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

TY - JOUR

T1 - The insulin-like growth factor I receptor regulates glucose transport by astrocytes

AU - Hernandez-Garzón, Edwin

AU - Fernandez, Ana M

AU - Perez-Alvarez, Alberto

AU - Genis, Laura

AU - Bascuñana, Pablo

AU - Fernandez de la Rosa, Ruben

AU - Delgado, Mercedes

AU - Angel Pozo, Miguel

AU - Moreno, Estefania

AU - McCormick, Peter J

AU - Santi, Andrea

AU - Trueba-Saiz, Angel

AU - Garcia-Caceres, Cristina

AU - Tschöp, Matthias H

AU - Araque, Alfonso

AU - Martin, Eduardo D

AU - Torres Aleman, Ignacio

N1 - © 2016 Wiley Periodicals, Inc.

PY - 2016/11

Y1 - 2016/11

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1002/glia.23035

DO - 10.1002/glia.23035

M3 - SCORING: Journal article

C2 - 27462832

VL - 64

SP - 1962

EP - 1971

JO - GLIA

JF - GLIA

SN - 0894-1491

IS - 11

ER -