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 Ca2+ 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.

Receptor Agonism and Antagonism of Dietary Bitter Compounds

“…Agonists recently identified (Dotson et al, 2008;Intelmann et al, 2009;Slack et al, 2010) were applied at EC 90 concentration. Because of low potency, agonists for hTAS2R5, hTAS2R7, and hTAS2R13 were used at their maximum applicable concentration that did not cause unspecific fluorescence signals in control cells.…”

Variation in the Ability to Taste Bitter Thiourea Compounds: Implications for Food Acceptance, Dietary Intake, and Obesity Risk in Children

“…These receptors likely play critical roles in nutrient detection. For example, bitter-taste receptors have been found to mediate glucose homeostasis (35) and secretion of the appetite-stimulating hormone ghrelin (70). Therefore, it is possible that variants in TAS2R genes could modulate appetite, food intake, and body weight through their functional roles in the gut.…”

The human bitter taste receptor hTAS2R39 is the primary receptor for the bitterness of theaflavins

“…[9][10][11][12] In the digestive tract, TAS2Rs are expressed in the endocrine cells of intestinal epithelial tissues and are known to participate in the secretion of incretins such as glucagon-like peptide-1 (GLP-1) and CCK. [13][14][15] Furthermore, it has been reported that bitter substances, such as denatonium, bind to tracheal smooth muscle, resulting in contraction of the bronchial tube. 16) We have previously reported that among the 25 human TAS2Rs (hTAS2Rs), the bitterness of catechins, which are precursors of theaflavins, is perceived by hTAS2R39 8) and hTAS2R14.…”