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Journal of Molecular Medicine

, Volume 97, Issue 8, pp 1085–1097 | Cite as

The median eminence as the hypothalamic area involved in rapid transfer of glucose to the brain: functional and cellular mechanisms

  • Fernando MartínezEmail author
  • Manuel Cifuentes
  • Juan Carlos Tapia
  • Francisco NualartEmail author
Original Article
  • 403 Downloads

Abstract

Our data proposes that glucose is transferred directly to the cerebrospinal fluid (CSF) of the hypothalamic ventricular cavity through a rapid “fast-track-type mechanism” that would efficiently stimulate the glucosensing areas. This mechanism would occur at the level of the median eminence (ME), a periventricular hypothalamic zone with no blood-brain barrier. This “fast-track” mechanism would involve specific glial cells of the ME known as β2 tanycytes that could function as “inverted enterocytes,” expressing low-affinity glucose transporters GLUT2 and GLUT6 in order to rapidly transfer glucose to the CSF. Due to the large size of tanycytes, the presence of a high concentration of mitochondria and the expression of low-affinity glucose transporters, it would be expected that these cells accumulate glucose in the endoplasmic reticulum (ER) by sequestering glucose-6-phosphate (G-6-P), in a similar way to that recently demonstrated in astrocytes. Glucose could diffuse through the cells by micrometric distances to be released in the apical region of β2 tanycytes, towards the CSF. Through this mechanism, levels of glucose would increase inside the hypothalamus, stimulating glucosensing mechanisms quickly and efficiently.

Key messages

• Glucose diffuses through the median eminence cells (β2 tanycytes), towards the hypothalamic CSF.

• Glucose is transferred through a rapid “fast-track-type mechanism” via GLUT2 and GLUT6.

• Through this mechanism, hypothalamic glucose levels increase, stimulating glucosensing.

Keywords

Tanycytes GLUT2 GLUT6 Median eminence Glucose sensing Brain Barrier 

Notes

Funding information

This work was supported by a Fondecyt Iniciación grant 11150678 and a CONICYT PIA ECM-12 grant. The funders had no role in the study.

Supplementary material

109_2019_1799_Fig6_ESM.png (11.3 mb)
Supplementary Figure 1

related to Figure 3. The main structural changes induced in β2 tanycytes is produced in the rostral area of the hypothalamus. A. Immunofluorescence and confocal microscopy analysis of *2 tanycytes (vimentin positive), located in the rostral ME (Bregma -2,12 mm) in normo, hyper and recovered normoglycemia conditions. B. Immunofluorescence and confocal microscopy analysis of *2 tanycytes (vimentin positive) located in the medial ME (Bregma -3,14 mm) in normo, hyper and recovered normoglycemia conditions. C. Immunofluorescence and confocal microscopy analysis of *2 tanycytes (vimentin positive), located in the caudal ME (Bregma -4,16 mm) in normo, hyper and recovered normoglycemia conditions. Scale bars; A-I, 100 *m. All images are representative of different biologically independent samples. A-C, n = 3. D-F, n = 3. G-I, n = 3. (PNG 11540 kb)

109_2019_1799_MOESM1_ESM.tif (14.9 mb)
Supplementary Figure 1

related to Figure 3. The main structural changes induced in β2 tanycytes is produced in the rostral area of the hypothalamus. A. Immunofluorescence and confocal microscopy analysis of *2 tanycytes (vimentin positive), located in the rostral ME (Bregma -2,12 mm) in normo, hyper and recovered normoglycemia conditions. B. Immunofluorescence and confocal microscopy analysis of *2 tanycytes (vimentin positive) located in the medial ME (Bregma -3,14 mm) in normo, hyper and recovered normoglycemia conditions. C. Immunofluorescence and confocal microscopy analysis of *2 tanycytes (vimentin positive), located in the caudal ME (Bregma -4,16 mm) in normo, hyper and recovered normoglycemia conditions. Scale bars; A-I, 100 *m. All images are representative of different biologically independent samples. A-C, n = 3. D-F, n = 3. G-I, n = 3. (PNG 11540 kb)

109_2019_1799_Fig7_ESM.png (7.9 mb)
Supplementary Figure 2

related Figure 5. The adenovirus specifically transduced ME hypothalamic tanycytes. A-D. Adenovirus AdshβGal-GFP, AdshGlut2-GFP and AdshGLUT6-GFP showed an efficient transduction in EM tanycytes. E-G. Cellular analysis of AdshβGal-GFP in ependymal cells and *2 tanycytes. H-K. Codistribution of vimentin-positive tanycytes and AdshβGal-GFP-positive cells in ME area. L. qRT-PCR analysis of GLUT2 expression in ME tissue samples after AdshβGal-GFP, AdshGlut2-GFP or AdshGLUT6-GFP intra-ventricular injection. M. qRT-PCR analysis of GLUT6 expression in ME tissue samples after AdshβGal-GFP, AdshGlut2-GFP or AdshGLUT6-GFP intra-ventricular injection. Data are mean + SD, from 4 animals for experimental condition. *P < 0.05; **P < 0.01; ns, not significant; ANOVA with post-hoc Tukey. IIIV. third ventricle. ME. Median eminence. Asterisk. Pars Tuberalis. Scale bars; A-D, 100 *m; H-J, 50 *m; K-N, 30 *m. All images are representative of different biologically independent samples. A, E-G, n = 2. B-C, n = 2. D, n = 2. H-K, n = 2. (PNG 8092 kb)

109_2019_1799_MOEMS2_ESM.tif (11.5 mb)
Supplementary Figure 2

related Figure 5. The adenovirus specifically transduced ME hypothalamic tanycytes. A-D. Adenovirus AdshβGal-GFP, AdshGlut2-GFP and AdshGLUT6-GFP showed an efficient transduction in EM tanycytes. E-G. Cellular analysis of AdshβGal-GFP in ependymal cells and *2 tanycytes. H-K. Codistribution of vimentin-positive tanycytes and AdshβGal-GFP-positive cells in ME area. L. qRT-PCR analysis of GLUT2 expression in ME tissue samples after AdshβGal-GFP, AdshGlut2-GFP or AdshGLUT6-GFP intra-ventricular injection. M. qRT-PCR analysis of GLUT6 expression in ME tissue samples after AdshβGal-GFP, AdshGlut2-GFP or AdshGLUT6-GFP intra-ventricular injection. Data are mean + SD, from 4 animals for experimental condition. *P < 0.05; **P < 0.01; ns, not significant; ANOVA with post-hoc Tukey. IIIV. third ventricle. ME. Median eminence. Asterisk. Pars Tuberalis. Scale bars; A-D, 100 *m; H-J, 50 *m; K-N, 30 *m. All images are representative of different biologically independent samples. A, E-G, n = 2. B-C, n = 2. D, n = 2. H-K, n = 2. (PNG 8092 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Laboratory of Neurobiology and Stem Cells, NeuroCellT, Department of Cellular Biology, Faculty of Biological SciencesUniversity of ConcepcionConcepciónChile
  2. 2.Center for Advanced Microscopy CMA BIO BIOUniversity of ConcepcionConcepciónChile
  3. 3.Departamento de Biología Celular, Facultad de Ciencias BiológicasUniversidad de ConcepciónConcepciónChile
  4. 4.Department of Cell Biology, Genetics and Physiology, IBIMA, BIONAND, Andalusian Center for Nanomedicine and Biotechnology and Networking Research Center on Bioengineering, Biomaterials and NanomedicineUniversity of MalagaMalagaSpain
  5. 5.Facultad de Ciencias de la SaludUniversidad de TalcaTalcaChile

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