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 Tc-99m 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.