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Hernandez-Garzón, E.* ; Fernandez, A.M.* ; Perez-Alvarez, A.* ; Genis, L.* ; Bascuñana, P.* ; de la Rosa, R.F.* ; Delgado, M.* ; Pozo, M.A.* ; Moreno, E.* ; McCormick, P.J.* ; Santi, A.* ; Trueba-Saiz, A.* ; García-Cáceres, C. ; Tschöp, M.H. ; Araque, A.* ; Martin, E.D.* ; Torres Aleman, I.*

The insulin-like growth factor I receptor regulates glucose transport by astrocytes.

Glia 64, 1962-1971 (2016)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Astrocytes ; Glucose Metabolism ; Glucose Transporter 1 ; Insulin Like Growth Factor I Receptor
ISSN (print) / ISBN 0894-1491
e-ISSN 1098-1136
Journal Glia
Quellenangaben Volume: 64, Issue: 11, Pages: 1962-1971 Article Number: , Supplement: ,
Publisher Wiley
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)