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

味觉功能中葡萄糖传感器作用的行政补充（多样性）

• 批准号: 10655237
• 负责人: Lindsey A Schier
• 金额: $ 9.71万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10655237
• 关键词: Administrative Supplement; Alpha-glucosidase; Automobile Driving; Binding; Body Composition; Calories; Carbohydrates; Cells; Complex; Consumption; Coupled; Data; Desire for food; Detection; Diabetes Mellitus; Diet; Diet Habits; Dietary Sugars; Digestion; Disaccharides; Electrophysiology (science); Energy Intake; Enzymes; Epidemic; Exposure to; Food; Food Preferences; Fostering; Fructose; G-Protein-Coupled Receptors; GTP-Binding Proteins; Glucokinase; Glucose; Goals; Health; Impairment; Ingestion; Intake; Laboratories; Learning; Ligands; Link; Maltose; Mediating; Metabolic; Metabolic Diseases; Methods; Modernization; Molecular; Monosaccharides; Motivation; Mus; Nerve; Neurons; Nucleus solitarius; Nutrient; Oral; Outcome; Outcome Study; Parents; Pathway interactions; Peripheral; Phosphorylation; Play; Population; Property; Research; Rodent; Role; Signal Transduction; Sweetening Agents; System; Taste Bud Cell; Taste Buds; Taste Perception; Taste preferences; Testing; Training; United States; Weight Gain; Work; blind; detection of nutrient; dietary; experience; falls; follow-up; genetic manipulation; glycemic control; graduate student; hedonic; novel; novel strategies; preference; rapid detection; receptor; receptor function; reinforcer; response; sensor; sugar; sweet receptor; sweet taste perception; taste system; transmission process; western diet

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.

项目概要 典型的西方饮食富含单糖，其美味是补充能量的主要因素 美国的卡路里摄入过多、体重增加和糖尿病。单一异二聚体 G 蛋白 哺乳动物味觉细胞中发现的偶联受体（T1R2+T1R3）被广泛认为是主要途径 所有单糖都会被检测到并通过味觉系统促进消耗。然而，最近的研究 我们实验室的研究表明，啮齿类动物对 含葡萄糖的糖类优于其他类型的甜味剂。母版 R01 提案中的初步调查结果 该应用揭示了葡萄糖激酶（一种参与其他葡萄糖代谢系统的磷酸化酶）， 在小鼠味觉细胞中表达，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，而沉默葡萄糖激酶会损害区分葡萄糖和其他葡萄糖的能力 糖、果糖。因此，我们的工作假设是葡萄糖激酶是 T1R2+T1R3 独立蛋白的一部分 味觉受体，在味觉系统中转导葡萄糖特异性信号。本次活动的总体目标 那么，行政多样性补充提案就是为了进一步明确这部小说的相对贡献。 味觉葡萄糖传感器对含葡萄糖糖的享乐吸引力。在目标 1 中，我们将确定哪个 膳食糖的类型调节对甜味敏感的小鼠味蕾细胞中葡萄糖激酶的表达，并且，使用 一种病毒基因沉默方法，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，我们将结合味觉受体功能的基因操作 通过电生理学来确定葡萄糖激酶依赖性味觉信号是如何一级编码的 甜味敏感和甜味不敏感小鼠味觉系统的中枢中继，以及这是如何发生的 饮食中接触单糖后，信息会被重新组织。这些目标的成果将有助于 确定营养物传感的新颖且潜在的关键方面，最终目标是确定新的 抑制食欲的策略。