Hertz M M, Paulson O B, Barry D I, Christiansen J S, Svendsen P A
J Clin Invest. 1981 Mar;67(3):597-604. doi: 10.1172/JCI110073.
The influence of insulin on unidirectional flux of glucose across the blood-brain barrier and on net uptake of glucose by the brain was investigated in seven fasting patients. The unidirectional extraction, E, of [14C]D-glucose was determined using 36Cl- as an intravascular reference, by the indicator dilution method. 0.4 U insulin/kg body wt was infused intravenously over 30 min while blood glucose was maintained constant by glucose infusion. Six determinations were made in each patient, two before, two during insulin infusion, and two after. In connection with each blood-brain barrier study, arterial and cerebral venous samples were taken for measurement of glucose, oxygen, insulin, K+, and phosphate. Cerebral blood flow (CBF) was measured in each patient. The main finding was an increased extraction of glucose from 14 to 21% and a highly significant increase in unidirectional flux (CBF X unidirectional extraction X arterial glucose concentration) from 0.46 to 0.66 mumol/g X min during insulin infusion (plasma insulin approximately 1,500 microU/ml). The net brain uptake of glucose (CBF X arterio-venous difference for glucose) as unaltered during the investigation period of 45 min, which is too short a time for insulin to penetrate the barrier. It follows that the backflux of glucose from the brain was increased during insulin application. The effect of insulin might be a speeding up of the glucose carrier in analogy to heart muscle.
在7名空腹患者中研究了胰岛素对葡萄糖跨血脑屏障单向通量及大脑葡萄糖净摄取的影响。采用示踪稀释法,以36Cl-作为血管内参考物,测定[14C]D-葡萄糖的单向摄取率E。在30分钟内静脉输注0.4U胰岛素/kg体重,同时通过输注葡萄糖维持血糖恒定。每位患者进行6次测定,分别在胰岛素输注前、输注期间和输注后各进行2次。在每次血脑屏障研究中,采集动脉血和脑静脉血样本,测定葡萄糖、氧气、胰岛素、钾离子和磷酸盐。测量每位患者的脑血流量(CBF)。主要发现是,在胰岛素输注期间(血浆胰岛素约为1500μU/ml),葡萄糖摄取率从14%增加到21%,单向通量(CBF×单向摄取率×动脉葡萄糖浓度)从0.46显著增加到0.66μmol/g·min。在45分钟的研究期间,大脑葡萄糖净摄取量(CBF×葡萄糖动静脉差值)未改变,这一时间过短,胰岛素无法穿透血脑屏障。由此可见,在应用胰岛素期间,大脑中葡萄糖的反向通量增加。胰岛素的作用可能类似于心肌,加速葡萄糖载体的转运。