| First Author | Hernandez-Garzón E | Year | 2016 |
| Journal | Glia | Volume | 64 |
| Issue | 11 | Pages | 1962-71 |
| PubMed ID | 27462832 | Mgi Jnum | J:235624 |
| Mgi Id | MGI:5796904 | Doi | 10.1002/glia.23035 |
| Citation | Hernandez-Garzon E, et al. (2016) The insulin-like growth factor I receptor regulates glucose transport by astrocytes. Glia 64(11):1962-71 |
| abstractText | 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. |
