Muller A F, Janssen J A, Hofland L J, Lamberts S W, Bidlingmaier M, Strasburger C J, van der Lely A J
Department of Internal Medicine, Erasmus Medical Center Rotterdam, 3015 Rotterdam, The Netherlands.
J Clin Endocrinol Metab. 2001 Feb;86(2):590-3. doi: 10.1210/jcem.86.2.7173.
The roles of GH and its receptor (GHR) in metabolic control are not yet fully understood. We studied the roles of GH and the GHR using the GHR antagonist pegvisomant for metabolic control of healthy nonobese men in fasting and nonfasting conditions. Ten healthy subjects were enrolled in a double blind, placebo-controlled study on the effects of pegvisomant on GHRH and GH-releasing peptide-6 (GHRP-6)-induced GH secretion before and after 3 days of fasting and under nonfasting conditions (n = 5). Under the condition of GHR blockade by pegvisomant in the nonfasting state, GHRP-6 (1 microg/kg) caused a increase in serum insulin (10.3 +/- 2.1 vs. 81.3 +/- 25.4 mU/L; P < 0.001) and glucose (4.2 +/- 0.3 vs. 6.0 +/- 0.6 mmol/L; P < 0.05) concentrations. In this group, a rapid decrease in serum free fatty acids levels was also observed. These changes were not observed under GHR blockade during fasting or in the absence of pegvisomant. We conclude that although these results were obtained from an acute study, and long-term administration of pegvisomant could render different results, blockade of the GHR in the nonfasting state induces tissue-specific changes in insulin sensitivity, resulting in an increase in glucose and insulin levels (indicating insulin resistance of liver/muscle), but probably also in an increase in lipogenesis (indicating normal insulin sensitivity of adipose tissue). These GHRP-6-mediated changes indicate that low GH bioactivity on the tissue level can induce changes in metabolic control, which are characterized by an increase in fat mass and a decrease in lean body mass. As a mechanism of these GHRP-6-mediated metabolic changes in the nonfasting state, direct nonpituitary-mediated GHRP-6 effects on the gastroentero-hepatic axis seem probable.
生长激素（GH）及其受体（GHR）在代谢控制中的作用尚未完全明确。我们使用GHR拮抗剂培维索孟研究了GH和GHR在空腹和非空腹条件下对健康非肥胖男性代谢控制的作用。10名健康受试者参与了一项双盲、安慰剂对照研究，该研究旨在观察培维索孟在空腹3天前后及非空腹条件下（n = 5）对生长激素释放激素（GHRH）和生长激素释放肽-6（GHRP-6）诱导的GH分泌的影响。在非空腹状态下，当培维索孟阻断GHR时，GHRP-6（1微克/千克）可导致血清胰岛素浓度升高（10.3±2.1对81.3±25.4 mU/L；P<0.001）和血糖浓度升高（4.2±0.3对6.0±0.6 mmol/L；P<0.05）。在该组中，还观察到血清游离脂肪酸水平迅速下降。在空腹期间或无培维索孟时进行GHR阻断时未观察到这些变化。我们得出结论，尽管这些结果来自一项急性研究，长期使用培维索孟可能会产生不同结果，但在非空腹状态下阻断GHR会诱导胰岛素敏感性发生组织特异性变化，导致血糖和胰岛素水平升高（表明肝脏/肌肉存在胰岛素抵抗），但也可能导致脂肪生成增加（表明脂肪组织胰岛素敏感性正常）。这些由GHRP-6介导的变化表明，组织水平上低GH生物活性可诱导代谢控制变化，其特征是脂肪量增加和瘦体重减少。作为非空腹状态下这些由GHRP-6介导的代谢变化的一种机制，GHRP-6对胃肠-肝轴的直接非垂体介导作用似乎是可能的。
