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Inhibition of Sham Feeding-Stimulated Human Gastric Acid Secretion by Glucagon-Like Peptide-2

Departments of Surgery (M.W., A.W.) and Clinical Biochemistry (L.H.), Rigshospitalet, DK-2100; Medical Physiology (B.H., J.J.H.), The Panum Institute DK-2200, University of Copenhagen, Copenhagen, Denmark

Address all correspondence and requests for reprints to: Jens J. Holst, Department of Medical Physiology, The Panum Institute, Blegdamsvej 3C, DK-2200 Copenhagen, Denmark. E-mail: holst{at}mfi.ku.dk

Glucagon-like peptide (GLP)-2 is formed from proglucagon in the intestinal L cells and is secreted postprandially in parallel with the insulinotropic hormone GLP-1, the latter of which, in addition, acts to inhibit gastric secretion and motility by inhibiting central parasympathetic outflow. We now studied the effect of GLP-2 on gastric secretion stimulated by sham feeding to test the hypothesis that also GLP-2 acts as an enterogastrone. Eight healthy volunteers were studied twice on separate days. They were sham fed with and without GLP-2 infused iv at a rate of 0.8 pmol/kg·min. Gastric contents were aspirated continuously by a nasogastric tube for determination of acid secretion, volume, and osmolarity. Sham feeding increased gastric acid secretion nearly 5-fold. Infusion of GLP-2 reduced incremental acid secretion by 65 ± 6%, compared with saline infusion (8.75 ± 0.37 vs. 3.04 ± 0.47 mmol x 60 min; P < 0.01). Plasma concentrations of GLP-2 rose from a basal mean of 3.3 ± 0.9 to a mean of 115 ± 8 pmol/L (range, 57–149 pmol/L) during infusion of GLP-2 and remained at basal level during saline infusion. Plasma concentrations of GLP-1, gastrin, cholecystokinin, and secretin remained low and unchanged on both study days. We conclude that GLP-2 is a powerful inhibitor of gastric acid secretion in man. Further investigations will show to what extent GLP-2 contributes to the inhibitory effects on gastric secretion exerted by hormones from the distal small intestine, under physiological circumstances.

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