The insulin-like growth factor I receptor regulates glucose transport by astrocytes
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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; Torres Aleman, Ignacio.
in: GLIA, Jahrgang 64, Nr. 11, 11.2016, S. 1962-71.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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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 -