Effects of glucagon-like peptide-1 and sympathetic stimulation on gastric accommodation in humans.

In humans, glucagon-like peptide-1 (GLP-1) delays gastric emptying by inhibiting vagal activity and also increases gastric volumes, by unclear mechanisms. Because GLP-1 inhibits intestinal motility by stimulating the sympathetic nervous system in rats, we assessed the effects of a GLP-1 agonist and yohimbine, an alpha(2)-adrenergic antagonist, on gastric volumes in humans. In this double-blind study, 32 healthy volunteers were randomized to placebo, a GLP-1 agonist, yohimbine or GLP-1 and yohimbine. Gastric volumes (fasting predrug and postdrug, and postprandial postdrug) were measured by (99m)Tc single photon emission computed tomography imaging. Plasma catecholamines and haemodynamic parameters were assessed. Compared with placebo, GLP-1 increased (P = 0.03) but yohimbine did not affect fasting gastric volume. However, GLP-1 plus yohimbine increased (P < 0.001) postprandial gastric accommodation vs placebo and vs GLP-1 alone [postprandial volume change = 542 +/- 29 mL (mean +/- SEM, placebo), 605 +/- 31 mL (GLP-1), 652 +/- 54 mL (yohimbine) and 810 +/- 37 mL (GLP-1 and yohimbine)]. Plasma noradrenaline and dihydroxyphenylglycol concentrations were higher for yohimbine vs placebo and for GLP-1 and yohimbine vs GLP-1. Yohimbine stimulates central sympathetic activity and in combination with GLP-1, augments postprandial accommodation in humans.