Jørgensen J O, Møller J, Alberti K G, Schmitz O, Christiansen J S, Orskov H, Moller N
University Department of Endocrinology and Internal Medicine, Aarhus Kommunehospital, Denmark.
J Clin Endocrinol Metab. 1993 Dec;77(6):1589-96. doi: 10.1210/jcem.77.6.8263146.
The metabolic effects of circadian GH levels in the very low physiological range are unknown. Therefore, we studied 1) GH-deficient patients on receiving GH replacement therapy in whom the last GH injection was replaced with a constant iv infusion starting at 24 h of either GH (35 micrograms/h) or saline (SAL), and 2) an untreated healthy control group. Glucose turnover, indirect calorimetry, and forearm exchange of metabolites were investigated the following day in the basal state (8-11 h) and during a euglycemic (11-13 H) and a hypoglycemic (13-14 h) glucose clamp. During infusion, steady state GH levels increased by 1.9 micrograms/L. Basal and insulin-stimulated energy expenditures (EE) were lower in the patients during SAL than during GH infusion, and the basal respiratory exchange ratio was also lower during GH treatment. Protein EE was elevated during SAL compared to GH infusion (P < 0.05). During the clamp, forearm glucose uptake decreased in the GH study compared to that in the SAL study ((P < 0.05). The patients in the SAL study were more sensitive to insulin during the clamp in terms of suppression of endogenous glucose production (EGP; P < 0.05) and infusion rate of glucose necessary to maintain euglycemia (M value; P < 0.01). Lipid oxidation, in particular in the basal state, was decreased during SAL compared to GH infusion (P < 0.01). The SAL-treated compared with the control group was characterized by decreased basal and insulin-stimulated EE (P < 0.01), increased protein EE (P < 0.01), and hypersensitivity to insulin in terms of suppression of EGP (P < 0.05) and M value (P < 0.01). During the hypoglycemic clamp, the patients in the SAL study were hypersensitive to the hypoglycemic actions of insulin in terms of increased M-value and suppression of EGP, and lipolysis was impaired, as judged by the inhibition of net forearm uptake of FFA. In conclusion, very low GH levels exert powerful actions on day-to-day metabolism, resulting in protein and glucose sparing at the expense of lipids.
极低生理范围内昼夜生长激素（GH）水平的代谢效应尚不清楚。因此，我们进行了以下研究：1）对接受GH替代治疗的GH缺乏患者，将其最后一次GH注射替换为从24小时开始的持续静脉输注，输注的是GH（35微克/小时）或生理盐水（SAL）；2）一个未经治疗的健康对照组。次日，在基础状态（8 - 11小时）、正常血糖（11 - 13小时）和低血糖（13 - 14小时）葡萄糖钳夹期间，研究葡萄糖周转率、间接测热法以及前臂代谢物交换情况。在输注过程中，稳态GH水平升高了1.9微克/升。与GH输注期间相比，SAL输注期间患者的基础和胰岛素刺激的能量消耗（EE）较低，GH治疗期间基础呼吸交换率也较低。与GH输注相比，SAL输注期间蛋白质EE升高（P < 0.05）。在葡萄糖钳夹期间，与SAL研究相比，GH研究中前臂葡萄糖摄取减少（P < 0.05）。在钳夹期间，就抑制内源性葡萄糖生成（EGP；P < 0.05）和维持正常血糖所需的葡萄糖输注速率（M值；P < 0.01）而言，SAL研究中的患者对胰岛素更敏感。与GH输注相比，SAL输注期间脂质氧化，特别是在基础状态下减少（P < 0.01）。与对照组相比，接受SAL治疗的患者其特征为基础和胰岛素刺激的EE降低（P < 0.01）、蛋白质EE升高（P < 0.01），以及在抑制EGP（P < 0.05）和M值（P < 0.01）方面对胰岛素过敏。在低血糖钳夹期间，就增加的M值和抑制EGP而言，SAL研究中的患者对胰岛素的低血糖作用过敏，并且根据前臂FFA净摄取的抑制判断，脂肪分解受损。总之，极低的GH水平对日常代谢产生强大作用，导致以脂质为代价节省蛋白质和葡萄糖。
