A study of hormone-expressing taste cels: in vivo and in vitro

表达激素味觉细胞的研究：体内和体外

• 批准号: 7963910
• 负责人: Josephine Egan
• 金额: $ 31.38万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7963910
• 关键词: Acids; Animals; Behavior; Cells; Citric Acid; Code; Eating; Enhancers; Esthesia; Exhibits; Feeding behaviors; Food; Food Preferences; GLP-I receptor; GTP-Binding Proteins; Gastric Emptying; Glucose; Homeostasis; Hormonal; Hormones; Hypersensitivity; In Vitro; L Cells; Lead; Mammals; Mediating; Metabolic; Modality; Molecular; Mus; Peripheral; Physiological; Play; Population; Protein Subunits; Regulation; Research; Role; Satiation; Site; Stimulus; Sucrose; Sweetening Agents; System; Taste Buds; Taste Perception; The Sun; Transgenic Mice; Type II Epithelial Receptor Cell; Type III Epithelial Receptor Cell; Wild Type Mouse; Work; alpha-gustducin; cell type; ghrelin; ghrelin receptor; glucagon-like peptide 1; in vivo; insulin secretion; rat Gnat3 protein; receptor; response; sweet receptor; sweet taste perception; trichlorosucrose

We found that GLP-1 is expressed in two populations of TCs: a subset of a-gustducin-expressing/T1R3 (sweet receptor)-expressing cells (called Type II cells), and a subset of serotonergic cells (called Type III cells). Dr Drucker provided us with transgenic mice that had their GLP-1 receptors obliterated (GLP1R KO mice) and we found that they exhibited reduced taste sensitivity to both nutritive and non-nutritive sweeteners, but displayed hypersensitivity to citric acid. This supports the notion that locally-produced GLP-1 regulates taste sensitivity. The differential responses of GLP-1R KO mice to preferred (sucrose and sucralose) and aversive taste (acid) stimuli may reflect the differential effects of GLP-1 secreted from subsets of Type II and Type III cells. These two cell types have several molecular and physiological differences and are therefore likely to play distinct roles in peripheral taste coding. Type II and Type III cells may provide distinct sites for modulation of taste coding, as well. The taste bud may serve as an important target for positive and negative hormonal modulators of taste sensitivity, thus providing a peripheral mechanism for the regulation of ingestive behaviors in the context of an animals metabolic state. Additionally, we have found that ghrelin, another gut hormone that regulates satiety and food-seeking behavior, is also produced inTCs, but not those that produce GLP-1. Utilizing mice that have their ghrelin receptors obliterated (Provided by Drs Smith and Sun) and comparing their taste responses to wild-type mice we found that ghrelin is an enhancer of sour and salty taste. This adds another function to ghrelin in regulating the types of food that mammals seek.

我们发现GLP-1在两种TC群体中表达：α-味蛋白表达/T1 R3（甜味受体）表达细胞（称为II型细胞）的亚群，和β-肾上腺素能细胞（称为III型细胞）的亚群。Drucker博士为我们提供了GLP-1受体被清除的转基因小鼠（GLP 1 R KO小鼠），我们发现它们对营养性和非营养性甜味剂的味觉敏感性降低，但对柠檬酸表现出超敏反应。这支持了本地产生的GLP-1调节味觉敏感性的观点。GLP-1 R KO小鼠对偏好（蔗糖和三氯蔗糖）和厌恶味道（酸）刺激的不同反应可能反映了II型和III型细胞亚群分泌的GLP-1的不同作用。这两种细胞类型具有几种分子和生理差异，因此可能在外周味觉编码中发挥不同的作用。II型和III型细胞也可以提供用于调节味觉编码的不同位点。味蕾可以作为味觉敏感性的正性和负性激素调节剂的重要靶点，从而在动物代谢状态的背景下提供用于调节摄食行为的外周机制。此外，我们还发现另一种调节饱腹感和觅食行为的肠道激素ghrelin也在TC中产生，但不产生GLP-1。利用消除了胃饥饿素受体的小鼠（由史密斯博士和孙博士提供），并将它们的味觉反应与野生型小鼠进行比较，我们发现胃饥饿素是酸味和咸味的增强剂。这增加了ghrelin在调节哺乳动物寻求食物类型方面的另一个功能。