Astrocytic Insulin Signaling Couples Brain Glucose Uptake with Nutrient Availability
Authors: Carmelo Quarta
Tim Gruber
Luis Varela
Matthias H Tschöp
Cristina García-Cáceres
C Ronald Kahn
Ophelia Le Thuc
Martin Jastroch
Chun-Xia Yi
Pia Johansson
Beata Legutko
Paul T Pfluger
Tamas L Horvath
Magdalena Götz
Jovica Ninkovic
Stephen C Woods
Ana M Fernandez
Ignacio Torres-Alemán
Serge Luquet
Yuanqing Gao
Klara Szigeti-Buck
Weikang Cai
Carola W Meyer
Journal: Cell (2016)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: astrocytes; glucose uptake; hypothalamus; insulin receptor.
Affiliations: Helmholtz Diabetes Center (HDC) & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Division of Metabolic Diseases, Technische Universität München, 80333 Munich, Germany., Program in Integrative Cell Signaling and Neurobiology of Metabolism, Section of Comparative Medicine, Yale University School of Medicine, New Haven, CT 06520, USA., Institute of Stem Cell Research Center, Helmholtz Zentrum München, 85764 Neuherberg, Germany; Physiological Genomics, Biomedical Center, Ludwigs-Maximilians-University, 80336 Munich, Germany; 7SYNERGY, Excellence Cluster Systems Neurology, Biomedical Center, Ludwigs-Maximilians-University, 80336 Munich, Germany., Section of Integrative Physiology and Metabolism, Joslin Diabetes Center and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA., Institute Cajal, CSIC, 28002 Madrid, Spain., Université Paris Diderot, Sorbonne Paris Cité, Unité de Biologie Fonctionnelle et Adaptative, CNRS UMR 8251, 75205 Paris, France., Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati, 2170 Galbraith Avenue, Cincinnati, OH 45237, USA., Helmholtz Diabetes Center (HDC) & German Center for Diabetes Research (DZD), Helmholtz Zentrum München, 85764 Neuherberg, Germany; Division of Metabolic Diseases, Technische Universität München, 80333 Munich, Germany. Electronic address: .

Abstract:  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. 

Retracted: No

PubPeer comments:
 FIG5E appears to be identical to Fig5B ![file] , 
 #1 The same electron micrograph of a cell was used to analyze both glial coverage (Fig. B) and synapses number (Fig. 5E). For the illustration of the GFAP-IR KO group, the same cell was used (glial coverage: Fig. 5B; synapses: Fig. 5E). , 
 Thank you for the clarification. ,