Evidence mapPaperPMID 36417883Full record

ArticleCell reports2022

Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis.

Wineke Bakker, Monica Imbernon, Casper Gravesen Salinas, Daniela Herrera Moro Chao, Rim Hassouna, Chloe Morel, Claire Martin, Caroline Leger, Raphael G P Denis, Julien Castel and 14 more

Open access · goldAbstract read
In one paragraph

Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.9field-weighted citation impact, top 8% 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

18 citing papers in PubMed, 29 citations in OpenAlex.

  1. Tanycytes: bloodhounds of the metabolic brain.Trends in endocrinology and metabolism: TEM · 2026
    Review
  2. Article
  3. The role of tanycytes in the regulation of energy balance.Reviews in endocrine & metabolic disorders · 2026
    Review
  4. Neurovascular plasticity as a modulator of hypothalamic function.Reviews in endocrine & metabolic disorders · 2026
    Review
  5. Article
  6. Review
  7. Glucagon-like peptide-1 receptor agonists for major neurocognitive disorders.Journal of neurology, neurosurgery, and psychiatry · 2025
    Review
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  9. Article
  10. Article
  11. Review
  12. Article
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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

24 authors at 6 institutions in 3 countries.

Wineke BakkerUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France; Global Drug Discovery, Novo Nordisk A/S, Måløv, Denmark. Electronic address: wineke.bakker@gmail.com.
Monica ImbernonUniversity Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, EGID, UMR-S 1172, 59000 Lille, France.
Casper Gravesen SalinasGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark; Image Analysis & Computer Graphics, Department of Applied Mathematics and Computer Science, Technical University of Denmark, Kgs. Lyngby, Denmark; Gubra ApS, Hørsholm Kongevej 11B, 2970 Hørsholm, Denmark.
Daniela Herrera Moro ChaoUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Rim HassounaUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Chloe MorelUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Claire MartinUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Caroline LegerUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Raphael G P DenisUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France; Institut Cochin, Université Paris Cité, INSERM U1016, CNRS UMR 8104, 75014 Paris, France.
Julien CastelUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Andreas PeterInstitute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany; Institute for Clinical Chemistry and Pathobiochemistry, Department for Diagnostic Laboratory Medicine, University Hospital of Tübingen, Tübingen, Germany.
Martin HeniDepartment of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology, University of Tübingen, Tübingen, Germany; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich at the University of Tübingen, Tübingen, Germany; German Center for Diabetes Research (DZD), Tübingen, Germany.
Walter MaetzlerDepartment of Neurodegenerative Diseases, Center of Neurology, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany; German Center for Neurodegenerative Diseases, Tübingen, Germany; Department of Neurology, University of Kiel, Kiel, Germany.
Heidi Solvang NielsenGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Manon DuquenneUniversity Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, EGID, UMR-S 1172, 59000 Lille, France.
Markus SchwaningerInstitute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.
Sofia LundhGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Wouter Frederic Johan HogendorfGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Giuseppe GangarossaUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France.
Anna SecherGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Jacob Hecksher-SørensenGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark; Gubra ApS, Hørsholm Kongevej 11B, 2970 Hørsholm, Denmark.
Thomas Åskov PedersenGlobal Drug Discovery, Novo Nordisk A/S, Måløv, Denmark.
Vincent PrevotUniversity Lille, Inserm, CHU Lille, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Lille Neuroscience & Cognition, EGID, UMR-S 1172, 59000 Lille, France.
Serge LuquetUniversité Paris Cité, CNRS, Unité de Biologie Fonctionnelle et Adaptative, 75013 Paris, France. Electronic address: serge.luquet@u-paris.fr.
Centre National de la Recherche Scientifique · FRNovo Nordisk (Denmark) · DKInserm · FRDeutsches Diabetes-Zentrum e.V. · DEGerman Center for Neurodegenerative Diseases · DEUniversity of Lübeck · DE

Funding

European Research Council 810331NIDDK NIH HHS U24 DK076169NIDDK NIH HHS U24 DK115255
6 · The paper itself

Abstract

Therapies based on glucagon-like peptide-1 (GLP-1) long-acting analogs and insulin are often used in the treatment of metabolic diseases. Both insulin and GLP-1 receptors are expressed in metabolically relevant brain regions, suggesting a cooperative action. However, the mechanisms underlying the synergistic actions of insulin and GLP-1R agonists remain elusive. In this study, we show that insulin-induced hypoglycemia enhances GLP-1R agonists entry in hypothalamic and area, leading to enhanced whole-body fat oxidation. Mechanistically, this phenomenon relies on the release of tanycyctic vascular endothelial growth factor A, which is selectively impaired after calorie-rich diet exposure. In humans, low blood glucose also correlates with enhanced blood-to-brain passage of insulin, suggesting that blood glucose gates the passage other energy-related signals in the brain. This study implies that the preventing hyperglycemia is important to harnessing the full benefit of GLP-1R agonist entry in the brain and action onto lipid mobilization and body weight loss.

Indexed as

Blood GlucoseVascular Endothelial Growth Factor ABrainGlucagon-Like Peptide 1HomeostasisHumansInsulinBlood GlucoseGlucagon-Like Peptide 1InsulinVascular Endothelial Growth Factor Abrain accessCP: Metabolismdiabetesglucagon-like peptide 1 analogsglycemic controlmetabolismnutrient partitioningobesitytanycyte

Identifiers

PMID36417883
PMCPMC9715912
OpenAlexW4309679218

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.