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oai:repisalud.isciii.es:20.500.12105/187102024-09-21T23:38:21Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16927

00925njm 22002777a 4500 dc 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 author 2022-07-14 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. 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 astrocytes insulin neurovascular coupling Insulin regulates neurovascular coupling through astrocytes.