Cited by 294Neuropeptides and Animal PhysiologyRegulation of Appetite and ObesityHeart Rate Variability and Autonomic Control

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Glucagon-Like Peptide-1-Responsive Catecholamine Neurons in the Area Postrema Link Peripheral Glucagon-Like Peptide-1 with Central Autonomic Control Sites

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Yamamoto, Hiroshi, Kishi, Toshiro, Lee, Charlotte E., Choi, Brian J., Fang, Hui, Hollenberg, Anthony N., Drucker, Daniel J., Elmquist, Joel K.·2003·The Journal of Neuroscience

DOI 10.1523/jneurosci.23-07-02939.2003PMC PMC6742071

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Abstract

Glucagon-like peptide-1 (GLP-1) released from the gut is an incretin that stimulates insulin secretion. GLP-1 is also a brain neuropeptide that has diverse central actions, including inhibition of food and water intake, gastric emptying, and stimulation of neuroendocrine responses characteristic of visceral illness. Both intravenous and intracerebroventricular administration of GLP-1 receptor (GLP-1R) agonists increase blood pressure and heart rate and induce Fos-like immunoreactivity (Fos-IR) in autonomic regulatory sites in the rat brain. The area postrema (AP) is a circumventricular organ and has been implicated in processing visceral sensory information. GLP-1Rs are densely expressed in the AP, and peripheral GLP-1R agonists induce Fos-IR in AP neurons to a greater degree than intracerebroventricular administration. Because the AP lacks a blood–brain barrier, we hypothesized that the AP is a key site for peripheral GLP-1 to activate central autonomic regulatory sites. In this study, we found that many tyrosine hydroxylase (TH)-containing neurons in the AP expressed GLP-1Rs and Fos-IR after intravenous GLP-1R agonists. Furthermore, intravenous but not intracerebroventricular GLP-1R agonists induced TH transcription in the AP in vivo. In addition, GLP-1R agonists directly activated TH transcription in an in vitro cell system. Finally, we found that GLP-1-responsive TH neurons in the AP innervate autonomic control sites, including the parabrachial nucleus, nucleus of solitary tract, and ventrolateral medulla. These findings suggest that catecholamine neurons in the AP link peripheral GLP-1 and central autonomic control sites that mediate the diverse neuroendocrine and autonomic actions of peripheral GLP-1.

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Authors: Yamamoto, H., Kishi, T., Lee, C. E., Choi, B. J., Fang, H., Hollenberg, A. N., Drucker, D. J., & Elmquist, J. K.
Affiliations: Beth Israel Deaconess Medical Center (US)
University of Toronto (CA)
ORCID: Yamamoto, Hiroshi
Lee, Charlotte E.
Hollenberg, Anthony N.
Drucker, Daniel J.
Elmquist, Joel K.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2003-04-01
Volume: 23
Issue: 7
Pages: 2939-2946
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.23-07-02939.2003
PMC: PMC6742071
OpenAlex: W2152880048
Cited by: 294
References: 60
Citations by year: 2026: 6 · 2025: 8 · 2024: 18 · 2023: 12 · 2022: 8 · 2021: 18 · 2020: 9 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 10 · 2015: 9 · 2014: 12 · 2013: 14 · 2012: 15
FWCI: 5.14
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01dk059751-02)
National Institute of Diabetes and Digestive and Kidney Diseases (P01DK056116, DK56116, DK 59751)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords: glucagon-like peptide-1, GLP-1 receptor, area postrema, catecholaminergic neurons, tyrosine hydroxylase, Fos expression, autonomic regulation, parabrachial nucleus, solitary tract nucleus, ventrolateral medulla, neuroendocrine response, incretins, blood pressure
MeSH terms: Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Catecholamines, Cell Line, Central Nervous System, Glucagon, Immunohistochemistry, Male, Neurons, Peptide Fragments, Peptides, Protein Precursors, RNA, Messenger, Tyrosine 3-Monooxygenase, Venoms, Transcriptional Activation, Rats, Sprague-Dawley, In Situ Hybridization, Solitary Nucleus, Autonomic Pathways, Receptors, Glucagon, Area Postrema, Rats, Glucagon-Like Peptide 1

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Glucagon-Like Peptide-1-Responsive Catecholamine Neurons in the Area Postrema Link Peripheral Glucagon-Like Peptide-1 with Central Autonomic Control Sites

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