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.
Highlights
Glucose uptake from the lumen into the epithelial cells of the small intestine is predominantly mediated by the sodium-coupled transporter SGLT-1 [1]
Further transport from the enterocytes to the blood stream is thought to be mediated by the facilitative uniporter glucose transporter 2 (GLUT-2), which exhibits, compared to SGLT-1, a low affinity, but high capacity for PLOS ONE | DOI:10.1371/journal.pone
Results are inconsistent since a structure-associated activity has not yet been demonstrated; whereas phloretin, myricetin, and quercetin affect glucose uptake via glucose transporters (GLUT) transporters, the polyphenols phloridzin and neohesperidin have been shown to decrease sodium-dependent glucose uptake, indicating a SGLT-1-dependent mechanism [13]
Summary
Glucose uptake from the lumen into the epithelial cells of the small intestine is predominantly mediated by the sodium-coupled transporter SGLT-1 [1]. Further transport from the enterocytes to the blood stream is thought to be mediated by the facilitative uniporter glucose transporter 2 (GLUT-2), which exhibits, compared to SGLT-1, a low affinity, but high capacity for PLOS ONE | DOI:10.1371/journal.pone.0171580. Homoeriodictyol increases glucose-uptake but decreases serotonin release via SGLT-1 Further transport from the enterocytes to the blood stream is thought to be mediated by the facilitative uniporter glucose transporter 2 (GLUT-2), which exhibits, compared to SGLT-1, a low affinity, but high capacity for PLOS ONE | DOI:10.1371/journal.pone.0171580 February 13, 2017
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