Nitrergic Contribution to Gastric Relaxation Induced by Glucagon-like Peptide-1 (Glp-1) in Healthy Adults.
From: Clinical Enteric Neuroscience Translational and Epidemiological Research Program, Mayo Clinic, 200 First St. S.W., Rochester, MN 55905, USA.
American journal of physiology. Gastrointestinal and liver physiology
- Publish Date: May 2007
- ISSN: 0193-1857
- Volume: 292
- Issue: 5
- Pages: G1359-65
- Medium: Print
- Language: English
- Citation (JAMA): Andrews Christopher N, Bharucha Adil E, Camilleri Michael, et al. Nitrergic Contribution to Gastric Relaxation Induced by Glucagon-like Peptide-1 (Glp-1) in Healthy Adults.. Am. J. Physiol. Gastrointest. Liver Physiol. May 2007;292:G1359-65
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 N(G)-monomethyl-L-arginine acetate (L-NMMA; 4 mg.kg(-1) x 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 (99m)Tc-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 < or = 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 < or = 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.
Mesh Headings (Keywords): Adolescent, Adult, Blood Glucose, Blood Pressure, Catecholamines, Double-Blind Method, Fasting, Female, Glucagon-Like Peptide 1, Heart Rate, Humans, Male, Middle Aged, Muscle Relaxation, Nitric Oxide, Nitric Oxide Synthase, Postprandial Period, Stomach, omega-N-Methylarginine
Check for Full Text / PubMed Unique Identifier (PMID): 17290009
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