Locatelli V, Miyoshi H, Bestetti G, Rossi G L, Müller E E
Brain Res. 1985 Aug 19;341(1):35-40. doi: 10.1016/0006-8993(85)91469-6.
The dynamics of growth hormone (GH) secretion in response to different GH secretagogues has been studied in adult freely moving male rats one month after induction of diabetes by single i.v. injection of streptozotocin (60 mg/kg). Baseline plasma GH concentrations and pituitary GH content were not different in streptozotocin-diabetic (St-D) rats and controls. Clonidine (0.15 mg/kg i.v.), an alpha 2-adrenergic agonist, failed to evoke GH release in St-D rats. Substitution therapy with insulin (1 IU/100 g b.wt.daily) delivered through subcutaneously implanted minipumps, allowed re-institution of a normal GH responsiveness to clonidine. At odds with clonidine, FK 33-824 (0.1 mg/kg i.v.), a potent analog of the opioid peptide Met-enkephalin, induced a similar rise in plasma GH levels in control and St-D rats. Finally, administration of a synthetic replicate of a GH-releasing hormone of human pancreatic origin, hpGRF-40 (2.5 micrograms/kg i.v.) elicited a higher GH response in St-D rats than in controls. These data indicate that in St-D rats: (1) an impaired function of noradrenergic pathways controlling GH release is present; (2) contrary to previous beliefs, an alpha 2-adrenergic mechanism is not involved in the GH-releasing effect of opioid peptides; and (3) pituitary GH responsiveness to hpGRF is increased.
通过单次静脉注射链脲佐菌素（60毫克/千克）诱导成年雄性自由活动大鼠患糖尿病一个月后，研究了生长激素（GH）对不同GH促分泌素分泌的动态变化。链脲佐菌素诱导糖尿病（St-D）大鼠和对照组的基线血浆GH浓度和垂体GH含量没有差异。α2肾上腺素能激动剂可乐定（0.15毫克/千克静脉注射）未能在St-D大鼠中引起GH释放。通过皮下植入微型泵每日给予胰岛素（1国际单位/100克体重）进行替代治疗，可使对可乐定的正常GH反应性恢复。与可乐定不同，阿片肽甲硫氨酸脑啡肽的强效类似物FK 33-824（0.1毫克/千克静脉注射）在对照大鼠和St-D大鼠中诱导血浆GH水平出现类似升高。最后，静脉注射人胰腺来源的生长激素释放激素hpGRF-40（2.5微克/千克）的合成复制品，在St-D大鼠中引起的GH反应高于对照组。这些数据表明，在St-D大鼠中：（1）存在控制GH释放的去甲肾上腺素能途径功能受损；（2）与先前的观点相反，α2肾上腺素能机制不参与阿片肽的GH释放作用；（3）垂体对hpGRF的GH反应性增加。
