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

TY - JOUR

T1 - Actions of prolonged ghrelin infusion on gastrointestinal transit and glucose homeostasis in humans

AU - Falkén, Y

AU - Hellström, P M

AU - Sanger, G J

AU - Dewit, O

AU - Dukes, G

AU - Grybäck, P

AU - Holst, Jens Juul

AU - Näslund, E

PY - 2010/6/1

Y1 - 2010/6/1

N2 - 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.

AB - 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.

KW - Adult

KW - Appetite

KW - Cecum

KW - Colon

KW - Double-Blind Method

KW - Energy Metabolism

KW - Gastric Emptying

KW - Gastrointestinal Tract

KW - Gastrointestinal Transit

KW - Ghrelin

KW - Glucagon-Like Peptide 1

KW - Glucose

KW - Homeostasis

KW - Humans

KW - Hunger

KW - Infusions, Intravenous

KW - Insulin

KW - Male

KW - Muscle Contraction

KW - Muscle, Smooth

KW - Satiety Response

U2 - 10.1111/j.1365-2982.2009.01463.x

DO - 10.1111/j.1365-2982.2009.01463.x

M3 - Journal article

C2 - 20100281

SN - 1350-1925

VL - 22

SP - e192-200

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

IS - 6

ER -