The flavanone homoeriodictyol increases SGLT-1-mediated glucose uptake but decreases serotonin release in differentiated Caco-2 cells

PLoS One. 2017 Feb 13;12(2):e0171580. doi: 10.1371/journal.pone.0171580. eCollection 2017.

Abstract

Flavanoids and related polyphenols, among them hesperitin, have been shown to modulate cellular glucose transport by targeting SGLT-1 and GLUT-2 transport proteins. We aimed to investigate whether homoeriodictyol, which is structurally related to hesperitin, affects glucose uptake in differentiated Caco-2 cells as a model for the intestinal barrier. The results revealed that, in contrast to other polyphenols, the flavanon homoeriodictyol promotes glucose uptake by 29.0 ± 3.83% at a concentration of 100 μM. The glucose uptake stimulating effect was sensitive to phloridzin, but not to phloretin, indicating an involvement of the sodium-coupled glucose transporter SGLT-1, but not of sodium-independent glucose transporters (GLUT). In addition, in contrast to the increased extracellular serotonin levels by stimulation with 500 mM D-(+)-glucose, treatment with 100 μM homoeriodictyol decreased serotonin release by -48.8 ± 7.57% in Caco-2 cells via a phloridzin-sensitive signaling pathway. Extracellular serotonin levels were also reduced by -57.1 ± 5.43% after application of 0.01 μM homoeriodictyol to human neural SH-SY5Y cells. In conclusion, we demonstrate that homoeriodictyol affects both the glucose metabolism and the serotonin system in Caco-2 cells via a SGLT-1-meditated pathway. Furthermore, the results presented here support the usage of Caco-2 cells as a model for peripheral serotonin release. Further investigations may address the value of homoeriodictyol in the treatment of anorexia and malnutrition through the targeting of SGLT-1.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Biological Transport / drug effects
  • Caco-2 Cells
  • Cell Differentiation
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Cyclic AMP / metabolism
  • Extracellular Space / drug effects
  • Extracellular Space / metabolism
  • Flavones / pharmacology*
  • Gene Expression / drug effects
  • Glucose / metabolism*
  • Glucose / pharmacology
  • Humans
  • Phlorhizin / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Sodium-Glucose Transporter 1 / genetics
  • Sodium-Glucose Transporter 1 / metabolism*

Substances

  • Flavones
  • SLC5A1 protein, human
  • Sodium-Glucose Transporter 1
  • Serotonin
  • Phlorhizin
  • Cyclic AMP
  • homoeriodictyol
  • Glucose

Grants and funding

The financial support by the Austrian Federal Ministry of Economy, Family and Youth and the Austrian National Foundation for Research, Technology and Development and the Symrise AG is gratefully acknowledged. KG contributed to the glucose uptake experiments, JH, JPL and GEK contributed to the study design and preparation of the manuscript.