Møller N, Møller J, Jørgensen J O, Ovesen P, Schmitz O, Alberti K G, Christiansen J S
University Department of Internal Medicine, (Endocrinology and Diabetes), Aarhus Kommunehospital, Denmark.
Clin Endocrinol (Oxf). 1993 Nov;39(5):577-81. doi: 10.1111/j.1365-2265.1993.tb02412.x.
Short-term, high dose growth hormone (GH) treatment has been advocated in many catabolic disease states. It is likely that some of the anabolic effects of GH are mediated through activation of lipolysis, but the metabolic impact of therapeutically relevant GH exposure is not known in detail. The present study was accordingly designed to assess the effects of such GH exposure on basal and insulin stimulated intermediary metabolism.
DESIGN, PATIENTS AND MEASUREMENTS: Six healthy young females were examined following daily injections of GH (12 IU/day) or saline for 2 weeks in a placebo controlled design. Each study consisted of a 3 hour basal period and a 2 hour hyperinsulinaemic euglycaemic clamp.
GH treatment caused (1) increased levels of IGF-I (382 +/- 46 vs 294 +/- 22 micrograms/l, P < 0.05) and (2) increased basal values of free fatty acids (714 +/- 40 (GH) vs 634 +/- 64 (placebo) mumol/l, P < 0.05), 3-hydroxybutyrate (118.3 +/- 42.8 (GH) vs 57.7 +/- 21.6 (placebo) mumol/l, P < 0.05), glycerol (54.3 +/- 8.2 (GH) vs 41.4 +/- 8.4 (placebo) mumol/l, P < 0.05) and forearm uptake of 3-hydroxybutyrate, together with increments of plasma glucose (5.28 +/- 0.11 (GH) vs 4.87 +/- 0.16 (placebo) mmol/l, P < 0.05). Basal forearm uptake of glucose, isotopically determined glucose turnover and serum levels of GH, insulin and C-peptide were unaltered. During the clamp GH treatment was associated with (1) a 40% decrease in the administered amount of glucose (M-value) (P < 0.05) and (2) a 70% decrease in forearm glucose uptake (P < 0.05). Indirect calorimetry revealed a 15% increase in resting energy expenditure (P < 0.05) and a decreased basal respiratory exchange ratio (0.75 (GH) vs 0.80 (placebo), P < 0.05), presumably reflecting increased lipid oxidation.
Administration of GH in a therapeutic dose for 2 weeks, despite apparently normal daytime levels of major metabolic hormones, induces significant increases in circulating lipid fuel substrates, increased energy expenditure and lipid oxidation, together with insulin resistance. Such effects should be considered when applying GH treatment schedules clinically.
在许多分解代谢疾病状态下，有人主张进行短期、高剂量生长激素（GH）治疗。GH的一些合成代谢作用可能是通过激活脂肪分解介导的，但治疗相关剂量的GH暴露对代谢的影响尚不清楚。因此，本研究旨在评估这种GH暴露对基础代谢和胰岛素刺激的中间代谢的影响。
设计、患者与测量方法：采用安慰剂对照设计，对6名健康年轻女性进行研究，她们每天注射GH（12国际单位/天）或生理盐水，持续2周。每项研究包括3小时的基础期和2小时的高胰岛素正常血糖钳夹试验。
GH治疗导致（1）胰岛素样生长因子-I水平升高（382±46对294±22微克/升，P<0.05），以及（2）基础游离脂肪酸值升高（714±40（GH）对634±64（安慰剂）微摩尔/升，P<0.05）、3-羟基丁酸升高（118.3±42.8（GH）对57.7±21.6（安慰剂）微摩尔/升，P<0.05）、甘油升高（54.3±8.2（GH）对41.4±8.4（安慰剂）微摩尔/升，P<0.05）和前臂对3-羟基丁酸的摄取增加，同时血糖升高（5.28±0.11（GH）对4.87±0.16（安慰剂）毫摩尔/升，P<0.05）。基础状态下前臂葡萄糖摄取、同位素测定的葡萄糖周转率以及GH、胰岛素和C肽的血清水平未改变。在钳夹试验期间，GH治疗与（1）葡萄糖输注量（M值）减少40%（P<0.05）以及（2）前臂葡萄糖摄取减少70%（P<0.05）相关。间接测热法显示静息能量消耗增加15%（P<0.05），基础呼吸交换率降低（0.75（GH）对0.80（安慰剂），P<0.05），这可能反映了脂质氧化增加。
给予治疗剂量的GH 2周，尽管主要代谢激素的日间水平看似正常，但会导致循环脂质燃料底物显著增加、能量消耗增加和脂质氧化增加，同时伴有胰岛素抵抗。在临床应用GH治疗方案时应考虑这些影响。
