期刊
CELL
卷 166, 期 4, 页码 867-880出版社
CELL PRESS
DOI: 10.1016/j.cell.2016.07.028
关键词
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资金
- Helmholtz Alliance ICEMED - Imaging and Curing Environmental Metabolic Diseases
- Humboldt Foundation
- Initiative and Networking Fund of the Helmholtz Association
- Deutsches Zentrum fur DiabetesForschung (DZD)
- Institute of Advanced Studies of Technische Universitat Munchen (IAS-TUM Hans-Fischer)
- DFG [SFB 1123, SFB 870, SFB 1757]
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 proopio-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.
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