Hypothalamic ependymal‐glial cells express the glucose transporter GLUT2, a protein involved in glucose sensing

Abstract

The GLUT2 glucose transporter and the K-ATP-sensitive potassium channels have been implicated as an integral part of the glucose-sensing mechanism in the pancreatic islet b cells. The expression of GLUT2 and K-ATP channels in the hypothalamic region suggest that they are also involved in a sensing mechanism in this area. The hypothalamic glial cells, known as tanycytes a and b, are specialized ependymal cells that bridge the cerebrospinal fluid and the portal blood of the median eminence. We used immunocytochemistry, in situ hybridization and transport analyses to demonstrate the glucose transporters expressed in tanycytes. Confocal microscopy using specific antibodies against GLUT1 and GLUT2 indicated that both transporters are expressed in a and b tanycytes. In addition, primary cultures of mouse hypothalamic tanycytes were found to express both GLUT1 and GLUT2 transporters. Transport studies, including 2-deoxyglucose and fructose uptake in the presence or absence of inhibitors, indicated that these transporters are functional in cultured tanycytes. Finally, our analyses indicated that tanycytes express the K-ATP channel subunit Kir6.1 in vitro. As the expression of GLUT2 and K-ATP channel is linked to glucose-sensing mechanisms in pancreatic b cells, we postulate that tanycytes may be responsible, at least in part, for a mechanism that allows the hypothalamus to detect changes in glucose concentrations.

Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior

“…Previously, we have characterized GLUT2 kinetic properties by evaluating glucose transport in tanycytes, showing GLUT1 and GLUT2 contributions. At 20 mM glucose, the relative contribution in transport was 30% and 70% for both transporters, respectively (Garcia et al, 2003). Here, tanycyte cultures transduced with AdshGlut2 showed a significant reduction of the incorporation of glucose, indicating loss of function.…”

“…In the central nervous system, GLUT2 immunohistochemical studies are limited by its low level of expression (Arluison, Quignon, Nguyen, et al, 2004; Garcia et al, 2003; Maekawa et al, 2000). However, those that exist have been corroborated by the use of mice expressing a fluorescent reporter gene (eYFP) under the control of the GLUT2 promoter, GLUT2‐eYFP mice (Mounien et al, 2010).…”

“…However, those that exist have been corroborated by the use of mice expressing a fluorescent reporter gene (eYFP) under the control of the GLUT2 promoter, GLUT2‐eYFP mice (Mounien et al, 2010). GLUT2 was found in neurons and astrocytes dispersed in many structures, including the hypothalamus, the brain stem, the thalamic area (Arluison, Quignon, Thorens, Leloup, & Penicaud, 2004; Labouebe, Boutrel, Tarussio, & Thorens, 2016) and in tanycytes (Garcia et al, 2003). Tanycytes are radial glial‐like cells surrounding the lateral walls of the infundibular recess (Recabal, Caprile, & Garcia‐Robles, 2017).…”

“…Although the expression of several proteins involved in the detection and response to glucose has been demonstrated in tanycytes (Cortes‐Campos et al, 2011; Garcia et al, 2003; Millan et al, 2010), there was no evidence of their involvement in the regulation of food intake. We used a molecular tool for in vivo GLUT2 knockdown in specific cells of the rat brain.…”

GLUT2, glucose sensing and glucose homeostasis

“…In rats, a careful immunohistochemical mapping of GLUT2 expression at the light and electron microscopy levels revealed its presence in most brain structures, and expression was found in neurons, astrocytes, endothelial cells and tanycytes, which are specialised astrocytes lining the lower part of the third ventricle [60][61][62]. In mice, using a genetic reporter system in which a fluorescent protein is expressed under the control of the Glut2 promoter (Glut2-Cre transgenic mice crossed with Rosa26tdTomato mice), the distribution of GLUT2 expressing cells in the brain was found to be very similar to that of the rat [63].…”