Inhibitory effect of glucagon-like peptide-1 on small bowel motility. Fasting but not fed motility inhibited via nitric oxide independently of insulin and somatostatin.
Year: 1998
Type: article
Abstract: Effects of glucagon-like peptide-1 (GLP-1)(7-36)amide on fasted and fed motility in the rat small intestine were investigated in relation to its dependence on nitric oxide (NO), insulin, and somatostatin.Small bowel electromyography was performed using bipolar electrodes implanted 15, 25, and 35 cm distal to pylorus, and transit was studied with a radioactive marker.In the fasted state, GLP-1 (5-20 pmol kg Ϫ 1 min Ϫ 1 ), reaching physiological plasma levels, prolonged the migrating myoelectric complex (MMC) cycle length along with slowed transit.This effect was antagonized by exendin(9-39)amide.The NO synthase inhibitor N -nitro-L -arginine (L-NNA) also blocked the response to GLP-1, whereas L -arginine restored the response.Insulin (80-200 pmol kg Ϫ 1 min Ϫ 1 ) induced irregular spiking, whereas somatostatin (100-500 pmol kg Ϫ 1 min Ϫ 1 ) increased the MMC cycle length, independently of NO.In the fed state, GLP-1 (20-40 pmol kg Ϫ 1 min Ϫ 1 ) reduced motility, an inhibition unaffected by L-NNA, whereas motility was stimulated by exendin(9-39)amide.Infusion of GLP-1 (20-100 pmol kg Ϫ 1 min Ϫ 1 ) did not affect plasma insulin, but somatostatin was increased.In conclusion, GLP-1 seems to inhibit small bowel motility directly via the GLP-1 receptor.Inhibition of fasting motility is dependent of NO and not mediated via insulin or somatostatin, whereas inhibition of fed motility is independent of NO. ( J. Clin.Invest.1998.102:764-774.)Key words: gastrointestinal motility • glucagon-like peptide-1 • migrating myoelectric complex • rat • small intestine Methods 107 male Sprague-Dawley rats (B&K, Sollentuna, Sweden) weighing 300-350 g were used for the study.The experimental protocol was approved by the local Ethics committee for animal experimentation in northern Stockholm, Sweden.Preparation of rats for electromyography.53 rats were anaesthetized with pentobarbital (50 mg kg Ϫ 1 intraperitoneally; Apoteksbolaget, Umeå, Sweden) and, through a midline incision, three bipolar stainless steel electrodes (SS-5T, Clark Electromedical Instruments, Reading, UK) were implanted into the muscular wall of the small intestine 15 (J1), 25 (J2), and 35 (J3) cm distal to the pylorus.All animals were supplied with one or two jugular vein catheters for administration of drugs.The electrodes and catheters were tunneled subcutaneously to exit at the back of the animal's neck.After surgery the animals were housed singly and allowed to recover for at least 7 d before experiments were undertaken.During recovery the rats were trained to accept experimental conditions.Experiments were then carried out in conscious animals after an 8-h fasting period in wirebottomed cages with free access to water.During the experiments, the rats were placed in Bollman cages.The electrodes were connected to an EEG preamplifier (7P5B) operating a Grass Polygraph 7B (Grass Instruments, Quincy, MA).The time constant was set at 0.015 s and the low and high cut-off frequencies were set at 10 and 35 Hz, respectively.
DOI: 10.1172/jci942
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1993285386