title: Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I.
abstract: Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.|CIBERNED, Madrid, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fernandez
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.|CIBERNED, Madrid, Spain.
authors.forename: Edwin
authors.initials: E
authors.lastname: Hernandez-Garzón
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.|CIBERNED, Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Perez-Domper
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.|Center for Molecular Neurobiology Hamburg, Hamburg, Germany.
authors.forename: Alberto
authors.initials: A
authors.lastname: Perez-Alvarez
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Sara
authors.initials: S
authors.lastname: Mederos
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.|CIBERNED, Madrid, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Santi
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.|CIBERNED, Madrid, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Trueba-Saiz
authors.affiliation: CIBERNED, Madrid, Spain.|Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Lucía
authors.initials: L
authors.lastname: García-Guerra
authors.affiliation: CIBERNED, Madrid, Spain.|Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Pose-Utrilla
authors.affiliation: Experimental and Clinical Research Center, Charité-Universitätsmedizin, Max Delbrück Center for Molecular Medicine, Berlin, Germany.|Brandenburg Heart Center and Medical University of Brandenburg, Brandenburg, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Fielitz
authors.affiliation: University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Eric N
authors.initials: EN
authors.lastname: Olson
authors.affiliation: Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Fernandez de la Rosa
authors.affiliation: Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Garcia Garcia
authors.affiliation: Pluridisciplinary Institute, Complutense University of Madrid, Madrid, Spain.
authors.forename: Miguel Angel
authors.initials: MA
authors.lastname: Pozo
authors.affiliation: CIBERNED, Madrid, Spain.|Instituto de Investigaciones Biomédicas "Alberto Sols," Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Teresa
authors.initials: T
authors.lastname: Iglesias
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Araque
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, University of Tsukuba, Tsukuba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Soya
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain.
authors.forename: Gertrudis
authors.initials: G
authors.lastname: Perea
authors.affiliation: Science and Technology Park, Institute for Research in Neurological Disabilities, University of Castilla-La Mancha, Albacete, Spain.
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Martin
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Madrid, Spain torres@cajal.csic.es.|CIBERNED, Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres Aleman
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001692:Biological Transport / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007118:Immunoassay; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D010957:Plasmids; D016133:Polymerase Chain Reaction; D049268:Positron-Emission Tomography
chemical_list: D051272:Glucose Transporter Type 1; D007328:Insulin; C495678:Slc2a1 protein, mouse; D019344:Lactic Acid; D007334:Insulin-Like Growth Factor I; D006003:Glycogen; D005947:Glucose