Giustina A, Bossoni S, Cimino A, Pizzocolo G, Romanelli G, Wehrenberg W B
Cattedra di Clinica Medica, University of Brescia, Italy.
J Clin Endocrinol Metab. 1990 Dec;71(6):1486-90. doi: 10.1210/jcem-71-6-1486.
In the present study we investigated the effects of the acetylcholinesterase inhibitor pyridostigmine (PD), which is hypothesized to decrease hypothalamic somatostatin tone, alone and in association with GH-releasing hormone (GHRH) on GH secretion in 18 type 1 diabetic patients and 12 normal subjects using a randomized double blind placebo-controlled protocol. All subjects received either 120 mg oral PD or placebo 60 min before iv injection of either human GHRH-(1-29) NH2 (100 micrograms) or sterile water (2 mL). In normal subjects both PD alone and GHRH alone caused a significant increase in GH. PD and GHRH acted in a synergistic fashion when combined. In diabetic patients the GH response to GHRH was variable. To segregate the responses, the ratio between the GH increase after GHRH plus PD and after GHRH alone was calculated for each subject. In 10 diabetic patients (group A) the ratio was lower than 2 SD (P less than 0.05) from the mean response of normal subjects. These patients showed an exaggerated GH increase after GHRH and a lower GH increase after PD with respect to normal subjects. Eight diabetic patients (group B) showed a ratio similar to that in normal subjects and similar GH responses to the stimuli. No significant differences were found between groups A and B with respect to age, body mass index, and blood glucose levels. Duration of diabetes was longer and basal GH levels were higher in group A. Hemoglobin-A1c was higher in group A, but of only borderline statistical significance (P = 0.052). Our data demonstrate that in diabetic patients with exaggerated GH responses to GHRH an increase in cholinergic tone does not affect GH secretion. These data suggest that in some type 1 diabetic patients an altered somatostatinergic control of GH secretion may contribute to their abnormal GH response to GHRH.
在本研究中，我们采用随机双盲安慰剂对照方案，研究了乙酰胆碱酯酶抑制剂吡啶斯的明（PD）单独及与生长激素释放激素（GHRH）联合应用对18例1型糖尿病患者和12例正常受试者生长激素（GH）分泌的影响。该抑制剂被认为可降低下丘脑生长抑素水平。所有受试者在静脉注射人GHRH-(1-29) NH2（100微克）或无菌水（2毫升）前60分钟，均接受120毫克口服PD或安慰剂。在正常受试者中，单独使用PD和单独使用GHRH均导致GH显著增加。PD和GHRH联合应用时具有协同作用。在糖尿病患者中，GH对GHRH的反应各不相同。为区分这些反应，计算了每个受试者在GHRH加PD后GH增加量与单独使用GHRH后GH增加量的比值。10例糖尿病患者（A组）的该比值低于正常受试者平均反应的2个标准差（P<0.05）。与正常受试者相比，这些患者在GHRH后GH增加量过大，而在PD后GH增加量较低。8例糖尿病患者（B组）的比值与正常受试者相似，对刺激的GH反应也相似。A组和B组在年龄、体重指数和血糖水平方面无显著差异。A组糖尿病病程较长，基础GH水平较高。A组糖化血红蛋白较高，但仅具有边缘统计学意义（P = 0.052）。我们的数据表明，在对GHRH有过度GH反应的糖尿病患者中，胆碱能张力增加并不影响GH分泌。这些数据表明，在一些1型糖尿病患者中，生长抑素能对GH分泌的控制改变可能导致其对GHRH的异常GH反应。
