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

我们发现GLP-1在TCS的两个群体中表达：表达α-Gustducin/T1R3(甜味受体)的细胞的子集(称为II型细胞)和5-羟色胺能细胞的子集(称为III型细胞)。这种不同的表达可能为了解GLP-1在味蕾中的不同功能提供了见解。德鲁克博士为我们提供了GLP-1受体缺失的转基因小鼠(GLP1R KO小鼠)，我们发现它们对营养和非营养甜味剂的味道敏感度降低，但对柠檬酸过敏。这支持了这样一种观点，即当地生产的GLP-1可以保持或增强甜味敏感性。GLP-1R KO小鼠对偏好刺激(蔗糖和三氯蔗糖)和厌恶味觉(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的不同效应。这两种细胞类型有几个分子和生理差异，因此很可能在外周味觉编码中扮演不同的角色。II型和III型细胞也可以为味觉编码的调制提供不同的位置。我们还发现，味觉细胞也很有优势，因为它们不含有二肽基肽酶4，这是一种负责降解GLP-1的酶。这表明GLP-1在味觉乳头中的浓度可以保持较高的活性，并强调了GLP-1在该特定部位的生理相关性。因此，味蕾可能是味觉敏感度正负调节因子的重要靶点，从而为在动物代谢状态下调节摄食行为提供了一种外周机制。此外，我们还发现，另一种调节饱腹感和觅食行为的胃肠激素Ghrelin也在味觉细胞中产生，但不是那些产生GLP-1的细胞。我们目前正在动物身上研究它的功能，利用Ghrelin受体消失的小鼠作为工具。

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.