The source of cerebral insulin
The source of cerebral insulin
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DOI：
10.1016/j.ejphar.2004.02.040
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发表时间：
2004-04-19
影响因子：
5
通讯作者：
Banks, WA
中科院分区：
文献类型：
--
作者：
Banks, WA
在整个中枢神经系统（CNS）中发现胰岛素及其受体。中枢神经系统施用的胰岛素可以发挥强大的作用，但共识是CNS中几乎没有产生胰岛素。因此，CNS胰岛素基本上取决于外周胰岛素跨越血脑屏障（BBB）的能力。已知胰岛素通过可饱和的传输机制越过BBB。该转运蛋白与其他转运蛋白有关肽或调节蛋白的一些主题相似性。它在整个中枢神经系统中分布不均匀，其嗅球的传输速率最快。它在尤基血糖水平上部分饱和，表明其主要信号功能发生在生理血液水平上，而不是作为降血糖事件的制动器。 BBB转运蛋白的一种可能功能是使中枢神经系统胰岛素充当外周胰岛素的反调节激素。转运蛋白受到调节，在发育过程中以及禁食，肥胖，冬眠，糖尿病和阿尔茨海默氏病。通过脂多糖增强胰岛素转运可能是细菌感染看到的胰岛素抵抗的基础。地塞米松抑制胰岛素转运可以是糖皮质激素治疗可增强食欲的基础。胰岛素本身也对BBB具有影响，从而改变了酶促和转运蛋白功能。总体而言，胰岛素的BBB转运提供了外周胰岛素在中枢神经系统内作用的机制，作为调节肽。 （c）2004 Elsevier B.V.保留所有权利。
Insulin and its receptor are found throughout the central nervous system (CNS). Insulin administered into the CNS can exert powerful effects, yet the consensus is that little or no insulin is produced in the CNS. Therefore, CNS insulin is essentially dependent on the ability of peripheral insulin to cross the blood-brain barrier (BBB). Insulin is known to cross the BBB by a saturable transport mechanism. This transporter shows some thematic similarities to other transporters for peptides or regulatory proteins. It is unevenly distributed throughout the CNS with the olfactory bulbs having the fastest transport rate of any brain region. It is partially saturated at euglycemic levels, suggesting that its main signaling function occurs at physiological blood levels, rather than as a brake to hypoglycemic events. One probable function of the BBB transporter is to allow CNS insulin to act as a counter-regulatory hormone to peripheral insulin. The transporter is regulated, with the transport rate of insulin being altered during development and by fasting, obesity, hibernation, diabetes mellitus and Alzheimer's disease. Enhancement of insulin transport by lipopolysaccharide could be the basis for the insulin resistance seen with bacterial infections. Inhibition of insulin transport across the BBB by dexamethasone could be the basis for the enhanced appetite seen with glucocorticoid treatments. Insulin itself also has effects on the BBB, altering enzymatic and transporter functions. Overall, BBB transport of insulin provides a mechanism for peripheral insulin to act within the CNS as a regulatory peptide. (C) 2004 Elsevier B.V. All rights reserved.