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

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-l-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.sup.G]-monomethyl-L-arginine acetate (L-NMMA; 4 mg x [kg.sup.-1] x [h.sup.-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 x [kg.sup.-1] x [h.sup.-1] infusion). Gastric volumes (fasting pre- and postdrug, postprandial postdrug) were measured by [sup.99m]Tc-single-photon-emission computed tomography imaging. GLP-1 increased (P = 0.04) fasting gastric volume by 83 [+ or -] 16 ml (vs. 17 [+ or -] 11 ml for placebo) and augmented (P [less than or equal to] 0.01) postprandial accommodation by 688 [+ or -] 165 ml (vs. 542 [+ or -] 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 [+ or -] 37 ml, P [less than or equal to] 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. accommodation; stomach; postprandial; diabetes; vagus doi:10.1152/ajpgi.00403.2006.