Glucagon-like peptide 1 (GLP-1) suppresses ghrelin levels in humans via increased insulin secretion

IntroductionGhrelin is an orexigenic peptide predominantly secreted by the stomach. Ghrelin plasma levels rise before meal ingestion and sharply decline afterwards, but the mechanisms controlling ghrelin secretion are largely unknown. Since meal ingestion also elicits the secretion of the incretin hormone glucagon-like peptide 1 (GLP-1), we examined whether exogenous GLP-1 administration reduces ghrelin secretion in humans.Patients and methods14 healthy male volunteers were given intravenous infusions of GLP-1(1.2 pmol·kg− 1 min− 1) or placebo over 390 min. After 30 min, a solid test meal was served. Venous blood was drawn frequently for the determination of glucose, insulin, C-peptide, GLP-1 and ghrelin.ResultsDuring the infusion of exogenous GLP-1 and placebo, GLP-1 plasma concentrations reached steady-state levels of 139 ± 15 pmol/l and 12 ± 2 pmol/l, respectively (p < 0.0001). During placebo infusion, ghrelin levels were significantly reduced in the immediate postprandial period (p < 0.001), and rose again afterwards. GLP-1 administration prevented the initial postprandial decline in ghrelin levels, possibly as a result of delayed gastric emptying, and significantly reduced ghrelin levels 150 and 360 min after meal ingestion (p < 0.05). The patterns of ghrelin concentrations in the experiments with GLP-1 and placebo administration were inversely related to the respective plasma levels of insulin and C-peptide.ConclusionsGLP-1 reduces the rise in ghrelin levels in the late postprandial period at supraphysiological plasma levels. Most likely, these effects are indirectly mediated through its insulinotropic action. The GLP-1-induced suppression of ghrelin secretion might be involved in its anorexic effects.