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

Hernandez-Garzón, Edwin, Fernandez, Ana M., Perez-Alvarez, Alberto, Genis, Laura, Bascuñana, Pablo, Fernandez de la Rosa, Ruben, Delgado, Mercedes, Angel Pozo, Miguel, Moreno, Estefania, McCormick, Peter J., Santi, Andrea, Trueba-Saiz, Angel, Garcia-Caceres, Cristina, Tschöp, Matthias H., Araque, Alfonso, Martin, Eduardo D. and Torres Aleman, Ignacio (2016) The insulin-like growth factor I receptor regulates glucose transport by astrocytes. Glia, 64 (11). 1962–1971. ISSN 0894-1491

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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

Item Type:	Article
Uncontrolled Keywords:	astrocytes,insulin like growth factor i receptor,glucose metabolism,glucose transporter 1
Faculty \ School:	Faculty of Science > School of Pharmacy
Depositing User:	Pure Connector
Date Deposited:	06 Oct 2016 13:00
Last Modified:	22 Oct 2022 01:25
URI:	https://ueaeprints.uea.ac.uk/id/eprint/60767
DOI:	10.1002/glia.23035

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