(P31-009-23) The Oral Metabolic Signaling Pathway for the Polyol Sweeteners Sorbitol, Allulose, and Erythritol Is Inhibited by Phlorizin

Objectives: We previously found that human oral glucose detection involves two pathways: 1) the sweetener transduction pathway via T1R2/T1R3 taste receptors and 2) a sodium-glucose co-transporter (SGLT). Not all sweeteners, however, engage both of these pathways. For example, although fructose and sucralose are sweet and engage the T1R2/T1R3 taste receptors, they do not engage the SGLT pathway.  Hence, the addition of sodium, which is co-transported with sugars by the sodium-glucose linked transporter (SGLT), enhances taste sensitivity to glucose but not fructose or sucralose. Furthermore, the addition of the SGLT1/2 inhibitor phlorizin impedes glucose detection but not detection of fructose or sucralose. We wondered whether we could understand the specificity of oral polyol transport in human taste by examining three additional stimuli: the glucose analog sorbitol, the fructose analog allulose, and the four-carbon polyol erythritol, which resembles a foreshortened sorbitol.

Methods: In a series of experiments, we compared oral detection thresholds of allulose, erythritol, and sorbitol with and without the addition of sodium (NaCl), which provides sodium that can be co-transported with glucose by SGLT. We also tested their thresholds in the presence of NaCl and the SGLT inhibitor phlorizin.

Results: The addition of NaCl did not lower the detection thresholds for allulose, erythritol, or sorbitol indicating that the SGLT may not be involved. When we compared oral detection thresholds for allulose, erythritol, and sorbitol with and without the SGLT inhibitor phlorizin, we observed inhibition of taste detection for all three. This inhibitory effect is not observed with fructose.

Conclusions: Thus, there is evidence that sorbitol, allulose, and erythritol are engaging a mechanism in human taste that is inhibited by phlorizin, but not enhanced by sodium. Although SGLT is a likely candidate, it is unclear why the addition of sodium is ineffective. There is also evidence that a metabolite of phlorizin, phloretin or phloridzin, may inhibit GLUT2 in addition to the SGLTs. Additionally, phlorizin may also block the KATP channel, another recently identified metabolic pathway in mice for oral carbohydrate sensing.

Funding Sources: Funding was provided to PASB by Suntory Beverage and Food Ltd.