ABSTRACT
Ghrelin release in man depends on the macronutrient composition of the test meal. The mechanisms contributing to the differential regulation are largely unknown. To elucidate their potential role, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP), insulin, gastrin and somatostatin were examined on isolated rat stomach ghrelin secretion, which offers the advantage of avoiding systemic interactions. Basal ghrelin secretion was in a range that did not permit to consistently evaluate inhibiting effects. Therefore, the effect of gastrointestinal hormones and insulin was analyzed during vagal prestimulation. GLP-1(7-36)amide 10(-8) and 10(-7) M decreased ghrelin secretion significantly. In contrast, GIP 10(-8) and 10(-7) M augmented not only prestimulated, but also basal ghrelin secretion (p<0.05). Insulin reduced ghrelin at 10(-10), 10(-8) and 10(-6) M (p<0.05). Both gastrin 10(-8) M and somatostatin 10(-6) M also significantly inhibited ghrelin secretion. These data demonstrate that GLP-1(7-36)amide, insulin, gastrin and somatostatin are potential candidates to contribute to the postprandially observed inhibition of ghrelin secretion with insulin being the most effective inhibitor in this isolated stomach model. GIP, on the other hand, could attenuate the postprandial decrease. Because protein-rich meals do not effectively stimulate GIP release, other as yet unknown intestinal factors must be responsible for protein-induced stimulation of ghrelin release.
Subject(s)
Gastric Inhibitory Polypeptide/metabolism , Glucagon/metabolism , Peptide Fragments/metabolism , Peptide Hormones/metabolism , Protein Precursors/metabolism , Animals , Dose-Response Relationship, Drug , Gastric Mucosa/metabolism , Gastrins/metabolism , Ghrelin , Glucagon-Like Peptide 1 , Glucagon-Like Peptides , Insulin/metabolism , Male , Radioimmunoassay , Rats , Rats, Wistar , Somatostatin/metabolism , Time FactorsABSTRACT
The mycotoxin patulin (PAT), which frequently occurs in apple juices, has previously been shown to be toxic and teratogenic. However, there is almost no data about its absorption and metabolism. Therefore, the enrichment of PAT in the tissue of perfused rat stomachs after luminal application and its vascular appearance was quantified by stable isotope dilution assays. After application of juices enriched with PAT at concentrations of 350 and 3.5 mg/l, respectively, the mycotoxin appeared almost instantly in the perfusate. Twenty-six to twenty-nine percent of PAT were removed from the gastric lumen over 55 min. From this quantity, 17% and 2% were transferred into vascular circulation and 3% and 0.06% were detectable in gastric tissue for the high and the low PAT dose, respectively. The disappearance of 8400 microg and 700 microg PAT, respectively, could be attributed in part to its reaction with intracellular glutathione (GSH). Regarding the GSH content in the tissue, a decrease of 87% compared to that of control stomachs was observed for the high PAT dose, whereas in the case of the low PAT dose no significant GSH degradation occurred. Thus our results show that even low concentrations of patulin penetrate the gastric wall. Toxic effects, however, are unlikely as most of the patulin is disintegrated.
