Impaired Leucine Oxidation During Hyperglycemia After Eccentric Exercise in Older Men

Abstract

Aging reduces insulin sensitivity in healthy sedentary adults, which may alter protein metabolism during periods of metabolic and physiologic stress. We determined the effects of age, and metabolic (hyperglycemia) and physiological [eccentric exercise (ECE)] stress, on whole-body amino acid turnover. [1-13C]-Leucine kinetics was measured in 8 healthy young (YM, 22±2 y; BMI 23±5 kg/m2) and 8 healthy older (OM, 66±6 y; BMI 25±3 kg/m2) men during fasting (F) and 3-hr hyperglycemic-hyperinsulinemic clamps (HG) that were performed before (CON) and 48 hours after ECE. Leucine oxidation (Lox) decreased (p<0.05) in YM during CON-HG, ECE-F and ECE-HG (CON-F 28.3±3.9; CON-HG 25.9±4.0; ECE-F 24.8±4.1; ECE-HG 21.4±3.2 μmol·kg FFM−1·h−1). In contrast, OM failed to suppress Lox from CON-F conditions (CON-F 26.0±3.9; CON-HG 26.8±3.7; ECE-F 25.1±5.7; ECE-HG 26.3±7.0 μmol·kg FFM−1·h−1; p>0.05). Insulin sensitivity was inversely correlated with Lox (r = −0.53; p<0.05) and was lower in OM (YM 7.1±0.6; OM 4.5±0.3 mg·kg FFM−1·min−1; p<0.05). Nonoxidative leucine disposal and leucine flux were not different between YM and OM (p>0.05). In conclusion, aging leads to an impaired capacity to adjust protein metabolism in response to metabolic or physiological stress, which is coupled with decreased insulin sensitivity. Supported by NIH grants T32DK007319 AG12834, AG15385, AG11811, RR000954, DK020579, DK056341