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
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 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
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 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
KW - astrocytes
KW - insulin like growth factor I receptor
KW - glucose metabolism
KW - glucose transporter 1
U2 - 10.1002/glia.23035
DO - 10.1002/glia.23035
M3 - Article
SN - 0894-1491
VL - 64
SP - 1962
EP - 1971
JO - Glia
JF - Glia
IS - 11
ER -