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

Edwin Hernandez-Garzón, Ana M. Fernandez, Alberto Perez-Alvarez, Laura Genis, Pablo Bascuñana, Ruben Fernandez de la Rosa, Mercedes Delgado, Miguel Angel Pozo, Estefania Moreno, Peter J. McCormick, Andrea Santi, Angel Trueba-Saiz, Cristina Garcia-Caceres, Matthias H. Tschöp, Alfonso Araque, Eduardo D. Martin, Ignacio Torres Aleman

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 18FGlucose 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.

Original languageEnglish (US)
Pages (from-to)1962-1971
Number of pages10
JournalGlia
Volume64
Issue number11
DOIs
StatePublished - Nov 1 2016

Bibliographical note

Publisher Copyright:
© 2016 Wiley Periodicals, Inc.

Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.

Keywords

  • astrocytes
  • glucose metabolism
  • glucose transporter 1
  • insulin like growth factor I receptor

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