RESISTANCE OF GROWTH-HORMONE SECRETION TO SOMATOSTATIN IN MEN WITH TYPE-I DIABETES-MELLITUS
RESISTANCE OF GROWTH-HORMONE SECRETION TO SOMATOSTATIN IN MEN WITH TYPE-I DIABETES-MELLITUS
复制标题
DOI：
10.2337/diabetes.40.10.1251
复制
发表时间：
1991-10-01
期刊：
影响因子：
7.7
通讯作者：
ABPLANALP, WA
中科院分区：
文献类型：
--
作者：
COHEN, RM;ABPLANALP, WA
在血糖控制不佳的糖尿病受试者和非糖尿病受试者之间，以剂量-反应方式比较了持续输注生长抑素（SRIF）对GH释放激素（GHRH）推注诱导的生长激素（GH）分泌的影响，以解决垂体对SRIF反应性改变导致人类糖尿病GH分泌过多的假设。 研究采用改良的正葡萄糖钳夹技术进行，以尽量减少葡萄糖和胰岛素的波动。 只有当SRIF剂量比非糖尿病受试者中可检测到的抑制剂量高15倍时，糖尿病受试者中GHRH诱导的GH分泌才能被抑制。 糖尿病受试者中计算的50%抑制剂量（ID 50）是非糖尿病受试者的4倍（P = 0.03）。 在糖尿病受试者中，强化胰岛素治疗2周后，尽管糖化血红蛋白显著下降，血浆胰岛素样生长因子I显著增加，但剂量-反应曲线的变化仍持续存在。 根据非糖尿病受试者中SRIF输注期间测量的浓度，在SRIF ID 50预测的血浆SRIF增量将导致垂体门静脉SRIF浓度处于最近动物研究报告的生理范围内，而糖尿病受试者中的ID 50约为该范围上限的1.5-2.5倍。 这些研究表明，垂体对SRIF作用的抵抗发生在胰岛素依赖性（I型）糖尿病男性中，处于生理浓度的激素水平，因此极有可能导致糖尿病患者GH分泌过多。
The effect of continuous infusions of somatostatin (SRIF) on growth hormone (GH) secretion induced by GH-releasing hormone (GHRH) bolus was compared in a dose-response manner between diabetic subjects in poor glycemic control and nondiabetic subjects to address the hypothesis that altered pituitary responsiveness to SRIF contributes to the hypersecretion of GH in diabetes mellitus in humans. Studies were conducted with a modification of the euglycemic clamp technique to minimize fluctuations in glucose and insulin. Suppression of GHRH-induced GH secretion was demonstrable in diabetic subjects only at a SRIF dose 15-fold higher than that at which suppression could be detected in nondiabetic subjects. The calculated 50% inhibitory dose (ID50) in diabetic subjects was 4-fold higher than that in nondiabetic subjects (P = 0.03). In diabetic subjects after 2 wk of intensive insulin management, the change in the dose-response curve persisted despite significant decrements in glycosylated hemoglobin and increments in plasma insulinlike growth factor I. The increment in plasma SRIF predicted at the SRIF ID50 from concentrations measured during the SRIF infusions in nondiabetic subjects would result in hypophyseal portal SRIF concentrations in the physiological range reported in recent animal studies, whereas those for the ID50 in diabetic subjects would be approximately 1.5-2.5 times the upper limit of that range. These studies indicate that pituitary resistance to the action of SRIF occurs in men with insulin-dependent (type I) diabetes at physiological concentrations of the hormone and is therefore highly likely to contribute to the hypersecretion of GH in diabetes.