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Diabetes. 2011 May;60(5):1561-5. doi: 10.2337/db10-0474. Epub 2011 Mar 23.

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

Author information

1
Diabeteszentrum Bad Lauterberg, Bad Lauterberg, Germany. nauck@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/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.

PMID:
21430088
PMCID:
PMC3292331
DOI:
10.2337/db10-0474
[Indexed for MEDLINE]
Free PMC Article

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