Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms.
Exogenous administration of glucagon-like peptide-1-(7-36) amide (GLP-1), an insulinotropic hormone, inhibits gastric emptying and acid secretion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and peripheral administration of the GLP-1 receptor antagonist exendin-(9-39) amide enhanced emptying of a glucose meal, whereas intracerebroventricular exendin was ineffective. The rate of saline emptying was attenuated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibition by GLP-1. Vagal afferent denervation abolished the central and peripheral action of GLP-1 on gastric emptying. Neither peripheral cholinergic nor adrenergic blockade altered the delay of methyl cellulose meal emptying by intracisternal GLP-1 injection. Acid secretion in conscious pylorus-ligated rats was inhibited by intracisternal GLP-1 administration, whereas systemic GLP-1 was ineffective. These results support the notion that GLP-1 receptors participate in the central and peripheral regulation of gastric function. Furthermore, vagal afferent nerves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiological modulator of gastric function.
Imeryüz
N
N
Department of Gastroenterology, School of Medicine, Marmara University, Istanbul, Turkey.
Yeğen
B C
BC
Bozkurt
A
A
Coşkun
T
T
Villanueva-Peñacarrillo
M L
ML
Ulusoy
N B
NB
D000818:Animals; D001786:Blood Glucose / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D003714:Denervation; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D005746:Gastric Emptying / Q000187:drug effects / Q000502:physiology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000502:physiology*; D005768:Gastrointestinal Hormones / Q000494:pharmacology; D052216:Glucagon-Like Peptide 1; D005947:Glucose / Q000378:metabolism; D007276:Injections, Intraventricular; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013270:Stomach / Q000294:innervation; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*; D014688:Venoms / Q000494:pharmacology; D017833:Visceral Afferents / Q000187:drug effects / Q000502:physiology*
D001786:Blood Glucose; D005768:Gastrointestinal Hormones; D010446:Peptide Fragments; D010455:Peptides; D014688:Venoms; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D005947:Glucose; D002211:Capsaicin