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Am J Physiol Endocrinol Metab 290: E1118-E1123, 2006. First published January 10, 2006; doi:10.1152/ajpendo.00576.2005
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The glucagon-like peptide-1 metabolite GLP-1-(9–36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

Juris J. Meier,1 Arnica Gethmann,1 Michael A. Nauck,2 Oliver Götze,1 Frank Schmitz,1 Carolyn F. Deacon,3 Baptist Gallwitz,1 Wolfgang E. Schmidt,1 and Jens J. Holst3

1Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Bochum; 2Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany; and 3Department of Medical Physiology, The Panum Institute, University of Copenhagen, Copenhagen, Denmark

Submitted 23 November 2005 ; accepted in final form 2 January 2006

Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7–36) amide is degraded to the metabolite GLP-1-(9–36) amide. The effects of GLP-1-(9–36) amide in humans are less well characterized. Fourteen healthy volunteers were studied with intravenous infusion of GLP-1-(7–36) amide, GLP-1-(9–36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements. Administration of GLP-1-(7–36) amide and GLP-1-(9–36) amide significantly raised total GLP-1 plasma levels. Plasma concentrations of intact GLP-1 increased to 21 ± 5 pmol/l during the infusion of GLP-1-(7–36) amide but remained unchanged during GLP-1-(9–36) amide infusion [5 ± 3 pmol/l; P < 0.001 vs. GLP-1-(7–36) amide administration]. GLP-1-(7–36) amide reduced fasting and postprandial glucose concentrations (P < 0.001) and delayed gastric emptying (P < 0.001). The GLP-1 metabolite had no influence on insulin or C-peptide concentrations. Glucagon levels were lowered by GLP-1-(7–36) amide but not by GLP-1-(9–36) amide. However, the postprandial rise in glycemia was reduced significantly (by ~6 mg/dl) by GLP-1-(9–36) amide (P < 0.05). In contrast, gastric emptying was completely unaffected by the GLP-1 metabolite. The GLP-1 metabolite lowers postprandial glycemia independently of changes in insulin and glucagon secretion or in the rate of gastric emptying. Most likely, this is because of direct effects on glucose disposal. However, the glucose-lowering potential of GLP-1-(9–36) amide appears to be small compared with that of intact GLP-1-(7–36) amide.

insulin secretion; gastric emptying; incretin hormones; glucose homeostasis


Address for reprint requests and other correspondence: J. J. Meier, Dept. of Medicine I, St. Josef-Hospital, Ruhr-Univ. Bochum, Gudrunstr. 56, 44791 Bochum, Germany (e-mail: juris.meier{at}rub.de)




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