Glucagon-like Peptide 1 Induces Natriuresis in Healthy Subjects and in Insulin-Resistant Obese Men

J Clin Endocrinol Metab. 2004 Jun;89(6):3055-61. doi: 10.1210/jc.2003-031403.

Abstract

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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • Cross-Over Studies
  • Double-Blind Method
  • Drinking / drug effects
  • Glomerular Filtration Rate / drug effects
  • Glucagon / administration & dosage*
  • Glucagon-Like Peptide 1
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Kidney Tubules, Proximal / drug effects
  • Kidney Tubules, Proximal / metabolism
  • Male
  • Natriuresis / drug effects*
  • Obesity / metabolism*
  • Peptide Fragments / administration & dosage*
  • Protein Precursors / administration & dosage*
  • Protons
  • Renin / metabolism
  • Renin-Angiotensin System / drug effects
  • Sodium / urine
  • Thirst / drug effects
  • Urine

Substances

  • Blood Glucose
  • Insulin
  • Peptide Fragments
  • Protein Precursors
  • Protons
  • Glucagon-Like Peptide 1
  • Glucagon
  • Sodium
  • Renin