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The insulin‐like growth factor I receptor regulates glucose transport by astrocytes
Author(s) -
HernandezGarzón Edwin,
Fernandez Ana M.,
PerezAlvarez Alberto,
Genis Laura,
Bascuñana Pablo,
Fernandez de la Rosa Ruben,
Delgado Mercedes,
Angel Pozo Miguel,
Moreno Estefania,
McCormick Peter J.,
Santi Andrea,
TruebaSaiz Angel,
GarciaCaceres Cristina,
Tschöp Matthias H.,
Araque Alfonso,
Martin Eduardo D.,
Torres Aleman Ignacio
Publication year - 2016
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23035
Subject(s) - glut1 , glucose transporter , astrocyte , biology , glucose transporter type 1 , glucose uptake , medicine , lrp1 , endocrinology , stimulation , somatosensory system , carbohydrate metabolism , snf3 , insulin , neuroscience , central nervous system , lipoprotein , ldl receptor , cholesterol
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