title: Bitter taste receptors influence glucose homeostasis.
abstract: TAS1R- and TAS2R-type taste receptors are expressed in the gustatory system, where they detect sweet- and bitter-tasting stimuli, respectively. These receptors are also expressed in subsets of cells within the mammalian gastrointestinal tract, where they mediate nutrient assimilation and endocrine responses. For example, sweeteners stimulate taste receptors on the surface of gut enteroendocrine L cells to elicit an increase in intracellular Ca(2+) and secretion of the incretin hormone glucagon-like peptide-1 (GLP-1), an important modulator of insulin biosynthesis and secretion. Because of the importance of taste receptors in the regulation of food intake and the alimentary responses to chemostimuli, we hypothesized that differences in taste receptor efficacy may impact glucose homeostasis. To address this issue, we initiated a candidate gene study within the Amish Family Diabetes Study and assessed the association of taste receptor variants with indicators of glucose dysregulation, including a diagnosis of type 2 diabetes mellitus and high levels of blood glucose and insulin during an oral glucose tolerance test. We report that a TAS2R haplotype is associated with altered glucose and insulin homeostasis. We also found that one SNP within this haplotype disrupts normal responses of a single receptor, TAS2R9, to its cognate ligands ofloxacin, procainamide and pirenzapine. Together, these findings suggest that a functionally compromised TAS2R receptor negatively impacts glucose homeostasis, providing an important link between alimentary chemosensation and metabolic disease.
authors.affiliation: Department of Anatomy & Neurobiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Cedrick D
authors.initials: CD
authors.lastname: Dotson
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Xu
authors.forename: Yu-Kyong
authors.initials: YK
authors.lastname: Shin
authors.forename: Stephan
authors.initials: S
authors.lastname: Vigues
authors.forename: Sandra H
authors.initials: SH
authors.lastname: Ott
authors.forename: Amanda E T
authors.initials: AE
authors.lastname: Elson
authors.forename: Hyun Jin
authors.initials: HJ
authors.lastname: Choi
authors.forename: Hillary
authors.initials: H
authors.lastname: Shaw
authors.forename: Josephine M
authors.initials: JM
authors.lastname: Egan
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Li
authors.forename: Nanette I
authors.initials: NI
authors.lastname: Steinle
authors.forename: Steven D
authors.initials: SD
authors.lastname: Munger
mesh_terms: D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism; D005190:Family; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D055697:Taste Perception / Q000235:genetics / Q000502:physiology; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; D000098706:Taste Receptors, Type 2; D005947:Glucose