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

表达激素味觉细胞的研究：体内和体外

• 批准号: 8335804
• 负责人: Josephine Egan
• 金额: $ 39.79万
• 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/8335804
• 关键词: Acids; Animals; Behavior; Cells; Citric Acid; Code; Eating; Enhancers; Esthesia; Exhibits; Feeding behaviors; Food; Food Preferences; GTP-Binding Proteins; Gastric Emptying; Glucagon; Glucose; Homeostasis; Hormonal; Hormones; Hypersensitivity; In Vitro; Islet Cell; L Cells; Lead; Mammals; Mediating; Metabolic; Modality; Molecular; Mus; Peptides; 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; 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. Additionally, Type II and Type III cells may provide distinct sites for modulation of taste coding. Glucagon along with GLP-1 is an active peptide that is derived from proglocagon. It had been thought to be only produced in alpay cells of islets. It now appears certain that it is produced in Type II taste cells where we found it to be a critical factor in modulation of 'sweetness'. 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. 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.

我们发现 GLP-1 在两个 TC 群体中表达：表达 a-味觉素/T1R3（甜味受体）的细胞亚群（称为 II 型细胞）和血清素能细胞亚群（称为 III 型细胞）。 Drucker 博士为我们提供了 GLP-1 受体被消除的转基因小鼠（GLP1R 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性。这支持了本地生产的 GLP-1 调节味觉敏感性的观点。 GLP-1R 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一些分子和生理学差异，因此可能在外周味觉编码中发挥不同的作用。此外，II 型和 III 型细胞可能为味觉编码的调节提供不同的位点。 胰高血糖素和 GLP-1 是一种源自高血糖素原的活性肽。 人们认为它只在胰岛的阿尔帕伊细胞中产生。 现在看来可以确定它是在 II 型味觉细胞中产生的，我们发现它是调节“甜味”的关键因素。 此外，我们发现胃饥饿素（另一种调节饱腹感和觅食行为的肠道激素）也在 TC 中产生，但在那些产生 GLP-1 的细胞中则不产生。利用生长素释放肽受体被消除的小鼠（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，我们发现生长素释放肽是酸味和咸味的增强剂。这增加了生长素释放肽的另一个功能，即调节哺乳动物寻求的食物类型。 味蕾可能作为味觉敏感性的正向和负向激素调节剂的重要靶标，从而为动物代谢状态下的摄入行为的调节提供外围机制。