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

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• 作者：Edwin Hernandez-Garzó ; n ; Ana M. Fernandez ; Alberto Perez-Alvarez ; Laura Genis ; Pablo Bascuñ ; ana ; 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. Tschö ; p ; Alfonso Araque ; Eduardo D. Martin and Ignacio Torres Aleman
• 刊名：Glia
• 出版年：2016
• 出版时间：November 2016
• 年：2016
• 卷：64
• 期：11
• 页码：1962-1971
• 全文大小：555K
• ISSN：1098-1136

文摘

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