Cited by 300Regulation of Appetite and ObesityDiabetes Treatment and ManagementNeuropeptides and Animal Physiology

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Evidence that Intestinal Glucagon-Like Peptide-1 Plays a Physiological Role in Satiety

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Williams, Diana L., Baskin, Denis G., Schwartz, Michael W.·2009·Endocrinology

DOI 10.1210/en.2008-1045PMC PMC2659282

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Abstract

A physiological role in satiety is proposed for glucagon-like peptide-1 (GLP-1), secreted by the distal intestine in response to ingested nutrients. Here we report that in rats, ip injection of the GLP-1 receptor (GLP-1-R) antagonist exendin 9-39 (Ex9) elicited hyperphagia, but only at times of day when intake is otherwise low. Furthermore, ip administration of Ex9 attenuated satiety induced by either a voluntarily consumed sucrose meal (by 100%) or an intragastric glucose load (by 40%). To determine whether these effects involve blockade of GLP-1-R in brain or at a peripheral site, we injected Ex9 either centrally (into the third ventricle) or peripherally (ip) prior to GLP-1 injected either centrally or peripherally. Anorexia induced by peripheral GLP-1 was fully blocked by peripheral, but not central, pretreatment with Ex9, whereas the opposite was true for anorexic effect of central GLP-1. Thus, ip Ex9 appears to attenuate satiety via peripheral GLP-1-R blockade. Finally, anorexia induced by ip injection of exendin-4 (a GLP-1-R agonist) was due to both reduced meal size and increased duration between meals. We conclude that GLP-1 released from the intestine in response to ingested nutrients is a physiologically active satiety signal.

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Authors: Williams, D. L., Baskin, D. G., & Schwartz, M. W.
Affiliations: Florida State University (US)
University of Washington (US)
VA Puget Sound Health Care System (US)
Corresponding author: Williams, Diana L.
ORCID: Williams, Diana L.
Baskin, Denis G.
Schwartz, Michael W.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 2008-12-12
Volume: 150
Issue: 4
Pages: 1680-1687
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/en.2008-1045
PMC: PMC2659282
OpenAlex: W2082052031
Cited by: 300
References: 31
Citations by year: 2026: 7 · 2025: 10 · 2024: 15 · 2023: 7 · 2022: 8 · 2021: 21 · 2020: 11 · 2019: 9 · 2018: 17 · 2017: 16 · 2016: 27 · 2015: 22 · 2014: 27 · 2013: 28 · 2012: 22
FWCI: 7.85
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute of Diabetes and Digestive and Kidney Diseases (DK-083042, P30-DK 17047, R01DK052989, DK-52989, K99DK078779, P01DK068384, DK-68384, P30DK035816, P30DK017047, R01DK083042)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: glucagon-like peptide-1, satiety, GLP-1 receptor, exendin-9-39, exendin-4, hyperphagia, anorexia, intestinal hormone secretion, meal size
MeSH terms: Glucagon-Like Peptide-1 Receptor, Exenatide, Animals, Anorexia, Eating, Injections, Male, Peptides, Satiety Response, Venoms, Receptors, Glucagon, Rats

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Evidence that Intestinal Glucagon-Like Peptide-1 Plays a Physiological Role in Satiety

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