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García-Cáceres, C. ; Quarta, C. ; Varela, L.* ; Gao, Y. ; Gruber, T. ; Legutko, B. ; Jastroch, M. ; Johansson, P.A. ; Ninkovic, J. ; Yi, C.-X. ; Le Thuc, O. ; Szigeti-Buck, K.* ; Cai, W.* ; Meyer, C.W. ; Pfluger, P.T. ; Fernandez, A.M.* ; Luquet, S.* ; Woods, S.C.* ; Torres-Alemán, I.* ; Kahn, C.R.* ; Götz, M. ; Horvath, T.L.* ; Tschöp, M.H.

Astrocytic insulin signaling couples brain glucose uptake with nutrient availability.

Cell 166, 867-880 (2016)
Publ. Version/Full Text Supplement DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Astrocytes ; Glucose Uptake ; Hypothalamus ; Insulin Receptor; Body-weight; Neuronal Dysfunction; Alzheimers-disease; Energy-metabolism; Barrier; Leptin; Cells; Transporter; Circuits; Mice
ISSN (print) / ISBN 0092-8674
e-ISSN 1097-4172
Journal Cell
Quellenangaben Volume: 166, Issue: 4, Pages: 867-880 Article Number: , Supplement: ,
Publisher Cell Press
Publishing Place Cambridge, Mass.
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Stem Cell Research (ISF)