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

Division of Gastroenterology and Department of Research (J.-P.G., S.T., C.B.), and Division of Clinical Pharmacology and Toxicology and Department of Research (H.G., J.D.), University Hospital, CH-4031 Basel, Switzerland; Central Laboratory and Division of Nephrology (A.B., A.R.H., M.K.), Kantonsspital Aarau, CH-5001 Aarau, Switzerland; Division of Nephrology (C.E.Z.), Clinica las Condes, Santiago, Chile; Division of Endocrinology (C.H.), Kantonsspital Luzern, CH-6000 Luzern, Switzerland; and Division of Gastroenterology and Department of Internal Medicine (B.G.), Klinikum Grosshardern, University Hospital, Ludwig Maximilian University, D-81377 Munich, Germany

Address all correspondence and requests for reprints to: Christoph Beglinger, M.D., Division of Gastroenterology, University Hospital CH-4031 Basel, Switzerland. E-mail: beglinger{at}tmr.ch.

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 iv 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.

This work was supported by a grant from the Swiss National Science Foundation (Nr. 3200-065588.01/1) and by a grant from the European Commission (Moebius-IST 1999-1159).

Abbreviations: AUC, Area under the curve; CH₂O, free water clearance; GFR, glomerular filtration rate; GLP-1, glucagon-like peptide-1-(7–36)-amide; HOMA, homeostasis model assessment; IR, insulin resistance; PRA, plasma renin activity; TcH₂O, free water reabsorption.

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