GLP-1 suppresses gastrointestinal motility and inhibits the migrating motor complex in healthy subjects and patients with irritable bowel syndrome.
Glucagon-like peptide-1 (GLP-1) is released after food intake to act as an incretin. GLP-1 also inhibits gastric emptying and increases satiety. In rats, GLP-1 inhibits small bowel motility. Our aim was to study the effects of GLP-1 on gastrointestinal motility in healthy subjects and patients with irritable bowel syndrome (IBS). Antro-duodeno-jejunal manometry was carried out during a 4-h control period with saline, followed by a 4-h period with intravenous GLP-1 (healthy: 0.7 and 1.2 pmol kg(-1) min(-1) (n = 16); IBS, 1.2 and 2.5 pmol kg(-1) min(-1) (n = 14). Plasma was analysed for GLP-1 and gut hormones, and gut tissue expression of GLP-1 receptor was studied. In healthy subjects, GLP-1 0.7 pmol kg(-1) min(-1) reduced the migrating motor complexes (MMCs) from a median of 2 (range 2-3) to 0.5 (0-2), and motility index from 4.9 +/- 0.1 to 4.3 +/- 0.3 ln Sigma(mmHg*s min(-1)) in jejunum, while GLP-1 1.2 pmol kg(-1) min(-1) diminished MMCs from 2 (2-3) to 1.5 (1-2.5), and motility index from 5.2 +/- 0.2 to 4.4 +/- 0.2. In IBS patients, GLP-1 1.2 pmol kg(-1) min(-1) reduced the MMCs from 2.5 (2-3.5) to 1 (0-1.5) without affecting motility index. At 2.5 pmol kg(-1) min(-1) GLP-1 decreased MMCs from 2 (1.5-3) to 1 (0.5-1.5), and motility index from 5.2 +/- 0.2 to 4.0 +/- 0.5. Motility responses to GLP-1 were similar in antrum and duodenum. Presence of the GLP-1 receptor in the gut was verified by reverse transcriptase PCR. In conclusion, the gut peptide GLP-1 decreases motility in the antro-duodeno-jejunal region and inhibits the MMC in healthy subjects and IBS patients.
Hellström
P M
PM
Department of Medicine, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden. per.hellstrom@ki.se
Näslund
E
E
Edholm
T
T
Schmidt
P T
PT
Kristensen
J
J
Theodorsson
E
E
Holst
J J
JJ
Efendic
S
S
D000293:Adolescent; D000328:Adult; D004386:Duodenum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D005260:Female; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use*; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000188:drug therapy / Q000503:physiopathology*; D007583:Jejunum / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D016065:Myoelectric Complex, Migrating / Q000187:drug effects / Q000502:physiology*; D011706:Pyloric Antrum / Q000187:drug effects / Q000294:innervation / Q000502:physiology
D052216:Glucagon-Like Peptide 1