| First Author | García-Cáceres C | Year | 2016 |
| Journal | Cell | Volume | 166 |
| Issue | 4 | Pages | 867-880 |
| PubMed ID | 27518562 | Mgi Jnum | J:236082 |
| Mgi Id | MGI:5804703 | Doi | 10.1016/j.cell.2016.07.028 |
| Citation | Garcia-Caceres C, et al. (2016) Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability. Cell 166(4):867-80 |
| abstractText | We report that astrocytic insulin signaling co-regulates hypothalamic glucose sensing and systemic glucose metabolism. Postnatal ablation of insulin receptors (IRs) in glial fibrillary acidic protein (GFAP)-expressing cells affects hypothalamic astrocyte morphology, mitochondrial function, and circuit connectivity. Accordingly, astrocytic IR ablation reduces glucose-induced activation of hypothalamic pro-opio-melanocortin (POMC) neurons and impairs physiological responses to changes in glucose availability. Hypothalamus-specific knockout of astrocytic IRs, as well as postnatal ablation by targeting glutamate aspartate transporter (GLAST)-expressing cells, replicates such alterations. A normal response to altering directly CNS glucose levels in mice lacking astrocytic IRs indicates a role in glucose transport across the blood-brain barrier (BBB). This was confirmed in vivo in GFAP-IR KO mice by using positron emission tomography and glucose monitoring in cerebral spinal fluid. We conclude that insulin signaling in hypothalamic astrocytes co-controls CNS glucose sensing and systemic glucose metabolism via regulation of glucose uptake across the BBB. |
