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。