Role of Metabolic Sensing in Human Sweet Taste

? DESCRIPTION (provided by applicant) There is overwhelming evidence that the sweet receptor subunits T1R2 and T1R3 are key to the sense of sweet taste in mice, as well as in humans. Despite the clear importance of T1R receptors to sweet taste, there is evidence that alternative pathways exist for detection or modulation of sweet taste. Commonalities among taste cells of tongue and taste-like endocrine cells of gut and pancreas make it plausible that intestinal-type sugar sensors (e.g., glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs)) or pancreatic-type metabolic sensors (ATP-gated KATP channels) might also be present in taste cells and function in sweet sensation of sugars. The main goal of this project is to identify and characterize T1R- independent mechanisms used by human taste receptor cells to sense sugars and calories. We hypothesize that sugar transporters and metabolic sensors underlie T1R-independent sugar sensing in human taste receptor cells. We also hypothesize that metabolic responses of human taste cells contribute to the perception of sweet taste and help impart the stronger preference for nutritive over non-caloric sweeteners. We hypothesize further that metabolism of glucose transported into sweet-responsive human taste cells leads to elevated intracellular ATP that closes the taste cell's KATP channels, depolarizing the cell. We will test these hypotheses using histological and functional studies in cultured human taste receptor cells and taste psychophysical tests in human subjects. Together these studies will determine if sugar transporters and KATP channels are present and active in human taste cells and if they are likely to contribute to sugar sensing and oral reward in human subjects. If this metabolic sensor in the sweet taste system can be stimulated without adding calories, it could provide an effective means to help reduce excess sugar in the US diet, thereby reducing the risk of obesity and other diseases associated with overconsumption of calories.