Rapid Tachyphylaxis of the Glucagon-Like Peptide 1–Induced Deceleration of Gastric Emptying in Humans
- 1Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany
- 2Conservative Emergency Room, Klinikum Krefeld, Krefeld, Germany
- 3Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
- 4Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum, Bochum, Germany
- Corresponding author: Michael A. Nauck, .
OBJECTIVE Glucagon-like peptide (GLP)-1 lowers postprandial glycemia primarily through inhibition of gastric emptying. We addressed whether the GLP-1–induced deceleration of gastric emptying is subject to rapid tachyphylaxis and if so, how this would alter postprandial glucose control.
RESEARCH DESIGN AND METHODS Nine healthy volunteers (25 ± 4 years old, BMI: 24.6 ± 4.7 kg/m2) were examined with intravenous infusion of GLP-1 (0.8 pmol · kg−1 . min−1) or placebo over 8.5 h. Two liquid mixed meals were administered at a 4-h interval. Gastric emptying was determined, and blood samples were drawn frequently.
RESULTS GLP-1 decelerated gastric emptying significantly more after the first meal compared with the second meal (P = 0.01). This was associated with reductions in pancreatic polypeptide levels (marker of vagal activation) after the first but not the second meal (P < 0.05). With GLP-1, glucose concentrations declined after the first meal but increased after the second meal (P < 0.05). The GLP-1–induced reductions in postprandial insulin and C-peptide levels were stronger during the first meal course (P < 0.05). Likewise, glucagon levels were lowered by GLP-1 after the first meal but increased after the second test meal (P < 0.05).
CONCLUSIONS The GLP-1–induced delay in gastric emptying is subject to rapid tachyphylaxis at the level of vagal nervous activation. As a consequence, postprandial glucose control by GLP-1 is attenuated after its chronic administration.
- Received May 24, 2010.
- Accepted February 21, 2011.
- © 2011 by the American Diabetes Association.
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