Glucagon-like peptide-1 inhibits gastric emptying via vagal afferent-mediated central mechanisms

Abstract

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.

The nucleus tractus solitarius: a portal for visceral afferent signal processing, energy status assessment and integration of their combined effects on food intake

“…9,10 Endogenous release or intraperitoneal GLP-1R agonist delivery triggers a set of responses that include reduced food intake, [11][12][13][14] inhibition of gastric emptying, 9,14 stimulation of glucosedependent insulin secretion 15,16 and tachycardia. [17][18][19][20][21] GLP-1R ligand is also supplied by proglucagon-expressing neurons of the caudal brainstem that project to GLP-1Rs, which are distributed throughout the brain.…”

Genetic variation inGlp1rexpression influences the rate of gastric emptying in mice

“…Exendin-(9-39) is a COOH-terminal fragment of exendin-4, a bioactive peptide that shares 50% structural homology with GLP-1 (19,53) and antagonizes the in vivo actions of GLP-1 (51). Administration of exendin-(9-39) to rats or human subjects increases gastric emptying (40) when given by peripheral but not central administration (21). In the present study, overnight fasted mice were injected intraperitoneally with 100 l of either PBS or exendin-(9-39) (Bachem) (0.25 mg/kg) immediately before re-feeding.…”

“…Systemic administration of GLP-1 in physiological amounts in both humans and animals potently inhibits gastric emptying (9,13,15,31,59,61), and this effect can be blocked by administration of the GLP-1 receptor antagonist exendin (21). The mechanism by which GLP-1 inhibits gastric emptying is thought to involve receptors located either in the central nervous system or associated with afferent pathways to the brain stem (9,21,60). In addition to the deceleration of gastric emptying, GLP-1 is involved in regulating satiety, as shown in normal-weight and obese men infused with GLP-1 (17,33,34).…”

Glucagon-like peptide-1 (7–36) amide: a central regulator of satiety and interoceptive stress

“…One possibility is that GLP-1-containing neurons or receptors are implicated in other neuropeptide-containing CNS circuitry or down-stream from classic neurotransmitter systems such as those containing noradrenalin, serotonin, or dopamine. Another possibility is that peripheral GLP-1 released by ileal stimulation acts on vagal (or visceral) afferent fibers, 27 where it could influence GLP-1 neuronal transmission in the CNS, analogous to that which has been proposed for another gut peptide, cholecystokinin (CCK). 28 This idea might fit with the location of GLP-1-containing neuronal cell bodies in the caudal aspect of the nucleus of the solitary tract (NTS) which project to thalamic and hypothalamic (i.e.…”