Glucagon-like peptide-1 is involved in sodium and water homeostasis in humans.
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.
Gutzwiller
Jean-Pierre
JP
Division of Gastroenterology and Department of Research, Basel, Switzerland.
Hruz
Petr
P
Huber
Andreas R
AR
Hamel
Christian
C
Zehnder
Carlos
C
Drewe
Juergen
J
Gutmann
Heike
H
Stanga
Zeno
Z
Vogel
Daniel
D
Beglinger
Christoph
C
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
D001786:Blood Glucose; D052216:Glucagon-Like Peptide 1; D012964:Sodium