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Pathways and genes of sweet taste cells

甜味细胞的通路和基因

基本信息

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
项目类别：
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

项目摘要

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（由申请人提供）：由Tas 1 r2和Tas 1 r3基因编码的甜味受体蛋白T1 r2 + T1 r3介导对无热量甜味剂的味觉反应。然而，我们组中产生的Tas 1 r3敲除小鼠保留了对葡萄糖和麦芽糖的味觉神经反应。在Tas 1 r3阳性味觉细胞中选择性表达的葡萄糖转运蛋白（GLUT）和代谢传感器（KATP）可能是Tas 1 r3基因敲除小鼠对糖的味觉反应的基础。tas 1 r3阳性味觉细胞也表达两种肠型酶，蔗糖酶-异麦芽糖酶和麦芽糖酶-葡糖淀粉酶，水解蔗糖和麦芽糖。这项资助的总体目标是阐明糖的味觉检测机制，并确定控制甜味反应味觉细胞产生的转录因子。这里提出的实验使用基因敲除小鼠和酶抑制剂来评估KATP、蔗糖酶-异麦芽糖酶和麦芽糖酶-葡糖淀粉酶参与对糖的味觉反应。在前两个目标的建议，我们联合收割机转基因，生理和行为的方法来确定：1。如果糖转运蛋白和KATP代谢传感器有助于糖的味觉转导，和2。如果在Tas 1 r3阳性味觉细胞中表达的肠二硫代磷酸酶有助于糖的味觉转导。在第三个目标中，我们建立在味觉细胞中表达的基因的生物信息学分析结果的基础上：（a）鉴定在Tas 1 r3+味觉细胞中选择性表达的转录因子，以及（B）确定在Tas 1 r3阳性味觉细胞中选择性表达的转录因子的缺失是否影响这些细胞的产生和功能。最终，这些研究可以提供为什么糖比无热量甜味剂更受欢迎的见解，导致上级无热量甜味剂的产生，并提供一种调节甜味反应味觉细胞的方法，以减少消耗糖的动力。这种多学科的方法有希望为甜味受体细胞的功能和调节提供重要的新见解。该建议与味觉功能、食欲、饱腹感、糖尿病和肥胖症具有医学相关性。