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

• Published in: Diabetes (New York, N.Y.) Vol. 60; no. 5; pp. 1561 - 1565
• Main Authors: Nauck, Michael A., Kemmeries, Guido, Holst, Jens J., Meier, Juris J.
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.05.2011
• Subjects: Adult; Amino acids; Biological and medical sciences; Blood Glucose - drug effects; C-Peptide - blood; Diabetes; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Gastric Emptying - drug effects; Gastrointestinal motility; Gastrointestinal system; Glucagon; Glucagon - blood; Glucagon-Like Peptide 1 - blood; Glucagon-Like Peptide 1 - pharmacology; Glucose; Humans; Influence; Long term care; Long-term care of the sick; Male; Meals; Medical sciences; Motility; Pathophysiology; Peptides; Phenols; Physiological aspects; Plasma; Postprandial Period; Research design; Sucrose; Tachyphylaxis; Young Adult; Germany; Endocrinopathy; Human; Stomach; Gastrointestinal hormone; Digestive system; Diabetes mellitus; Gastric emptying; Glucagon like peptide 1
• ISSN: 0012-1797; 1939-327X; 1939-327X
• DOI: 10.2337/db10-0474

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. 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. 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). 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.