Publication:
Insulin regulates neurovascular coupling through astrocytes.

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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

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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.

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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

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Keywords

astrocytes, insulin, neurovascular coupling

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