Endogenous Glucagon-Like Peptide-1 Slows Gastric Emptying in Healthy Subjects, Attenuating Postprandial Glycemia

Abstract

The role of glucagon-like peptide-1 (GLP-1) in the regulation of gastric emptying is uncertain. The aim of this study was to determine the effects of endogenous GLP-1 on gastric emptying, glucose absorption, and glycemia in health. Ten healthy fasted subjects (eight males, two females; 48 +/- 7 yr) received the specific GLP-1 antagonist, exendin(9-39) amide [ex(9-39)NH(2)] (300 pmol/kg x min iv), or placebo, between -30 and 180 min in a randomized, double-blind, crossover fashion. At 0 min, a mashed potato meal ( approximately 2600 kJ) containing 3 g 3-ortho-methyl-D-glucose (3-OMG) and labeled with 20 MBq (99m)Technetium-sulphur colloid was eaten. Gastric emptying, including the time taken for 50% of the meal to empty from the stomach (T50), blood glucose, plasma 3-OMG, and plasma insulin were measured. Ex(9-39)NH(2) accelerated gastric emptying [T50 ex(9-39)NH(2), 68 +/- 8 min, vs. placebo, 83 +/- 7 min; P < 0.001] and increased the overall glycemic response to the meal [area under the curve (0-180 min) ex(9-39)NH(2), 1540 +/- 106 mmol/liter x min, vs. placebo, 1388 +/- 90 mmol/liter x min; P < 0.02]. At 60 min, ex(9-39)NH(2) increased the rise in glycemia [ex(9-39)NH(2), 9.9 +/- 0.5 mmol/liter, vs. placebo, 8.4 +/- 0.5 mmol/liter; P < 0.01], plasma 3-OMG [ex(9-39)NH(2), 0.25 +/- 0.01 mmol/liter, vs. placebo, 0.21 +/- 0.01 mmol/liter; P < 0.05], and plasma insulin [ex(9-39)NH(2), 82 +/- 13 mU/liter, vs. placebo, 59 +/- 9 mU/liter; P < 0.05] concentrations. There was a close within-subject correlation between glycemia and gastric emptying [e.g. at 60 min, the increment in blood glucose and gastric emptying (T50); r = -0.89; P < 0.001]. GLP-1 plays a physiological role to slow gastric emptying in health, which impacts on glucose absorption and, hence, postprandial glycemia.