Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans

Abstract

Background: Glucagon-like peptide-1(7-36)amide (GLP-1) is a gut hormone released postprandially. Synthetic GLP-1 strongly inhibits gastric emptying in healthy subjects and in patients with diabetes mellitus.

Aims: To investigate the effects of GLP-1 on antro-pyloro-duodenal motility in humans.

Methods: Eleven healthy male volunteers were studied on two separate days. On the interdigestive study day, a basal period was followed by a 60 minute period of saline infusion and two further 60 minute periods of intravenous infusion of GLP-1 0.4 and 1.2 pmol/kg/min to achieve postprandial and supraphysiological plasma levels, respectively. On the postprandial study day, the same infusions were coadministered with intraduodenal lipid perfusion at 2.5 ml/min (2.5 kcal/min) followed by another 60 minutes of recording after cessation of GLP-1. Antro-pyloro-duodenal motility was measured by perfusion manometry.

Results: GLP-1 significantly inhibited the number and amplitudes of antral and duodenal contractions in the interdigestive state and after administration of duodenal lipid. It abolished interdigestive antral wave propagation. In the interdigestive state, GLP-1 dose dependently increased pyloric tone and significantly stimulated isolated pyloric pressure waves (IPPW). Pyloric tone increased with duodenal lipid, and this was further enhanced by GLP-1. GLP-1 transiently restored the initial IPPW response to duodenal lipid which had declined with lipid perfusion. Plasma levels of pancreatic polypeptide were dose dependently diminished by GLP-1 with and without duodenal lipid.

Conclusions: GLP-1 inhibited antro-duodenal contractility and stimulated the tonic and phasic motility of the pylorus. These effects probably mediate delayed gastric emptying. Inhibition of efferent vagal activity may be an important mechanism. As postprandial plasma levels of GLP-1 are sufficient to appreciably affect motility, we believe that endogenous GLP-1 is a physiological regulator of motor activity in the antro-pyloro-duodenal region.

Figure 1

Plasma immunoreactivities of GLP-1 in response to intravenous infusions of saline, and GLP-1(7-36)amide 0.4 and 1.2 pmol/kg/min with concomitant duodenal perfusion of saline or lipid 2.5 kcal/min in 11 healthy volunteers (mean (SEM)). For statistical analysis, see table 1.

Figure 2

Contraction frequencies (top) and amplitudes (bottom) in the antrum and duodenum in response to intravenous infusions of saline, and GLP-1(7-36)amide 0.4 and 1.2 pmol/kg/min during concomitant duodenal perfusion of saline (A) or lipid 2.5 kcal/min (B) in 11 healthy volunteers (mean (SEM)). For statistical analysis, see table 2.

Figure 3

Isolated pyloric pressure waves (IPPW) (A) and pyloric tone (B) in response to intravenous infusions of saline, and GLP-1(7-36)amide 0.4 and 1.2 pmol/kg/min during concomitant duodenal perfusion of saline (top) or lipid 2.5 kcal/min (bottom) in 11 healthy volunteers (mean (SEM)). *p<0.05 for comparison of times indicated by the arrows (paired t test). For further statistical analysis, see table 3.

Figure 4

Occurrence of duodenal phase III-like activity with duodenal perfusion of saline (A) or lipid 2.5 kcal/min (B) in 11 healthy volunteers. In seven of 11 subjects, an activity front was seen within 10 minutes after the start of the low dose infusion of GLP-1 in the interdigestive state or duodenal lipid perfusion in the postprandial studies, respectively. The length of the solid bars represents the length of contraction burst.

Figure 5

Manometric tracings showing the effects of intravenous infusion of GLP-1 0.4 pmol/kg/min during duodenal perfusion of saline (A) and lipid 2.5 kcal/min (B). In the interdigestive state (A), GLP-1 immediately inhibited antro-duodenal motility and induced a sustained increase in basal pyloric pressure with concomitant short lasting stimulation of IPPWs. During duodenal lipid perfusion (B), antral and duodenal contractility were completely abolished by GLP-1, and basal pyloric pressure further increased in addition to the effect of lipid alone, paralleled by stimulation of IPPWs.

Figure 6

Effects of intravenous infusions of saline, and GLP-1(7-36)amide 0.4 and 1.2 pmol/kg/min on plasma glucose (A) and immunoreactivities of glucagon (B), insulin (C), and pancreatic polypeptide (D) during concomitant duodenal perfusion of saline or lipid 2.5 kcal/min in 11 healthy volunteers. Mean (SEM) of incremental values over basal. For statistical analysis, see table 1.