2026-07-21T16:29:04Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/187102024-09-21T23:38:21Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927
Repisalud author Fernandez, Ana M author Martinez-Rachadell, Laura author Navarrete, Marta author Pose-Utrilla, Julia author Davila, Jose Carlos author Pignatelli, Jaime author Diaz-Pacheco, Sonia author Guerra-Cantera, Santiago author Viedma-Moreno, Emilia author Palenzuela, Rocio author Ruiz de Martin Esteban, Samuel author Mostany, Ricardo author Garcia-Caceres, Cristina author Tschöp, Matthias author Iglesias, Teresa author de Ceballos, Maria L author Gutierrez, Antonia author Torres Aleman, Ignacio 2024-02-27T15:09:52Z 2024-02-27T15:09:52Z 2022-07-14 10.1073/pnas.2204527119 1091-6490 Proceedings of the National Academy of Sciences of the United States of America http://hdl.handle.net/10668/19668 35858325 http://hdl.handle.net/20.500.12105/18710 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. eng astrocytes insulin neurovascular coupling Insulin regulates neurovascular coupling through astrocytes. research article