Role of Metabolic Sensing in Human Sweet Taste

代谢传感在人类甜味中的作用

• 批准号: 9029886
• 负责人: Paul A. S Breslin
• 金额: $ 32.93万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9029886
• 关键词: Admixture; American; Animals; Beverages; Calories; Cell physiology; Cells; Data; Detection; Diabetes Mellitus; Diet; Disease; Esthesia; Fructose; Functional Imaging; Glucose; Glucose Transporter; Goals; Human; Human Biology; Intake; Intestines; Knockout Mice; Macronutrients Nutrition; Mediating; Messenger RNA; Metabolic; Metabolic syndrome; Metabolism; Mono-S; Monosaccharides; Mus; Nucleic Acids; Obesity; Oral; Oral cavity; Pancreas; Pathway interactions; Perception; Potassium Channel; Protein Subunits; Psychometrics; Psychophysics; Quinine; Receptor Cell; Research; Rewards; Role; Salts; Sampling; Signal Transduction; Sodium; Stimulus; Sweetening Agents; System; T1R receptor; Taste Buds; Taste Perception; Techniques; Testing; Therapeutic; Tissues; Tongue; base; glucose transport; glucose uptake; gut endocrine cell; human subject; improved; inhibitor/antagonist; obesity risk; preference; prevent; public health relevance; research study; response; sensor; sugar; sweet receptor; sweet taste perception; sweetened beverage; symporter; taste system; taste transduction

 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.

 描述（由申请人提供） 有压倒性的证据表明，甜味受体亚基 T1R2 和 T1R3 对于小鼠以及人类的甜味感至关重要。尽管 T1R 受体对甜味的重要性显而易见，但有证据表明存在检测或调节甜味的替代途径。舌头的味觉细胞与肠道和胰腺的味觉样内分泌细胞之间的共性使得“肠型”糖传感器（例如，葡萄糖转运蛋白（GLUT）和钠-葡萄糖共转运蛋白（SGLT））或“胰腺型”代谢传感器（ATP门控的KATP通道）也可能存在于味觉细胞和胰腺中。 作用于糖的甜味。该项目的主要目标是识别和表征人类味觉受体细胞用来感知糖和卡路里的 T1R 独立机制。我们假设糖转运蛋白和代谢传感器是人类味觉受体细胞中独立于 T1R 的糖感应的基础。我们还假设人类味觉细胞的代谢反应有助于甜味的感知，并有助于赋予营养性甜味剂比无热量甜味剂更强烈的偏好。我们进一步假设，转运到对甜味敏感的人类味觉细胞中的葡萄糖代谢会导致细胞内 ATP 升高，从而关闭味觉细胞的 KATP 通道，使细胞去极化。我们将使用培养的人类味觉受体细胞的组织学和功能研究以及人类受试者的味觉心理物理测试来检验这些假设。这些研究将共同​​确定人类味觉细胞中糖转运蛋白和 KATP 通道是否存在并活跃，以及它们是否可能有助于人类受试者的糖感知和口腔奖励。如果甜味系统中的这种代谢传感器能够在不增加热量的情况下受到刺激，那么它可以提供一种有效的手段来帮助减少美国饮食中的过量糖分，从而降低肥胖和与过度消耗热量相关的其他疾病的风险。