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

The ventromedial hypothalamus (VMH) has been proposed to be a glucose senso r within the brain and appears to play a critical role in initiating the co unterregulatory response to hypoglycemia. Transport of glucose across the b rain capillaries and into neurons in this region is mediated by different i soforms of the sodium-independent glucose transporter gene family. The obje ctive 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 sec tions 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 cel ls 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 GLUT I with GLUT1 and with the tight junction protein Z O-1 in the VMH and suggested that VMH GLUT4 expression was restricted to th e BBB. The role of GLUT4 in the brain and within the VMH is unknown, but gi ven its location on the BBB, it may participate in brain sensing of blood g lucose concentrations. (C) 2001 Elsevier Science B,V. All rights reserved.