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NEUROREGULATION AND MOTILITY

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

¹Clinical Enteric Neuroscience Translational and Epidemiological Research Program, ²Department of Neurology, and ³Division of Biostatistics, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

Submitted 30 August 2006 ; accepted in final form 29 January 2007

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·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.

accommodation; stomach; postprandial; diabetes; vagus

This article has been cited by other articles:

				A. E. Bharucha, N. Charkoudian, C. N. Andrews, M. Camilleri, D. Sletten, A. R. Zinsmeister, and P. A. Low Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2008; 295(3): R874 - R880. [Abstract] [Full Text] [PDF]