Increased thirst and plasma arginine vasopressin levels during 2-deoxy-D-glucose-induced glucoprivation in humans.
Increased thirst and plasma arginine vasopressin levels during 2-deoxy-D-glucose-induced glucoprivation in humans.
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在 2-脱氧-D-葡萄糖诱导的人类葡萄糖缺乏期间，口渴和血浆精氨酸加压素水平增加。
DOI：
10.1172/jci110121
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Robertson,GL
中科院分区：
文献类型：
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作者：
Thompson,DA;Campbell,RG;Lilavivat,U;Welle,SL;Robertson,GL
胰岛素诱导的低血糖（机制不明）可增加人体血浆精氨酸加压素（AVP）水平。通过给24名正常志愿者静脉输注2-脱氧-d-葡萄糖（50 mg/kg）（葡萄糖利用的竞争性抑制剂）或生理盐水（假手术），研究了中枢神经系统葡萄糖缺乏期间AVP水平升高的机制。一些输注与神经药理学阻断剂（安慰剂）联合给药。在一组（n= 5）中研究了2-脱氧-d-葡萄糖（2DG）诱导的葡萄糖代谢和AVP分泌的行为、生理、代谢和激素相关性，该组（n= 5）预先给予马吲哚（1 mg/口服，每日3次），一种有效的去甲肾上腺素和多巴胺再摄取阻滞剂，或安慰剂1周。第二组（n= 5）在2DG给药前和给药期间接受普萘洛尔（3 mg/3 min，随后80 μg/min）或生理盐水输注。单独使用2DG，血浆AVP水平从基线时的1.3±0.3 pg/ml增加到60 min时的4.5±1.4 pg/ml的峰值，并持续升高150 min。2DG给药后30 - 180 min，与假给药志愿者相比，2DG给药志愿者的饮水量增加。肾上腺素显著升高和去甲肾上腺素轻微升高与血糖和肾素活性升高以及血浆钾降低相关。血浆钠和渗透压一过性升高，平均动脉压（MAP）下降。然而，这些变化是小的和不稳定的，不能解释所观察到的口渴和AVP水平的增加。马吲哚预处理防止MAP下降和血浆肾素活性（PRA）增加后，2DG输注没有修改增加口渴，水的摄入量，或AVP对葡萄糖缺乏的反应。普萘洛尔预处理可有效地阻断β-肾上腺素受体，如MAP和血浆肾上腺素升高，并消除2DG诱导的糖缺乏过程中RPA的升高，但不能抑制AVP和口渴反应。一位颈髓切除的患者缺乏下行交感神经流出，在钠、儿茶酚胺和PRA没有增加的情况下，对2DG诱导的葡萄糖缺乏有增强的口渴反应。因此，2DG管理激活机制增加口渴和AVP是无关的变化，外周儿茶酚胺，MAP，PRA，和渗透压。
Insulin-induced hypoglycemia by unknown mechanism(s) increases plasma arginine vasopressin (AVP) levels in humans. Mechanisms for increased AVP levels during central nervous system glucoprivation were investigated by administering 20-min i.v. infusions of 2-deoxy-d-glucose (50 mg/kg), a competitive inhibitor of glucose utilization, or normal saline (sham), to 24 normal volunteers. Some of the infusions were administered in combination with neuropharmacological blocking agents (placebo). The behavioral, physiological, metabolic, and hormonal correlates of 2-deoxy-d-glucose (2DG)-induced gluco-privation and AVP secretion were studied in a group (n= 5) pretreated for 1 wk with either mazindol (1 mgper osthree times per day), a potent norepinephrine and dopamine-reuptake blocker, or placebo. A second group (n= 5) received either propranolol (3 mg/3 min followed by 80 μg/min) or normal saline infusion before and during 2DG administration. With 2DG alone, plasma AVP levels increased from 1.3±0.3 pg/ml at base line to a peak of 4.5±1.4 pg/ml at 60 min and remained elevated for 150 min. From 30 to 180 min after 2DG administration, the 2DG-infused volunteers increased their water intake in comparison with sham-infused volunteers. Marked increases in epinephrine and slight increases in norepinephrine were associated with increases in plasma glucose and renin activity and decreases in plasma potassium. Plasma sodium and osmolality increased transiently and mean arterial pressure (MAP) fell. These changes, however, were small and inconstant and could not account for the observed increases in thirst and AVP levels. Pretreatment with mazindol prevented the decrease in MAP and the increase in plasma renin activity (PRA) following 2DG infusions without modifying increased thirst, water intake, or AVP responses to glucoprivation. Pretreatment with propranolol effectively blocked β-adrenoreceptors as evidenced by increased MAP and plasma epinephrine, and abolition of the RPA increases during 2DG-induced glycoprivation, but did not suppress AVP and thirst responses. A cervical cord-sectioned patient lacking descending sympathetic out-flow had a potentiated thirst response to 2DG-induced glucoprivation in the absence of increases in sodium, catecholamines, and PRA. Thus 2DG administration activates mechanisms for increased thirst and AVP which are unrelated to changes in peripheral catecholamines, MAP, PRA, and osmolality.