Glucagon-like peptide-1 receptor stimulation increases blood pressure and heart rate and activates autonomic regulatory neurons
Open accessAbstract
Glucagon-like peptide-1 (GLP-1) released from the gut functions as an incretin that stimulates insulin secretion.GLP-1 is also a brain neuropeptide that controls feeding and drinking behavior and gastric emptying and elicits neuroendocrine responses including development of conditioned taste aversion.Although GLP-1 receptor (GLP-1R) agonists are under development for the treatment of diabetes, GLP-1 administration may increase blood pressure and heart rate in vivo.We report here that centrally and peripherally administered GLP-1R agonists dose-dependently increased blood pressure and heart rate.GLP-1R activation induced c-fos expression in the adrenal medulla and neurons in autonomic control sites in the rat brain, including medullary catecholamine neurons providing input to sympathetic preganglionic neurons.Furthermore, GLP-1R agonists rapidly activated tyrosine hydroxylase transcription in brainstem catecholamine neurons.These findings suggest that the central GLP-1 system represents a regulator of sympathetic outflow leading to downstream activation of cardiovascular responses in vivo.
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Peripheral and central GLP-1 agonists activate the adrenal medulla and autonomic regulatory neurons in the rat brain.
“Peripheral and central GLP-1 agonists induce c-fos expression, suggesting they activate the adrenal medulla and autonomic regulatory neurons in the rat brain (53).”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [53]
GLP-1 receptor agonists have dose-dependent chronotropic and pressor responses in rodents.
“GLP-1 receptor agonists have dose-dependent chronotropic and pressor responses in rodents (5, 53)”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [53]
There is evidence that GLP-1 increases sympathetic activity in rats.
“In addition to regulating glycemia, there is evidence that the neuropeptide GLP-1, administered peripherally or centrally, inhibits vagal activity in animals and humans (19, 50, 51) and increases sympathetic activity in rats (52, 53).”
From Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans (2008) · cites this paper as [53]
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Self-citation
- Authors
- Yamamoto, H., Lee, C. E., Marcus, J. N., Williams, T. D., Overton, J. M., Lopez, M. E., Hollenberg, A. N., Baggio, L., Saper, C. B., Drucker, D. J., & Elmquist, J. K.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Florida State University (US)
- University of Toronto (CA)
- Corresponding author
- Elmquist, Joel K.
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2002-07-01
- Volume
- 110
- Issue
- 1
- Pages
- 43-52
- ISSN
- 0021-9738 (ISSN-L)
- OpenAlex
- W4252795044
- Cited by
- 429
- References
- 44
- Citations by year
- 2026: 11 · 2025: 4 · 2024: 11 · 2023: 7 · 2022: 14 · 2021: 19 · 2020: 16 · 2019: 15 · 2018: 13 · 2017: 18 · 2016: 21 · 2015: 25 · 2014: 30 · 2013: 32 · 2012: 30
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- glucagon-like peptide-1, GLP-1 receptor agonists, blood pressure, heart rate, autonomic regulation, sympathetic nervous system, catecholaminergic neurons, adrenal medulla, Fos expression, tyrosine hydroxylase, brainstem, cardiovascular response, incretins
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