Behavioral and neural measures of oral carbohydrate and sweetener reward signals

摘要 T1R3小鼠味觉细胞的代谢信号通路与胰岛细胞相似 从葡萄糖中感觉到卡路里。这个信号通路由葡萄糖转运体(Gluts和SGLT)组成， 葡萄糖激酶和三磷酸腺苷门控钾通道(KATP)。人类味觉细胞也有类似的途径。口服液 二糖酶，最早发现于肠道的刷状边缘，表达出断链的糖苷键 在啮齿动物中口服；但是，除了我们未发表的初步数据外，这还没有在人类身上显示出来。我们 假设口服双糖酶是释放葡萄糖和其他单糖激活 代谢信号通路。我们还假设，人类体内的这些酶能够使新陈代谢 味觉细胞的反应有助于转导和感知二糖的味道。我们建议这一点 与非卡路里甜味剂相比，人们对双糖的偏好更强。我们进一步假设， 从二糖裂解中释放葡萄糖，将其运输到味觉细胞，并通过代谢产生三磷酸腺苷 会产生味觉信号。这一信号也可能对人类的预期代谢反应有贡献 碳水化合物耐量测试。在目标1中，我们将确定口服代谢信号是否有助于 人类对双糖的感知、代谢耐受性、喜好和偏好。在目标2中，我们将确定 口服代谢信号是否影响大鼠的舔舔和动机行为，以及这些信号在大脑中的位置 信号已被记录。如果糖奖励信号可以通过调节口服双糖酶活性来操纵， 然后，开发一种策略，在减少糖摄入量的同时最大化回报，应该有治疗作用。 提高我们对口服葡萄糖代谢信号在人类味觉中的作用的理解应该会有所帮助 预防和减少肥胖、糖尿病和代谢综合征，这些疾病约占三分之一 美国人。

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found in the brush border of the gut, that sever glycosidic bonds are expressed orally in rodents; but, beyond our unpublished preliminary data, this has not been shown in humans.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.