Publication: Insulin regulates neurovascular coupling through astrocytes.
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Identifiers
Date
2022-07-14
Authors
Fernandez, Ana M
Martinez-Rachadell, Laura
Navarrete, Marta
Pose-Utrilla, Julia
Davila, Jose Carlos
Pignatelli, Jaime
Diaz-Pacheco, Sonia
Guerra-Cantera, Santiago
Viedma-Moreno, Emilia
Palenzuela, Rocio
Advisors
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
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.
Description
MeSH Terms
Animals
Astrocytes
Brain
Glial Fibrillary Acidic Protein
Glucose
Insulin
Mice
Mice, Knockout
Neovascularization, Physiologic
Neurovascular Coupling
Reactive Oxygen Species
Receptor, Insulin
Vascular Endothelial Growth Factor A
Astrocytes
Brain
Glial Fibrillary Acidic Protein
Glucose
Insulin
Mice
Mice, Knockout
Neovascularization, Physiologic
Neurovascular Coupling
Reactive Oxygen Species
Receptor, Insulin
Vascular Endothelial Growth Factor A
DeCS Terms
CIE Terms
Keywords
astrocytes, insulin, neurovascular coupling