Insulin detemir is not transported across the blood-brain barrier.
Insulin detemir is not transported across the blood-brain barrier.
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DOI：
10.1016/j.peptides.2010.09.011
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发表时间：
2010-12
期刊：
影响因子：
3
通讯作者：
Mooradian AD
中科院分区：
文献类型：
--
作者：
Banks WA;Morley JE;Lynch JL;Lynch KM;Mooradian AD
地特米胰岛素对中枢神经系统(CNS)的作用与人胰岛素不同。据推测，这是由于地特胰岛素穿过血脑屏障(BBB)的能力改变所致。在这里，我们测量了血脑屏障对地替尼胰岛素的通透性。我们用放射性碘标记地特胰岛素(I-DET)，并检测其通过小鼠血脑屏障的能力。在静脉注射后，通过存在或不存在过量胰岛素地替米星的脑血流灌注来评估渗透性。我们还评估了地特胰岛素抑制人胰岛素跨血脑屏障转运的能力。I-DET在静脉注射后或通过脑灌流研究时都不会越过血脑屏障，这是一种去除或减少循环蛋白影响的方法。在抑制放射性人胰岛素跨血脑屏障运输方面，未标记的地替米尔的效力约为人胰岛素的10倍。地特胰岛素的中枢神经系统谱改变可能是由于它很难获得中枢神经系统受体，以及人胰岛素不能通过血脑屏障造成的。
Insulin detemir has a different profile of action on the central nervous system (CNS) than human insulin. It has been hypothesized that this is caused by an altered ability of insulin detemir to cross the blood-brain barrier (BBB). Here, we measured the permeability of the BBB to insulin detemir. We labeled insulin detemir with radioactive iodine (I-Det) and examined its ability to cross the BBB of the mouse. Permeation was assessed after intravenous injection and by brain perfusion in the presence or absence of excess insulin detemir. The ability of insulin detemir to inhibit human insulin transport across the BBB was also assessed. I-Det did not cross the BBB either after intravenous injection or when studied by brain perfusion, a method which removes or reduces the influence of circulating proteins. Unlabeled detemir was about 10 times less potent than human insulin at inhibiting the transport of radioactive human insulin across the BBB. The altered CNS profile of insulin detemir may be caused by its poor access to CNS receptors and by a block of human insulin from crossing the BBB.
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