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Cited by 127Diabetes Treatment and ManagementElectrolyte and hormonal disordersRegulation of Appetite and Obesity

Glucagon-Like Peptide-1 Is Involved in Sodium and Water Homeostasis in Humans

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Gutzwiller, Jean-Pierre, Hruz, Petr, Huber, Andreas R., Hamel, Christian, Zehnder, Carlos, Drewe, Juergen, Gutmann, Heike, Stanga, Zeno +2 more·2006·Digestion
DOI 10.1159/000094334
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Abstract

In previous studies with glucagon-like peptide-1 (GLP-1) we have observed that this peptide modulates fluid intake and increases renal sodium excretion in healthy volunteers and in patients with diabetes mellitus type 2. The effect of GLP-1 on thirst, water intake and on osmoregulation has, however, not been examined in detail in humans. Methods: Seventeen healthy male subjects were enrolled in two double-blind, placebo-controlled studies. In study part A, 8 volunteers participated in a protocol with an intravenous salt load of 26.7 ± 0.9 g comparing the effect of an infusion of GLP-1 (1.5 pmol/kg × min) to isotonic saline (placebo). Sodium excretion and water intake were measured. In part B, 9 volunteers were challenged with an oral salt load of 27.7 ± 0.5 g; sodium excretion and water intake were determined comparing an infusion of GLP-1 (1.5 pmol/kg × min) to isotonic saline (placebo). In part C, intestinal biopsies along the gastrointestinal tract were obtained from 14 healthy subjects. Expression of human GLP-1 receptor mRNA was measured by real-time polymerase chain reaction. Results: In study part A, an increase in renal sodium excretion was demonstrated: FeNa rose from 1.6 ± 0.3 (placebo) to 2.7 ± 0.2% (GLP-1; p = 0.0005). There was no difference in water consumption between the two treatments: 1,291 ± 69 (saline) vs. 1,228 ± 74 ml (GLP-1; p = 0.49). In part B, an oral salt challenge of 27.7 ± 0.5 g led to an increased renal excretion of sodium during GLP-1: FeNa increased from 1.6 ± 0.2% (placebo) to 2.0 ± 0.2% (GLP-1; p = 0.012). In contrast to part A, oral water intake was reduced by 36% under GLP-1 treatment: 1,848 ± 331 ml (placebo) vs. 1,181 ± 177 ml (GLP-1; p = 0.0414). Three subjects in part B did not finish treatment with GLP-1 because of diarrhea. Human GLP-1 receptor mRNA expression was highest in the proximal human small intestine compared to terminal ileum and colon (p < 0.02). Conclusions: GLP-1 acts on renal tissue reducing sodium absorption, probably via similar sodium transporters, which also may be localized in the gastrointestinal tract. This hypothesis needs to be confirmed by further studies.

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  • In one study, osmotic diarrhea occurred 8 h after infusion of GLP-1 peptide.

    “In one study, osmotic diarrhea occurred 8 h after infusion of GLP-1 peptide (47), and GLP-1RAs have been shown to reduce intestinal uptake of glucose and lipids (48, 49).”

    From Safety of Semaglutide (2021) · cites this paper as [47]

  • Semaglutide's effects in suppressing consummatory behaviors are not specific to alcohol and might be driven by its ability to reduce appetite and thirst, palatability for sweet, and/or metabolic energy needs and calorie intake.

    “From a mechanistic standpoint, these results suggest that semaglutide’s effects in suppressing consummatory behaviors are not specific to alcohol and might be driven by its ability to reduce appetite and thirst, such as the need for general fluid intake (55–60), palatability for sweet (taste) (61–64), and/or metabolic energy needs and calorie intake (24, 65–68).”

    From The glucagon-like peptide-1 (GLP-1) analogue semaglutide reduces alcohol drinking and modulates central GABA neurotransmission (2023) · cites this paper as [58]

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Research works printed but not linked: 4

  1. Holst JJ: Enteroglucagon. Annu Rev Physiol 1997; 59: 257-271.
  2. Welch I, Saunders K, Read NW: Effect of il- eal and intravenous infusions of fat emul- sions on feeding and satiety in human volun- teers. Gastroenterology 1985; 89: 1293-1297.
  3. Stamler J: The INTERSALT Study: back- ground, methods, findings, and implica- tions. Am J Clin Nutr 1997; 65: 626-642.
  4. Tanaka T, Mizumoto A, Muramatsu S, Mo- chiki E, Haga N, Suzuki H, Itoh Z: Postpran- dial normal saline intake delays gastric emp- tying of solids in conscious dogs. Dig Dis Sci 1999; 44: 1516-1524.

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Authors
Gutzwiller, J.-P., Hruz, P., Huber, A. R., Hamel, C., Zehnder, C., Drewe, J., Gutmann, H., Stanga, Z., Vogel, D., & Beglinger, C.
Affiliations
  • Kantonsspital Aarau (CH)
  • Clínica Las Condes (CL)
  • University Hospital of Basel (CH)
  • University Hospital of Bern (CH)
ORCID
Venue
Digestion
Publisher
S. Karger AG
Published
2006
Volume
73
Issue
2-3
Pages
142-150
ISSN
  • 0012-2823 (ISSN-L)
  • 1421-9867
DOI
10.1159/000094334
OpenAlex
W2059555444
Cited by
127
References
23
Citations by year
2026: 10 · 2025: 6 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 4 · 2020: 2 · 2019: 8 · 2018: 2 · 2017: 7 · 2016: 12 · 2015: 9 · 2014: 10 · 2013: 13 · 2012: 3
FWCI
1.81
Type
journal article
Language
en
Open access
Licence
Locations
  • Digestion (publishedVersion)
  • PubMed (publishedVersion)
  • BORIS (University Library Bern) (submittedVersion, other-oa)
  • Open Access CRIS of the University of Bern
Funders
  • National Science Foundation
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Electrolyte and hormonal disorders
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
Keywords
glucagon-like peptide-1, sodium homeostasis, water homeostasis, thirst, water intake, renal sodium excretion, osmoregulation, salt loading, gastrointestinal tract, type 2 diabetes, fluid intake regulation, GLP-1 receptor antagonists, vasopressin
MeSH terms
Adult, Analysis of Variance, Blood Glucose, Body Water, Double-Blind Method, Homeostasis, Humans, Male, Natriuresis, Sodium, Thirst, Area Under Curve, Reverse Transcriptase Polymerase Chain Reaction, Glucagon-Like Peptide 1

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