title: 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.
  
  
  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
  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.affiliation: Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, SE-182 88 Stockholm, Sweden. ylva.falken@ds.se
authors.forename: Y
authors.initials: Y
authors.lastname: Falkén
authors.forename: P M
authors.initials: PM
authors.lastname: Hellström
authors.forename: G J
authors.initials: GJ
authors.lastname: Sanger
authors.forename: O
authors.initials: O
authors.lastname: Dewit
authors.forename: G
authors.initials: G
authors.lastname: Dukes
authors.forename: P
authors.initials: P
authors.lastname: Grybäck
authors.forename: J J
authors.initials: JJ
authors.lastname: Holst
authors.forename: E
authors.initials: E
authors.lastname: Näslund
mesh_terms: D000328:Adult; D001066:Appetite / Q000187:drug effects; D002432:Cecum / Q000187:drug effects / Q000502:physiology; D003106:Colon / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D004734:Energy Metabolism / Q000187:drug effects; D005746:Gastric Emptying; D041981:Gastrointestinal Tract / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects*; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D006815:Hunger / Q000187:drug effects; D007262:Infusions, Intravenous; D007328:Insulin / Q000378:metabolism; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D012528:Satiety Response / Q000187:drug effects
chemical_list: D054439:Ghrelin; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005947:Glucose