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Acute changes in systemic glycemia gate access and action of GLP-1R agonist on brain structures controlling energy homeostasis.
Cell Rep. 41:111698 (2022)
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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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Brain Access ; Cp: Metabolism ; Diabetes ; Glucagon-like Peptide 1 Analogs ; Glycemic Control ; Metabolism ; Nutrient Partitioning ; Obesity ; Tanycyte
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
Journal
Cell Reports
Quellenangaben
Volume: 41,
Issue: 8,
Article Number: 111698
Publisher
Cell Press
Non-patent literature
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Reviewing status
Peer reviewed