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

• Published in: PloS one Vol. 19; no. 11; p. e0313128
• Main Authors: Palmer, R. Kyle, Nechiporenko, Anna B., Ilies, Marc A., Winnig, Marcel, Gravina, Stephen A., Tiwari, Rashmi, Prakash, Indra
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 18.11.2024; Public Library of Science (PLoS)
• Subjects: Adult; Analysis; Animals; Benzene Derivatives; Binding sites; Biology and Life Sciences; Carbohydrates; Cell activation; CHO Cells; Cricetinae; Cricetulus; Engineering and Technology; Epithelial cells; Evaluation; Female; Glucose; Glucose - metabolism; Glucose tolerance tests; Glucose transport; Homeostasis; Human subjects; Humans; Hypotheses; Inhibitors; Male; Medicine and Health Sciences; Membrane potential; Membrane Potentials - drug effects; Membranes; Phlorhizin - pharmacology; Physical Sciences; Potassium; Protein transport; Proteins; Receptors; Receptors, G-Protein-Coupled - metabolism; Saccharides; Signal transduction; Social Sciences; Sodium; Sodium chloride; Sodium-Glucose Transporter 1 - metabolism; Sucrose; Sweet taste; Sweeteners; Taste; Taste - physiology; Taste buds; Taste Buds - drug effects; Taste Buds - metabolism; Taste discrimination; Taste receptor neurons; Taste receptors; Taste thresholds; Young Adult; United States
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0313128

The sweet taste of saccharides, such as sucrose and glucose, and other sweeteners is known to result from activation of the TAS1R2/R3 receptor expressed in taste receptor cells (TRCs) of the taste bud. Recent reports have suggested the existence of an additional sweet taste signaling pathway for metabolizable saccharides that is dependent on the activity of glucose transporters, especially SGLT1, also expressed in TRCs. We have investigated the potential contribution of SGLT1 to glucose taste signaling in humans. Concentration-response analysis of glucose mediated changes in membrane potential measured in Chinese hamster ovary (CHO) cells transiently expressing the human SGLT1 (hSGLT1) yielded an EC50 value of 452 μM. The SGLT inhibitor phlorizin inhibited the membrane potential response to 10 mM glucose with an IC50 of 3.5 μM. In contrast, EC50 values of 127 and 132 mM were obtained from concentration-response analysis of glucose taste in vehicles of water or 20 mM NaCl, respectively, by rapid throughput taste discrimination with human subjects. Lactisole, an antagonist of TAS1R2/R3, at a concentration of 1 mM completely inhibited taste responses to glucose concentrations of 250 mM and below. Phlorizin (0.2 mM) and the high potency SGLT1-selective inhibitor mizagliflozin (10 μM) failed to inhibit glucose taste detection measured at peri-threshold concentrations in the rapid throughput taste discrimination assay. A Yes/No experiment using the taste discrimination assay revealed that 0.2 mM phlorizin was discriminable from water for some subjects. Taken together the results indicate that agonist activation of TAS1R2/R3 is sufficient to account for all glucose taste without contribution by an alternative SGLT-mediated signaling pathway. Furthermore, the taste of phlorizin could be a confounding variable for studies evaluating a role for SGLTs in taste.