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Fernandez, A.M.* ; Martinez-Rachadell, L.* ; Navarrete, M.* ; Pose-Utrilla, J.* ; Davila, J.C.* ; Pignatelli, J.* ; Diaz-Pacheco, S.* ; Guerra-Cantera, S.* ; Viedma-Moreno, E.* ; Palenzuela, R.* ; Ruiz de Martin Esteban, S.* ; Mostany, R.* ; García-Cáceres, C. ; Tschöp, M.H. ; Iglesias, T.* ; de Ceballos, M.L.* ; Gutierrez, A.* ; Torres Aleman, I.*

Insulin regulates neurovascular coupling through astrocytes.

Proc. Natl. Acad. Sci. U.S.A. 119:e2204527119 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Mice with insulin receptor (IR)-deficient astrocytes (GFAP-IR knockout [KO] mice) show blunted responses to insulin and reduced brain glucose uptake, whereas IR-deficient astrocytes show disturbed mitochondrial responses to glucose. While exploring the functional impact of disturbed mitochondrial function in astrocytes, we observed that GFAP-IR KO mice show uncoupling of brain blood flow with glucose uptake. Since IR-deficient astrocytes show higher levels of reactive oxidant species (ROS), this leads to stimulation of hypoxia-inducible factor-1α and, consequently, of the vascular endothelial growth factor angiogenic pathway. Indeed, GFAP-IR KO mice show disturbed brain vascularity and blood flow that is normalized by treatment with the antioxidant N-acetylcysteine (NAC). NAC ameliorated high ROS levels, normalized angiogenic signaling and mitochondrial function in IR-deficient astrocytes, and normalized neurovascular coupling in GFAP-IR KO mice. Our results indicate that by modulating glucose uptake and angiogenesis, insulin receptors in astrocytes participate in neurovascular coupling.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Astrocytes ; Insulin ; Neurovascular Coupling
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 119, Issue: 29, Pages: , Article Number: e2204527119 Supplement: ,
Publisher National Academy of Sciences
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)