Mauras N, Beaufrere B
Nemours Children's Clinic, Jacksonville, Florida 32207.
J Clin Endocrinol Metab. 1995 Mar;80(3):869-74. doi: 10.1210/jcem.80.3.7533772.
To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) could serve as a protein-sparing nondiabetogenic agent, 21 healthy volunteers (mean age, 25 +/- 1 yr) were studied in 3 similar clinical models: rhIGF-I alone, rhIGF-I and prednisone, and prednisone alone. In study A, 6 subjects received infusions of [14C]leucine and [2H2]glucose before and after 5-7 days of rhIGF-I (100 micrograms/kg, sc, twice daily, followed by 16 h of a 10 micrograms/kg.h continuous sc infusion). The rate of appearance (Ra) of leucine, an estimate of whole body proteolysis, did not change significantly, whereas leucine oxidation decreased (-31 +/- 4%; P = 0.001), hence the nonoxidative leucine disposal (NOLD) increased significantly (P = 0.04). These effects are similar to those reported with high dose hGH. Plasma glucose concentrations did not change despite a significant reduction in circulating insulin concentrations (-58 +/- 11%; P = 0.01) and an increase in the glucose Ra (+12 +/- 5%; P = 0.04). After rhIGF-I treatment, plasma IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 all increased significantly, whereas IGFBP-3 did not change. In study B, seven subjects received rhIGF-I combined with oral prednisone (0.8 mg/kg.day) for 5 days. Group C (n = 8) received only prednisone. In group B, both the leucine Ra and oxidation increased (Ra, +7 +/- 3%; oxidation, +45 +/- 13%), but this increase was significantly less than that seen in group C (Ra, +25 +/- 5%; oxidation, 117 +/- 17%; P < 0.005 vs. group B). Group B showed no significant changes in postabsorptive glucose concentrations despite marked reductions in circulating insulin levels, in contrast to the increase in insulin and glucose concentrations observed in group C. In conclusion, 100 micrograms/g rhIGF-I, given twice daily, 1) has GH-like effects on whole body protein metabolism, 2) markedly diminishes the protein catabolic effect of glucocorticosteroids, and 3) is nondiabetogenic in prednisone-treated humans. This agent offers promise in the treatment of protein catabolic states.
为研究重组人生长激素释放因子（rhIGF-I）是否可作为一种节省蛋白质且不致糖尿病的药物，我们在3种相似的临床模型中对21名健康志愿者（平均年龄25±1岁）进行了研究：单独使用rhIGF-I、rhIGF-I与泼尼松联用、单独使用泼尼松。在研究A中，6名受试者在接受rhIGF-I（100微克/千克，皮下注射，每日2次，随后以10微克/千克·小时的速度持续皮下注射16小时）治疗5 - 7天前后，分别输注[14C]亮氨酸和[2H2]葡萄糖。亮氨酸的出现率（Ra）是全身蛋白水解的一个指标，其并未显著改变，而亮氨酸氧化减少（-31±4%；P = 0.001），因此非氧化亮氨酸处置（NOLD）显著增加（P = 0.04）。这些效应与高剂量hGH报道的效应相似。尽管循环胰岛素浓度显著降低（-58±11%；P = 0.01）且葡萄糖Ra增加（+12±5%；P = 0.04），但血浆葡萄糖浓度并未改变。rhIGF-I治疗后，血浆IGF-I、胰岛素样生长因子结合蛋白-1（IGFBP-1）和IGFBP-2均显著增加，而IGFBP-3未改变。在研究B中，7名受试者接受rhIGF-I与口服泼尼松（0.8毫克/千克·天）联合治疗5天。C组（n = 8）仅接受泼尼松治疗。在B组中，亮氨酸Ra和氧化均增加（Ra，+7±3%；氧化，+45±13%），但这种增加显著低于C组（Ra，+25±5%；氧化，117±17%；与B组相比，P < 0.005）。尽管循环胰岛素水平显著降低，但B组空腹血糖浓度无显著变化，这与C组观察到的胰岛素和葡萄糖浓度增加形成对比。总之，每日2次给予100微克/克rhIGF-I，1）对全身蛋白质代谢具有类似生长激素的作用，2）显著减轻糖皮质激素的蛋白质分解代谢作用，3）在接受泼尼松治疗的人类中不致糖尿病。这种药物在治疗蛋白质分解代谢状态方面具有前景。
