Mechanism of Exercise Training in Lean Insulin-Resistant Non-Diabetics

The study is designed to test the following primary hypothesis:

• Aerobic exercise training will improve insulin sensitivity in insulin resistant subjects through changes in the major cellular signaling pathways and and/or their regulators.

Accordingly, the proposed study is designed to accomplish the following specific aims:

• Quantitate how exercise training improves insulin sensitivity and decreases cardiovascular risk factors in a general population of lean, nondiabetic, insulin resistant subjects. Effects on known cardiovascular risk factors including blood pressure and serum lipoproteins will be evaluated. Change in regional adiposity will also be measured
• Determine the effects of a program of regular aerobic exercise on in the insulin receptor signaling pathway. Biopsies of vastus lateralis muscle from insulin resistant subjects will be obtained before and after a hyperinsulinemic glucose clamp. This procedure will take place in the untrained state and after exercise training. The investigators will measure changes in the insulin receptor and the activity of the major components of the intracellular insulin signaling pathway. The investigators will also look intracellular proteins that regulate this signaling pathway.