Maccario M, Procopio M, Grottoli S, Oleandri S E, Razzore P, Camanni F, Ghigo E
Department of Clinical Pathophysiology, University of Turin, Italy.
J Clin Endocrinol Metab. 1995 Dec;80(12):3774-8. doi: 10.1210/jcem.80.12.8530634.
It is known that spontaneous and stimulated GH secretion is reduced in obesity. On the other hand, it has been recently reported that, in obese subjects, plasma GH levels did not change during a hyperglycemic clamp. To further study the sensitivity of somatotrope cells to inhibitory influences in obesity, we studied the effect of somatostatin, pirenzepine, or glucose on the GH response to GHRH or arginine in 32 obese patients and 30 controls. Basal GH levels were lower in obese than in normal subjects (1.0 +/- 0.6 vs. 4.8 +/- 0.7 micrograms/L, P < 0.05), while insulin-like growth factor-I levels were similar in both groups (137.3 +/- 13.2 vs. 138.8 +/- 12.2 micrograms/L). In obese as well as in control subjects pirenzepine abolished the GH response to either GHRH (AUC0-120: 43.7 +/- 9.6 vs. 258.3 +/- 59.9 micrograms/L/h, P < 0.04 and 113.0 +/- 75.0 vs. 870.5 +/- 255 micrograms/L.h, P < 0.01, respectively) or arginine (6.5 +/- 2.5 vs. 118.7 +/- 55.9 micrograms/L.h, P < 0.05 and 47.7 +/- 7.3 vs. 334.0 +/- 157.5 micrograms/L.h, P < 0.01, respectively). Differently from pirenzepine, glucose blunted the GH response to either GHRH or arginine in control subjects (260.8 +/- 38.3 vs. 479.5 +/- 83.9 micrograms/L.h, P < 0.03 and 294.8 +/- 46.3 vs. 625.1 +/- 139.1 micrograms/L.h, P < 0.05, respectively), but failed to modify it in obese patients (193.7 +/- 39.4 vs. 172.4 +/- 33.6 micrograms/L.h and 121.1 +/- 43.4 vs. 155.1 +/- 39.7 micrograms/L.h, respectively). On the other hand, somatostatin deeply blunted the GHRH-induced GH release in obese patients (58.5 +/- 25.4 vs. 548.7 +/- 196.6 micrograms/L.h, P < 0.05) as well as in controls (181.4 +/- 44.4 vs. 759.7 +/- 46.6 micrograms/L.h, P < 0.04). In conclusion, our results show that, in obesity, the stimulated GH release is refractory to the inhibitory effect of glucose but not of pirenzepine, in spite of their likely common mechanism of action, i.e. increase of hypothalamic somatostatin release. Exogenous somatostatin is able to abolish GH secretion both in normal and obese subjects. These data suggest the existence of a peculiar inhability of hyperglycemia to trigger somatostatinergic release in obesity.
已知肥胖症患者的自发性和刺激性生长激素（GH）分泌会减少。另一方面，最近有报道称，在肥胖受试者中，高血糖钳夹期间血浆GH水平并未改变。为了进一步研究肥胖症中生长激素细胞对抑制性影响的敏感性，我们研究了生长抑素、哌仑西平或葡萄糖对32例肥胖患者和30例对照者对生长激素释放激素（GHRH）或精氨酸的GH反应的影响。肥胖患者的基础GH水平低于正常受试者（1.0±0.6 vs. 4.8±0.7微克/升，P<0.05），而两组的胰岛素样生长因子-I水平相似（137.3±13.2 vs. 138.8±12.2微克/升）。在肥胖患者和对照受试者中，哌仑西平均消除了对GHRH（0 - 120分钟曲线下面积：43.7±9.6 vs. 258.3±59.9微克/升·小时，P<0.04和113.0±75.0 vs. 870.5±255微克/升·小时，P<0.01）或精氨酸（6.5±2.5 vs. 118.7±55.9微克/升·小时，P<0.05和47.7±7.3 vs. 334.0±157.5微克/升·小时，P<0.01）的GH反应。与哌仑西平不同，葡萄糖减弱了对照受试者对GHRH或精氨酸的GH反应（分别为260.8±38.3 vs. 479.5±83.9微克/升·小时，P<0.03和294.8±46.3 vs. 625.1±139.1微克/升·小时，P<0.05），但在肥胖患者中未能改变这种反应（分别为193.7±39.4 vs. 172.4±33.6微克/升·小时和121.1±43.4 vs. 155.1±39.7微克/升·小时）。另一方面，生长抑素显著减弱了肥胖患者（58.5±25.4 vs. 548.7±196.6微克/升·小时，P<0.05）以及对照者（181.4±44.4 vs. 759.7±46.6微克/升·小时，P<0.04）中GHRH诱导的GH释放。总之，我们的结果表明，在肥胖症中，尽管葡萄糖和哌仑西平可能具有共同的作用机制，即增加下丘脑生长抑素的释放，但刺激的GH释放对葡萄糖的抑制作用具有抗性，而对哌仑西平的抑制作用不具有抗性。外源性生长抑素能够消除正常和肥胖受试者的GH分泌。这些数据表明肥胖症中存在高血糖触发生长抑素能释放的特殊无能。
