Giustina A, Desenzani P, Perini P, Bazzigaluppi E, Bodini C, Bossoni S, Poiesi C, Wehrenberg W B, Bosi E
Department of Internal Medicine and Chemistry, University of Brescia, Italy.
Metabolism. 1997 Apr;46(4):382-7. doi: 10.1016/s0026-0495(97)90052-4.
Insulin-dependent (type I) diabetic patients are known to have an exaggerated growth hormone (GH) response to GH-releasing hormone (GHRH), which is hypothesized to be due to a decrease in somatostatin tone. The aim of the study was to ascertain the influence of the presence and activity of the autoimmune process involving a key enzyme (glutamic acid decarboxylase [GAD]) in the synthetic pathway of a neurotransmitter regulating somatostatin secretion, ie, gamma-aminobutyric acid (GABA), on the GH response to GHRH alone or combined with an acetylcholinesterase inhibitor, pyridostigmine (PD), in patients with type I diabetes mellitus. Twenty non-obese type I diabetic patients and 17 normal subjects underwent an intravenous (IV) injection of 100 micrograms GHRH(1-29)NH2. Twelve of 20 diabetic subjects and all of the control subjects also underwent a second experimental procedure, administration of 120 mg oral PD 60 minutes before IV injection of 100 micrograms GHRH. Diabetic subjects with serum GAD antibody (GADA) levels more than 3 U (n = 10) showed significantly higher serum GH levels after GHRH injection as compared both with diabetic patients with GADA less than 3 U (n = 10) and with normal controls, whether expressed as absolute or peak values. GH peaks after GHRH were significantly (rs = .46, P < .05) correlated with the level of GADA in the whole population of type I diabetic subjects studied. PD significantly enhanced the GH response to GHRH, in terms of both absolute and peak values, in patients without GADA (n = 6) and in normal subjects. On the contrary, PD failed to enhance the GH response to GHRH in diabetic patients with GADA (n = 6). Our findings suggest that autoimmunity may play a key role in determining the exaggerated GH response to GHRH in type I diabetes mellitus. The mechanism underlying this effect is hypothesized to be the production of antibodies to GAD, a key enzyme in the synthesis of GABA, and in turn a reduced GABAergic stimulatory tone on somatostatin production at the hypothalamic level.
已知胰岛素依赖型（I型）糖尿病患者对生长激素释放激素（GHRH）的生长激素（GH）反应过度，据推测这是由于生长抑素张力降低所致。本研究的目的是确定涉及一种关键酶（谷氨酸脱羧酶[GAD]）的自身免疫过程的存在和活性对调节生长抑素分泌的神经递质（即γ-氨基丁酸[GABA]）合成途径的影响，以及该自身免疫过程对I型糖尿病患者单独使用GHRH或联合使用乙酰胆碱酯酶抑制剂吡啶斯的明（PD）时GH对GHRH反应的影响。20名非肥胖I型糖尿病患者和17名正常受试者接受了100微克GHRH(1-29)NH2的静脉注射。20名糖尿病受试者中的12名以及所有对照受试者还接受了第二个实验程序，即在静脉注射100微克GHRH前60分钟口服120毫克PD。血清GAD抗体（GADA）水平超过3 U的糖尿病受试者（n = 10）在注射GHRH后，无论以绝对值还是峰值表示，其血清GH水平均显著高于GADA低于3 U的糖尿病患者（n = 10）和正常对照。在整个研究的I型糖尿病受试者群体中，GHRH后的GH峰值与GADA水平显著相关（rs = .46，P < .05）。在无GADA的患者（n = 6）和正常受试者中，PD在绝对值和峰值方面均显著增强了GH对GHRH的反应。相反，在有GADA的糖尿病患者（n = 6）中，PD未能增强GH对GHRH的反应。我们的研究结果表明，自身免疫可能在决定I型糖尿病患者对GHRH的过度GH反应中起关键作用。据推测，这种效应的潜在机制是产生针对GAD的抗体，GAD是GABA合成中的关键酶，进而在下丘脑水平上对生长抑素产生的GABA能刺激张力降低。
