Acetylcholine Regulates Ghrelin Secretion in Humans

Abstract

Ghrelin secretion has been reportedly increased by fasting and energy restriction but decreased by food intake, glucose, insulin, and somatostatin. However, its regulation is still far from clarified. The cholinergic system mediates some ghrelin actions, e.g. stimulation of gastric contractility and acid secretion and its orexigenic activity. To clarify whether ghrelin secretion undergoes cholinergic control in humans, we studied the effects of pirenzepine [PZ, 100 mg per os (by mouth)], a muscarinic antagonist, or pyridostigmine (PD, 120 mg per os), an indirect cholinergic agonist, on ghrelin, GH, insulin, and glucose levels in six normal subjects. PD increased (P < 0.05) GH (change in area under curves, mean +/- SEM, 790.9 +/- 229.3 microg(*)min/liter) but did not modify insulin and glucose levels. PZ did not significantly modify GH, insulin, and glucose levels. Circulating ghrelin levels were increased by PD (11290.5 +/- 6688.7 pg(*)min/ml; P < 0.05) and reduced by PZ (-23205.0 +/- 8959.5 pg(*)min/ml; P < 0.01). The PD-induced ghrelin peak did not precede that of GH. In conclusion, circulating ghrelin levels in humans are increased and reduced by cholinergic agonists and antagonists, respectively. Thus, ghrelin secretion is under cholinergic, namely muscarinic, control in humans. The variations in circulating ghrelin levels induced by PD and PZ are unlikely to mediate the cholinergic influence on GH secretion.

Changes in 24-h area-under-the-curve ghrelin values following diet-induced weight loss are associated with loss of fat-free mass, but not with changes in fat mass, insulin levels or insulin sensitivity

“…Alternatively, an indirect mechanism might include changes in hormonal or inflammatory signals not measured here, or alternatively, in parasympathetic nervous system signaling that accompany weight loss. 27,28 In conclusion, in this preliminary study, the rise in ghrelin levels after diet-induced weight loss correlated best with the fall in fat free mass and not with changes in fat-mass, insulin levels, or insulin sensitivity. If this finding is replicated in larger studies, then two intriguing possibilities are raised.…”

Plasma Ghrelin Concentrations in Different Clinical Stages of Diabetic Complications and Glycemic Control in Japanese Diabetics

“…The vagal nerve conveys ghrelin-mediated signals for GH secretion and food intake from the stomach to the brain [33]. Circulating ghrelin levels in humans were increased and reduced by cholinergic agonists and antagonists, respectively [34]. A postprandial decrease in the ghrelin level was not found in sheep treated with cholinergic blockers [35].…”

Prokinetics stimulate the increase of ghrelin in mice

“…Erythromycin occupies the motilin receptors in human, which enhances intestinal motility through the cholinergic activity (24). Because it is a well-established fact that acetylcholine provokes the increase in ghrelin (25), the relation between erythromycin and ghrelin can be anticipated in humans. On the other hand, rodents lack the motilin receptors (26).…”