title: Nutrient-induced glucagon like peptide-1 release is modulated by serotonin.
abstract: 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.
authors.affiliation: Top Institute Food and Nutrition, Nieuwe Kanaal 9A, Wageningen, 6709 PA, The Netherlands; Netherlands Organization for Applied Scientific Research TNO, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands; Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD, Wageningen, The Netherlands. Electronic address: dina.ripken@tno.nl.
authors.forename: Dina
authors.initials: D
authors.lastname: Ripken
authors.affiliation: Top Institute Food and Nutrition, Nieuwe Kanaal 9A, Wageningen, 6709 PA, The Netherlands; Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD, Wageningen, The Netherlands.
authors.forename: Nikkie
authors.initials: N
authors.lastname: van der Wielen
authors.affiliation: Netherlands Organization for Applied Scientific Research TNO, Utrechtseweg 48, 3704 HE, Zeist, The Netherlands.
authors.forename: Heleen M
authors.initials: HM
authors.lastname: Wortelboer
authors.affiliation: Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD, Wageningen, The Netherlands.
authors.forename: Jocelijn
authors.initials: J
authors.lastname: Meijerink
authors.affiliation: Division of Human Nutrition, Wageningen University, Bomenweg 2, 6703 HD, Wageningen, The Netherlands.
authors.forename: Renger F
authors.initials: RF
authors.lastname: Witkamp
authors.affiliation: Top Institute Food and Nutrition, Nieuwe Kanaal 9A, Wageningen, 6709 PA, The Netherlands.
authors.forename: Henk F J
authors.initials: HF
authors.lastname: Hendriks
mesh_terms: D000818:Animals; D002364:Caseins / Q000378:metabolism*; D002460:Cell Line; D003986:Dibenzocycloheptenes; D019422:Dietary Sucrose / Q000378:metabolism*; D045786:Diterpenes, Kaurane / Q000378:metabolism; D004759:Enterochromaffin Cells / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000187:drug effects / Q000378:metabolism*; D005473:Fluoxetine / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D012450:Safflower Oil / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D034421:Sus scrofa; D013549:Sweetening Agents / Q000378:metabolism*; D000097789:Glucagon-Like Peptide-1 Receptor Agonists
chemical_list: D002364:Caseins; D003986:Dibenzocycloheptenes; D019422:Dietary Sucrose; D045786:Diterpenes, Kaurane; D005473:Fluoxetine; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D006576:Heterocyclic Compounds, 4 or More Rings; D012450:Safflower Oil; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; D013549:Sweetening Agents; D000097789:Glucagon-Like Peptide-1 Receptor Agonists; C025474:rebaudioside A; C522667:asenapine
keywords: GLP-1; Serotonin; nutrients; rebaudioside A; small intestine