Sweet Taste Receptors As Metabolic Regulators: TAS1R2-TAS1R3 Activation or Inhibition Differentially Affects Glucose Metabolism in Humans

Objectives: In taste bud cells, sweetness is identified through activation of the sweet taste receptor, TAS1R2-TAS1R3. Beyond the mouth, sweet taste receptors are present in intestinal enteroendocrine cells and in pancreatic β cells. The objective of this study was to determine whether systemic activation and inhibition of TAS1R2-TAS1R3 with sucralose and sodium lactisole, respectively, affects glucose metabolism and whether these effects were correlated with oral taste abilities. Methods: In a randomized crossover design, twelve healthy adults completed oral glucose tolerance tests with 75 g glucose load alone, or 75 g glucose mixed with 5 mM sucralose. In a second experiment, ten healthy adults completed OGTTs with 75 g glucose or 75 g glucose mixed with 2 mM sodium lactisole. Plasma glucose, insulin, glucagon and GLP-1 were measured at baseline and up to 120 minutes after consumption. Participants also were tested for taste responsiveness to sucralose and sodium lactisole. Results: When sucralose was added to the OGTT, participants had elevated plasma insulin responses compared to their baseline (p=0.056). Oral sucralose sensitivity, measured by sweetness ratings, were correlated with early increases (15 minute AUC) in both plasma glucose and insulin (p< 0.05). When sodium lactisole was added to the OGTT, participants had no change in glucose or insulin responses. Sensitivity to lactisole inhibition of sweetness was correlated with an overall depression of plasma glucose from the lactisole OGTT (120 minute AUC) (R2=0.84, p< 0.01). Conclusions: In summary, activation of sweet taste receptors throughout the body increased insulin release in oral glucose tolerance tests. Effects of sucralose and sodium lactisole were correlated with an individual's taste sensitivity. Our future research will examine whether SNPs in the TAS1R2 or TAS1R3 genes are associated with dysglycemias. TAS1R2-TAS1R3 may be a clinically relevant target for metabolic control in dysglycemia and diabetes. Funding Sources: Supported by NIH R01DC014286, R21 DC020365 to PASB.