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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Intramural Research (Z01)
Project #
1Z01AG000291-01
Application #
7732188
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2008
Total Cost
$221,322
Indirect Cost
Name
National Institute on Aging
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Egan, Josephine M; Margolskee, Robert F (2008) Taste cells of the gut and gastrointestinal chemosensation. Mol Interv 8:78-81
Jang, Hyeung-Jin; Kokrashvili, Zaza; Theodorakis, Michael J et al. (2007) Gut-expressed gustducin and taste receptors regulate secretion of glucagon-like peptide-1. Proc Natl Acad Sci U S A 104:15069-74