학술논문

Glucose transporter 2 mediates the hypoglycemia-induced increase in cerebral blood flow.
Document Type
Academic Journal
Author
Lei H; 1 AIT, Center for Biomedical Imaging (CIBM-AIT), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; 2 Department of Radiology, University of Geneva, Geneva, Switzerland.; Preitner F; 3 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.; 4 Mouse Metabolic Evaluation Facility, Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.; Labouèbe G; 3 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.; Gruetter R; 1 AIT, Center for Biomedical Imaging (CIBM-AIT), Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.; 2 Department of Radiology, University of Geneva, Geneva, Switzerland.; 5 Department of Radiology, University of Lausanne, Lausanne, Switzerland.; Thorens B; 3 Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
Source
Publisher: SAGE Publications Country of Publication: United States NLM ID: 8112566 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-7016 (Electronic) Linking ISSN: 0271678X NLM ISO Abbreviation: J Cereb Blood Flow Metab Subsets: MEDLINE
Subject
Language
English
Abstract
Glucose transporter 2 ( Glut2 )-positive cells are sparsely distributed in brain and play an important role in the stimulation of glucagon secretion in response to hypoglycemia. We aimed to determine if Glut2 -positive cells can influence another response to hypoglycemia, i.e. increased cerebral blood flow (CBF). CBF of adult male mice devoid of Glut2 , either globally ( ripglut1:glut2 - / - ) or in the nervous system only (NG2KO), and their respective controls were studied under basal glycemia and insulin-induced hypoglycemia using quantitative perfusion magnetic resonance imaging at 9.4 T. The effect on CBF of optogenetic activation of hypoglycemia responsive Glut2 -positive neurons of the paraventricular thalamic area was measured in mice expressing channelrhodopsin2 under the control of the Glut2 promoter. We found that in both ripglut1:glut2 - / - mice and NG2KO mice, CBF in basal conditions was higher than in their respective controls and not further activated by hypoglycemia, as measured in the hippocampus, hypothalamus and whole brain. Conversely, optogenetic activation of Glut2 -positive cells in the paraventricular thalamic nucleus induced a local increase in CBF similar to that induced by hypoglycemia. Thus, Glut2 expression in the nervous system is required for the control of CBF in response to changes in blood glucose concentrations.