Muscle insulin resistance amended with exercise training: Role of GLUT4 expression

Purpose: Muscle insulin resistance is characterized by the inability of a normal insulin concentration to produce a favorable rate of glucose uptake. The muscle of the obese Zucker rat is highly insulin resistant. The purpose of this review is to discuss the cellular defects associated with the muscle insulin resistance of the obese Zucker rat, as well as the mechanisms by which exercise training alleviates or compensates for these defects. Emphasis will be given to the importance of an increased GLUT4 expression on alleviating muscle insulin resistance. Methods: A review of the relative research from my laboratory and the scientific literature was performed to obtain information on the muscle insulin resistance of the obese Zucker rat and its response to exercise training. Results: The insulin resistance of the obese Zucker rat results from defects in the insulin signaling cascade, which limits translocation of the glucose transporter GLUT4 to the plasma membrane upon insulin binding to its receptor. Exercise training improves the muscle insulin resistance of obese Zucker rat but does not correct the defects in insulin signaling or GLUT4 translocation. The improvement in insulin resistance, i.e., glucose transport, is correlated with an increased expression of GLUT4 protein. Preventing GLUT4 overexpression during exercise training will inhibit the improvement in insulin-stimulated glucose transport. Conclusion: Exercise training does not correct but compensates for the defects in muscle insulin resistance by increasing expression of GLUT4. This increase in GLUT4 protein is essential for the improvement in muscle insulin resistance.