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

我们发现GLP-1在两种TC群体中表达：α-味蛋白表达/T1 R3（甜味受体）表达细胞（称为II型细胞）的亚群，和β-肾上腺素能细胞（称为III型细胞）的亚群。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。这支持了本地产生的GLP-1调节味觉敏感性的观点。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。另外，II型和III型细胞可以提供用于调节味觉编码的不同位点。 胰高血糖素沿着GLP-1是衍生自胰高血糖素原的活性肽。 它被认为只在胰岛的α细胞中产生。 现在可以肯定的是，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，我们还发现，另一种调节饱腹感和觅食行为的肠道激素ghrelin也在TC中产生，但不产生GLP-1。利用消除了胃饥饿素受体的小鼠（由Smith和Sun博士提供），并将它们的味觉反应与野生型小鼠进行比较，我们发现胃饥饿素是酸味和咸味的增强剂。这增加了ghrelin在调节哺乳动物寻求食物类型方面的另一个功能。 味蕾可以作为味觉敏感性的正性和负性激素调节剂的重要靶点，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。 最近，我们发现，随着年龄的增长，味蕾中调节甜味敏感性的激素数量减少，对甜味或咸味的敏感性减弱，导致缺乏对食物的欣赏。我们现在正在启动一项味蕾干细胞的研究，以引出未来细胞类型决定的控制机制。 设法改善这种看法将提高老年人的生活质量。

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 proglucagon. It had been thought to be only produced in alpha 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 in TCs, 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. More recently, we have found that, with age, the number of hormones modulating sweet sensitivity is decreased in taste buds and sensitivity to sweet or salt taste is dimnished, leading to a lack of appreciation of food. We are now initiating a study of stem cells in taste buds in order to eliciting the control mechanism for cell type decisions in the future. Finding ways to improve such perceptions would improve quality of life for the elderly.