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 (GLUT1^ΔGFAP 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 d

SUBMITTER: Ardanaz CG 

PROVIDER: S-EPMC11488540 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature