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Am J Physiol Regul Integr Comp Physiol 277: R910-R916, 1999;
0363-6119/99 $5.00
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Vol. 277, Issue 3, R910-R916, September 1999

GLP-1 slows solid gastric emptying and inhibits insulin, glucagon, and PYY release in humans

Erik Näslund1, Jesper Bogefors2, Staffan Skogar2, Per Grybäck3, Hans Jacobsson4, Jens Juul Holst5, and Per M. Hellström2

1 Division of Surgery, Danderyd Hospital, Karolinska Institutet, SE-182 88; Departments of 2 Gastroenterology and Hepatology, 3 Radiology, and 4 Nuclear Medicine, Karolinska Hospital, 171 76 Stockholm, Sweden; and 5 Department of Medical Physiology, University of Copenhagen, Copenhagen, DK-1017 Denmark

The aim of the present study was to assess the effect of glucagon-like peptide-1 (GLP-1) on solid gastric emptying and the subsequent release of pancreatic and intestinal hormones. In eight men [age 33.6 ± 2.5 yr, body mass index 24.1 ± 0.9 (means ± SE)], scintigraphic solid gastric emptying during infusion of GLP-1 (0.75 pmol · kg-1 · min-1) or saline was studied for 180 min. Concomitantly, plasma concentrations of C- and N-terminal GLP-1, glucose, insulin, C-peptide, glucagon, and peptide YY (PYY) were assessed. Infusion of GLP-1 resulted in a profound inhibition of both the lag phase (GLP-1: 91.5, range 73.3-103.6 min vs. saline: 19.5, range 10.2-43.4 min) and emptying rate (GLP-1: 0.34, range 0.06-0.56 %/min vs. saline: 0.84, range 0.54-1.33 %/min; P < 0.01 for both) of solid gastric emptying. Concentrations of both intact and total GLP-1 were elevated to supraphysiological levels. Plasma glucose and glucagon concentrations were below baseline during infusion of GLP-1 in contrast to saline infusion, where concentrations were elevated above baseline (both P < 0.001). The insulin and C-peptide responses were lower during infusion with GLP-1 than with saline (P < 0.004 and P < 0.001, respectively). Plasma PYY concentrations decreased below baseline during GLP-1 infusion in contrast to saline, where concentrations were elevated above baseline (P = 0.04). Infusion of GLP-1 inhibits solid gastric emptying with secondary effects on the release of insulin, C-peptide, and glucagon, resulting in lower plasma glucose concentrations. In addition, the release of PYY into the circulation is inhibited by GLP-1 infusion, suggesting a negative feedback of GLP-1 on the function of the L-cell.

glucagon-like peptide-1; peptide YY; radionuclide; ileal break; gut peptides


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