Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats

Abstract

Glucagon-like peptide-1(7-36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5-170 pmol.kg(-1).min(-1)) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol.kg(-1).min(-1) and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7-50 pmol.kg(-1).min(-1)) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol.kg(-1).min(-1) and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5-50 pmol.kg(-1).min(-1)) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.

Gut peptides in the control of food intake

“…However, prolonged intravenous infusions or bolus administration of GLP-1 analogs that are resistant to DPP-IV degradation result in significant food intake suppressions. 34,35 Similar to the actions of PYY(3-36), GLP-1 reduces meal size and increases the satiety ratio. These effects are seen across multiple meals even at times after infusions.…”

The vagus nerve, food intake and obesity

“…Peripheral administration of GLP-1 or its stable analog exendin-4, the naturally occurring peptide from the Gila monster lizard, enhance satiation and reduce food intake in humans and rats (Gutzwiller et al, 1999;Chelikani et al, 2005b). Because of rapid breakdown by dipeptidyl peptidase-VI, endogenously secreted GLP-1 has a very short half-life in plasma.…”

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.…”