title: The insulin-like growth factor I receptor regulates glucose transport by astrocytes.
abstract: Previous findings indicate that reducing brain insulin-like growth factor I receptor (IGF-IR) activity promotes ample neuroprotection. We now examined a possible action of IGF-IR on brain glucose transport to explain its wide protective activity, as energy availability is crucial for healthy tissue function. Using (18) FGlucose PET we found that shRNA interference of IGF-IR in mouse somatosensory cortex significantly increased glucose uptake upon sensory stimulation. In vivo microscopy using astrocyte specific staining showed that after IGF-IR shRNA injection in somatosensory cortex, astrocytes displayed greater increases in glucose uptake as compared to astrocytes in the scramble-injected side. Further, mice with the IGF-IR knock down in astrocytes showed increased glucose uptake in somatosensory cortex upon sensory stimulation. Analysis of underlying mechanisms indicated that IGF-IR interacts with glucose transporter 1 (GLUT1), the main facilitative glucose transporter in astrocytes, through a mechanism involving interactions with the scaffolding protein GIPC and the multicargo transporter LRP1 to retain GLUT1 inside the cell. These findings identify IGF-IR as a key modulator of brain glucose metabolism through its inhibitory action on astrocytic GLUT1 activity. GLIA 2016;64:1962-1971.
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.|Ciberned, Spain.
authors.forename: Edwin
authors.initials: E
authors.lastname: Hernandez-Garzón
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.|Ciberned, Spain.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Fernandez
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.|Center for Molecular Neurobiology Hamburg, Hamburg, Germany.
authors.forename: Alberto
authors.initials: A
authors.lastname: Perez-Alvarez
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.|Ciberned, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Genis
authors.affiliation: Pluridisciplinary Institute, Complutense University, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bascuñana
authors.affiliation: Pluridisciplinary Institute, Complutense University, Madrid, Spain.
authors.forename: Ruben
authors.initials: R
authors.lastname: Fernandez de la Rosa
authors.affiliation: Pluridisciplinary Institute, Complutense University, Madrid, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.affiliation: Pluridisciplinary Institute, Complutense University, Madrid, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Angel Pozo
authors.affiliation: Ciberned, Spain.|Dept Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.
authors.forename: Estefania
authors.initials: E
authors.lastname: Moreno
authors.affiliation: Ciberned, Spain.|Dept Biochemistry and Molecular Biology, University of Barcelona, Barcelona, Spain.|School of Pharmacy, University of East Anglia, Norwich, Norfolk, United Kingdom.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCormick
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.|Ciberned, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Santi
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.|Ciberned, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Trueba-Saiz
authors.affiliation: Institute for Diabetes and Obesity, Munich, Germany.
authors.forename: Cristina
authors.initials: C
authors.lastname: Garcia-Caceres
authors.affiliation: Institute for Diabetes and Obesity, Munich, Germany.
authors.forename: Matthias H
authors.initials: MH
authors.lastname: Tschöp
authors.affiliation: Cajal Institute, CSIC, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Araque
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, CSIC, Madrid, Spain. torres@cajal.csic.es.|Ciberned, Spain. torres@cajal.csic.es.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Torres Aleman
mesh_terms: D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D019921:Biotinylation; D001921:Brain / Q000166:cytology / Q000000981:diagnostic imaging; D002478:Cells, Cultured; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005944:Glucosamine / Q000031:analogs & derivatives / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000172:deficiency / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010812:Physical Stimulation; D021381:Protein Transport / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection; D014738:Vibrissae / Q000502:physiology
chemical_list: D005904:Glial Fibrillary Acidic Protein; D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; C519530:insulin-like growth factor-1, mouse; C045400:6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)aminoglucose; D049452:Green Fluorescent Proteins; D007334:Insulin-Like Growth Factor I; D009327:4-Chloro-7-nitrobenzofurazan; D005947:Glucose; D005944:Glucosamine
keywords: astrocytes; glucose metabolism; glucose transporter 1; insulin like growth factor I receptor