Effect of LPS on the permeability of the blood-brain barrier to insulin
Effect of LPS on the permeability of the blood-brain barrier to insulin
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DOI：
10.1016/s0006-8993(00)03247-9
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发表时间：
2001-03-30
期刊：
影响因子：
2.9
通讯作者：
Morley, JE
中科院分区：
文献类型：
--
作者：
Xaio, HP;Banks, WA;Morley, JE
胰岛素已成为一种重要的神经肽。胰岛素的中枢作用似乎与外围的作用相反。胰岛素通过饱和的运输系统穿过血脑屏障(BBB)。血脑屏障对胰岛素的通透性可因各种事件而改变，但目前尚无研究探讨感染或炎症时血脑屏障对胰岛素的通透性，这些状态可导致外周胰岛素抵抗。我们观察了细菌内毒素和强大的细胞因子释放剂脂多糖(LPS)对CD-1小鼠血脑屏障对人胰岛素通透性的影响。腹腔注射脂多糖显著增加脑对I-131-胰岛素的摄取，并破坏血脑屏障对I-125-白蛋白的摄取。减去脑/血清中I-125-白蛋白的比值后，脑/血清中胰岛素的比值增加：10.38+/-0.70mul/g(内毒素)vs.3.62+/-0.27mul/g(无内毒素)，P<；0.0001，表明内毒素增加了胰岛素的摄取，而不依赖于血脑屏障的破坏。胰岛素摄取量的增加是由于饱和转运的增强。内毒素注射前10min给予吲哚美辛可增加血脑屏障的破坏，但不增加胰岛素的转运。一氧化氮合酶(NO)抑制剂氨基鸟苷对胰岛素或白蛋白摄取无影响，而NG-硝基-L-精氨酸甲酯((L)-NAME)可促进胰岛素转运，但不破坏血脑屏障。我们的结论是，内毒素不受干扰地增加胰岛素通过血脑屏障的饱和转运，而前列腺素则不受抑制而增强。这种转运的增加可能会增强胰岛素的中枢作用，从而导致感染和炎症所致的外周胰岛素抵抗。爱思唯尔科学公司出版。
Insulin has emerged as an important neuropeptide. Central actions of insulin appear to oppose those in the periphery. Insulin is transported across the blood-brain barrier (BBB) by a saturable transport system. The permeability of the BBB to insulin is altered by various events, but no studies exist that have examined the permeability of the BBB to insulin during infection or inflammation, states which can induce peripheral insulin resistance. We looked at the effects of lipopolysaccharide (LPS), a bacterial endotoxin and a powerful cytokine releaser, on the permeability of the BBB to human insulin in CD-1 mice. Intraperitoneal injections of LPS significantly increased the uptake by the brain of I-131-insulin and disrupted the BBB to I-125-albumin. After subtraction of the brain/serum ratio for I-125-albumin, brain/serum ratios for insulin were increased: 10.38 +/- 0.70 mul/g (LPS) vs. 3.62 +/- 0.27 mul/g (no LPS), P < 0.0001, showing that LPS increased the uptake of insulin independent of BBB disruption. This increase in insulin uptake was due to enhanced saturable transport. Pretreatment with indomethacin 10 min before LPS injections enhanced BBB disruption, but not insulin transport. Pretreatment with the nitric oxide (NO) synthase inhibitor aminoguanidine had no effect on insulin or albumin uptake, but pretreatment with NG-nitro-L-arginine methyl ester ((L)-NAME) enhanced insulin transport, but not BBB disruption. We conclude that LPS increases the saturable transport of insulin across the BBB independent of disruption and prostaglandins with potentiation by NO inhibition. Such increased transport could potentiate the central effects of insulin and so contribute to the peripheral insulin resistance seen with infection and inflammation. Published by Elsevier Science B.V.