Aerobic Exercise Overcomes the Age-Related Insulin Resistance of Muscle Protein Metabolism by Improving Endothelial Function and Akt/Mammalian Target of Rapamycin Signaling

Muscle protein metabolism is resistant to insulin's anabolic effect in healthy older subjects. This is associated with reduced insulin vasodilation. We hypothesized that aerobic exercise restores muscle protein anabolism in response to insulin by improving vasodilation in older subjects. We measured blood flow, endothelin-1, Akt/mammalian target of rapamycin (mTOR) signaling, and muscle protein kinetics in response to physiological local hyperinsulinemia in two groups of older subjects following a bout of aerobic exercise (EX group: aged 70 +/- 2 years; 45-min treadmill walk, 70% heart rate max) or rest (CTRL group: aged 68 +/- 1 years). Baseline endothelin-1 was lower and blood flow tended to be higher in the EX group, but protein kinetics was not different between groups. Insulin decreased endothelin-1 (P < 0.05) in both groups, but endothelin-1 remained higher in the CTRL group (P < 0.05) and blood flow increased only in the EX group (EX group: 3.8 +/- 0.7 to 5.3 +/- 0.8; CTRL group: 2.5 +/- 0.2 to 2.6 +/- 0.2 ml x min(-1) x 100 ml leg(-1)). Insulin improved Akt phosphorylation in the EX group and increased mTOR/S6 kinase 1 phosphorylation and muscle protein synthesis (EX group: 49 +/- 11 to 89 +/- 23; CTRL group: 58 +/- 8 to 57 +/- 12 nmol x min(-1) x 100 ml leg(-1)) in the EX group only (P < 0.05). Because breakdown did not change, net muscle protein balance became positive only in the EX group (P < 0.05). In conclusion, a bout of aerobic exercise restores the anabolic response of muscle proteins to insulin by improving endothelial function and Akt/mTOR signaling in older subjects.