Giordano M, Castellino P, DeFronzo R A
Department of Medicine, Division of Diabetes, University of Texas Health Science Center at San Antonio, Texas.
Diabetes. 1996 Apr;45(4):393-9. doi: 10.2337/diab.45.4.393.
We investigated the effects of graded hyperaminoacidemia on protein metabolism in eight healthy, young (25 +/- 2 years), normal weight (BMI = 25 +/- 1 kg/m2), overnight-fasted human subjects. A balanced amino acid solution was infused for 180 min at five different rates: 0.5 (study I), 1.0 (study II), 2.0 (study III), 4.0 (study IV). and 6.0 (study V) mg x kg-1 x min-1 on separate days in random order. Studies were performed with [1-14C]leucine infusion and indirect calorimetry to calculate leucine oxidation (LOX), nonoxidative leucine disposal (NOLD) (an index of protein synthesis), and endogenous leucine flux (ELF) (an index of proteolysis). Basal total plasma amino acid concentrations averaged 1.85 +/- 0.1 mmol/l and increased to 2.27 +/- 0.1, 2.70 +/- 0.2, 3.84 +/- 0.2, 5.87 +/- 0.4, and 7.52 +/- 0.3 mmol/l in studies I-V, respectively. ELF decreased from a basal value of 2.27 +/- 0.2 to 2.12 +/- 0.2, 1.97 +/- 0.1, 1.73 +/- 0.2, 1.67 +/- 0.3, and 1.65 +/- 0.1 micromol x kg-1 x min-1 in studies I-V, respectively (P < 0.05 for study I vs. basal, P < 0.01 for studies II-V vs. basal, and NS for studies IV and V vs. study III). LOX increased from a basal value of 0.31 +/- 0.04 to 0.38 +/- 0.05, 0.41 +/- 0.02, 0.64 +/- 0.04, 1.11 +/- 0.07, and 1.56 +/- 0.05 micromol x kg-1 x min-1 in studies I-V (all P < 0.01 vs. basal; P < 0.05-0.01 for each study vs. preceding study). Basal NOLD averaged 1.96 +/- 0.2 and did not change significantly in studies I and II (2.03 +/- 0.2 and 2.10 +/- 0.1 micromol x kg-1 x min-1). In contrast, a significant increase in NOLD was observed in studies III, IV, and V (to 2.3 +/- 0.15, 2.74 +/- 0.2, and 3.25 +/- 0.7 micromol x kg-1 x min-1, respectively; all P < 0.01 vs. basal; P < 0.05-0.01 for each study vs. preceding study). The net leucine balance (difference between ELF and NOLD)(-0.31 +/- 0.06 micromol x kg-1 x min-1) became less negative in study I (P < 0.01 vs. basal) and positive during studies II-V when the rise in plasma total amino acid levels was >/= 50% above basal level (P < 0.01 vs. each preceding study). In conclusion, NOLD, ELF, and LOX exhibit a differential responsiveness to acute changes in substrate availability: 1) small increments (25-50%) in plasma amino acid levels inhibit ELF and stimulate LOX but have no effect on NOLD; 2) stimulation of NOLD is observed only with increments in plasma amino acid levels >/= 100% above basal values; and 3) increments in plasma amino acid concentrations > 100% above basal values cause a progressive dose-related increase in LOX and NOLD but do not induce any further inhibition of ELF.
我们研究了分级高氨基酸血症对8名健康、年轻（25±2岁）、体重正常（BMI = 25±1 kg/m²）、过夜禁食的人类受试者蛋白质代谢的影响。在五个不同速率下，将平衡氨基酸溶液输注180分钟：0.5（研究I）、1.0（研究II）、2.0（研究III）、4.0（研究IV）和6.0（研究V）mg·kg⁻¹·min⁻¹，在不同日期以随机顺序进行。通过输注[1-¹⁴C]亮氨酸和间接量热法进行研究，以计算亮氨酸氧化（LOX）、非氧化亮氨酸处理（NOLD）（蛋白质合成指标）和内源性亮氨酸通量（ELF）（蛋白水解指标）。基础血浆总氨基酸浓度平均为1.85±0.1 mmol/l，在研究I - V中分别升至2.27±0.1、2.70±0.2、3.84±0.2、5.87±0.4和7.52±0.3 mmol/l。ELF从基础值2.27±0.2分别降至研究I - V中的2.12±0.2、1.97±0.1、1.73±0.2、1.67±0.3和1.65±0.1 μmol·kg⁻¹·min⁻¹（研究I与基础值相比P < 0.05，研究II - V与基础值相比P < 0.01，研究IV和V与研究III相比无显著差异）。LOX从基础值0.31±0.04分别升至研究I - V中的0.38±0.05、0.41±0.02、0.64±0.04、1.11±0.07和1.56±0.05 μmol·kg⁻¹·min⁻¹（与基础值相比均P < 0.01；各研究与前一研究相比P < 0.05 - 0.01）。基础NOLD平均为1.96±0.2，在研究I和II中无显著变化（分别为2.03±0.2和2.10±0.1 μmol·kg⁻¹·min⁻¹）。相比之下，在研究III、IV和V中观察到NOLD显著增加（分别升至2.3±0.15、2.74±0.2和3.25±0.7 μmol·kg⁻¹·min⁻¹；与基础值相比均P < 0.01；各研究与前一研究相比P < 0.05 - 0.01）。净亮氨酸平衡（ELF与NOLD之差）（-0.31±0.06 μmol·kg⁻¹·min⁻¹）在研究I中变得不那么负（与基础值相比P < 0.01），在研究II - V中当血浆总氨基酸水平升高≥基础水平的50%时变为正值（与每个前一研究相比P < 0.01）。总之，NOLD、ELF和LOX对底物可用性的急性变化表现出不同的反应性：1）血浆氨基酸水平小幅升高（25 - 50%）会抑制ELF并刺激LOX，但对NOLD无影响；2）仅在血浆氨基酸水平升高≥基础值的100%时观察到NOLD受到刺激；3）血浆氨基酸浓度升高>基础值的100%会导致LOX和NOLD呈剂量相关的逐渐增加，但不会进一步抑制ELF。
