Administrative Supplement (Diversity) to Roles for Glucosensors in Taste Function

项目摘要 典型的西方饮食中含有单糖，它们可口的味道是促进饮食健康的主要因素。 热量摄入过多、体重增加和糖尿病。单个异二聚体G蛋白 在哺乳动物味觉细胞中发现的偶联受体（T1R2+T1R3）被广泛认为是通过 其中所有单糖都被检测到并通过味觉系统促进消耗。然而，最近的研究表明， 从我们的实验室发现，啮齿动物来响应更积极的orosensory属性， 比其他类型的甜味剂含葡萄糖的糖。R01提案中的初步调查结果 并且该申请揭示了葡糖激酶，一种参与其它葡萄糖传感系统的磷酸化酶， 在鼠味觉细胞中表达，受能量状态和饮食调节。味觉葡萄糖激酶的激活 增强葡萄糖食欲，而沉默葡萄糖激酶则会损害将葡萄糖与其他葡萄糖区分开来的能力 糖果糖因此，我们的工作假设是，葡萄糖激酶是T1R2+T1R3非依赖性 在味觉系统中传递葡萄糖特异性信号的味觉受体。这个项目的总体目标是 行政多元化的补充建议，则是为了进一步阐明这部小说的相关贡献 味觉葡萄糖传感器对含葡萄糖的糖的享乐吸引力。在目标1中，我们将确定 不同类型的膳食糖调节糖敏感小鼠味蕾细胞中葡萄糖激酶的表达， 一种病毒发生沉默的方法，将研究舌葡萄糖激酶是否是享乐所必需的。 葡萄糖二糖的吸引力。在目标2中，我们将联合收割机结合味觉受体功能的遗传操作， 用电生理学来确定葡萄糖激酶依赖的味觉信号是如何在一级编码的， 中枢中继味觉系统在甜敏感和甜不敏感小鼠，以及如何这 在饮食中接触单糖后，信息被重组。这些目标的成果将有助于 确定营养感测的新的和潜在的关键方面，最终目标是确定新的 控制食欲的策略。

PROJECT SUMMARY The typical Western diet is loaded with simple sugars, and their palatable taste is a predominant factor fueling excess calorie intake, body weight gain, and diabetes in the United States. A single heterodimeric G-protein coupled receptor (T1R2+T1R3) found in mammalian taste cells is widely considered the principal means through which all simple sugars are detected and promote consumption via the gustatory system. Yet, recent studies from our laboratory revealed that rodents come to respond more positively to the orosensory properties of glucose-containing sugars than other types of sweeteners. The preliminary findings in the parent R01 proposal and this application reveal that glucokinase, a phosphorylating enzyme involved in other glucosensing systems, is expressed in murine taste cells, is regulated by energy status, and diet. Activation of gustatory glucokinase bolsters glucose appetite, while silencing glucokinase impairs the ability to discriminate glucose from another sugar, fructose. Accordingly, our working hypothesis is that glucokinase is part of a T1R2+T1R3-independent taste receptor that transduces glucose-specific signals in the gustatory system. The overall goal of this administrative diversity supplement proposal, then, is to further clarify relative contributions of this novel gustatory glucosensor to the hedonic appeal of glucose-containing sugars. In Aim 1, we will determine which types of dietary sugars regulate glucokinase expression in the taste bud cells of sweet-sensitive mice, and, using a virogenetic silencing approach, will investigate whether lingual glucokinase is required for the hedonic appeal of glucose disaccharides. In Aim 2, we will combine genetic manipulation of taste receptor function with electrophysiology to determine how glucokinase-dependent taste signals are encoded at the first order central relay of the gustatory system in sweet-sensitive and sweet-insensitive mice, and how this information is reorganized after dietary exposure to simple sugars. The outcomes of these aims will help identify novel and potentially critical aspects of nutrient sensing, with the ultimate goal of identifying new strategies to curb appetite.