Original Paper

Glucagon-Like Peptide-1 Is Involved in Sodium and Water Homeostasis in Humans
Jean-Pierre Gutzwiller^a, Petr Hruz^a, Andreas R. Huber^c, Christian Hamel^a, Carlos Zehnder^d, Juergen Drewe^b, Heike Gutmann^b, Zeno Stanga^e, Daniel Vogel^a, Christoph Beglinger<sup>a

a</sup>Division of Gastroenterology and Department of Research, and
^bDepartment of Clinical Pharmacology, University Hospital, Basel, and
^cCentral Laboratory, Kantonsspital Aarau, Aarau, Switzerland;
^dDivision of Nephrology, Clinica las Condes, Santiago, Chile;
^eDivision of Nutrition, University Hospital, Berne, Switzerland

Address of Corresponding Author

Digestion 2006;73:142-150 (DOI: 10.1159/000094334)

  Key Words

• Glucagon-like peptide-1
• Natriuresis
• Thirst regulation

  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.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Christoph Beglinger, MD
Division of Gastroenterology University Hospital
CH-4031 Basel (Switzerland)
Tel. +41 61 265 51 75, Fax +41 61 265 53 52, E-Mail beglinger@tmr.ch

  Article Information

Received: November 23, 2005
Accepted: April 11, 2006
Published online: June 29, 2006
Number of Print Pages : 9
Number of Figures : 5, Number of Tables : 3, Number of References : 24