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

我们发现GLP-1在两种TCs群体中表达：表达a-gustducin /T1R3（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）。Drucker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性和非营养性甜味剂的味觉敏感性都降低了，但对柠檬酸表现出过敏。这支持了本地产生的GLP-1调节味觉敏感性的观点。GLP-1R 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。这两种细胞类型在分子和生理上有一些差异，因此可能在外周味觉编码中发挥不同的作用。此外，II型和III型细胞可能提供不同的味觉编码调制位点。胰高血糖素和GLP-1是一种活性肽，由胰高血糖素衍生而来。它一直被认为只在胰岛的细胞中产生。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寻找食物行为的肠道激素ghrelin也会产生intc，但不会产生GLP-1。利用胃饥饿素受体缺失的小鼠（由史密斯和孙博士提供），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。这为胃饥饿素增加了另一项功能，即调节哺乳动物寻找的食物类型。味蕾可能是味觉敏感的正、负激素调节的重要靶点，从而为动物代谢状态下的摄食行为调节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.