title: Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans.
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 x 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 x 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.
authors.affiliation: Division of Gastroenterology and Department of Research, Basel, Switzerland.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Gutzwiller
authors.forename: Petr
authors.initials: P
authors.lastname: Hruz
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Huber
authors.forename: Christian
authors.initials: C
authors.lastname: Hamel
authors.forename: Carlos
authors.initials: C
authors.lastname: Zehnder
authors.forename: Juergen
authors.initials: J
authors.lastname: Drewe
authors.forename: Heike
authors.initials: H
authors.lastname: Gutmann
authors.forename: Zeno
authors.initials: Z
authors.lastname: Stanga
authors.forename: Daniel
authors.initials: D
authors.lastname: Vogel
authors.forename: Christoph
authors.initials: C
authors.lastname: Beglinger
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D001834:Body Water / Q000378:metabolism; D004311:Double-Blind Method; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D006706:Homeostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012964:Sodium / Q000378:metabolism; D013894:Thirst / Q000187:drug effects
chemical_list: D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D012964:Sodium