Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men.
Glucagon-like peptide-1-(7-36)-amide (GLP-1) is involved in satiety control and glucose homeostasis. Animal studies suggest a physiological role for GLP-1 in water and salt homeostasis. This study's aim was to define the effects of GLP-1 on water and sodium excretion in both healthy and obese men. Fifteen healthy subjects and 16 obese men (mean body mass index, 36 kg/m2) were examined in a double-blind, placebo-controlled, crossover study to demonstrate the effects of a 3-h infusion of GLP-1 on urinary sodium excretion, urinary output, and the glomerular filtration rate after an i.v. 9.9-g salt load. Infusion of GLP-1 evoked a dose-dependent increase in urinary sodium excretion in healthy subjects (from 74 +/- 8 to 143 +/- 18 mmol/180 min, P = 0.0013). In obese men, there was a significant increase in urinary sodium excretion (from 59 to 96 mmol/180 min, P = 0.015), a decrease in urinary H+ secretion (from 1.1 to 0.3 pmol/180 min, P = 0.013), and a 6% decrease in the glomerular filtration rate (from 151 +/- 8 to 142 +/- 8 ml/min, P = 0.022). Intravenous infusions of GLP-1 enhance sodium excretion, reduce H+ secretion, and reduce glomerular hyperfiltration in obese men. These findings suggest an action at the proximal renal tubule and a potential renoprotective effect.
Gutzwiller
Jean-Pierre
JP
Division of Gastroenterology and Department of Research, University Hospital, CH-4031 Basel, Switzerland.
Tschopp
Stefan
S
Bock
Andreas
A
Zehnder
Carlos E
CE
Huber
Andreas R
AR
Kreyenbuehl
Monika
M
Gutmann
Heike
H
Drewe
Jürgen
J
Henzen
Christoph
C
Goeke
Burkhard
B
Beglinger
Christoph
C
D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004326:Drinking / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D005934:Glucagon / Q000008:administration & dosage*; D052216:Glucagon-Like Peptide 1; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects*; D009765:Obesity / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage*; D011498:Protein Precursors / Q000008:administration & dosage*; D011522:Protons; D012083:Renin / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013894:Thirst / Q000187:drug effects; D014556:Urine
D001786:Blood Glucose; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D011522:Protons; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D012964:Sodium; D012083:Renin