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在两个TC的种群中表达：表达A-糖蛋白表达/T1R3（甜蜜受体）表达细胞的子集（称为II型细胞），以及一个血清素能细胞的子集（称为IIII型细胞）。 这种发散的表达可能会提供对GLP-1在味蕾中不同功能作用的见解。 Drucker博士为我们提供了具有GLP-1受体的转基因小鼠（GLP1R KO小鼠），我们发现它们对营养和非营养甜味剂的味觉敏感性降低，但对柠檬酸表现出高敏性。这支持了局部生产的GLP-1以维持或增强甜味敏感性的概念。 GLP-1R KO小鼠对首选（蔗糖和甲氯酸酯）和厌恶味（酸）刺激的差异反应可能反映了从II型和III型细胞子集分泌的GLP-1的差异作用。这两种细胞类型具有几种分子和生理差异，因此很可能在外围味觉编码中起着不同的作用。 II型和III型细胞也可能提供不同的位点，以调制口味编码。我们还发现，味道细胞也具有特权，因为它们不含二肽基肽酶4，这是一种负责降解GLP-1的酶。 这表明GLP-1浓度可以保持较高和活跃的味觉乳头状，并强调了该特定部位GLP-1的生理相关性。因此，味蕾可以作为味觉敏感性的正阳性和负调节剂的重要目标，从而为在动物代谢状态的背景下为调节摄入行为的调节提供了外围机制。此外，我们发现，调节饱腹感和寻求食物行为的另一种肠道激素也是在味觉细胞中产生的，而不是产生GLP-1的肠系膜。我们目前正在研究其在动物中的功能，该功能是用作其生长素释放蛋白受体的工具小鼠。