Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans.

Abstract

BACKGROUND:

Ghrelin is produced by enteroendocrine cells in the gastric mucosa and stimulates gastric emptying in healthy volunteers and patients with gastroparesis in short-term studies. The aim of this study was to evaluate effects of intravenous ghrelin on gastrointestinal motility and glucose homeostasis during a 6-h infusion in humans.

METHODS:

Ghrelin (15 pmol kg(-1) min(-1)) or saline was infused intravenously for 360 min after intake of radio-opaque markers, acetaminophen, and lactulose after a standardized breakfast in 12 male volunteers. Gastric emptying, orocecal transit, colonic transit, postprandial plasma concentrations of glucose, insulin, glucagon-like peptide-1 (GLP-1), and peptide YY were assessed. In vitro studies of gastrointestinal muscle contractility were performed.

KEY RESULTS:

The gastric emptying rate was faster for ghrelin compared to saline (P = 0.002) with a shorter half-emptying time (50.3 +/- 3.9 vs 59.9 +/- 4.4 min, P = 0.004). There was no effect of ghrelin on orocecal or colonic transit. Postprandial elevations of plasma glucose, insulin, and GLP-1 occurred 15 min earlier and were higher with ghrelin. The insulinogenic index did not change during ghrelin infusion. Basal in vitro contractility was unaffected by ghrelin.

CONCLUSIONS & INFERENCES:

The effect of a 6-h ghrelin infusion on gastrointestinal motility is limited to the stomach without affecting orocecal or colonic transit. Plasma glucose, insulin, and GLP-1 are elevated postprandially, probably as a result of the hastened gastric emptying. Changes in glucose homeostasis as a consequence of stimulated gastric emptying and hormone release, need to be taken into account in the use of pharmacological stimulants for the treatment of motility disorders.

• Authors: Y Falkén, P M Hellström, G J Sanger, O Dewit, G Dukes, P Grybäck, J J Holst, E Näslund
• Journal: Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society (Neurogastroenterol Motil) Vol. 22 Issue 6 Pg. e192-200 (Jun 2010) ISSN: 1365-2982 [Electronic] England
• PMID: 20100281 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Ghrelin
• Insulin
• Glucagon-Like Peptide 1
• Glucose

Topics

• Adult
• Appetite (drug effects)
• Cecum (drug effects, physiology)
• Colon (drug effects, physiology)
• Double-Blind Method
• Energy Metabolism (drug effects)
• Gastric Emptying
• Gastrointestinal Tract (drug effects)
• Gastrointestinal Transit (drug effects)
• Ghrelin (administration & dosage, pharmacology)
• Glucagon-Like Peptide 1 (metabolism)
• Glucose (metabolism)
• Homeostasis (drug effects)
• Humans
• Hunger (drug effects)
• Infusions, Intravenous
• Insulin (metabolism)
• Male
• Muscle Contraction (drug effects)
• Muscle, Smooth (drug effects)
• Satiety Response (drug effects)