APPS November 2002 Meeting Abstract 237

Exercise can enhance the metabolic action of insulin¹ and subsequently plays an important role in the treatment and prevention of skeletal muscle insulin resistance, which is a common metabolic defect characteristic of a number of diseases, including type 2 diabetes and obesity. The underlying mechanism/s responsible for the beneficial effect of exercise on insulin action are equivocal. However, evidence is now emerging which demonstrates that exercise can influence specific events in the insulin signalling cascade. Exercise does not appear to alter insulin binding or activation of the insulin receptor², but rather, influences insulin signalling downstream at the level of insulin receptor substrates 1 (IRS-1) and 2 (IRS-2), and associated phosphatidylinositiol 3-kinase activity. Recent findings demonstrate that an acute bout of exercise can markedly enhance insulin-mediated IRS-2 signalling in skeletal muscle³. In contrast, insulin-mediated IRS-1 signalling is reduced⁴ or unchanged⁵ following exercise. These findings suggest that activation of IRS-1 and -2 are differentially regulated in skeletal muscle in response to exercise. However, it remains to be determined as to how these changes in insulin signalling are mediated in the period following exercise. It is possible that exercise influences insulin signalling through changes in the cellular localisation of insulin signalling molecules within the muscle or by altering currently unidentified signalling intermediates. Further research is also required to address the specific physiological responses that are mediated by these exercise-induced changes in insulin signalling. Advancements in elucidating the underlying mechanisms whereby exercise improves insulin action is likely to lead to novel treatments and/or therapies that will aid in enhancing skeletal muscle function in health and disease.