Glucagon-like peptide-1 (GLP-1) action in the mouse area postrema neurons
Abstract
Glucagon-like peptide-1 (GLP-1) is a peptide hormone and member of the incretin family. GLP-1 related drugs, such as liraglutide, are widely used to treat diabetic patients and work by stimulating pancreatic β cells to increase glucose-dependent insulin secretion. However, extrapancreatic effects, such as appetite suppression or emesis, are observed in response to GLP-1 receptor agonists. In this study we used the in vitro patch-clamp method in acute brainstem preparations of mice and demonstrated that GLP-1 acts directly on area postrema neurons. It is known that activation of the area postrema is related to the induction of homeostatic autonomic nervous systems, including nausea. Approximately,half of the neurons tested in the area postrema were excited by GLP-1 in the presence of tetrodotoxin, and is thought to be through adenylate cyclase-cAMP pathways. Excitation was not frequently observed in nucleus tractus solitaries neurons or in area postrema neurons from GLP-1 receptor knock-out mice. These results indicate that GLP-1 receptor agonists excite area postrema neurons and potentially leading to the expression of extra-pancreatic effects. This is the first study to show that GLP-1 directly activates area postrema neurons.
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An alternative explanation for GI symptoms is direct interaction of GLP-1RAs with GLP-1R in brain regions such as the brainstem (area postrema, nucleus tractus solitarii), which are not protected by the blood-brain barrier and are typically involved in medication-induced nausea.
“an alternative explanation, albeit not mutually exclusive, is direct interaction of GLP-1RAs with GLP-1R in brain regions such as the brainstem (area postrema, nucleus tractus solitarii), which are not protected by the blood-brain barrier, and are typically involved in medication-induced nausea (chemosensitive area) (54–56).”
From The science of safety: adverse effects of GLP-1 receptor agonists as glucose-lowering and obesity medications (2026) · cites this paper as [55]
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- Authors
- Kawatani, M., Yamada, Y., & Kawatani, M.
- Affiliations
- Akita University (JP)
- Corresponding author
- Kawatani, Masahiro
- Venue
- Peptides
- Publisher
- Elsevier BV
- Published
- 2018-09
- Volume
- 107
- Pages
- 68-74
- ISSN
- 0196-9781 (ISSN-L)
- OpenAlex
- W2887194013
- Cited by
- 32
- References
- 51
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 4
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Peptides (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- glucagon-like peptide-1, GLP-1 receptor, GLP-1 receptor agonists, liraglutide, nausea, vomiting, nucleus tractus solitarius, neuronal excitation
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Animals, Female, Male, Mice, Inbred C57BL, Neurons, Mice, Knockout, Patch-Clamp Techniques, Area Postrema, Mice, Glucagon-Like Peptide 1
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