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.
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