Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans.
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.
Falkén
Y
Y
Division of Surgery, Department of Clinical Sciences, Danderyd Hospital, Karolinska Institute, SE-182 88 Stockholm, Sweden. ylva.falken@ds.se
Hellström
P M
PM
Sanger
G J
GJ
Dewit
O
O
Dukes
G
G
Grybäck
P
P
Holst
J J
JJ
Näslund
E
E
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
D054439:Ghrelin; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005947:Glucose