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.
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-1min-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 Nomega-nitro- L-arginine (L-NNA) also blocked the response to GLP-1, whereas L-arginine restored the response. Insulin (80-200 pmol kg-1min-1) induced irregular spiking, whereas somatostatin (100-500 pmol kg-1min-1) increased the MMC cycle length, independently of NO. In the fed state, GLP-1 (20-40 pmol kg-1min-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-1min-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.
Department of Medicine, Karolinska Hospital, Karolinska Institute, SE-171 76 Stockholm, Sweden.
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Tolessa
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Gutniak
J J
JJ
Holst
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Efendic
P M
PM
Hellström
D000818:Animals; D004347:Drug Interactions; D004435:Eating / Q000502:physiology; D004576:Electromyography; D005215:Fasting / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005772:Gastrointestinal Transit / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin / Q000097:blood / Q000494:pharmacology; D007421:Intestine, Small / Q000187:drug effects*; D008297:Male; D016065:Myoelectric Complex, Migrating / Q000187:drug effects; D009569:Nitric Oxide / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018027:Receptors, Glucagon / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013004:Somatostatin / Q000097:blood / Q000494:pharmacology
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D007328:Insulin; D010446:Peptide Fragments; D011498:Protein Precursors; D018027:Receptors, Glucagon; D019335:Nitroarginine; D009569:Nitric Oxide; D013004:Somatostatin; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D019001:Nitric Oxide Synthase