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Soo-Kyung Kim, Yalu Chen, Ravinder Abrol, William A Goddard, Brian Guthrie
The sweet taste in humans is mediated by the TAS1R2/TAS1R3 G protein-coupled receptor (GPCR), which belongs to the class C family that also includes the metabotropic glutamate and γ-aminobutyric acid receptors. We report here the predicted 3D structure of the full-length TAS1R2/TAS1R3 heterodimer, including the Venus Flytrap Domains (VFDs) [in the closed-open (co) active conformation], the cysteine-rich domains (CRDs), and the transmembrane domains (TMDs) at the TM56/TM56 interface. We observe that binding of agonists to VFD2 of TAS1R2 leads to major conformational changes to form a TM6/TM6 interface between TMDs of TAS1R2 and TAS1R3, which is consistent with the activation process observed biophysically on the metabotropic glutamate receptor 2 homodimer...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
Heather Benford, Matei Bolborea, Eric Pollatzek, Kristina Lossow, Irm Hermans-Borgmeyer, Beihui Liu, Wolfgang Meyerhof, Sergey Kasparov, Nicholas Dale
Hypothalamic tanycytes are glial-like glucosensitive cells that contact the cerebrospinal fluid of the third ventricle, and send processes into the hypothalamic nuclei that control food intake and body weight. The mechanism of tanycyte glucosensing remains undetermined. While tanycytes express the components associated with the glucosensing of the pancreatic β cell, they respond to nonmetabolisable glucose analogues via an ATP receptor-dependent mechanism. Here, we show that tanycytes in rodents respond to non-nutritive sweeteners known to be ligands of the sweet taste (Tas1r2/Tas1r3) receptor...
May 2017: Glia
Patrick O'Brien, Christopher Peter Corpe
BACKGROUND: The gastrointestinal tract is responsible for the assimilation of nutrients and plays a key role in the regulation of nutrient metabolism and energy balance. The molecular mechanisms by which intestinal sugar transport are regulated are controversial. Based on rodent studies, two models currently exist that involve activation of the sweet-taste receptor, T1R2/3: an indirect model, whereby luminal carbohydrates activate T1R2/3 expressed on enteroendocrine cells, resulting in the release of gut peptides which in turn regulate enterocyte sugar transport capacity; and a direct model, whereby T1R2/3 expressed on the enterocyte regulates enterocyte function...
2016: PloS One
Emiko Nishi, Kei Tsutsui, Hiroo Imai
Taste sensitivity differs among animal species depending on feeding habitat. To humans, sucrose is one of the sweetest natural sugars, and this trait is expected to be similar in other primates. However, previous behavioral tests have shown that some primate species have equal preferences for maltose and sucrose. Because sweet tastes are recognized when compounds bind to the sweet taste receptor Tas1R2/Tas1R3, we evaluated the responses of human and Japanese macaque Tas1R2/Tas1R3 to various natural sugars using a heterologous expression system...
December 16, 2016: Scientific Reports
Lurong Zhang, Xiudao Song, Liang Zhou, Guoqiang Liang, Heng Xu, Fei Wang, Fei Huang, Guorong Jiang
BACKGROUND: Our recent findings support the idea that 3-deoxyglucosone (3DG), a dietary composition, has been suggested as an independent factor for the development of prediabetes. Secretion of glucagon-like peptide-1 (GLP-1) has been suggested to be impaired in T2DM and in conditions associated with hyperglycemia. Since low oral bioavailability of 3DG has been indicated in a single administration study, in the present study we examined if 3DG is capable of accumulating in intestinal tissue of rats after 2-week administration of 3DG, and the 3DG treatment affects GLP-1 secretion and glucose tolerance...
2016: Diabetology & Metabolic Syndrome
Chenggu Cai, Hua Jiang, Lei Li, Tianming Liu, Xuejie Song, Bo Liu
Sweet state is a basic physiological sensation of humans and other mammals which is mediated by the broadly acting sweet taste receptor-the heterodimer of Tas1r2 (taste receptor type 1 member 2) and Tas1r3 (taste receptor type 1 member 3). Various sweeteners interact with either Tas1r2 or Tas1r3 and then activate the receptor. In this study, we cloned, expressed and functionally characterized the taste receptor Tas1r2 from a species of Old World monkeys, the rhesus monkey. Paired with the human TAS1R3, it was shown that the rhesus monkey Tas1r2 could respond to natural sugars, amino acids and their derivates...
2016: PloS One
Sunil K Sukumaran, Karen K Yee, Shusuke Iwata, Ramana Kotha, Roberto Quezada-Calvillo, Buford L Nichols, Sankar Mohan, B Mario Pinto, Noriatsu Shigemura, Yuzo Ninomiya, Robert F Margolskee
The primary sweet sensor in mammalian taste cells for sugars and noncaloric sweeteners is the heteromeric combination of type 1 taste receptors 2 and 3 (T1R2+T1R3, encoded by Tas1r2 and Tas1r3 genes). However, in the absence of T1R2+T1R3 (e.g., in Tas1r3 KO mice), animals still respond to sugars, arguing for the presence of T1R-independent detection mechanism(s). Our previous findings that several glucose transporters (GLUTs), sodium glucose cotransporter 1 (SGLT1), and the ATP-gated K(+) (KATP) metabolic sensor are preferentially expressed in the same taste cells with T1R3 provides a potential explanation for the T1R-independent detection of sugars: sweet-responsive taste cells that respond to sugars and sweeteners may contain a T1R-dependent (T1R2+T1R3) sweet-sensing pathway for detecting sugars and noncaloric sweeteners, as well as a T1R-independent (GLUTs, SGLT1, KATP) pathway for detecting monosaccharides...
May 24, 2016: Proceedings of the National Academy of Sciences of the United States of America
Nicholas Steven Archer, Dongli Liu, Jan Shaw, Garry Hannan, Konsta Duesing, Russell Keast
Variability in human taste perception is associated with both genetic and environmental factors. The influence of taste receptor expression on this variability is unknown, in part, due to the difficulty in obtaining human oral tissue that enables quantitative expression measures of taste genes. In a comparison of six current techniques (Oragene RNeasy Kit, Isohelix swab, Livibrush cytobrush, tongue saliva, cheek saliva collection, and fungiform papillae biopsy), we identify the fungiform papillae biopsy is the optimal sampling technique to analyse human taste gene expression...
2016: PloS One
Keisuke Sanematsu, Masayuki Kitagawa, Ryusuke Yoshida, Satoru Nirasawa, Noriatsu Shigemura, Yuzo Ninomiya
Acidification of the glycoprotein, miraculin (MCL), induces sweet taste in humans, but not in mice. The sweet taste induced by MCL is more intense when acidification occurs with weak acids as opposed to strong acids. MCL interacts with the human sweet receptor subunit hTAS1R2, but the mechanisms by which the acidification of MCL activates the sweet taste receptor remain largely unexplored. The work reported here speaks directly to this activation by utilizing a sweet receptor TAS1R2 + TAS1R3 assay. In accordance with previous data, MCL-applied cells displayed a pH dependence with citric acid (weak acid) being right shifted to that with hydrochloric acid (strong acid)...
2016: Scientific Reports
Omar Ramos-Lopez, Arturo Panduro, Erika Martinez-Lopez, Sonia Roman
Some high-carbohydrate diets may lead to obesity and multiple metabolic disorders, including hypertriglyceridemia (HTG). This lipid abnormality is considered an important risk factor for cardiovascular disease and type 2 diabetes. The sweet taste receptor TAS1R2 polymorphism (Ile191Val) has been reported to be associated with carbohydrate intake. The aim of this study was to analyze the association of the TAS1R2 gene polymorphism with carbohydrate intake and HTG among the population of West Mexico. In a cross-sectional study, 441 unrelated subjects were analyzed for TAS1R2 genotypes (Ile/Ile, Ile/Val and Val/Val) by an allelic discrimination assay...
February 19, 2016: Nutrients
J Tomás, C R A Santos, T Quintela, I Gonçalves
The choroid plexus (CP) located in brain ventricles, by forming the interface between the blood and the cerebrospinal fluid (CSF) is in a privileged position to monitor the composition of these body fluids. Yet, the mechanisms involved in this surveillance system remain to be identified. The taste transduction pathway senses some types of molecules, thereby evaluating the chemical content of fluids, not only in the oral cavity but also in other tissues throughout the body, such as some cell types of the airways, the gastrointestinal tract, testis and skin...
April 21, 2016: Neuroscience
Andre G Dias, Karen M Eny, Moira Cockburn, Winnie Chiu, Daiva E Nielsen, Lisa Duizer, Ahmed El-Sohemy
BACKGROUND/AIMS: To determine whether variation in the TAS1R2 gene affects sucrose taste perception and sugar intake. METHODS: Participants were men (n = 238) and women (n = 458) aged 20-29 years. A subset (n = 95) with body mass index (BMI) data available completed a sensory analysis study. A food frequency questionnaire assessed dietary intake, and eight polymorphisms were genotyped (rs12033832, rs12137730, rs35874116, rs3935570, rs4920564, rs4920566, rs7513755 and rs9701796)...
2015: Journal of Nutrigenetics and Nutrigenomics
Antonietta Robino, Lorenzo Bevilacqua, Nicola Pirastu, Roberta Situlin, Roberto Di Lenarda, Paolo Gasparini, Chiara Ottavia Navarra
The aim of the study was to assess the relationship between sweet taste genes and dental caries prevalence in a large sample of adults. In addition, the association between sweet liking and sugar intake with dental caries was investigated. Caries was measured by the decayed, missing, filled teeth (DMFT) index in 647 Caucasian subjects (285 males and 362 females, aged 18-65 years), coming from six villages in northeastern Italy. Sweet liking was assessed using a 9-point scale, and the mean of the liking given by each individual to specific sweet food and beverages was used to create a sweet liking score...
September 2015: Genes & Nutrition
Lydie Izakovicova Holla, Petra Borilova Linhartova, Svetlana Lucanova, Jakub Kastovsky, Kristina Musilova, Michaela Bartosova, Martina Kukletova, Lubomir Kukla, Ladislav Dusek
OBJECTIVE: Dental caries is one of the most frequent multifactorial diseases. Among the numerous factors influencing the risk of caries, genetics plays a substantial role, with heritability ranging from 40 to 60%. Gene variants affecting taste preference and glucose transport were recently associated with caries risk. The aim of this study was to analyze two common polymorphisms in the sweet taste receptor (TAS1R2) and glucose transporter (GLUT2) genes in children with dental caries and healthy controls in the Czech population...
2015: Caries Research
Michelle M Sandau, Jason R Goodman, Anu Thomas, Joseph B Rucker, Nancy E Rawson
BACKGROUND: Domestic cats (felis catus) have a reputation for being rather unpredictable in their dietary choices. While their appetite for protein or savory flavors is consistent with their nutritional needs, their preference among protein-sufficient dietary options may relate to differences in the response to other flavor characteristics. Studies of domestic cat taste perception are limited, in part, due to the lack of receptor sequence information. Several studies have described the phylogenetic relationship of specific cat taste receptor sequences as compared with other carnivores...
2015: BMC Neuroscience
Eda Haznedaroğlu, Meliha Koldemir-Gündüz, Nur Bakır-Coşkun, Hasan M Bozkuş, Penbe Çağatay, Belgin Süsleyici-Duman, Ali Menteş
Sweet taste is a powerful factor influencing food acceptance. The peripheral taste response to sugar is mediated by the TAS1R2/TAS1R3 taste receptors. The aim of the study was to determine the relationship between TAS1R2 (rs35874116 or rs9701796) and/or TAS1R3 (rs307355) single nucleotide polymorphisms with dental caries experience in schoolchildren. A total of 184 schoolchildren aged between 7 and 12 years (101 girls, 83 boys) were included in the study. Genomic DNA was extracted from saliva samples and the genotypes were identified by qPCR...
2015: Caries Research
Guangjian Liu, Lutz Walter, Suni Tang, Xinxin Tan, Fanglei Shi, Huijuan Pan, Christian Roos, Zhijin Liu, Ming Li
BACKGROUND: Umami and sweet tastes are two important basic taste perceptions that allow animals to recognize diets with nutritious carbohydrates and proteins, respectively. Until recently, analyses of umami and sweet taste were performed on various domestic and wild animals. While most of these studies focused on the pseudogenization of taste genes, which occur mostly in carnivores and species with absolute feeding specialization, omnivores and herbivores were more or less neglected. Catarrhine primates are a group of herbivorous animals (feeding mostly on plants) with significant divergence in dietary preference, especially the specialized folivorous Colobinae...
2014: Frontiers in Zoology
Keisuke Sanematsu, Ryusuke Yoshida, Noriatsu Shigemura, Yuzo Ninomiya
Detection of tastes is critical for animals. Sweet, umami and bitter taste are mediated by G-protein-coupled receptors that are expressed in the taste receptor cells. TAS1Rs which belong to class C G-protein-coupled receptors form heterodimeric complexes to function as sweet (TAS1R2 + TAS1R3) or umami (TAS1R1 + TAS1R3) taste receptors. Umami taste is also considered to be mediated by mGluRs. TAS2Rs belong to class A G-protein-coupled receptors and are responsible for bitter taste. After activation of these receptors, their second messenger pathways lead to depolarization and intracellular calcium increase in taste receptor cells...
2014: Current Pharmaceutical Biotechnology
Hiroshi Tomonari, Hirohito Miura, Makoto Ooki, Ayumi Nakayama, Shuitsu Harada
Neural responses to sweet and bitter stimuli in the rat and mouse are compared to the expression of the molecular taste receptors, Tas1r2/Tas2rs. Integrated taste responses from the greater superficial petrosal nerve (GSP) innervating the soft palate (SP) and the chorda tympani (CT) nerve innervating the fungiform papillae (FF) were recorded in C57BL mice and SD rats. The sum of the phasic and tonic response magnitudes (SRM) was calculated by summating all relative mean responses to a concentration series of QHCl (10(-6)-10(-2)M) or Suc (10(-4)-1...
May 21, 2014: Neuroscience Letters
A Bassoli, G Borgonovo, F Caremoli, G Mancuso
The taste of different enantiomeric forms of amino acids has been deeply investigated because it represents the most impressive case of correlation between stereochemistry and flavour. Herein, we aimed to elucidate the molecular activity of d- and l-amino acids using an in vitro system based on a cellular model overexpressing sweet and bitter receptors, and to analyse the correlation between in vitro and sensory studies. With our work we demonstrated specific enantiomeric activities for several amino acids on TAS1R2-TAS1R3 sweet receptor...
May 1, 2014: Food Chemistry
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