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

Department of Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Germany.
Regulatory Peptides (Impact Factor: 1.83). 10/2007; 143(1-3):64-8. DOI: 10.1016/j.regpep.2007.03.002
Source: PubMed


Ghrelin 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.
14 healthy male volunteers were given intravenous infusions of GLP-1(1.2 pmol x 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.
During 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.
GLP-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.

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    • "nt in comparison to high content in carbohydrates and associated with short - term control of food intake ( Gibbons et al . , 2013 ) . Additionally , GLP - 1 modulates plasma ghrelin in the postprandial period preventing an immediate decrease in ghrelin levels after the meal and suppressing the subsequent increase in the late postprandial period ( Hagemann et al . , 2007 ) . In an animal model , enhanced protein - mediated GLP - 1 secretion after duodenal administration of zein hydrolysate was inhibited through vagal denervation , whereas the effect of jejunal and ileal administration P a g e | 38 was maintained , highlighting the different mechanisms of GLP - 1 secretion throughout the gastrointestinal"
    02/2015, Degree: PhD, Supervisor: Francisco Castro e Sousa
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    • "Ghrelin stimulates appetite and food intake and is secreted in the stomach. In healthy individuals, the ghrelin plasma concentrations increase during fasting and are suppressed by meal intake [46], likely via postprandial hyperinsulinemia [47], [48]. "
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    ABSTRACT: The intake of meat, particularly processed meat, is a dietary risk factor for diabetes. Meat intake impairs insulin sensitivity and leads to increased oxidative stress. However, its effect on postprandial gastrointestinal hormone (GIH) secretion is unclear. We aimed to investigate the acute effects of two standardized isocaloric meals: a processed hamburger meat meal rich in protein and saturated fat (M-meal) and a vegan meal rich in carbohydrates (V-meal). We hypothesized that the meat meal would lead to abnormal postprandial increases in plasma lipids and oxidative stress markers and impaired GIH responses.
    PLoS ONE 09/2014; 9(9):e107561. DOI:10.1371/journal.pone.0107561 · 3.23 Impact Factor
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    • "Glucose-stimulated insulin secretion is reduced with exogenous ghrelin in humans [14] and rats [15]. On the other hand, it is reported that glucagon-like peptide-1 (GLP-1) reduces the rise in ghrelin levels in the late postprandial period at supraphysiological plasma levels through its insulinotropic action [16]. Interestingly, Radulescu et al. reported that different type of food intake resulted in different response of insulin, GLP-1, and ghrelin secretion [17]. "
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    ABSTRACT: As a regulator of food intake and energy metabolism, the role of ghrelin in glucose metabolism is still not fully understood. In this study, we determined the in vivo effect of ghrelin on incretin effect. We demonstrated that ghrelin inhibited the glucose-stimulated release of glucagon-like peptide-1 (GLP-1) when infused into the portal vein of Wistar rat. Hepatic vagotomy diminished the inhibitory effect of ghrelin on glucose-stimulated GLP-1 secretion. In addition, phentolamine, a nonselective α receptor antagonist, could recover the decrease of GLP-1 release induced by ghrelin infusion. Pralmorelin (an artificial growth hormone release peptide) infusion into the portal vein could also inhibit the glucose-stimulated release of GLP-1. And growth hormone secretagogue receptor antagonist, [D-lys3]-GHRP-6, infusion showed comparable increases of glucose stimulated GLP-1 release compared to ghrelin infusion into the portal vein. The data showed that intraportal infusion of ghrelin exerted an inhibitory effect on GLP-1 secretion through growth hormone secretagogue receptor 1α (GHS1α receptor), which indicated that the downregulation of ghrelin secretion after food intake was necessary for incretin effect. Furthermore, our results suggested that the enteric neural net involved hepatic vagal nerve and sympathetic nerve mediated inhibition effect of ghrelin on incretin effect.
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