  In type 2 diabetes, the insulin receptor substrate-1 is not phosphorylated; this inhibits phosphatidylinositol 3-kinase (PI3K) and prevents glucose uptake.  However, AMPK stimulation bypasses this insulin-signaling pathway and increases the GLUT-4 translocation across the plasma membrane in the muscle.  It has been found that even after 24 hours, residual effects of exercise would result in an increase in insulin sensitivity and modest glucose uptake (Musi et al., 2001).    

During exercise, there are two pathways that stimulate AMPK.  In the first pathway, skeletal muscle contraction is activated by the depolarization of T-tubules and membrane.  This stimulates the secretion of Ca2+ from the SR and activates CAMKII.  The other pathway that activates AMPK is initiated when ratios of energy (ATP) and creatine phosphate are low (Holloszy, 2005).  AMPK stimulates TBC1D1 protein and AS160, the link between AMPK and insulin-signaling pathway.  It addition, AMPK conserves energy by turning on ATP-generation pathways.  The TBC1D1 protein ultimately activates the GLUT-4 transporter protein, however the signaling mechanism that controls the glucose transporter protein is unknown.  The activation of AMPK due to exercise contributes to improvements in lipid and glucose metabolism (Sriwijikamol, et al., 2007).  According to a study by Sriwijikamol et al. (2007), aerobic exercise for 40 minutes at moderate intensity, decreased mean plasma glucose levels in the type 2 diabetic subjects by 1.3 mmol/l.  It is suggested that the AMPK stimulation can help to correct insulin resistance and high-to-moderate intensity exercise has also shown significant improvements in glucose uptake.  

Overall, exercise is a critically important component to regulate glucose metabolism, especially in type 2 diabetics.