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- 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 Tc-99m- 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.