Effects of insulin and amino acids on leucine metabolism in young and middle-aged humans

Summary Background Aging is characterized by loss of muscle mass. In healthy subjects this process is associated with hormone and nutritional changes which take place over many decades. Aim of the study To investigate the effects of insulin and amino acids on amino acid metabolism in middle-aged humans. Methods We evaluated leucine kinetics by means of the intravenous infusion of [ 1 14C] leucine, in 8 young (age 24±2 yr, BMI 21±2 kg/m2) and in 6 middle-aged (age 53±4 yr, BMI 26±1 kg/m2) healthy subjects. Studies were performed under fasting conditions (basal), and after 180 min of euglycemic hyperinsulinemic clamp (study I), or 180 min of euglycemic hyperinsulinemia in combination with an intravenous amino acid infusion (study II). Results In the basal state endogenous leucine flux (ELF, an index of proteolysis), normalized for IBW, averaged 1.71±0.12 and 1.66±0.14 μmol/kg · min in young and middle-aged subjects, respectively. Basal leucine oxidation (0.22±0.03 vs 0.28±0.03 μmol/kg · min, p < 0.05) was lower in middle-aged with respect to young subjects. Non-oxidative leucine disposal (NOLD, an index of protein synthesis: 1.44±0.11 vs 1.43±0.11 μmol/kg · min) was similar in young and middle-aged subjects, respectively. In response to insulin (study I) the absolute and percent decline of ELF and LOX were similar in young and middle-aged subjects: ELF declined to 1.0±0.06 μmol/kg · min (-39±5%) and 1.07±0.14 μmol/kg · min (-36±4%), in young and middle-aged, respectively (both p < 0.01 vs basal); LOX declined to 0.21±0.02 μmol/kg · min (-35±3%), and 0.18±0.05 μmol/kg · min (-28±3%, p < 0.05 vs basal) in young and middle-aged individuals respectively (both p < 0.01 vs basal). In contrast, insulin-mediated whole-body glucose uptake was lower in middle-aged subjects (6.6±1.4 mg/kg · min) with respect to young individuals (8.1±1.7 mg/kg · min, p < 0.05). During study II (insulin plus AA) a significant rise in NOLD was obtained in both young (1.72±0.10 μmol/kg · min, p < 0.01 vs basal) and middle-aged subjects (1.76±0.25 μmol/kg · min, p < 0.01 vs basal). Similarly, net leucine balance rose significantly in both young (+0.62±0.13 vs -0.25±0.02 μmol/kg · min, p < 0.01 vs basal) and middle-aged subjects (+0.37±0.08 vs -0.22±0.03 μmol/kg · min, p < 0.01 vs basal) suggesting that the anabolic response to amino acids is preserved in middle-aged subjects. Conclusions In middle-aged subjects we observed 1) a moderate decline in basal leucine oxidation; 2) a normal antiproteolytic response to insulin and a reduction in glucose uptake; and 3) a normal anabolic response to AA plus insulin. In conclusion, the data provide evidence for a normal regulation of protein anabolism and an early dissociation between the metabolic effects of insulin on glucose uptake and proteolysis in middle-aged subjects.