Luzi L, Giordano M, Castellino P
Università degli Studi di Milano, San Raffaele Scientific Institute, Italy.
Eur J Nutr. 2001 Jun;40(3):106-12. doi: 10.1007/s003940170010.
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.
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).
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 micromol/kg x min in young and middle-aged subjects, respectively. Basal leucine oxidation (0.22 +/- 0.03 vs 0.28 +/- 0.03 micromol/ kg x 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 micromol/kg x 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 1.05 +/- 0.06 micromol/kg x min (-39 +/- 5 %) and 1.07 +/- 0.14 micromol/kg x min (-36 +/- 4%), in young and middle-aged, respectively (both p < 0.01 vs basal); LOX declined to 0.21 +/- 0.02 micromol/kg min (-35 +/- 3 %), and 0.18 +/- 0.05 micromol/kg x 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 x 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 micromol/kg x min, p < 0.01 vs basal) and middle-aged subjects (1.76 +/- 0.25 micromol/kg x min, p < 0.01 vs basal). Similarly, net leucine balance rose significantly in both young (+0.62 +/- 0.13 vs -0.25 +/- 0.02 micromol/kg x min, p < 0.01 vs basal) and middle-aged subjects (+0.37 +/- 0.08 vs -0.22 +/- 0.03 micromol/ kg x min, p < 0.01 vs basal) suggesting that the anabolic response to amino acids is preserved in middle-aged subjects.
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.
衰老的特征是肌肉质量的丧失。在健康受试者中，这一过程与数十年来发生的激素和营养变化有关。本研究的目的是研究胰岛素和氨基酸对中年人体内氨基酸代谢的影响。
我们通过静脉输注[1-(14C)]亮氨酸来评估8名年轻（年龄24±2岁，体重指数21±2kg/M2）和6名中年（年龄53±4岁，体重指数26±1kg/M2）健康受试者的亮氨酸动力学。研究在空腹条件下（基础状态）进行，以及在正常血糖高胰岛素钳夹180分钟后（研究I），或在正常血糖高胰岛素血症结合静脉氨基酸输注180分钟后（研究II）进行。
在基础状态下，以理想体重校正的内源性亮氨酸通量（ELF，蛋白水解的指标）在年轻和中年受试者中分别平均为1.71±0.12和1.66±0.14微摩尔/千克×分钟。中年受试者的基础亮氨酸氧化（0.22±0.03对0.28±0.03微摩尔/千克×分钟，p<0.05）低于年轻受试者。非氧化亮氨酸处置（NOLD，蛋白质合成的指标：1.44±0.11对1.43±0.11微摩尔/千克×分钟）在年轻和中年受试者中相似。对胰岛素的反应（研究I），年轻和中年受试者中ELF和亮氨酸氧化（LOX）的绝对下降和百分比下降相似：年轻受试者中ELF降至1.05±0.06微摩尔/千克×分钟（-39±5%），中年受试者中降至1.07±0.14微摩尔/千克×分钟（-36±4%）（两者均p<0.01对基础状态）；年轻个体中LOX降至0.21±0.02微摩尔/千克×分钟（-35±3%），中年个体中降至0.18±0.05微摩尔/千克×分钟（-28±3%，p<0.05对基础状态）（两者均p<0.01对基础状态）。相比之下，中年受试者的胰岛素介导的全身葡萄糖摄取（6.6±1.4毫克/千克×分钟）低于年轻个体（8.1±1.7毫克/千克×分钟，p<0.05）。在研究II（胰岛素加氨基酸）期间，年轻（1.72±0.10微摩尔/千克×分钟，p<0.01对基础状态）和中年受试者（1.76±0.25微摩尔/千克×分钟，p<0.01对基础状态）的NOLD均显著升高。同样，年轻（+0.62±0.13对-0.25±0.02微摩尔/千克×分钟，p<0.01对基础状态）和中年受试者（+0.37±0.08对-0.22±0.03微摩尔/千克×分钟，p<0.01对基础状态）的净亮氨酸平衡均显著升高，表明中年受试者对氨基酸的合成代谢反应得以保留。
在中年受试者中，我们观察到：1）基础亮氨酸氧化适度下降；2）对胰岛素的正常抗蛋白水解反应和葡萄糖摄取减少；3）对氨基酸加胰岛素的正常合成代谢反应。总之，这些数据为中年受试者蛋白质合成代谢的正常调节以及胰岛素对葡萄糖摄取和蛋白水解的代谢作用之间的早期分离提供了证据。
