Coiro V, Volpi R, Capretti L, Speroni G, Caffarri G, Chiodera P
Department of Internal Medicine, School of Medicine, University of Parma, Italy.
Clin Endocrinol (Oxf). 1997 Jan;46(1):115-9. doi: 10.1046/j.1365-2265.1997.d01-1745.x.
At present, there are no reports in the literature of studies in humans concerning a possible role of nitric oxide (NO) in the regulation of pancreatic endocrine secretions, whereas studies in the rat provided discrepant results. The aim of this study was to clarify whether NO is involved in the control of insulin and/or glucagon secretion in basal conditions and/or in response to arginine or glucose administration in normal male subjects.
We investigated whether an intravenous infusion of the NO synthase (NOS) inhibitor L-NAME, at a dose previously demonstrated not to produce blood pressure alterations or untoward side-effects, modifies insulin and/or glucagon secretory patterns.
Fourteen healthy male volunteers aged 24-35 years, within 10-13% of their ideal body weight and without family history of diabetes mellitus or other endocrine diseases.
Seven normal men were treated intravenously with L-arginine (30 g in 50 ml of normal saline over 30 minutes) or glucose (0.33 g/kg body weight in a bolus) with or without the concomitant infusion of L-NAME (90 micrograms/kg in 50 ml of normal saline). L-NAME was infused for 30 minutes before and during arginine infusion and over 30 minutes before and 30 minutes after glucose injection. Another group of 7 men was infused over 60 minutes with L-NAME (90 micrograms/kg in 50 ml of normal saline) alone or saline alone.
Basal and L-arginine or glucose induced glucagon secretions and basal and glucose stimulated insulin secretions were not altered by L-NAME administration. In contrast, the drug produced a partial but significant decrease in the insulin response to L-arginine. In fact, the mean peak insulin response to L-arginine was 5.3 times (53 +/- 5 mU/l (mean +/- SE)) higher than basal value (10 +/- 2) in the absence of L-NAME, but only 3.33 times (40 +/- 4) higher than baseline (12 +/- 3) during the infusion of the NOS-inhibitor.
These data suggest that NO at least partially mediates the stimulatory action of L-arginine on insulin secretion in normal human subjects.
目前，尚无关于一氧化氮（NO）在调节人类胰腺内分泌分泌中可能作用的文献报道，而在大鼠中的研究结果存在差异。本研究的目的是阐明在正常男性受试者中，NO是否参与基础状态下和/或对精氨酸或葡萄糖给药的反应中胰岛素和/或胰高血糖素分泌的控制。
我们研究了静脉输注一氧化氮合酶（NOS）抑制剂L-NAME（剂量先前已证明不会引起血压改变或不良副作用）是否会改变胰岛素和/或胰高血糖素的分泌模式。
14名年龄在24 - 35岁之间的健康男性志愿者，体重在理想体重的10 - 13%以内，无糖尿病或其他内分泌疾病家族史。
7名正常男性静脉注射L-精氨酸（30克溶于50毫升生理盐水中，30分钟内注射完毕）或葡萄糖（0.33克/千克体重，静脉推注），同时或不同时输注L-NAME（90微克/千克溶于50毫升生理盐水中）。在精氨酸输注前和输注期间以及葡萄糖注射前30分钟和注射后30分钟内，L-NAME均输注30分钟。另一组7名男性单独输注L-NAME（90微克/千克溶于50毫升生理盐水中）或生理盐水60分钟。
给予L-NAME后，基础状态下以及L-精氨酸或葡萄糖诱导的胰高血糖素分泌，基础状态下以及葡萄糖刺激的胰岛素分泌均未改变。相比之下，该药物使胰岛素对L-精氨酸的反应出现部分但显著的降低。实际上，在未使用L-NAME时，胰岛素对L-精氨酸的平均峰值反应比基础值（10±2）高5.3倍（53±5 mU/l（平均值±标准误）），而在输注NOS抑制剂期间，仅比基线值（12±3）高3.33倍（40±4）。
这些数据表明，在正常人类受试者中，NO至少部分介导了L-精氨酸对胰岛素分泌的刺激作用。
