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Article Dans Une Revue Cell Reports Année : 2022

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

Andreas Peter
  • Fonction : Auteur
Martin Heni
  • Fonction : Auteur
Walter Maetzler
  • Fonction : Auteur
Heidi Solvang Nielsen
  • Fonction : Auteur
Manon Duquenne
  • Fonction : Auteur
Markus Schwaninger
  • Fonction : Auteur
Sofia Lundh
  • Fonction : Auteur
Anna Secher
  • Fonction : Auteur
Jacob Hecksher-Sørensen
  • Fonction : Auteur
Thomas Åskov Pedersen
  • Fonction : Auteur
Vincent Prevot
  • Fonction : Auteur

Résumé

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.
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Dates et versions

hal-04227827 , version 1 (04-10-2023)

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Wineke Bakker, Monica Imbernon, Casper Gravesen Salinas, Daniela Herrera Moro Chao, Rim Hassouna, et al.. Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis. Cell Reports, 2022, 41 (8), pp.111698. ⟨10.1016/j.celrep.2022.111698⟩. ⟨hal-04227827⟩
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