Evidence map›Paper›PMID 32404031›Full record

ArticleCirculation research2020

Role of the GLUT1 Glucose Transporter in Postnatal CNS Angiogenesis and Blood-Brain Barrier Integrity.

Koen Veys, Zheng Fan, Moheb Ghobrial, Ann Bouché, Melissa García-Caballero, Kim Vriens, Nadine Vasconcelos Conchinha, Aline Seuwen, Felix Schlegel, Tatiane Gorski and 17 more

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Article in Circulation research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
141citing papers in PubMed, 3 pooled it
12.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

141 citing papers in PubMed, 3 syntheses or guidelines pooled it, 248 citations in OpenAlex.

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81 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

27 authors at 10 institutions in 7 countries.

Koen Veys *From the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Zheng Fan *Laboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Moheb GhobrialLaboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Ann BouchéFrom the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Melissa García-CaballeroFrom the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Kim VriensLaboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology (K. Vriens, S.-M.F.), KU Leuven.
Nadine Vasconcelos ConchinhaFrom the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Aline SeuwenInstitute for Biomedical Engineering (A. Seuwen, F.S., A. Schroeter), UZH/ETHZ, Zurich, Switzerland.
Felix SchlegelInstitute for Biomedical Engineering (A. Seuwen, F.S., A. Schroeter), UZH/ETHZ, Zurich, Switzerland.
Tatiane GorskiLaboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Melissa CrabbéNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, University Hospitals Leuven, Belgium (M.C., C.C., K.V.L.).
Paola GilardoniLaboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Raphaela ArdicogluLaboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Johanna SchaffenrathNeuroscience Center Zurich (J.S., A.K.), UZH/ETHZ, Zurich, Switzerland.
Cindy CasteelsNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, University Hospitals Leuven, Belgium (M.C., C.C., K.V.L.).
Gino De SmetDepartment of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, Vrije Universiteit Brussel (G.D.S., I.S.).
Ilse SmoldersDepartment of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Center for Neurosciences, Vrije Universiteit Brussel (G.D.S., I.S.).
Koen Van LaereNuclear Medicine and Molecular Imaging, Department of Imaging and Pathology, KU Leuven, University Hospitals Leuven, Belgium (M.C., C.C., K.V.L.).
E Dale AbelLaboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
Sarah-Maria FendtLaboratory of Cellular Metabolism and Metabolic Regulation, Department of Oncology (K. Vriens, S.-M.F.), KU Leuven.
Aileen SchroeterInstitute for Biomedical Engineering (A. Seuwen, F.S., A. Schroeter), UZH/ETHZ, Zurich, Switzerland.
Joanna KaluckaFrom the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Anna Rita CantelmoFrom the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Thomas WälchliGroup of CNS Angiogenesis and Neurovascular Link, Neuroscience Center Zurich, University of Zurich (UZH) and ETHZ and Division of Neurosurgery, USZ, Zurich (M.G., T.W.).
Annika KellerNeuroscience Center Zurich (J.S., A.K.), UZH/ETHZ, Zurich, Switzerland.
Peter CarmelietFrom the Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology (K. Veys, A.B., M.G.-C., N.V.C., J.K., A.R.C., P.C.), KU Leuven.
Katrien De BockLaboratory of Exercise and Health, Department of Health Sciences and Technology, Swiss Federal Institute of Technology (ETHZ) Zurich (Z.F., M.G., T.G., P.G., R.A., K.D.B.).
VIB-KU Leuven Center for Cancer Biology · BEDepartment of Medical Sciences · BYInstitute for Biomedical Engineering · CHKU Leuven · BEVrije Universiteit Brussel · BEAarhus University · DKInserm · FRUniversity Health Network · CAUniversity of Iowa · USUniversity of Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

rationaleEndothelial cells (ECs) are highly glycolytic and generate the majority of their energy via the breakdown of glucose to lactate. At the same time, a main role of ECs is to allow the transport of glucose to the surrounding tissues. GLUT1 (glucose transporter isoform 1/

objectiveWe evaluated the role of GLUT1 in endothelial metabolism and function during postnatal CNS development as well as at the adult BBB. METHODS AND

resultsInhibition of GLUT1 decreases EC glucose uptake and glycolysis, leading to energy depletion and the activation of the cellular energy sensor AMPK (AMP-activated protein kinase), and decreases EC proliferation without affecting migration. Deletion of GLUT1 from the developing postnatal retinal endothelium reduces retinal EC proliferation and lowers vascular outgrowth, without affecting the number of tip cells. In contrast, in the brain, we observed a lower number of tip cells in addition to reduced brain EC proliferation, indicating that within the CNS, organotypic differences in EC metabolism exist. Interestingly, when ECs become quiescent, endothelial glycolysis is repressed, and GLUT1 expression increases in a Notch-dependent fashion. GLUT1 deletion from quiescent adult ECs leads to severe seizures, accompanied by neuronal loss and CNS inflammation. Strikingly, this does not coincide with BBB leakiness, altered expression of genes crucial for BBB barrier functioning nor reduced vascular function. Instead, we found a selective activation of inflammatory and extracellular matrix related gene sets.

conclusionsGLUT1 is the main glucose transporter in ECs and becomes uncoupled from glycolysis during quiescence in a Notch-dependent manner. It is crucial for developmental CNS angiogenesis and adult CNS homeostasis but does not affect BBB barrier function.

Indexed as

Neovascularization, PhysiologicRetinal VesselsAMP-Activated Protein KinasesAnimalsBlood-Brain BarrierBrainCell MovementCell ProliferationEndothelial CellsEndotheliumEndothelium, VascularEnergy MetabolismGlucoseGlucose Transporter Type 1GlycolysisHumansAMP-Activated Protein KinasesGlucoseGlucose Transporter Type 1SLC2A1 protein, humanSlc2a1 protein, mouseblood-brain barrierendotheliumextracellular matrixglucose transportglycolysishomeostasis

Identifiers

PMID32404031
PMCPMC7386868
OpenAlexW3024580289

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.