RT Journal Article
T1 Insulin regulates neurovascular coupling through astrocytes.
A1 Fernandez, Ana M
A1 Martinez-Rachadell, Laura
A1 Navarrete, Marta
A1 Pose-Utrilla, Julia
A1 Davila, Jose Carlos
A1 Pignatelli, Jaime
A1 Diaz-Pacheco, Sonia
A1 Guerra-Cantera, Santiago
A1 Viedma-Moreno, Emilia
A1 Palenzuela, Rocio
A1 Ruiz de Martin Esteban, Samuel
A1 Mostany, Ricardo
A1 Garcia-Caceres, Cristina
A1 Tschöp, Matthias
A1 Iglesias, Teresa
A1 de Ceballos, Maria L
A1 Gutierrez, Antonia
A1 Torres Aleman, Ignacio
K1 astrocytes
K1 insulin
K1 neurovascular coupling
AB 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.
YR 2022
FD 2022-07-14
LK http://hdl.handle.net/10668/19668
UL http://hdl.handle.net/10668/19668
LA en
DS RISalud
RD Apr 7, 2025