Press M, Caprio S, Tamborlane W V, Bhushan R, Thorner M, Vale W, Rivier J, Sherwin R S
Department of Medicine, Yale University School of Medicine, New Haven, CT 06510.
Diabetes. 1992 Jan;41(1):17-21. doi: 10.2337/diab.41.1.17.
In poorly controlled insulin-dependent diabetes mellitus (IDDM), hyperglycemia fails to inhibit the pituitary response to growth hormone-releasing factor (GRF). To evaluate whether this derangement is reversed by a simultaneous elevation of circulating insulin, 0.3 micrograms/kg i.v. GRF 1-40 was administered to nine poorly controlled IDDM subjects (HbA1 greater than 11.1%) with and without concomitant infusion of insulin. In the absence of insulin, the poorly controlled IDDM subjects demonstrated a growth hormone response to GRF similar to that of nondiabetic subjects, despite marked hyperglycemia (approximately 16.8 mM). When insulin was infused into these same patients (insulin clamp) to produce combined hyperinsulinemia (528 +/- 90 pM) and hyperglycemia (16.5 +/- 1.98 mM), the GRF-induced growth hormone rise was markedly exaggerated (65 +/- 11 vs. 20 +/- 4 micrograms/L without insulin infusion, P less than 0.001). This enhancement of GRF-stimulated growth hormone release by insulin was strikingly attenuated (22 +/- 7 micrograms/L) in five well-controlled diabetic subjects studied under conditions of similar hyperinsulinemia (486 +/- 84 pM) and hyperglycemia (16.41 +/- 0.95 mM). In contrast, in nondiabetic subjects, acute hyperinsulinemia reduced the growth hormone response to GRF. We conclude that the failure of hyperglycemia to block the pituitary response to GRF in poorly controlled diabetes is not attributable to the lack of a coincident increase in circulating insulin. The paradoxical stimulatory effect of insulin on GRF-induced growth hormone release may contribute to the high spontaneous growth hormone levels characteristically seen in poorly controlled insulin-treated patients, and its attenuation after intensive insulin therapy may contribute to the reversal of growth hormone hypersecretion in well-controlled diabetic patients.
在胰岛素依赖型糖尿病（IDDM）控制不佳时，高血糖无法抑制垂体对生长激素释放因子（GRF）的反应。为评估循环胰岛素同时升高是否能纠正这种紊乱，对9名控制不佳的IDDM患者（糖化血红蛋白大于11.1%）静脉注射0.3微克/千克的GRF 1 - 40，部分患者同时输注胰岛素。在未输注胰岛素时，尽管存在明显高血糖（约16.8毫摩尔/升），控制不佳的IDDM患者对GRF的生长激素反应与非糖尿病患者相似。当对这些患者进行胰岛素输注（胰岛素钳夹）以产生联合高胰岛素血症（528±90皮摩尔/升）和高血糖（16.5±1.98毫摩尔/升）时，GRF诱导的生长激素升高明显加剧（65±11对未输注胰岛素时的20±4微克/升，P＜0.001）。在5名血糖控制良好的糖尿病患者中，在类似高胰岛素血症（486±84皮摩尔/升）和高血糖（16.41±0.95毫摩尔/升）条件下进行研究，胰岛素对GRF刺激的生长激素释放的这种增强作用明显减弱（22±7微克/升）。相反，在非糖尿病患者中，急性高胰岛素血症会降低对GRF的生长激素反应。我们得出结论，在控制不佳的糖尿病中，高血糖未能阻断垂体对GRF的反应并非由于循环胰岛素缺乏同步增加。胰岛素对GRF诱导的生长激素释放的矛盾刺激作用可能导致胰岛素治疗控制不佳的患者中典型出现的高自发性生长激素水平，而强化胰岛素治疗后这种作用的减弱可能有助于血糖控制良好的糖尿病患者生长激素分泌过多的逆转。
