%0 Journal Article
%A Fernandez, Ana M
%A Martinez-Rachadell, Laura
%A Navarrete, Marta
%A Pose-Utrilla, Julia
%A Davila, Jose Carlos
%A Pignatelli, Jaime
%A Diaz-Pacheco, Sonia
%A Guerra-Cantera, Santiago
%A Viedma-Moreno, Emilia
%A Palenzuela, Rocio
%A Ruiz de Martin Esteban, Samuel
%A Mostany, Ricardo
%A Garcia-Caceres, Cristina
%A Tschöp, Matthias
%A Iglesias, Teresa
%A de Ceballos, Maria L
%A Gutierrez, Antonia
%A Torres Aleman, Ignacio
%T Insulin regulates neurovascular coupling through astrocytes.
%D 2022
%U http://hdl.handle.net/10668/19668
%X 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.
%K astrocytes
%K insulin
%K neurovascular coupling
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