Effects of glucagon-like peptide-1(7-36)amide on motility and sensation of the proximal stomach in humans

Abstract

Background: Glucagon-like peptide-1(7-36)amide (GLP-1) retards gastric emptying, reduces food intake, and inhibits antroduodenal and stimulates pyloric motility.

Aims: To assess the effects of synthetic GLP-1 on fundus tone and volume waves, gastric compliance, and perception of gastric distension.

Subjects: Eleven healthy male volunteers.

Methods: Background infusions were saline, or GLP-1 at 0.3 or 0.9 pmol/ kg/min on separate days in random order. Interdigestive fundus motility was recorded by barostat (maximum capacity of intragastric bag 1200 ml) during basal and peptide periods of 60 minutes each. Thereafter stepwise isobaric distensions were performed with ongoing peptide infusion, and gastric sensation was scored.

Results: Low and high loads of GLP-1 induced physiological and supraphysiological plasma immunoreactivities, respectively. GLP-1 dose dependently diminished fundus tone (162.9 (15.0) and 259.5 (17.2) v 121.1 (6.0) ml with saline; p<0.0001). It greatly reduced volume waves and total volume displaced by these events (p<0.0001). Gastric compliance derived from isobaric distension rose in a dose related manner (42.6 (5.5) and 63.6 (7.7) v 27.0 (3.5) ml/mm Hg; p=0.0004) with a concomitant reduction of the pressure at half maximum bag volume (6.4 (0.4) and 5.5 (0.4) v 7.2 (0.1) mm Hg; p<0.0001). GLP-1 did not change perception of isobaric distension but reduced the perception score related to corresponding bag volume (p<0.0001).

Conclusions: GLP-1 is a candidate physiological inhibitory regulator of fundus motility. It allows the stomach to afford a larger volume without increase in sensation.

Figure 1

Effect of physiological (0.3 pmol/kg/min (0.3)) and supraphysiological (0.9 pmol/kg/min (0.9)) intravenous (iv) loads of glucagon-like peptide-1(7–36)amide (GLP-1) on blood glucose and plasma immunoreactivities of gastrointestinal hormones in 11 healthy volunteers. GLP-1 dose dependently reduced blood glucose (C) and increased immunoreactive (IR)-GLP-1 (A) (p<0.0001; two way repeated measures ANOVA). IR-insulin was unaltered during steady state infusion. Only the high GLP-1 load reduced IR-pancreatic polypeptide (PP) (p<0.05).

Figure 2

Original recording of intragastric bag volume in a sample subject. The baseline volume tracings denote fundus tone; phasic downward deflections exceeding 30 ml refer to volume waves. Glucagon-like peptide-1(7–36)amide (GLP-1) 0.3 pmol/kg/min (0.3) and 0.9 pmol/kg/min (0.9) dose dependently raised the baseline, representing a reduction in tone, and suppressed volume waves.

Figure 3

Effect of physiological (0.3 pmol/kg/min (0.3)) and supraphysiological (0.9 pmol/kg/min (0.9)) intravenous (iv) loads of glucagon-like peptide-1(7–36)amide (GLP-1) on fundus tone represented by bag volume (A), frequency of volume waves (B), and total volume displaced by these phasic events (volume wave index (C)) in 11 healthy volunteers. GLP-1 dose dependently relaxed the fundus and reduced both parameters characterising volume waves (p<0.0001; two way repeated measures ANOVA).

Figure 4

Effect of physiological (0.3 pmol/kg/min (0.3)) and supraphysiological (0.9 pmol/kg/min (0.9)) intravenous (iv) loads of glucagon-like peptide-1(7–36)amide (GLP-1) on compliance of the proximal stomach (A) and perception (B) of isobaric distensions in 11 healthy volunteers. GLP-1 dose dependently increased linear compliance defined as the linear slope after the inflection point of the curve (p=0.0004; (A) upper panel), and non-linear compliance derived from the power exponential model by increasing the slope of the curve (decreasing σ), and therefore reducing the pressure at half the maximum bag volume (P½) (p<0.0001; (A) lower panel). GLP-1 enhanced volume accommodation (p=0.0008) but did not influence perception (p=0.513; (B) upper panel). Therefore, the perception/volume relationship was dose dependently reduced with GLP-1 (p<0.0001; (B) lower panel). GLP-1 allowed the stomach to afford a greater volume without increase in perception. MDP, minimal distending pressure. *p<0.05 versus saline, †p<0.05 versus GLP-1 0.3 pmol/kg/min. Differences in compliance (A) were compared using one way repeated measures ANOVA and differences in perception (B) using two way repeated measures ANOVA.