Glucagon-like peptide 2 inhibits ghrelin secretion in humans

The growth hormone secretagogue receptor ligand ghrelin is known to play a pivotal role in the central nervous control of energy homeostasis. Circulating ghrelin levels are high under fasting conditions and decline after meal ingestion, but the mechanisms underlying the postprandial drop in ghrelin levels are poorly understood. In the present study we addressed, whether (1) exogenous GLP-2 administration decreases ghrelin levels and (2) what other endogenous factors are related to ghrelin secretion under fasting conditions.

Fifteen healthy male volunteers were studied with the intravenous infusion of GLP-2 (2 pmol l(-1) min(-1)) or placebo over 120 min in the fasting state. Plasma concentrations of glucose, insulin, C-peptide, glucagon, intact GLP-2 and ghrelin were determined.

During the infusion of GLP-2, plasma concentrations of intact GLP-2 increased from 10.0+/-1.5 pmol/l to steady-state levels of 207.7+/-8.3 pmol/l (p < 0.0001). Administration of GLP-2 led to an approximately 10% reduction in ghrelin concentrations, whereas placebo administration was without an effect (p < 0.001). After cessation of the GLP-2 infusion, ghrelin levels returned to baseline values, and were no longer different from those in the placebo experiments. There was a strong inverse linear relationship between the fasting concentrations of ghrelin and the respective levels of glucose, insulin and C-peptide (r = 0.49, p < 0.01; r = 0.55, p < 0.01 and r = 0.59, p < 0.001, respectively). In contrast, there was no detectable association between fasting ghrelin levels and the ambient concentrations of glucagon or intact GLP-2.

GLP-2 inhibits ghrelin secretion in humans at plasma levels of approximately 200 pmol/l. However, the physiological importance of this effect appears to be minor compared to the actions of insulin and glucose.