Rasmussen M H, Juul A, Kjems L L, Skakkebaek N E, Hilsted J
Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark.
J Clin Endocrinol Metab. 1995 Mar;80(3):796-801. doi: 10.1210/jcem.80.3.7533771.
Obesity is associated with a marked reduction in the spontaneous secretion of GH. To investigate the effect of acute alterations in calorie intake on GH release, 24-hr spontaneous GH release was measured during habitual calorie intake as well as during a short term, very low calorie diet (VLCD) in 6 obese subjects, 5 obese subjects after weight loss, and 5 normal, age- and sex-matched control subjects. Integrated 20-min samples were obtained over 24-h on two occasions in each subject using a constant blood withdrawal technique. In addition, basal levels of serum insulin-like growth factor-I (IGF-I), IGF-binding protein-1 (IGFBP-1), IGF-binding protein-3 (IGFBP-3), insulin, pro-insulin, and blood glucose were measured during habitual energy intake as well as during the hypocaloric diet. Twenty-four-hour GH release profiles and IGFBP-1 were decreased, and insulin as well as proinsulin levels were elevated in obese subjects compared to those in normal age- and sex-matched controls. No differences between obese subjects and normal controls were present regarding IGF-I, IGFBP-3, or IGF-I/IGFBP-3 molar ratio. In the last 24 h during the 96-h VLCD, an increase in 24-h GH release and basal IGFBP-1 levels and a decrease in basal insulin levels occurred in the normal controls, whereas no such changes were observed in the obese subjects. After caloric restriction 24-hr GH release, IGFBP-1 levels and insulin levels were similar in control subjects and obese subjects after weight loss. This suggests a reversible defect in GH release, rather than a persistent preexisting disorder. It is hypothesized that enhanced bioavailability of IGF-I, acting in concert with elevated proinsulin and insulin levels, may account for the lack of stimulation of 24-hr GH release by the hypocaloric diet in obese subjects. We conclude that the increase in 24-h spontaneous GH release and IGFBP-1 levels observed in normal subjects during the last 24 h of a 96-h VLCD is abolished in obese subjects. The lack of short term hypocaloric stimulation of spontaneous GH release may promote the retention of body fat and perpetuate the obese state.
肥胖与生长激素（GH）的自发分泌显著减少有关。为了研究热量摄入的急性改变对GH释放的影响，对6名肥胖受试者、5名减肥后的肥胖受试者以及5名年龄和性别匹配的正常对照受试者，在习惯性热量摄入期间以及短期极低热量饮食（VLCD）期间测量了24小时的GH自发释放情况。使用恒速采血技术，在每位受试者的24小时内分两次采集20分钟的综合样本。此外，在习惯性能量摄入期间以及低热量饮食期间，测量了血清胰岛素样生长因子-I（IGF-I）、IGF结合蛋白-1（IGFBP-1）、IGF结合蛋白-3（IGFBP-3）、胰岛素、胰岛素原和血糖的基础水平。与年龄和性别匹配的正常对照相比，肥胖受试者的24小时GH释放曲线和IGFBP-1降低，胰岛素以及胰岛素原水平升高。肥胖受试者与正常对照在IGF-I、IGFBP-3或IGF-I/IGFBP-3摩尔比方面没有差异。在96小时VLCD的最后24小时，正常对照的24小时GH释放和基础IGFBP-1水平增加，基础胰岛素水平降低，而肥胖受试者未观察到此类变化。热量限制后，对照受试者和减肥后的肥胖受试者的24小时GH释放、IGFBP-1水平和胰岛素水平相似。这表明GH释放存在可逆性缺陷，而非持续性的既往疾病。据推测，IGF-I生物利用度的提高，与升高的胰岛素原和胰岛素水平共同作用，可能是肥胖受试者低热量饮食未能刺激24小时GH释放的原因。我们得出结论，在96小时VLCD的最后24小时，正常受试者中观察到的24小时自发GH释放和IGFBP-1水平的增加在肥胖受试者中消失。缺乏对自发GH释放的短期低热量刺激可能会促进体脂的保留并使肥胖状态持续存在。
