Effect of taste receptor protein T1R3 on the development of islet tissue of the murine pancreas

2019 ◽  
Vol 484 (1) ◽  
pp. 117-120
Author(s):  
V. O. Murovets ◽  
E. A. Sozontov ◽  
T. G. Zachepilo
Keyword(s):  
Parent Strain ◽  
Gene Knockout ◽  
Taste Receptor ◽  
Morphological Characteristics ◽  
Sweet Taste ◽  
Pancreatic Tissue ◽  
Receptor Protein ◽  
Gene Encoding ◽  
Islet Tissue ◽  
Knockout Animals

Protein T1R3, the main subunit of sweet, as well as amino acid, taste receptor, is expressed in the epithelium of the tongue and gastro intestinal tract, in β–cells of the pancreas, hypothalamus, and numerous other organs. Recently, convincing witnesses of T1R3 involvement in control of carbohydrate and lipid metabolism, and control of production of incretines and insulin, have been determined. In the study on Tas1r3-gene knockout mouse strain and parent strain C57Bl/6J as control, priority data concerning the effect of T1R3 on the morphological characteristics of Langerhans islets in the pancreas, are obtained. In Tas1r3 knockout animals, it is found that the size of the islets and their density in pancreatic tissue are reduced, as compared to the parent strain. Additionally, a decrease of expression of active caspase-3 in islets of gene-knockouts is demonstrated. The obtained data show that the lack of a functional, gene encoding sweet-taste receptor protein causes a dystrophy of the islet tissue and associates to the development of pathological changes in the pancreas specific to type-2 diabetes and obesity in humans.

scholarly journals Ultimate Molecular Theory of Bitter Taste

2021 ◽  
Author(s):  
Huazhong He
Keyword(s):  
Binding Sites ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Protein ◽  
Helical Structures ◽  
Sweet Taste Receptor ◽  
Multiple Binding Sites ◽  
Multiple Receptors ◽  
Multiple Binding

More than thirty years ago, I proposed a theory about sweet and bitter molecules’ recognition by protein helical structures. Unfortunately the papers could not go to public platform until now. Inspired by the sweet taste theory<sup>1,2</sup>, this bitter taste theory conveys that bitter molecules are recognized by receptor protein helical structures. The recognition process is a dynamic action, in which the receptor protein helices have a torsion-spring-like oscillation between helical structures of 3.6 and 4 amino acids per turn. Based on the characteristics of the bitter receptor protein helix oscillation, it perfectly explains why in bitter molecules, only one unit of hydrogen donor (DH) or hydrogen acceptor (B) is enough in helping molecules to elicit bitter taste. The potential DH and B in bitter receptor are any NH or O of receptor’s peptide NHs and Os, which are the ones forming intramolecular H-bonds responsible for the formation of receptor protein helical structures. Furthermore, only one unit of DH or B is allowed for structurally simple ligands. As recognition sites are only associated with a small fraction – helix structure of whole bitter receptor, multiple binding sites or multiple receptors are well expected. As the oscillation may have different extent, it translates to bitterness intensity. According to ligand-receptor binding motion, bitter receptor could be divided into two kinds of spaces, which are similar to the situation in sweet taste receptor: main and side grooves. These have been discussed in context and especially great details in paper titled deciphering aspartyl peptide sweeteners <sup>2</sup>.

scholarly journals T1r3 taste receptor involvement in gustatory neural responses to ethanol and oral ethanol preference

2010 ◽  
Vol 41 (3) ◽  
pp. 232-243 ◽  
Author(s):  
Susan M. Brasser ◽  
Meghan B. Norman ◽  
Christian H. Lemon
Keyword(s):  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Protein ◽  
Wild Type ◽  
Ethanol Preference ◽  
Background Strain ◽  
Neurobiological Substrates ◽  
High Concentrations ◽  
Gustatory Neurons ◽  
Deficient Mice

Elevated alcohol consumption is associated with enhanced preference for sweet substances across species and may be mediated by oral alcohol-induced activation of neurobiological substrates for sweet taste. Here, we directly examined the contribution of the T1r3 receptor protein, important for sweet taste detection in mammals, to ethanol intake and preference and the neural processing of ethanol taste by measuring behavioral and central neurophysiological responses to oral alcohol in T1r3 receptor-deficient mice and their C57BL/6J background strain. T1r3 knockout and wild-type mice were tested in behavioral preference assays for long-term voluntary intake of a broad concentration range of ethanol, sucrose, and quinine. For neurophysiological experiments, separate groups of mice of each genotype were anesthetized, and taste responses to ethanol and stimuli of different taste qualities were electrophysiologically recorded from gustatory neurons in the nucleus of the solitary tract. Mice lacking the T1r3 receptor were behaviorally indifferent to alcohol (i.e., ∼50% preference values) at concentrations typically preferred by wild-type mice (5–15%). Central neural taste responses to ethanol in T1r3-deficient mice were significantly lower compared with C57BL/6J controls, a strain for which oral ethanol stimulation produced a concentration-dependent activation of sweet-responsive NTS gustatory neurons. An attenuated difference in ethanol preference between knockouts and controls at concentrations >15% indicated that other sensory and/or postingestive effects of ethanol compete with sweet taste input at high concentrations. As expected, T1r3 knockouts exhibited strongly suppressed behavioral and neural taste responses to sweeteners but did not differ from wild-type mice in responses to prototypic salt, acid, or bitter stimuli. These data implicate the T1r3 receptor in the sensory detection and transduction of ethanol taste.

scholarly journals Ultimate Molecular Theory of Bitter Taste

2021 ◽  
Author(s):  
Huazhong He
Keyword(s):  
Binding Sites ◽  
Bitter Taste ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Protein ◽  
Helical Structures ◽  
Sweet Taste Receptor ◽  
Multiple Binding Sites ◽  
Multiple Receptors ◽  
Multiple Binding

More than thirty years ago, I proposed a theory about sweet and bitter molecules’ recognition by protein helical structures. Unfortunately the papers could not go to public platform until now. Inspired by the sweet taste theory<sup>1,2</sup>, this bitter taste theory conveys that bitter molecules are recognized by receptor protein helical structures. The recognition process is a dynamic action, in which the receptor protein helices have a torsion-spring-like oscillation between helical structures of 3.6 and 4 amino acids per turn. Based on the characteristics of the bitter receptor protein helix oscillation, it perfectly explains why in bitter molecules, only one unit of hydrogen donor (DH) or hydrogen acceptor (B) is enough in helping molecules to elicit bitter taste. The potential DH and B in bitter receptor are any NH or O of receptor’s peptide NHs and Os, which are the ones forming intramolecular H-bonds responsible for the formation of receptor protein helical structures. Furthermore, only one unit of DH or B is allowed for structurally simple ligands. As recognition sites are only associated with a small fraction – helix structure of whole bitter receptor, multiple binding sites or multiple receptors are well expected. As the oscillation may have different extent, it translates to bitterness intensity. According to ligand-receptor binding motion, bitter receptor could be divided into two kinds of spaces, which are similar to the situation in sweet taste receptor: main and side grooves. These have been discussed in context and especially great details in paper titled deciphering aspartyl peptide sweeteners <sup>2</sup>.

scholarly journals Multimodal Ligand Binding Studies of Human and Mouse G-Coupled Taste Receptors to Correlate Their Species-Specific Sweetness Tasting Properties

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2531 ◽  
Author(s):  
Fariba Assadi-Porter ◽  
James Radek ◽  
Hongyu Rao ◽  
Marco Tonelli
Keyword(s):  
Ligand Binding ◽  
Conformational Changes ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Protein ◽  
In Vitro Assays ◽  
Resonance Spectroscopy ◽  
Binding Studies ◽  
Scanning Calorimetry ◽  
Species Specific

Taste signaling is a complex process that is linked to obesity and its associated metabolic syndromes. The sweet taste is mediated through a heterodimeric G protein coupled receptor (GPCR) in a species-specific manner and at multi-tissue specific levels. The sweet receptor recognizes a large number of ligands with structural and functional diversities to modulate different amplitudes of downstream signaling pathway(s). The human sweet-taste receptor has been extremely difficult to study by biophysical methods due to the difficulty in producing large homogeneous quantities of the taste-receptor protein and the lack of reliable in vitro assays to precisely measure productive ligand binding modes that lead to activation of the receptor protein. We report here a multimodal high throughput assay to monitor ligand binding, receptor stability and conformational changes to model the molecular ligand-receptor interactions. We applied saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR) complemented by differential scanning calorimetry (DSC), circular dichroism (CD) spectroscopy, and intrinsic fluorescence spectroscopy (IF) to characterize binding interactions. Our method using complementary NMR and biophysical analysis is advantageous to study the mechanism of ligand binding and signaling processes in other GPCRs.

scholarly journals Multimodal Ligand Binding Studies of Human and Mouse G-Coupled Taste Receptors to Correlate with their Species-Specific Sweetness Properties

2018 ◽  
Author(s):  
Fariba M. Assadi-Porter ◽  
James Radek ◽  
Hongyo Rao ◽  
Marco Tonelli
Keyword(s):  
Ligand Binding ◽  
Conformational Changes ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Protein ◽  
In Vitro Assays ◽  
Resonance Spectroscopy ◽  
Binding Studies ◽  
Scanning Calorimetry ◽  
Species Specific

Taste signaling is a complex process that is linked to obesity and its associated metabolic syndromes. The sweet taste is mediated through a heterodimeric G protein coupled receptor (GPRC) in a species-specific manner and at multi-tissue specific levels. The sweet receptor recognizes a large number of ligands with structural and functional diversities to modulate different amplitudes of downstream signaling pathway(s). The human sweet-taste receptor has been extremely difficult to study by biophysical methods due to inadequate methods for producing large homogeneous quantities of the taste-receptor protein and a lack of reliable in vitro assays to precisely measure productive ligand binding modes leading to activity upon their interactions with the receptor protein. We report a multimodal high throughput assays to monitor ligand binding, receptor stability and conformational changes to model the molecular interactions between ligand-receptor. We applied saturation transfer difference nuclear magnetic resonance spectroscopy (STD-NMR) complemented by differential scanning calorimetry (DSC), circular dichroism (CD) spectroscopy, and intrinsic fluorescence spectroscopy (IF) to characterize binding interactions. Our method using complementary NMR and biophysical analysis is advantageous to study the mechanism of ligand binding and signaling processes in other GPCRs.

scholarly journals Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6-Tas1r3 congenic mice

2007 ◽  
Vol 32 (1) ◽  
pp. 82-94 ◽  
Author(s):  
Masashi Inoue ◽  
John I. Glendinning ◽  
Maria L. Theodorides ◽  
Sarah Harkness ◽  
Xia Li ◽  
...  
Keyword(s):  
Amino Acids ◽  
Genetic Architecture ◽  
Allelic Variation ◽  
Monosodium Glutamate ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Receptor Protein ◽  
Chorda Tympani Nerve ◽  
Congenic Mice ◽  
Wide Range

The Tas1r3 gene encodes the T1R3 receptor protein, which is involved in sweet taste transduction. To characterize ligand specificity of the T1R3 receptor and the genetic architecture of sweet taste responsiveness, we analyzed taste responses of 129.B6- Tas1r3 congenic mice to a variety of chemically diverse sweeteners and glucose polymers with three different measures: consumption in 48-h two-bottle preference tests, initial licking responses, and responses of the chorda tympani nerve. The results were generally consistent across the three measures. Allelic variation of the Tas1r3 gene influenced taste responsiveness to nonnutritive sweeteners (saccharin, acesulfame-K, sucralose, SC-45647), sugars (sucrose, maltose, glucose, fructose), sugar alcohols (erythritol, sorbitol), and some amino acids (d-tryptophan, d-phenylalanine, l-proline). Tas1r3 genotype did not affect taste responses to several sweet-tasting amino acids (l-glutamine, l-threonine, l-alanine, glycine), glucose polymers (Polycose, maltooligosaccharide), and nonsweet NaCl, HCl, quinine, monosodium glutamate, and inosine 5′-monophosphate. Thus Tas1r3 polymorphisms affect taste responses to many nutritive and nonnutritive sweeteners (all of which must interact with a taste receptor involving T1R3), but not to all carbohydrates and amino acids. In addition, we found that the genetic architecture of sweet taste responsiveness changes depending on the measure of taste response and the intensity of the sweet taste stimulus. Variation in the T1R3 receptor influenced peripheral taste responsiveness over a wide range of sweetener concentrations, but behavioral responses to higher concentrations of some sweeteners increasingly depended on mechanisms that could override input from the peripheral taste system.

The Effect of the Taste Receptor Protein T1R3 on the Development of Islet Tissue of the Murine Pancreas

2019 ◽  
Vol 484 (1) ◽  
pp. 1-4
Author(s):  
V. O. Murovets ◽  
E. A. Sozontov ◽  
T. G. Zachepilo
Keyword(s):  
Taste Receptor ◽  
Receptor Protein ◽  
Islet Tissue

Abstract P514: The Role Of Sweet And Umami Taste Receptors In The Heart

2021 ◽  
Vol 129 (Suppl_1) ◽  
Author(s):  
Maria Papadaki ◽  
Sara Osorio- Valencia ◽  
Jonathan A Kirk
Keyword(s):  
Monosodium Glutamate ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Left Ventricular ◽  
Nutrient Sensing ◽  
Neonatal Rat ◽  
Receptor Protein ◽  
Taste Receptors ◽  
Umami Taste ◽  
Nutrient Environment

The tongue can distinguish between five different tastes via the taste receptors, which are G-protein coupled receptors (GPCRs). There are two classes of taste receptors, the TAS1 (T1) and TAS2 (T2) families, and the T1R1-T1R3 dimer senses the umami taste and T1R2-T1R3 senses the sweet taste. Recently, the taste receptors have also been found in the brain, lungs, intestine and pancreas, where they sense changes in the nutrient environment and respond through GPCR signalling. Given the importance of glucose and amino acid metabolism in the heart, we hypothesized that the sweet and umami taste receptors have an important function in the heart. Using a variety of technologies and disease states, we have identified that T1R1, T1R2 and T1R3 are expressed in the heart. More specifically, mass spectrometry of a dog model of dyssynchrony has shown the presence of T1R1, T1R3 and T1R2. RNA seq of human patients who received a Left Ventricular Assist device and those who did not also revealed the presence of T1R1 and T1R3. The expression of these proteins was also confirmed using Western blot. We further showed T1R2 and T1R3 protein is localized in the plasma membrane of the cardiomyocytes by immunofluorescence (colocalized with Na/K ATPase) and PM enrichment. When we compared the taste receptor protein levels in dilated cardiomyopathy (DCM) compared to donor heart tissue, we found that T1R2 was overexpressed in DCM, showing that taste receptors may be important in nutrient sensing in disease. Furthermore, when neonatal rat ventricular myocytes were treated with sweet and umami agonists (aspartame for the sweet taste receptor and monosodium glutamate for the umami receptor), they had increased calcium transients as shown by an increase in peak calcium. Cardiomyocytes treated with aspartame also showed a decrease in time to relax. We hypothesize that in the heart, sweet and umami receptors induce positive inotropy upon a change in nutrient environment.

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