The antagonistic metabolite of GLP-1, GLP-1 (9-36)amide, does not influence gastric emptying and hunger sensations in man

Abstract

Objective. Glucagon-like peptide-1 (GLP-1 (7-36)amide) is an intestinal hormone that is released in response to meal ingestion. GLP-1 reduces postprandial gastric and exocrine pancreatic secretion and is believed to inhibit gastric emptying. Furthermore, GLP-1 may play a role in hunger and thirst regulation. In vivo, GLP-1 is rapidly (within minutes) converted into a metabolite, GLP-1 (9-36)amide, which has been shown to act as a GLP-1 receptor antagonist in vitro and in anaesthetized pigs. The purpose of this study was to assess the effect of infusion of GLP-1 (9-36)amide on hunger ratings and antral emptying of a meal. Material and methods. Six healthy volunteers were tested in a double-blind, placebo-controlled fashion. Antral emptying of a liquid meal and hunger ratings were determined using ultrasound technology and visual analogue scale scoring during infusions of saline or GLP-1 (9-36)amide (5 pmol/kg body wt/min) resulting in supraphysiological concentrations. Results. Infusion of GLP-1 (9-36)amide had no effect on gastric emptying or the sensation of hunger compared to saline. Conclusions. Our findings suggests that the rapid formation of the antagonistic metabolite does not influence gastric emptying and hunger ratings in humans even when it is present in supraphysiological concentrations.