Rapid Tachyphylaxis of the Glucagon-Like Peptide 1–Induced Deceleration of Gastric Emptying in Humans

  1. Juris J. Meier4
  1. 1Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany
  2. 2Conservative Emergency Room, Klinikum Krefeld, Krefeld, Germany
  3. 3Department of Medical Physiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
  4. 4Department of Medicine I, St. Josef-Hospital, Ruhr-University of Bochum, Bochum, Germany
  1. Corresponding author: Michael A. Nauck, nauck{at}diabetezentrum.de.

Abstract

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.

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  1. Diabetes vol. 60 no. 5 1561-1565
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