Flakoll P J, Kulaylat M, Frexes-Steed M, Hourani H, Brown L L, Hill J O, Abumrad N N
Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee 37232.
Am J Physiol. 1989 Dec;257(6 Pt 1):E839-47. doi: 10.1152/ajpendo.1989.257.6.E839.
Leucine (LEU) kinetics were assessed using a primed-continuous infusion of L-[1-14C]LEU in normal overnight-fasted male volunteers during a basal period and an experimental period where insulin (INS) was infused at either 0.6, 1.2, 2.5, 5.0, 10, or 20 mU.kg-1.min-1 with euglycemia maintained. Two protocols were used: 1) subjects were allowed to develop hypoaminoacidemia or 2) plasma essential amino acids (AA) were maintained near basal levels by frequently monitoring plasma LEU in conjunction with variable infusions of an AA solution (LEU infused = 0.41, 0.72, 0.93, 1.03, 1.31, and 1.35 mumol.kg-1.min-1 at escalating INS doses, respectively). Basal rates of LEU appearance (Ra), nonoxidative disappearance (NORd) and oxidative disappearance (OXRd) were similar in both protocols (means = 1.74, 1.40, and 0.36 mumol.kg-1.min-1, respectively). INS infusions without AA resulted in a progressive decrement in LEU Ra (14 to 45%), NORd (16-41%), and OXRd (3-56%) compared with basal values. The infusion of AA resulted in an additional reduction in endogenous Ra (P less than 0.01; approximately 100% suppression achieved at plasma INS greater than 1,000 microU/ml) and a blunting of NORd reduction (P less than 0.05) at each dose of INS. Observed differences in INS's suppression of LEU Ra between the two protocols suggests the existence of a component of whole body proteolysis that is highly dependent on circulating plasma AA. Therefore, hypoaminoacidemia associated with INS treatment would appear to blunt the responsiveness of INS's suppression of protein breakdown and in the presence of near basal plasma AA, proteolytic suppression by INS is enhanced.
在基础期和实验期，通过对正常隔夜禁食男性志愿者进行L-[1-14C]亮氨酸的首剂-持续输注来评估亮氨酸（LEU）动力学。实验期内，以0.6、1.2、2.5、5.0、10或20 mU·kg-1·min-1的速率输注胰岛素（INS）并维持血糖正常。采用了两种方案：1）让受试者发生低氨基酸血症；2）通过频繁监测血浆亮氨酸并结合可变输注氨基酸溶液（在递增的胰岛素剂量下，亮氨酸输注量分别为0.41、0.72、0.93、1.03、1.31和1.35 μmol·kg-1·min-1），使血浆必需氨基酸（AA）维持在接近基础水平。两种方案中亮氨酸的基础出现率（Ra）、非氧化消失率（NORd）和氧化消失率（OXRd）相似（均值分别为1.74、1.40和0.36 μmol·kg-1·min-1）。与基础值相比，不补充氨基酸的胰岛素输注导致亮氨酸Ra逐渐降低（14%至45%）、NORd降低（16% - 41%）以及OXRd降低（3% - 56%）。氨基酸输注导致内源性Ra进一步降低（P < 0.01；在血浆胰岛素大于1000 μU/ml时实现约100%抑制），并且在每个胰岛素剂量下NORd降低程度减弱（P < 0.05）。两种方案中观察到的胰岛素对亮氨酸Ra抑制作用的差异表明，存在一个高度依赖循环血浆氨基酸的全身蛋白质水解成分。因此，与胰岛素治疗相关的低氨基酸血症似乎会减弱胰岛素对蛋白质分解抑制的反应性，而在血浆氨基酸接近基础水平时，胰岛素对蛋白水解的抑制作用会增强。
