Behavioral and neural measures of oral carbohydrate and sweetener reward signals

点击翻译按钮获取中文摘要

Abstract The metabolic signaling pathway in T1r3+ mouse taste cells are similar to that found in pancreatic beta islet cells that sense calories from glucose. This signaling pathway is comprised of glucose transporters (GLUTs & SGLTs), glucokinase, and the ATP-gated potassium channel (KATP). Human taste cells have a similar pathway. The oral disaccharidase enzymes, first found in the brush border of the gut, that sever glycosidic bonds are expressed orally in rodents; but, beyond our unpublished preliminary data, this has not been shown in humans. We hypothesize that oral disaccharidases are necessary to free glucose and other monosaccharides to activate the metabolic signaling pathway. We also hypothesize that these enzymes in humans enable the metabolic responses of taste cells to contribute to transduction and perception of disaccharide taste. We propose that this results in stronger preferences for disaccharides over non-caloric sweeteners. We hypothesize further that the release of glucose from disaccharide cleaving, its transport into taste cells, and its metabolism to generate ATP leads to taste signaling. This signal may also contribute to anticipatory metabolic responses in humans during carbohydrate tolerance tests. In Aim 1 we will determine whether oral metabolic signaling contributes to disaccharide perception, metabolic tolerance, liking and preference in humans. In Aim 2 we will determine whether oral metabolic signals influence licking and motivated behaviors in rats and where in the brain these signals are registered. If sugar reward signaling can be manipulated by modulating oral disaccharidase activity, then there should be therapeutic utility to developing a strategy to maximize reward while reducing sugar intake. Improving our understanding of the role oral glucose metabolic signaling plays in human taste should help prevent and reduce obesity, diabetes, and metabolic syndrome that afflict approximately one-third of all Americans.