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Cited by 13Gastrointestinal motility and disordersRegulation of Appetite and ObesityNausea and vomiting management

Centrally located GLP-1 receptors modulate gastric slow waves and cardiovascular function in ferrets consistent with the induction of nausea

Lu, Zengbing, Yeung, Chi-Kong, Lin, Ge, Yew, David T.W., Andrews, P.L.R., Rudd, John A.·2017·Neuropeptides
DOI 10.1016/j.npep.2017.04.006
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Abstract

Glucagon-like peptide-1 (GLP-1) receptor agonists are indicated for the treatment of Type 2 diabetes and obesity, but can cause nausea and emesis in some patients. GLP-1 receptors are distributed widely in the brain, where they contribute to mechanisms of emesis, reduced appetite and aversion, but it is not known if these centrally located receptors also contribute to a modulation of gastric slow wave activity, which is linked causally to nausea. Our aim was to investigate the potential of the GLP-1 receptor agonist, exendin-4, administered into the 3rd ventricle to modulate emesis, feeding and gastric slow wave activity. Thermoregulation and cardiovascular parameters were also monitored, as they are disturbed during nausea. Ferrets were used as common laboratory rodents do not have an emetic reflex. A guide cannula was implanted into the 3rd ventricle for delivering a previously established dose of exendin-4 (10nmol), which had been shown to induce emesis and behaviours indicative of 'nausea'. Radiotelemetry recorded gastric myoelectric activity (GMA; slow waves), blood pressure and heart rate variability (HRV), and core temperature; food intake and behaviour were also assessed. Exendin-4 (10nmol, i.c.v.) decreased the dominant frequency of GMA, with an associated increase in the percentage of bradygastric power (lasting ~4h). Food intake was inhibited in all animals, with 63% exhibiting emesis. Exendin-4 also increased blood pressure (lasting ~24h) and heart rate (lasting ~7h), decreased HRV (lasting ~24h), and caused transient hyperthermia. None of the above parameters were emesis-dependent. The present study shows for the first time that gastric slow waves may be modulated by GLP-1 receptors in the brain through mechanisms that appear independent from emesis. Taken together with a reduction in HRV, the findings are consistent with changes associated with the occurrence of nausea in humans.

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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 [56]

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Authors
Lu, Z., Yeung, C.-K., Lin, G., Yew, D. T. W., Andrews, P. L. R., & Rudd, J. A.
Affiliations
  • Chinese University of Hong Kong (HK)
  • St George's, University of London (GB)
Corresponding author
Rudd, John A.
ORCID
Venue
Neuropeptides
Publisher
Elsevier BV
Published
2017-10
Volume
65
Pages
28-36
ISSN
0143-4179 (ISSN-L)
DOI
10.1016/j.npep.2017.04.006
OpenAlex
W2606365219
Cited by
13
References
62
Citations by year
2026: 4 · 2025: 2 · 2023: 1 · 2021: 2 · 2020: 2 · 2018: 1 · 2017: 1
FWCI
1.11
Type
journal article
Language
en
Open access
closed
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neuropeptides (publishedVersion)
  • PubMed (publishedVersion)
Funders
Research Council of Hong Kong (CUHK 473909)
Topics
  • Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Surgery › Nausea and vomiting management
Keywords
GLP-1 receptor, exendin-4, nausea, gastric slow waves, gastric myoelectrical activity, vomiting, intracerebroventricular administration, heart rate variability, blood pressure, hyperthermia, dietary intake, cardiovascular function, ferrets
MeSH terms
Glucagon-Like Peptide-1 Receptor, Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Animals, Blood Pressure, Body Temperature, Cardiovascular Physiological Phenomena, Eating, Ferrets, Gastrointestinal Motility, Heart Rate, Male, Nausea, Peptides, Venoms, Vomiting

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