Effects of metoclopramide on duodenal motility and flow events, glucose absorption, and incretin hormone release in response to intraduodenal glucose infusion.
The contribution of small intestinal motor activity to nutrient absorption is poorly defined. A reduction in duodenal flow events after hyoscine butylbromide, despite no change in pressure waves, was associated with reduced secretion of the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) and a delay in glucose absorption. The aim of this study was to investigate the effect of metoclopramide on duodenal motility and flow events, incretin hormone secretion, and glucose absorption. Eight healthy volunteers (7 males and 1 female; age 29.8 ± 4.6 yr; body mass index 24.5 ± 0.9 kg/m²) were studied two times in randomized order. A combined manometry and impedance catheter was used to measure pressure waves and flow events in the same region of the duodenum simultaneously. Metoclopramide (10 mg) or control was administered intravenously as a bolus, followed by an intraduodenal glucose infusion for 60 min (3 kcal/min) incorporating the ¹⁴C-labeled glucose analog 3-O-methylglucose (3-OMG). We found that metoclopramide was associated with more duodenal pressure waves and propagated pressure sequences than control (P < 0.05 for both) during intraduodenal glucose infusion. However, the number of duodenal flow events, blood glucose concentration, and plasma 3-[¹⁴C]OMG activity did not differ between the two study days. Metoclopramide was associated with increased plasma concentrations of GLP-1 (P < 0.05) and GIP (P = 0.07) but lower plasma insulin concentrations (P < 0.05). We concluded that metoclopramide was associated with increased frequency of duodenal pressure waves but no change in duodenal flow events and glucose absorption. Furthermore, GLP-1 and GIP release increased with metoclopramide, but insulin release paradoxically decreased.
Kuo
Paul
P
Royal Adelaide Hospital, University of Adelaide, Australia.
Bellon
Max
M
Wishart
Judith
J
Smout
André J
AJ
Holloway
Richard H
RH
Fraser
Robert J L
RJ
Horowitz
Michael
M
Jones
Karen L
KL
Rayner
Christopher K
CK
D019325:3-O-Methylglucose / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists / Q000494:pharmacology; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005749:Gastric Inhibitory Polypeptide / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005769:Gastrointestinal Motility / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000097:blood / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage* / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D054795:Incretins / Q000378:metabolism*; D007328:Insulin; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D010528:Peristalsis / Q000187:drug effects
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D018492:Dopamine Antagonists; D054795:Incretins; D007328:Insulin; D019325:3-O-Methylglucose; D005749:Gastric Inhibitory Polypeptide; D052216:Glucagon-Like Peptide 1; D005947:Glucose; D008787:Metoclopramide