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: 7732188
• 负责人: Josephine Egan
• 金额: $ 22.13万
• 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/7732188
• 关键词: Acids; Animals; Appetitive Behavior; Behavior; Cells; Citric Acid; Code; Dipeptidyl Peptidases; Eating; Enzymes; Esthesia; Exhibits; Feeding behaviors; Food; Food Preferences; GLP-I receptor; GTP-Binding Proteins; Gastric Emptying; Glucose; Homeostasis; Hormones; Hypersensitivity; In Vitro; L Cells; Mammals; Mediating; Metabolic; Modality; Molecular; Mus; Peripheral; Physiological; Play; Population; Protein Subunits; Regulation; Role; Satiation; Site; Stimulus; Sucrose; Sweetening Agents; System; Taste Buds; Taste Perception; Transgenic Mice; Type II Epithelial Receptor Cell; Type III Epithelial Receptor Cell; Work; alpha-gustducin; cell type; ghrelin; ghrelin receptor; glucagon-like peptide 1; in vivo; insight; insulin secretion; rat Gnat3 protein; receptor; response; sweet receptor; sweet taste perception; tongue papilla; tool; 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). This divergent expression may provide insights into distinct functional roles of GLP-1 within the taste bud. 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 to maintain or enhance sweet 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. We also found that taste cells are also privileged in that they do not contain dipeptidyl peptidase 4, an enzyme responsible for degrading GLP-1. This indicates that GLP-1 concentrations can remain high and active within taste papillae and underscores the physiological relevance of GLP-1 in that particular site. Therefore, the taste bud may serve as an important target for positive and negative 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 in taste cells, but not those that produce GLP-1. We are presently investigating its function in animals, utilizing as a tool mice that have their ghrelin receptors obliterated.

我们发现GLP-1在两种TC群体中表达：表达α-味觉蛋白/表达T1 R3（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）。 这种不同的表达可以提供对味蕾内GLP-1的不同功能作用的见解。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。这支持了本地生产的GLP-1维持或增强甜味敏感性的观点。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。我们还发现味觉细胞的优势还在于它们不含二肽基肽酶4，一种负责降解GLP-1的酶。 这表明GLP-1浓度可以在味觉乳头内保持高水平和活性，并强调了GLP-1在该特定部位的生理相关性。因此，味蕾可以作为味觉敏感性的正调节剂和负调节剂的重要靶点，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也在味觉细胞中产生，但不是那些产生GLP-1的细胞。我们目前正在研究其在动物中的功能，利用其生长激素受体被清除的小鼠作为工具。