Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults

Christopher N. Andrews, Adil E. Bharucha, Michael Camilleri, Phillip A. Low, Barbara Seide, Duane Burton, Kari Baxter, Alan R. Zinsmeister

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

The incretin glucagon-like peptide-1 (GLP-1), which is used to treat diabetes mellitus, delays gastric emptying by inhibiting vagal activity. GLP-1 also increases fasting and postprandial gastric volume in humans. On the basis of animal studies, we hypothesized that nitric oxide mediates the effects of GLP-1 on gastric volumes. To assess the effects of nitrergic blockade on GLP-1-induced gastric accommodation in humans, in this double-blind study, 31 healthy volunteers were randomized to placebo (i.e., saline), GLP-1, or the nitric oxide synthase inhibitor NG-monomethyl-L-arginine acetate (L-NMMA; 4 mg·kg-1·h-1) alone or with GLP-1. Thereafter, 16 additional subjects were randomized to GLP-1 alone or together with a higher dose of L-NMMA (10 mg/kg bolus plus 8 mg·kg -1·h-1 infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by 99mTc-single- photon-emission computed tomography imaging. GLP-1 increased (P = 0.04) fasting gastric volume by 83 ± 16 ml (vs. 17 ± 11 ml for placebo) and augmented (P ≤ 0.01) postprandial accommodation by 688 ± 165 ml (vs. 542 ± 29 ml for placebo). L-NMMA (low dose) alone did not affect fasting or postprandial gastric volume. L-NMMA (low dose) did not attenuate the effect of GLP-1 on gastric volumes. In contrast, L-NMMA (high dose) did not affect fasting volume but blunted GLP-1-mediated postprandial accommodation (postprandial change = 494 ± 37 ml, P ≤ 0.01 vs. GLP-1 alone). These data are consistent with the hypothesis that nitric oxide partly mediates the effects of GLP-1 on postprandial but not fasting gastric volumes in humans.

Original languageEnglish (US)
Pages (from-to)G1359-G1365
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number5
DOIs
StatePublished - May 1 2007

Keywords

  • Accommodation
  • Diabetes
  • Postprandial
  • Stomach
  • Vagus

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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