Journal Article

Bitter Taste Receptors Influence Glucose Homeostasis

Shin, Yu-Kyong, Steinle, Nanette I., Ott, Sandra H., Zhang, Lan, Shaw, Hillary, Xu, Hong, Li, Xiaodong, Dotson, Cedrick D., Mitchell, Braxton D., Elson, Amanda E. T., Munger, Steven D., Vigues, Stephan, Choi, Hyun Jin, Egan, Josephine M.

2008

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Biochemistry/Biomacromolecule-Ligand Interactions / Biosynthesis / Bitter taste / Blood glucose / Calcium (intracellular) / Calcium ions / Chemoreception / Chromosomes / Diabetes / Diabetes and Endocrinology / Diabetes mellitus / Diabetes mellitus (non-insulin dependent) / Diabetes Mellitus, Type 2 - genetics / Diabetes Mellitus, Type 2 - metabolism / Endocrinology / Enteroendocrine Cells - metabolism / Family / Food intake / Gastrointestinal system / Gastrointestinal tract / Gene Frequency / Genes / Genetic Predisposition to Disease / Genomes / Genotype / Glucagon / Glucagon-like peptide 1 / Glucose / Glucose - metabolism / Glucose tolerance / Glucose tolerance test / Gustatory system / Haplotypes / Homeostasis / Homeostasis - genetics / Humans / Insulin / L cells / Linkage Disequilibrium / Medicine / Metabolic disorders / Middle Aged / Neurobiology / Neuroscience/Sensory Systems / Neurosciences / Nutrient uptake / Ofloxacin / Older people / Physiological aspects / Polymorphism, Single Nucleotide / Receptors / Receptors, G-Protein-Coupled - genetics / Receptors, G-Protein-Coupled - metabolism / Receptors, G-Protein-Coupled - physiology / Rodents / Secretion / Single-nucleotide polymorphism / Sweet taste / Sweeteners / Taste / Taste (Sense) / Taste Perception - genetics / Taste Perception - physiology / Taste receptors / Tongue / Type 2 diabetes