Oehri M, Ninnis R, Girard J, Frey F J, Keller U
Department of Research and of Internal Medicine, University Hospital Basel, Switzerland.
Am J Physiol. 1996 Apr;270(4 Pt 1):E552-8. doi: 10.1152/ajpendo.1996.270.4.E552.
The effects of similar increases in total insulin-like growth factor I (IGF-I) plasma concentrations achieved by either recombinant human (rh) growth hormone (GH) or rhIGF-I administration on whole body protein and glucose kinetics were assessed. Twenty-six healthy subjects received methylprednisolone (0.5 mg.kg-1.day-1 orally) during 6 days in combination with either placebo (saline sc), GH (0.3 mg.kg-1.day-1 sc), or IGF-I (80 micrograms.kg-1.day-1 sc) in a double-blind randomized fashion. Glucocorticoid administration resulted in protein catabolism as indicated by an increase in leucine flux and a 62 +/- 13% increase in leucine oxidation ([1-13C]leucine infusion technique); this increase was abolished by GH (-1 +/- 18%) as was statistically insignificant during IGF-I treatment (+53 +/- 25%). GH increased endogenous glucose production by 28 +/- 8%, augmented glucocorticoid-induced insulin resistance of peripheral glucose clearance (euglycemic clamp), and increased circulating lipids. IGF-I administration resulted in both increased endogenous glucose production and increased peripheral glucose clearance such that plasma glucose concentrations remained unchanged by IGF-I. IGF-I lowered circulating GH and insulin and altered IGF binding proteins, which all may have reduced bioactivity of IGF-I. The data demonstrate that, in spite of similar total IGF-I plasma concentrations during treatment, GH and IGF-I exert markedly different effects on whole body leucine, glucose, and lipid metabolism.
评估了通过给予重组人生长激素（rhGH）或重组人胰岛素样生长因子I（rhIGF-I）使血浆中总胰岛素样生长因子I（IGF-I）浓度相似升高后，对全身蛋白质和葡萄糖动力学的影响。26名健康受试者在6天内口服甲泼尼龙（0.5mg·kg⁻¹·d⁻¹），并以双盲随机方式联合给予安慰剂（皮下注射生理盐水）、生长激素（皮下注射0.3mg·kg⁻¹·d⁻¹）或胰岛素样生长因子I（皮下注射80μg·kg⁻¹·d⁻¹）。糖皮质激素给药导致蛋白质分解代谢，表现为亮氨酸通量增加和亮氨酸氧化增加62±13%（采用[1-¹³C]亮氨酸输注技术）；生长激素可消除这种增加（-1±18%），而在胰岛素样生长因子I治疗期间这种增加无统计学意义（+53±25%）。生长激素使内源性葡萄糖生成增加28±8%，增强了糖皮质激素诱导的外周葡萄糖清除胰岛素抵抗（正常血糖钳夹），并增加了循环脂质。给予胰岛素样生长因子I导致内源性葡萄糖生成增加和外周葡萄糖清除增加，使得胰岛素样生长因子I给药后血浆葡萄糖浓度保持不变。胰岛素样生长因子I降低了循环中的生长激素和胰岛素，并改变了胰岛素样生长因子结合蛋白，所有这些都可能降低了胰岛素样生长因子I的生物活性。数据表明，尽管治疗期间血浆总胰岛素样生长因子I浓度相似，但生长激素和胰岛素样生长因子I对全身亮氨酸、葡萄糖和脂质代谢的影响明显不同。
