Nutrient-induced glucagon like peptide-1 release is modulated by serotonin

• Published in: The Journal of nutritional biochemistry 2016-06, Vol.32, p.142-150
• Main Authors: Ripken, Dina, van der Wielen, Nikkie, Wortelboer, Heleen M., Meijerink, Jocelijn, Witkamp, Renger F., Hendriks, Henk F.J.
• Format: Article
• Language: English
• Subjects: Animals; Caseins - metabolism; Cell Line; Dietary Sucrose - metabolism; Diterpenes, Kaurane - metabolism; Enterochromaffin Cells - secretion; Enteroendocrine Cells - drug effects; Enteroendocrine Cells - metabolism; Enteroendocrine Cells - secretion; Fluoxetine - pharmacology; Gene Expression Regulation - drug effects; GLP-1; Glucagon-Like Peptide 1 - secretion; Glucagon-Like Peptide-1 Receptor - agonists; Glucagon-Like Peptide-1 Receptor - antagonists & inhibitors; Glucagon-Like Peptide-1 Receptor - metabolism; Heterocyclic Compounds, 4 or More Rings - pharmacology; In Vitro Techniques; Male; Mice; Nutrients; Rebaudioside A; Safflower Oil - metabolism; Serotonin; Serotonin - metabolism; Serotonin - secretion; Serotonin Antagonists - pharmacology; Serotonin Uptake Inhibitors - pharmacology; Small intestine; Sus scrofa; Sweetening Agents - metabolism
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2016.03.006

Glucagon like peptide-1 (GLP-1) and serotonin are both involved in food intake regulation. GLP-1 release is stimulated upon nutrient interaction with G-protein coupled receptors by enteroendocrine cells (EEC), whereas serotonin is released from enterochromaffin cells (ECC). The central hypothesis for the current study was that nutrient-induced GLP-1 release from EECs is modulated by serotonin through a process involving serotonin receptor interaction. This was studied by assessing the effects of serotonin reuptake inhibition by fluoxetine on nutrient-induced GLP-1, PYY and CCK release from isolated pig intestinal segments. Next, serotonin-induced GLP-1 release was studied in enteroendocrine STC-1 cells, where effects of serotonin receptor inhibition were studied using specific and non-specific antagonists. Casein (1% w/v), safflower oil (3.35% w/v), sucrose (50mM) and rebaudioside A (12.5mM) stimulated GLP-1 release from intestinal segments, whereas casein only stimulated PYY and CCK release. Combining nutrients with fluoxetine further increased nutrient-induced GLP-1, PYY and CCK release. Serotonin release from intestinal tissue segments was stimulated by casein and safflower oil while sucrose and rebaudioside A had no effect. The combination with fluoxetine (0.155μM) further enhanced casein and safflower oil induced-serotonin release. Exposure of ileal tissue segments to serotonin (30μM) stimulated GLP-1 release whereas it did not induce PYY and CCK release. Serotonin (30 and 100μM) also stimulated GLP-1 release from STC-1 cells, which was inhibited by the non-specific 5HT receptor antagonist asenapine (1 and 10μM). These data suggest that nutrient-induced GLP-1 release is modulated by serotonin through a receptor mediated process.