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 secr etion in humans. The role of GLP-1 as a regulator of gastric function is elusive. In gastric fistula rats, vagal afferent denervation and pe ripheral administration of the GLP-1 receptor antagonist exendin-(9-39 ) amide enhanced emptying of a glucose meal, whereas intracerebroventr icular exendin was ineffective. The rate of saline emptying was attenu ated by peripheral as well as by central administration of GLP-1, and pretreatment with exendin by the respective routes reversed the inhibi tion by GLP-1. Vagal afferent denervation abolished the central and pe ripheral action of GLP-1 on gastric emptying. Neither peripheral choli nergic nor adrenergic blockade altered the delay of methyl cellulose m eal emptying by intracisternal GLP-1 injection. Acid secretion in cons cious pylorus-ligated rats was inhibited by intracisternal GLP-1 admin istration, whereas systemic GLP-1 was ineffective. These results suppo rt the notion that GLP-1 receptors participate in the central and peri pheral regulation of gastric function. Furthermore, vagal afferent ner ves mediate the inhibitory action of GLP-1 on gastric motor function. GLP-1 may be a candidate brain-gut peptide that acts as a physiologica l modulator of gastric function.