Pathways and genes of sweet taste cells

甜味细胞的通路和基因

• 批准号: 9232128
• 负责人: Robert F. Margolskee
• 金额: $ 30.98万
• 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: 2015-03-01 至 2020-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9232128
• 关键词: Adrenergic alpha-Antagonists; Affect; Alpha-glucosidase; Behavioral; Binding; Bioinformatics; Biological Assay; Brush Border; Calories; Carbohydrates; Cell Lineage; Cell physiology; Cells; Country; Desire for food; Detection; Diabetes Mellitus; Disaccharidases; Disaccharides; Dose; Enzyme Inhibitor Drugs; Enzymes; Epidemic; Generations; Genes; Glucose; Glucose Transporter; Glyburide; Goals; Grant; Immunohistochemistry; In Situ Hybridization; Intestines; Killer Cells; Knock-out; Knockout Mice; Knowledge; Lead; Left; Maltose; Mediating; Medical; Metabolic; Metabolic Diseases; Metabolism; Methods; Modeling; Mus; Nerve; Obesity; Pathway interactions; Physiological; Potassium Channel; Receptor Cell; Regulation; Role; Satiation; Sucrase; Sucrose; Sweetening Agents; Taste Buds; Taste Perception; Testing; Tissues; Transgenic Organisms; Type II Epithelial Receptor Cell; Wild Type Mouse; Work; caspase 14; experimental study; glucose transport; glucose uptake; inhibitor/antagonist; insight; interdisciplinary approach; knockout gene; public health relevance; receptor; response; selective expression; sensor; sucrase-isomaltase-maltase; sugar; sweet receptor; sweet taste perception; taste transduction; transcription factor; transcriptomics

 DESCRIPTION (provided by applicant): The sweet taste receptor protein T1r2+T1r3, encoded by the Tas1r2 and Tas1r3 genes, mediates taste responses to non-caloric sweeteners. However, Tas1r3 knockout mice generated in our group retain taste nerve responses to glucose and maltose. Glucose transporters (GLUTs) and metabolic sensors (KATP) expressed selectively in Tas1r3-positive taste cells may underlie taste responses of Tas1r3 knockout mice to sugars. Tas1r3-positive taste cells also express two intestinal type enzymes, sucrase-isomaltase and maltase-glucoamylase, that hydrolyze sucrose and maltose. The general goals of this grant are to elucidate the mechanisms underlying taste detection of sugars and to identify transcription factors that control the generation of sweet-responsive taste cells. The experiments proposed here use gene knockout mice and enzyme inhibitors to assess the involvement of KATP, sucrase-isomaltase and maltase-glucoamylase in taste responses to sugars. In the first two aims of the proposal we combine transgenic, physiological and behavioral methods to determine: 1. If sugar transporters and KATP metabolic sensors contribute to taste transduction of sugars, and 2. If intestinal disaccharidase enzymes expressed in Tas1r3-positive taste cells contribute to taste transduction of sugars. In the third aim we build on results from bioinformatic analysis of genes expressed in taste cells to: (a) Identify transcription factors selectively expressed in Tas1r3+ taste cells, and (b) Determine if loss of transcription factors selectively expressed in Tas1r3-positive taste cells affects generation and function of these cells. Ultimately, these studies may provide insights into why sugars are preferred over non-caloric sweeteners, lead to the generation of superior non-caloric sweeteners, and provide a means to regulate sweet-responsive taste cells so as to decrease the drive for consuming sugar. This multidisciplinary approach has promise for providing significant new insights into the function and regulation of sweet taste receptor cells. This proposal has medical relevance to gustatory function, appetite, satiety, diabetes and obesity.

 描述（由适用提供）：由TAS1R2和TAS1R3基因编码的甜味受体蛋白T1R2+T1R3，介导对非含量甜味剂的味道反应。但是，我们组中产生的TAS1R3敲除小鼠保留了对葡萄糖和麦芽糖的味觉神经反应。葡萄糖转运蛋白（Gluts）和代谢传感器（KATP）在TAS1R3阳性味觉细胞中选择性表达，可能是Tas1r3敲除小鼠对糖的味觉反应的基础。 TAS1R3阳性味道细胞还表达了两种肠道类型酶，Sucrase-异藻酶和麦芽酶 - 葡萄糖酰基酶，它们水解蔗糖和麦芽糖。该赠款的一般目标是阐明糖的味觉检测的基础机制，并确定控制甜反应性味觉细胞产生的转录因子。此处提出的实验使用基因基因敲除小鼠和酶抑制剂评估Katp，Sucrase-异藻酶和麦芽糖酶 - 葡萄糖酰基酶在对糖的味道反应中的参与。在该提案的前两个目标中，我们将转基因，物理和行为方法结合在一起，以确定：1。如果糖转运蛋白和KATP代谢传感器有助于糖的味道转移，而2。如果在Tas1R3阳性味道细胞中表达的肠道杀菌酶酶有助于糖的味道转移。在第三个目标中，我们基于对味道细胞中表达的基因的生物信息学分析的结果：（a）在Tas1r3+味道细胞中选择性地识别转录因子，以及（b）确定在TAS1R3阳性味觉细胞中选择性表达的转录因子是否会影响这些细胞的产生和功能。最终，这些研究可能会提供有关为什么糖优于非热甜味剂，导致产生优质的非热甜味剂，并提供一种调节甜味反应性味觉细胞的方法，从而减少食用糖的驱动力，从而提供见解。这种多学科方法有望为甜味受体细胞的功能和调节提供重要的新见解。该提案与味觉功能，食欲，饱腹感，糖尿病和肥胖具有医学相关性。