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Randomized Controlled Trial
. 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

Michael A Nauck  1 , Guido Kemmeries, Jens J Holst, Juris J Meier
Affiliations
Randomized Controlled Trial

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

Michael A Nauck et al. Diabetes. 2011 May.

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.

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Figures

FIG. 1.
FIG. 1.
Plasma concentrations of GLP-1 (A), glucose (C), insulin (D), glucagon (E), C-peptide (F), PP (G), and GIP (H), and gastric emptying (B) after instilling two liquid test meals (amino acids and sucrose) via a nasogastric tube into the stomach at 0 and 240 min in nine healthy young volunteers during the intravenous infusion of GLP-1 (0.8 pmol · kg−1 ⋅ min−1) or placebo. Mean ± SEM. P values were calculated by repeated-measures ANOVA. *Significant (P < 0.05) differences at specific time points between experiments with placebo and GLP-1. †Significant difference from the corresponding time point after the first meal during the exogenous administration of GLP-1.
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References

    1. Meier JJ, Nauck MA. Glucagon-like peptide 1 (GLP-1) in biology and pathology. Diabetes Metab Res Rev 2005;21:91–117 - PubMed
    1. Drucker DJ. Enhancing incretin action for the treatment of type 2 diabetes. Diabetes Care 2003;26:2929–2940 - PubMed
    1. Holst JJ. Treatment of type 2 diabetes mellitus with agonists of the GLP-1 receptor or DPP-IV inhibitors. Expert Opin Emerg Drugs 2004;9:155–166 - PubMed
    1. Nauck MA, Kleine N, Ørskov C, Holst JJ, Willms B, Creutzfeldt W. Normalization of fasting hyperglycaemia by exogenous glucagon-like peptide 1 (7-36 amide) in type 2 (non-insulin-dependent) diabetic patients. Diabetologia 1993;36:741–744 - PubMed
    1. Meier JJ, Gallwitz B, Salmen S, et al. Normalization of glucose concentrations and deceleration of gastric emptying after solid meals during intravenous glucagon-like peptide 1 in patients with type 2 diabetes. J Clin Endocrinol Metab 2003;88:2719–2725 - PubMed

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