Berneis K, Ninnis R, Girard J, Frey B M, Keller U
Department of Research, University Hospital Basel, Switzerland.
J Clin Endocrinol Metab. 1997 Aug;82(8):2528-34. doi: 10.1210/jcem.82.8.4143.
Treatment with insulin-like growth factor I (IGF-I) alone failed to affect glucocorticoid-induced protein catabolism in a previous study from our laboratory. To assess the effects of the combination of IGF-I and GH in a similar protocol, 24 normal subjects received (in a double-blind, randomized, placebo-controlled manner) s.c. injections of either GH alone (0.3 IU/kg.day), the combination of IGF-I (80 micrograms/kg.day) and GH (0.3 IU/kg.day), or placebo for a period of 6 days during which they were treated with methylprednisolone (0.5 mg/kg.day). Whole-body protein kinetics measured, using the [1-13C]-leucine infusion technique, demonstrated that leucine flux (a parameter of protein breakdown) increased during administration of glucocorticoids alone (placebo group) and during GH-treatment, whereas the glucocorticoid-induced increase was abolished during IGF-I plus GH (P < 0.03 vs. GH). Leucine oxidation (a parameter of irreversible protein catabolism) increased in the placebo group (+60 +/- 14.5%, P < 0.005, day 7 vs. day 1), remained unchanged in the GH group (+2.5 +/- 10%), and decreased in the combination group (-17.7 +/- 3.3%, P < 0.002, day 7 vs. day 1). Glucose MCR decreased in the group receiving placebo (P < 0.05) and remained unchanged during combined treatment with IGF-I plus GH. It is concluded that glucocorticoid-induced protein, catabolism (leucine oxidation) is abolished during coadministration of GH (anticatabolic effect), whereas treatment with IGF-I and GH results in a net anabolic effect without adverse effects on peripheral glucose clearance.
在我们实验室之前的一项研究中，单独使用胰岛素样生长因子I（IGF-I）治疗未能影响糖皮质激素诱导的蛋白质分解代谢。为了在类似方案中评估IGF-I和生长激素（GH）联合使用的效果，24名正常受试者（采用双盲、随机、安慰剂对照方式）皮下注射单独的GH（0.3 IU/kg·天）、IGF-I（80微克/kg·天）与GH（0.3 IU/kg·天）的组合或安慰剂，为期6天，在此期间他们接受甲泼尼龙（0.5 mg/kg·天）治疗。使用[1-13C]-亮氨酸输注技术测量全身蛋白质动力学，结果表明，单独使用糖皮质激素（安慰剂组）和GH治疗期间，亮氨酸通量（蛋白质分解的一个参数）增加，而在IGF-I加GH联合治疗期间，糖皮质激素诱导的增加被消除（与GH组相比，P<0.03）。安慰剂组亮氨酸氧化（不可逆蛋白质分解的一个参数）增加（+60±14.5%，P<0.005，第7天与第1天相比），GH组保持不变（+2.5±10%），联合治疗组降低（-17.7±3.3%，P<0.002，第7天与第1天相比）。接受安慰剂组的葡萄糖代谢清除率降低（P<0.05），在IGF-I加GH联合治疗期间保持不变。得出的结论是，在GH共同给药期间，糖皮质激素诱导的蛋白质分解代谢（亮氨酸氧化）被消除（抗分解代谢作用），而IGF-I和GH治疗产生净合成代谢作用，且对周围葡萄糖清除无不良影响。
