%0 Journal Article
%A Bakker, Wineke
%A Imbernon, Monica
%A Salinas, Casper Gravesen
%A Moro Chao, Daniela Herrera
%A Hassouna, Rim
%A Morel, Chloe
%A Martin, Claire
%A Leger, Caroline
%A Denis, Raphael G P
%A Castel, Julien
%A Peter, Andreas
%A Heni, Martin
%A Maetzler, Walter
%A Nielsen, Heidi Solvang
%A Duquenne, Manon
%A Schwaninger, Markus
%A Lundh, Sofia
%A Johan Hogendorf, Wouter Frederic
%A Gangarossa, Giuseppe
%A Secher, Anna
%A Hecksher-Sørensen, Jacob
%A Pedersen, Thomas Åskov
%A Prevot, Vincent
%A Luquet, Serge
%T Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis.
%J Cell reports
%V 41
%N 8
%@ 2211-1247
%C [New York, NY]
%I Elsevier
%M DZNE-2022-01738
%P 111698
%D 2022
%X 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.
%K Humans
%K Blood Glucose: metabolism
%K Vascular Endothelial Growth Factor A: metabolism
%K Glucagon-Like Peptide 1: metabolism
%K Insulin: metabolism
%K Homeostasis
%K Brain: metabolism
%K CP: Metabolism (Other)
%K brain access (Other)
%K diabetes (Other)
%K glucagon-like peptide 1 analogs (Other)
%K glycemic control (Other)
%K metabolism (Other)
%K nutrient partitioning (Other)
%K obesity (Other)
%K tanycyte (Other)
%K Blood Glucose (NLM Chemicals)
%K Vascular Endothelial Growth Factor A (NLM Chemicals)
%K Glucagon-Like Peptide 1 (NLM Chemicals)
%K Insulin (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%2 pmc:PMC9715912
%$ pmid:36417883
%R 10.1016/j.celrep.2022.111698
%U https://pub.dzne.de/record/165605