title: Rapid tachyphylaxis of the glucagon-like peptide 1-induced deceleration of gastric emptying in humans.
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.
  
  
  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.
authors.affiliation: Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany. nauck@diabetezentrum.de
authors.forename: Michael A
authors.initials: MA
authors.lastname: Nauck
authors.forename: Guido
authors.initials: G
authors.lastname: Kemmeries
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.forename: Juris J
authors.initials: JJ
authors.lastname: Meier
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood; D005746:Gastric Emptying / Q000187:drug effects*; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000494:pharmacology*; D006801:Humans; D008297:Male; D019518:Postprandial Period; D013618:Tachyphylaxis; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D052216:Glucagon-Like Peptide 1; D005934:Glucagon