INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I ENHANCE HUMAN SKELETAL-MUSCLE PROTEIN ANABOLISM DURING HYPERAMINOACIDEMIA BY DIFFERENT MECHANISMS
INSULIN AND INSULIN-LIKE GROWTH-FACTOR-I ENHANCE HUMAN SKELETAL-MUSCLE PROTEIN ANABOLISM DURING HYPERAMINOACIDEMIA BY DIFFERENT MECHANISMS
复制标题
DOI：
10.1172/jci118217
复制
发表时间：
1995-10-01
影响因子：
15.9
通讯作者：
BARRETT, EJ
中科院分区：
文献类型：
--
作者：
FRYBURG, DA;JAHN, LA;BARRETT, EJ
胰岛素抑制人肌肉中蛋白质的分解，从而增加蛋白质合成代谢，而IGF-I主要通过刺激蛋白质合成来促进肌肉蛋白质合成，因为血浆氨基酸的增加或减少可能会影响肌肉中的蛋白质周转，并改变肌肉对胰岛素和/或IGF-I的反应。本研究旨在探讨胰岛素和IGF-I在高氨基酸血症时对人肌肉蛋白质周转的影响。我们测量了22名吸收后成人在持续输注[H-3]苯丙氨酸的过程中双前臂的苯丙氨酸平衡和[H-3]苯丙氨酸动力学。在此基础上，在开始全身输注平衡氨基酸混合物后3和6小时，使动脉苯丙氨酸浓度增加约两倍，在整个6小时内，10名受试者在一条臂动脉局部注射胰岛素(每公斤0.035毫微米/分钟)，而另外12名受试者分别在输注手臂内注射胰岛素或胰岛素样生长因子-I(100 ng/分钟/公斤)以提高胰岛素或胰岛素样生长因子-I浓度。在每项研究中，对侧手臂作为单独氨基酸(AA)的同时对照。在两项研究中，在单独的AA臂中，高氨基酸血症逆转了肌肉吸收后苯丙氨酸的净释放到净摄取(P<；0.025)，这是由于刺激肌肉蛋白质合成，在注入激素的手臂中，添加胰岛素或IGF-I促进了苯丙氨酸平衡的更大的正向移动比单独AA臂(P<；0.01)，使用胰岛素，增强的合成代谢是由于抑制了蛋白质的降解(P<；0.02)，而IGF-I通过进一步刺激蛋白质合成而增强合成代谢(P<；0.02)，我们得出结论：(A)高氨基酸血症专门刺激肌肉蛋白质合成；(6)胰岛素，即使与高氨基酸血症一起，也仅通过抑制蛋白质分解来改善肌肉蛋白质平衡；以及(C)高氨基酸血症与IGF-I联合比单独使用更能促进蛋白质合成。
Insulin inhibits proteolysis in human muscle thereby increasing protein anabolism, In contrast, IGF-I promotes muscle protein anabolism principally by stimulating protein synthesis, As increases or decreases of plasma amino acids may affect protein turnover in muscle and also alter the muscle's response to insulin and/or IGF-I, this study was designed to examine the effects of insulin and IGF-I on human muscle protein turnover during hyperaminoacidemia. We measured phenylalanine balance and [H-3]phenylalanine kinetics in both forearms of 22 postabsorptive adults during a continuous [H-3]phenylalanine infusion. Measurements were made basally and at 3 and 6 h after beginning a systemic infusion of a balanced amino acid mixture that raised arterial phenylalanine concentration about twofold, Throughout the 6 h, 10 subjects received insulin locally (0.035 mU/min per kg) into one brachial artery while 12 other subjects were given intraaterial IGF-I (100 ng/min per kg) to raise insulin or IGF-I concentrations, respectively, in the infused arm, The contralateral arm in each study served as a simultaneous control for the effects of amino acids (aa) alone.Glucose uptake and lactate release increased in the insulin- and IGF-I-infused forearms (P < 0.01) but did not change in the contralateral (aa alone) forearm in either study, In the aa alone arm in both studies, hyperaminoacidemia reversed the postabsorptive net phenylalanine release by muscle to a net uptake (P < 0.025, for each) due to a stimulation of muscle protein synthesis, In the hormone-infused arms, the addition of either insulin or IGF-I promoted greater positive shifts in phenylalanine balance than the aa alone arm (P < 0.01), With insulin, the enhanced anabolism was due to inhibition of protein degradation (P < 0.02), whereas IGF-I augmented anabolism by a further stimulation of protein synthesis above aa alone (P < 0.02), We conclude that: (a) hyperaminoacidemia specifically stimulates muscle protein synthesis; (6) insulin, even with hyperaminoacidemia, improves muscle protein balance solely by inhibiting proteolysis; and (c) hyperaminoacidemia combined with IGF-I enhances protein synthesis more than either alone.