Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis Journal Article


Authors: Ardanaz, C. G.; de la Cruz, A.; Minhas, P. S.; Hernández-Martín, N.; Pozo, M. Á; Valdecantos, M. P.; Valverde, ÁM; Villa-Valverde, P.; Elizalde-Horcada, M.; Puerta, E.; Ramírez, M. J.; Ortega, J. E.; Urbiola, A.; Ederra, C.; Ariz, M.; Ortiz-de-Solórzano, C.; Fernández-Irigoyen, J.; Santamaría, E.; Karsenty, G.; Brüning, J. C.; Solas, M.
Article Title: Astrocytic GLUT1 reduction paradoxically improves central and peripheral glucose homeostasis
Abstract: Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity of the main astrocyte glucose transporter, i.e., GLUT1, for brain glucose metabolism has not been defined. Unexpectedly, we found that brain glucose metabolism was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1ΔGFAP mice). These mice also exhibited improved peripheral glucose metabolism especially in obesity, rendering them metabolically healthier. Mechanistically, we observed that GLUT1-deficient astrocytes exhibited increased insulin receptor-dependent ATP release, and that both astrocyte insulin signaling and brain purinergic signaling are essential for improved brain function and systemic glucose metabolism. Collectively, we demonstrate that astrocytic GLUT1 is central to the regulation of brain energetics, yet its depletion triggers a reprogramming of brain metabolism sufficient to sustain energy requirements, peripheral glucose homeostasis, and cognitive function.
Keywords: signal transduction; genetics; mouse; animal; metabolism; animals; mice; mice, knockout; astrocyte; obesity; brain; insulin; glucose; adenosine triphosphate; homeostasis; energy metabolism; knockout mouse; astrocytes; glucose transporter 1; glucose transporter type 1; insulin receptor; receptor, insulin; slc2a1 protein, mouse
Journal Title: Science Advances
Volume: 10
Issue: 42
ISSN: 2375-2548
Publisher: Amer Assoc Advancement Science  
Date Published: 2024-10-18
Start Page: eadp1115
Language: English
DOI: 10.1126/sciadv.adp1115
PUBMED: 39423276
PROVIDER: scopus
PMCID: PMC11488540
DOI/URL:
Notes: Source: Scopus
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  1. Paras Singh Minhas
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