A study of hormone-expressing taste cells: 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)。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。此外，II型和III型细胞可以为味觉编码的调制提供不同的位置。胰高血糖素和GLP-1是孕激素来源的一种活性多肽。它曾被认为只在胰岛的阿尔佩细胞中产生。现在看来，它肯定是在II型味觉细胞中产生的，在那里我们发现它是调节“甜味”的关键因素。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TCs中产生，但不是那些产生GLP-1的TCs。利用Ghrelin受体消失的小鼠(由DRS Smith和Sun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Ghrelin是酸味和咸味的增强剂。这为Ghrelin在调节哺乳动物寻找的食物类型方面增加了另一种功能。味蕾可以作为正负向激素调节味觉敏感性的重要靶点，从而为在动物代谢状态下调节摄食行为提供了一种外围机制。

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.