Investigation of the Contribution of Glucose Transport to Detection of Glucose Taste by Human Subjects in a Rapid Throughput Taste Discrimination Assay

Abstract

<b>Abstract ID 21690</b> <b>Poster Board 409</b> The GPCR heterodimer TAS1R2/TAS1R3 expressed in specialized cells in the taste bud is known to be the principle mediator of sweet taste signaling to agonists such as glucose. Recent evidence has suggested an additional taste signaling pathway specific to glucose and potentially other metabolizable saccharides through a sodium-dependent glucose transporter protein (SGLT) also in taste cells. We previously used a rapid throughput taste discrimination assay for human subjects to characterize concentration-dependence of the taste of agonists of TAS1R2/TAS1R3 (Palmer et&nbsp;al, 2021, JPET, 377:133-145). In this assay, subjects self-administer 200 μl of tastant solution drawn by an electronic pipette from randomly presented wells of a 96-well plate. Responses to taste stimuli are registered by touching predesignated targets on a touch-sensitive laptop display, and are reinforced by the immediate appearance of a virtual poker chip that carries actual monetary value. We now are using this approach to pharmacologically investigate the contribution of the proposed SGLT taste signaling pathway by testing the effects of sodium (co-transported with glucose) and the non-selective SGLT inhibitor phlorizin on glucose taste discrimination. Two male and 2 female adults served as subjects in a rapid throughput discrimination between glucose and water taste stimuli presented randomly across 96 trials per test. The test followed a forced choice method of constant stimuli (MCS) design to determine the discriminability of 5 different randomly presented concentrations of glucose (20, 40, 60, 80 and 100 mM; 12 trials each per test) from water (36 trials per test). Touch responses on a “sweet”-designated target during trials of any glucose concentration were reinforced with a 20-cent poker chip, as were responses on a “water”-designated target on trials of water. Errors (i.e., touching the “sweet” target on water trials, or “water” target on glucose trials) were penalized by a 10-cent subtraction from the subject’s cumulative score. Each subject was tested 6 times on this design. Signal detection analysis of the resulting dataset averaged across all subjects and all tests yielded a d’ value for discriminability 0.55 for 20 mM glucose, indicating that this concentration was near an empirical threshold for detection. The test was repeated with 20 mM NaCl replacing water as a stimulus and as the solvent for all glucose concentrations. Discriminability of glucose was increased when dissolved in 20 mM NaCl; the d’ value for 20 mM glucose under these conditions increased to 1.01, indicating that the presence of sodium enhanced detection of glucose. However, and in contrast to a recent publication (Breslin et&nbsp;al, 2021, PLoS One, 16(10):e0256989), addition of 200 μM phlorizin had no impact on discriminability of any concentration of glucose dissolved in water. Thus, the enhancing effect of sodium on discriminability of low glucose concentrations does not appear to involve an SGLT.