Hartman M L, Clayton P E, Johnson M L, Celniker A, Perlman A J, Alberti K G, Thorner M O
Department of Medicine, University of Virginia Health Sciences Center, Charlottesville 22908.
J Clin Invest. 1993 Jun;91(6):2453-62. doi: 10.1172/JCI116480.
To determine if insulin-like growth factor I (IGF-I) inhibits pulsatile growth hormone (GH) secretion in man, recombinant human IGF-I (rhIGF-I) was infused for 6 h at 10 micrograms.kg-1.h-1 during a euglycemic clamp in 10 normal men who were fasted for 32 h to enhance GH secretion. Saline alone was infused during an otherwise identical second admission as a control. As a result of rhIGF-I infusion, total and free IGF-I concentrations increased three- and fourfold, respectively. Mean GH concentrations fell from 6.3 +/- 1.6 to 0.59 +/- 0.07 micrograms/liter after 120 min. GH secretion rates, calculated by a deconvolution algorithm, decreased with a t 1/2 of 16.6 min and remained suppressed thereafter. Suppression of GH secretion rates occurred within 60 min when total and free IGF-I concentrations were 1.6-fold and 2-fold above baseline levels, respectively, and while glucose infusion rates were < 1 mumol.kg-1.min-1. During saline infusion, GH secretion rates remained elevated. Infusion of rhIGF-I decreased the mass of GH secreted per pulse by 84% (P < 0.01) and the number of detectable GH secretory pulses by 32% (P < 0.05). Plasma insulin and glucagon decreased to nearly undetectable levels after 60 min of rhIGF-I. Serum free fatty acids, beta-hydroxybutyrate, and acetoacetate were unaffected during the first 3 h of rhIGF-I but decreased thereafter to 52, 32, and 50% of levels observed during saline. We conclude that fasting-enhanced GH secretion is rapidly suppressed by a low-dose euglycemic infusion of rhIGF-I. This effect of rhIGF-I is likely mediated through IGF-I receptors independently of its insulin-like metabolic actions.
为了确定胰岛素样生长因子I（IGF-I）是否抑制人类的脉冲式生长激素（GH）分泌，在10名禁食32小时以增强GH分泌的正常男性进行正常血糖钳夹期间，以10微克·千克⁻¹·小时⁻¹的速度输注重组人IGF-I（rhIGF-I）6小时。在另一次相同的住院期间，仅输注生理盐水作为对照。输注rhIGF-I后，总IGF-I和游离IGF-I浓度分别增加了三倍和四倍。120分钟后，平均GH浓度从6.3±1.6微克/升降至0.59±0.07微克/升。通过反卷积算法计算的GH分泌率下降，半衰期为16.6分钟，此后一直受到抑制。当总IGF-I和游离IGF-I浓度分别比基线水平高1.6倍和2倍时，且葡萄糖输注率<1微摩尔·千克⁻¹·分钟⁻¹，GH分泌率在60分钟内就开始受到抑制。在输注生理盐水期间，GH分泌率保持升高。输注rhIGF-I使每个脉冲分泌的GH量减少了84%（P<0.01），可检测到的GH分泌脉冲数减少了32%（P<0.05）。rhIGF-I输注60分钟后，血浆胰岛素和胰高血糖素降至几乎无法检测的水平。在rhIGF-I输注的前3小时，血清游离脂肪酸、β-羟基丁酸和乙酰乙酸未受影响，但此后分别降至输注生理盐水期间观察到水平的52%、32%和50%。我们得出结论，低剂量正常血糖输注rhIGF-I可迅速抑制禁食增强的GH分泌。rhIGF-I的这种作用可能是通过IGF-I受体介导的，与其胰岛素样代谢作用无关。
