Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans

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Michael A Nauck, Guido Kemmeries, Jens Juul Holst, Juris J Meier

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/m(2)) 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
Original languageEnglish
JournalDiabetes
Volume60
Issue number5
Pages (from-to)1561-5
Number of pages5
ISSN0046-0192
DOIs
Publication statusPublished - 2011

    Research areas

  • Adult, Blood Glucose, C-Peptide, Gastric Emptying, Glucagon, Glucagon-Like Peptide 1, Humans, Male, Postprandial Period, Tachyphylaxis, Young Adult

ID: 40321041