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Diurnal variation of leptin entry from blood to brain involving partial saturation of the transport system

机译:瘦素从血液进入大脑的昼夜变化涉及运输系统的部分饱和

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The blood-brain barrier (BBB) regulates the amount of peripherally produced leptin reaching the brain. Knowing that the blood concentration of leptin has a circadian rhythm, we investigated whether the influx of leptin at the BBB followed the same pattern in three main sets of experiments. (a): The entry of I-125-leptin from blood to brain was measured in mice every 4 h, as indicated by the influx rate of I-125-leptin 1-10 min after an iv bolus injection. The blood concentration of endogenous leptin was measured at the same times. Blood leptin concentrations were higher at night and early morning (peak at 0800 h) and lower during the day (nadir at 1600 h). By contrast, the influx of I-125-leptin was fastest at 2000 h and slowest at 0400 h. Addition of unlabeled leptin (1 mug/mouse) significantly decreased the influx rate of I-125-leptin at all time points, indicating saturability of the transport system. The unlabeled leptin also abolished the diurnal variation of the influx of I-125-leptin. (b): The entry of I-125-leptin into spinal cord was faster than that into brain and showed a different diurnal pattern. The greatest influx occurred at 2400 h and the slowest at 0800 h. In spinal cord, unlike brain, unlabeled leptin (1 mug/mouse) neither inhibited the influx of I-125-leptin nor abolished the diurnal rhythm. (c): Higher concentrations of unlabeled leptin (5 mug/mouse) inhibited the uptake of I-125-leptin in spinal cord as well as in brain, but not in muscle. This experiment measured uptake 10 min after iv injection at 0600 h (beginning of the light cycle) and 1800 h (beginning of the dark cycle). Thus, influx of I-125-leptin into the CNS shows diurnal variation, indicating a circadian rhythm in the transport system at the BBB, saturation of the leptin transport system shows differences between the brain and spinal cord, and blood concentrations of leptin suggest that partial saturation of the transport system occurs at physiological concentrations of circulating leptin, contributing to the differing diurnal patterns in brain and spinal cord. Together, the results show that the BBB is actively involved in the neuroendocrine regulation of feeding behavior. (C) 2001 Elsevier Science Inc. All rights reserved. [References: 31]
机译:血脑屏障(BBB)调节到达大脑的外周产生的瘦素的量。知道瘦素的血液浓度具有昼夜节律,我们在三组主要实验中研究了瘦素在BBB的流入是否遵循相同的模式。 (a):每4小时测量一次小鼠中I-125-瘦素从血液进入大脑的速度,静脉推注后1-10分钟I-125-瘦素的流入速率表明。同时测量内源性瘦素的血药浓度。晚上和清晨(0800小时达到峰值)的血液瘦素浓度较高,而白天(1600小时最低点)则较低。相比之下,I-125瘦素的流入在2000 h最快,而在0400 h最慢。在所有时间点添加未标记的瘦蛋白(每杯1杯)显着降低I-125瘦蛋白的流入速率,表明运输系统的饱和度。未标记的瘦素也消除了I-125-瘦素涌入的昼夜变化。 (b):I-125瘦素进入脊髓的速度比进入大脑的速度更快,并且表现出不同的昼夜模式。最大的涌入发生在2400 h,最慢的发生在0800 h。在脊髓中,与大脑不同,未标记的瘦素(1杯/小鼠)既不会抑制I-125瘦素的涌入,也不会消除昼夜节律。 (c):较高浓度的未标记瘦蛋白(5杯/小鼠)抑制了I-125-瘦素在脊髓以及大脑中的摄取,但没有抑制肌肉中的摄取。该实验测量了在0600 h(光周期开始)和1800 h(黑暗周期开始)静脉注射后10分钟的吸收。因此,I-125瘦素流入CNS呈昼夜变化,表明BBB转运系统的昼夜节律,瘦素转运系统饱和表明大脑和脊髓之间存在差异,瘦素的血药浓度提示运输系统的部分饱和发生在循环瘦素的生理浓度下,导致大脑和脊髓的昼夜模式不同。在一起,结果表明血脑屏障积极参与进食行为的神经内分泌调节。 (C)2001 Elsevier Science Inc.保留所有权利。 [参考:31]

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