使用亮氨酸钳夹技术来证明胰岛素样生长因子-I在正常人体内能积极刺激蛋白质合成。

Use of a leucine clamp to demonstrate that IGF-I actively stimulates protein synthesis in normal humans.

作者信息

Russell-Jones D L, Umpleby A M, Hennessy T R, Bowes S B, Shojaee-Moradie F, Hopkins K D, Jackson N C, Kelly J M, Jones R H, Sönksen P H

机构信息

Department of Medicine, United Medical School, London, United Kingdom.

出版信息

Am J Physiol. 1994 Oct;267(4 Pt 1):E591-8. doi: 10.1152/ajpendo.1994.267.4.E591.

DOI:10.1152/ajpendo.1994.267.4.E591

PMID:7943309

Abstract

Insulin-like growth factor I (IGF-I) is thought to mediate the anabolic action of growth hormone. A glucose and amino acid clamp technique was used to investigate the effects of a 3-h intravenous infusion of either 43.7 pmol.kg-1.min-1 (20 micrograms.kg-1.h-1) IGF-I or 3.4 pmol.kg-1.min-1 (0.5 mU.kg-1.min-1) insulin on whole body leucine turnover in five normal human volunteers. During the IGF-I infusion, IGF-I levels increased (P < 0.01; 26.6 +/- 2.8 to 88.9 +/- 14.2 nmol/l) and insulin levels fell (P < 0.05; 0.096 +/- 0.018 to 0.043 +/- 0.009 nmol/l). During the insulin infusion, insulin levels increased (P < 0.01; 0.057 +/- 0.013 to 0.340 +/- 0.099 nmol/l), and there was no change in IGF-I. There was no significant change in leucine production rate (Ra; a measure of protein degradation) during the IGF-I infusion (2.23 +/- 0.17 to 2.13 +/- 0.2 mumol.kg-1.min-1), but there was an increase (P < 0.03) in nonoxidative leucine disposal rate (Rd; a measure of protein synthesis; 1.83 +/- 0.15 to 2.05 +/- 0.21 mumol.kg-1.min-1). In contrast, insulin reduced (P < 0.02) leucine Ra (1.81 +/- 0.24 to 1.47 +/- 0.24 mumol.kg-1.min-1) and had no effect on nonoxidative leucine Rd (1.44 +/- 0.25 to 1.41 +/- 0.22 mumol.kg-1.min-1). We conclude that IGF-I, under conditions of adequate substrate supply, directly increases protein synthesis in contrast to insulin, which exerts its anabolic action by reducing proteolysis.

摘要

胰岛素样生长因子I（IGF-I）被认为介导生长激素的合成代谢作用。采用葡萄糖和氨基酸钳夹技术，研究了对5名正常人类志愿者静脉输注3小时、剂量分别为43.7 pmol·kg⁻¹·min⁻¹（20μg·kg⁻¹·h⁻¹）的IGF-I或3.4 pmol·kg⁻¹·min⁻¹（0.5 mU·kg⁻¹·min⁻¹）的胰岛素对全身亮氨酸周转率的影响。在输注IGF-I期间，IGF-I水平升高（P<0.01；从26.6±2.8升至88.9±14.2 nmol/L），胰岛素水平下降（P<0.05；从0.096±0.018降至0.043±0.009 nmol/L）。在输注胰岛素期间，胰岛素水平升高（P<0.01；从0.057±0.013升至0.340±0.099 nmol/L），IGF-I无变化。在输注IGF-I期间，亮氨酸生成率（Ra；蛋白质降解的指标）无显著变化（从2.23±0.17降至2.13±0.2μmol·kg⁻¹·min⁻¹），但非氧化亮氨酸处置率（Rd；蛋白质合成的指标）升高（P<0.03；从1.83±0.15升至2.05±0.21μmol·kg⁻¹·min⁻¹）。相反，胰岛素降低了（P<0.02）亮氨酸Ra（从1.81±0.24降至1.47±0.24μmol·kg⁻¹·min⁻¹），对非氧化亮氨酸Rd无影响（从1.44±0.25降至1.41±0.22μmol·kg⁻¹·min⁻¹）。我们得出结论，在底物供应充足的情况下，IGF-I直接增加蛋白质合成，而胰岛素则通过减少蛋白水解发挥其合成代谢作用。