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Effect of the Artificial Sweetener, Acesulfame Potassium, a Sweet Taste Receptor Agonist, on Glucose Uptake in Small Intestinal Cell Lines

Abstract

Introduction

Sweet taste receptors may enhance glucose absorption.

Aim

This study aimed to explore the cell biology of sweet taste receptors on glucose uptake.

Hypothesis

Artificial sweeteners increase glucose uptake via activating sweet taste receptors in the enterocyte to translocate GLUT2 to the apical membrane through the PLC βII pathway.

Methods

Caco-2, RIE-1, and IEC-6 cells, starved from glucose for 1 h were pre-incubated with 10 mM acesulfame potassium (AceK). Glucose uptake was measured by incubating cells for 1 to 10 min with 0.5–50 mM glucose with or without U-73122, chelerythrine, and cytochalasin B.

Results

In Caco-2 and RIE-1 cells, 10 mM AceK increased glucose uptake by 20–30 % at glucose >25 mM, but not in lesser glucose concentrations (<10 mM), nor at 1 min or 10 min incubations. U-73122 (PLC βII inhibitor) inhibited uptake at glucose >25 mM and for 5 min incubation; chelerythrine and cytochalasin B had similar effects. No effect occurred in IEC-6 cells.

Summary

Activation of sweet taste receptors had no effect on glucose uptake in low (<25 mM) glucose concentrations but increased uptake at greater concentrations (>25 mM).

Conclusions

Role of artificial sweeteners on glucose uptake appears to act in part by effects on the enterocyte itself.

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Acknowledgments

The authors wish to thank Deborah Frank for her expertise in the preparation of the manuscript.

This work was supported in part by NIH grant R01 DK039337 (MGS).

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Corresponding author

Correspondence to Michael G. Sarr.

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Discussant

Dr. Jeffrey B. Matthews (Chicago, IL): In this excellent presentation, the authors have shown that the mechanisms of glucose absorption by enterocytes involves multiple interacting transport pathways that are complexly regulated through kinase signaling triggered by substrate itself. Here, they show, in essence, that the gut "tastes" not only sugar but also an artificial sweetener molecule and rapidly adjusts surface absorptive capacity in response.

I have two questions for the authors. First, you showed that the artificial sweetener specifically activated GLUT-2 mediated glucose absorption. Does it also affect absorption of non-sugar substances such as amino acids or larger molecules either by a similar mechanism or by an increase in paracellular permeability? Second, can you speculate on the mechanisms accounting for the transient response you observed, which seemed to be gone by 10 min? Was GLUT-2 rapidly re-internalized?

Closing Discussant

Dr. Ye Zheng: Q1. The artificial sweetener sucralose has been demonstrated by Mace et al. (2009) in mice intestine to increase glucose uptake by translocation of GLUT2 into the apical membrane and to decrease peptide uptake by trafficking the peptide transporter PEPT1 away from the apical membrane.

Q2. It was surprising that the 10-min incubation with artificial sweetener, acesulfamine K, did not further increase glucose uptake when compared to control. One possible mechanism is that during the 10-min incubation, cells had already maximized the process of GLUT2 translocation, and acesulfamine K had no further synergistic effect on translocating more GLUT2 transporters to the apical membrane.

This work will be presented in part at the SSAT in Digestive Disease Week, on May 22, 2012.

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Zheng, Y., Sarr, M.G. Effect of the Artificial Sweetener, Acesulfame Potassium, a Sweet Taste Receptor Agonist, on Glucose Uptake in Small Intestinal Cell Lines. J Gastrointest Surg 17, 153–158 (2013). https://doi.org/10.1007/s11605-012-1998-z

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  • DOI: https://doi.org/10.1007/s11605-012-1998-z

Keywords

  • Sweet taste receptor
  • Acesulfame potassium
  • GLUT2
  • PLC βII