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

J Nutr Biochem. 2016 Jun;32:142-50. doi: 10.1016/j.jnutbio.2016.03.006. Epub 2016 Mar 29.


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.

Keywords: GLP-1; Serotonin; nutrients; rebaudioside A; small intestine.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Caseins / metabolism*
  • Cell Line
  • Dietary Sucrose / metabolism*
  • Diterpenes, Kaurane / metabolism
  • Enterochromaffin Cells / metabolism
  • Enteroendocrine Cells / drug effects
  • Enteroendocrine Cells / metabolism*
  • Fluoxetine / pharmacology
  • Gene Expression Regulation / drug effects
  • Glucagon-Like Peptide 1 / metabolism*
  • 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
  • Safflower Oil / metabolism*
  • Serotonin / metabolism*
  • Serotonin Antagonists / pharmacology
  • Serotonin Uptake Inhibitors / pharmacology
  • Sus scrofa
  • Sweetening Agents / metabolism*


  • Caseins
  • Dietary Sucrose
  • Diterpenes, Kaurane
  • Glucagon-Like Peptide-1 Receptor
  • Heterocyclic Compounds, 4 or More Rings
  • Serotonin Antagonists
  • Serotonin Uptake Inhibitors
  • Sweetening Agents
  • Fluoxetine
  • Serotonin
  • Safflower Oil
  • Glucagon-Like Peptide 1
  • rebaudioside A
  • asenapine