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葡萄糖转运蛋白1(GLUT1)与葡萄糖转运蛋白4(GLUT4)在大鼠腹内侧下丘脑血脑屏障中的共定位

Co-localization of GLUT1 and GLUT4 in the blood-brain barrier of the rat ventromedial hypothalamus.

作者信息

Ngarmukos C, Baur E L, Kumagai A K

机构信息

Department of Internal Medicine, 5570 MSRB-2, Box 0678, University of Michigan Medical School, Ann Arbor, MI 48109, USA.

出版信息

Brain Res. 2001 May 4;900(1):1-8. doi: 10.1016/s0006-8993(01)02184-9.

DOI:10.1016/s0006-8993(01)02184-9
PMID:11325341
Abstract

The ventromedial hypothalamus (VMH) has been proposed to be a glucose sensor within the brain and appears to play a critical role in initiating the counterregulatory response to hypoglycemia. Transport of glucose across the brain capillaries and into neurons in this region is mediated by different isoforms of the sodium-independent glucose transporter gene family. The objective of the present study was to identify the specific glucose transporter isoforms present, as well as their cellular localization, within the VMH. Immunohistochemistry was performed for GLUT1, GLUT2 and GLUT4 in frozen sections of hypothalami from normal rats. GLUT1 was present on the endothelial cells of the blood-brain barrier (BBB) of the VMH. GLUT2 immunoreactivity was seen in the ependymal cells of the third ventricle and in scattered cells in the arcuate and periventricular nuclei. There was no GLUT2 expression in the VMH. The insulin-sensitive GLUT4 isoform was localized to vascular structures within the VMH. Double-labeled immunohistochemistry demonstrated co-localization of GLUT4 with GLUT1 and with the tight junction protein ZO-1 in the VMH and suggested that VMH GLUT4 expression was restricted to the BBB. The role of GLUT4 in the brain and within the VMH is unknown, but given its location on the BBB, it may participate in brain sensing of blood glucose concentrations.

摘要

腹内侧下丘脑(VMH)被认为是大脑中的葡萄糖传感器,并且在启动对低血糖的反调节反应中似乎起着关键作用。葡萄糖穿过脑毛细血管并进入该区域神经元的转运是由钠非依赖性葡萄糖转运蛋白基因家族的不同异构体介导的。本研究的目的是确定VMH中存在的特定葡萄糖转运蛋白异构体及其细胞定位。对正常大鼠下丘脑冰冻切片进行了GLUT1、GLUT2和GLUT4的免疫组织化学检测。GLUT1存在于VMH血脑屏障(BBB)的内皮细胞上。在第三脑室的室管膜细胞以及弓状核和室周核中的散在细胞中可见GLUT2免疫反应性。VMH中没有GLUT2表达。胰岛素敏感的GLUT4异构体定位于VMH内的血管结构。双重标记免疫组织化学显示GLUT4与GLUT1以及紧密连接蛋白ZO-1在VMH中共定位,并表明VMH中GLUT4的表达仅限于BBB。GLUT4在大脑和VMH中的作用尚不清楚,但鉴于其在BBB上的位置,它可能参与大脑对血糖浓度的感知。

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