Sodium-dependent glucose co-transport proteins (SGLTs) are not involved in human glucose taste detection

The sweet taste of saccharides, such as sucrose and glucose, is primarily attributed to the activation of the TAS1R2/TAS1R3 receptor in taste receptor cells (TRCs) of the taste buds. However, recent studies have suggested the existence of an additional sweet taste signaling pathway for metabolizable saccharides, involving glucose transporters like SGLT1, which are also expressed in TRCs. To assess the role of SGLT1 in glucose taste signaling in humans, we conducted a series of experiments.

Membrane potential changes in Chinese hamster ovary (CHO) cells transiently expressing human SGLT1 (hSGLT1) were measured in response to glucose. The concentration-response analysis revealed an EC50 value of 452 μM. The SGLT inhibitor phlorizin blocked the response to 10 mM glucose with an IC50 of 3.5 μM. In contrast, human taste discrimination assays yielded EC50 values of 127 mM and 132 mM for glucose in water and 20 mM NaCl, respectively. The TAS1R2/TAS1R3 antagonist lactisole (1 mM) completely inhibited taste responses to glucose concentrations of 250 mM or lower. However, phlorizin (0.2 mM) and the SGLT1-selective inhibitor mizagliflozin (10 μM) did not inhibit glucose taste detection at peri-threshold concentrations in the human taste discrimination assay.

A separate Yes/No experiment showed that some subjects could distinguish 0.2 mM phlorizin from water, suggesting phlorizin itself has a detectable taste. These findings indicate that activation of TAS1R2/TAS1R3 fully accounts for glucose taste, with no contribution from an alternative SGLT1-mediated pathway. Additionally,KWA 0711 the taste of phlorizin may confound studies exploring the role of SGLTs in taste perception.