Introducing a New Model of Sweet Taste Receptor, a Class C G-protein Coupled Receptor (C GPCR)

2019 ◽  
Vol 77 (3) ◽  
pp. 227-243 ◽  
Author(s):  
Elaheh Kashani-Amin ◽  
Amirhossein Sakhteman ◽  
Bagher Larijani ◽  
Azadeh Ebrahim-Habibi
Keyword(s):  
G Protein ◽  
Taste Receptor ◽  
Sweet Taste ◽  
G Protein Coupled Receptor ◽  
New Model ◽  
Sweet Taste Receptor ◽  
Class C ◽  
G Protein Coupled

scholarly journals Minireview: Nutrient Sensing by G Protein-Coupled Receptors

2013 ◽  
Vol 27 (8) ◽  
pp. 1188-1197 ◽  
Author(s):  
Eric M. Wauson ◽  
Andrés Lorente-Rodríguez ◽  
Melanie H. Cobb
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
G Protein ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Nutrient Sensing ◽  
G Protein Coupled Receptors ◽  
Amino Acid Availability ◽  
Class C ◽  
G Protein Coupled

G protein-coupled receptors (GPCRs) are membrane proteins that recognize molecules in the extracellular milieu and transmit signals inside cells to regulate their behaviors. Ligands for many GPCRs are hormones or neurotransmitters that direct coordinated, stereotyped adaptive responses. Ligands for other GPCRs provide information to cells about the extracellular environment. Such information facilitates context-specific decision making that may be cell autonomous. Among ligands that are important for cellular decisions are amino acids, required for continued protein synthesis, as metabolic starting materials and energy sources. Amino acids are detected by a number of class C GPCRs. One cluster of amino acid-sensing class C GPCRs includes umami and sweet taste receptors, GPRC6A, and the calcium-sensing receptor. We have recently found that the umami taste receptor heterodimer T1R1/T1R3 is a sensor of amino acid availability that regulates the activity of the mammalian target of rapamycin. This review focuses on an array of findings on sensing amino acids and sweet molecules outside of neurons by this cluster of class C GPCRs and some of the physiologic processes regulated by them.

scholarly journals Gustducin couples fatty acid receptors to GLP-1 release in colon

2013 ◽  
Vol 304 (6) ◽  
pp. E651-E660 ◽  
Author(s):  
Yan Li ◽  
Zaza Kokrashvili ◽  
Bedrich Mosinger ◽  
Robert F. Margolskee
Keyword(s):  
Small Intestine ◽  
Fatty Acid ◽  
G Protein ◽  
Lithocholic Acid ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Enteroendocrine Cells ◽  
G Protein Coupled Receptor ◽  
Glucagon Like Peptide 1 ◽  
G Protein Coupled

Sweet taste receptor subunits and α-gustducin found in enteroendocrine cells of the small intestine have been implicated in release of the incretin hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) in response to glucose and noncaloric sweeteners. α-Gustducin has also been found in colon, although its function there is unclear. We examined expression of α-gustducin, GLP-1, and GIP throughout the intestine. The number of α-gustducin-expressing cells and those coexpressing α-gustducin together with GLP-1 and/or GIP increased from small intestine to colon. α-Gustducin also was coexpressed with fatty acid G protein-coupled receptor (GPR) 40, GPR41, GPR43, GPR119, GPR120, and bile acid G protein-coupled receptor TGR5 in enteroendocrine cells of the colon. In colon, GPR43 was coexpressed with GPR119 and GPR120, but not with TGR5. Treatment of colonic mucosa isolated from wild-type mice with acetate, butyrate, oleic acid, oleoylethanolamide, or lithocholic acid stimulated GLP-1 secretion. However, GLP-1 release in response to these fatty acids was impaired in colonic tissue from α-gustducin knockout mice.

scholarly journals Structural architecture of a dimeric class C GPCR based on co-trafficking of sweet taste receptor subunits

2019 ◽  
Vol 294 (13) ◽  
pp. 4759-4774 ◽  
Author(s):  
Jihye Park ◽  
Balaji Selvam ◽  
Keisuke Sanematsu ◽  
Noriatsu Shigemura ◽  
Diwakar Shukla ◽  
...  
Keyword(s):  
Taste Receptor ◽  
Sweet Taste ◽  
Sweet Taste Receptor ◽  
Class C ◽  
Structural Architecture

scholarly journals Conformational dynamics of a class C G-protein-coupled receptor

Nature ◽  
2015 ◽  
Vol 524 (7566) ◽  
pp. 497-501 ◽  
Author(s):  
Reza Vafabakhsh ◽  
Joshua Levitz ◽  
Ehud Y. Isacoff
Keyword(s):  
G Protein ◽  
Conformational Dynamics ◽  
G Protein Coupled Receptor ◽  
Class C ◽  
G Protein Coupled

scholarly journals Expression of Na+/glucose co-transporter 1 (SGLT1) is enhanced by supplementation of the diet of weaning piglets with artificial sweeteners

2010 ◽  
Vol 104 (5) ◽  
pp. 637-646 ◽  
Author(s):  
Andrew W. Moran ◽  
Miran A. Al-Rammahi ◽  
Daleep K. Arora ◽  
Daniel J. Batchelor ◽  
Erin A. Coulter ◽  
...  
Keyword(s):  
G Protein ◽  
Endocrine Cells ◽  
Taste Receptor ◽  
Gut Hormones ◽  
Sweet Taste ◽  
Inhibitory Effect ◽  
Enteroendocrine Cells ◽  
Artificial Sweeteners ◽  
Weaning Piglets ◽  
G Protein Coupled

In an intensive livestock production, a shorter suckling period allows more piglets to be born. However, this practice leads to a number of disorders including nutrient malabsorption, resulting in diarrhoea, malnutrition and dehydration. A number of strategies have been proposed to overcome weaning problems. Artificial sweeteners, routinely included in piglets' diet, were thought to enhance feed palatability. However, it is shown in rodent models that when included in the diet, they enhance the expression of Na+/glucose co-transporter (SGLT1) and the capacity of the gut to absorb glucose. Here, we show that supplementation of piglets' feed with a combination of artificial sweeteners saccharin and neohesperidin dihydrochalcone enhances the expression of SGLT1 and intestinal glucose transport function. Artificial sweeteners are known to act on the intestinal sweet taste receptor T1R2/T1R3 and its partner G-protein, gustducin, to activate pathways leading to SGLT1 up-regulation. Here, we demonstrate that T1R2, T1R3 and gustducin are expressed together in the enteroendocrine cells of piglet intestine. Furthermore, gut hormones secreted by the endocrine cells in response to dietary carbohydrates, glucagon-like peptides (GLP)-1, GLP-2 and glucose-dependent insulinotrophic peptide (GIP), are co-expressed with type 1 G-protein-coupled receptors (T1R) and gustducin, indicating that L- and K-enteroendocrine cells express these taste elements. In a fewer endocrine cells, T1R are also co-expressed with serotonin. Lactisole, an inhibitor of human T1R3, had no inhibitory effect on sweetener-induced SGLT1 up-regulation in piglet intestine. A better understanding of the mechanism(s) involved in sweetener up-regulation of SGLT1 will allow the identification of nutritional targets with implications for the prevention of weaning-related malabsorption.

scholarly journals Intestinal alteration of a-gustducin and sweet taste signaling pathway in metabolic diseases is partly rescued after weight loss and diabetes remission

2021 ◽  
Author(s):  
Léa Le Gléau ◽  
Christine Rouault ◽  
Céline Osinski ◽  
Edi Prifti ◽  
Hédi Antoine Soula ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
G Protein ◽  
Metabolic Diseases ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Fecal Microbiota ◽  
Diabetes Remission ◽  
Sweet Taste Receptor ◽  
A Subunit ◽  
Altered Gene

Carbohydrates and sweeteners are detected by the sweet taste receptor in enteroendocrine cells (EEC). This receptor is coupled to the gustducin G-protein, which a-subunit is encoded by GNAT3 gene. In intestine, the activation of sweet taste receptor triggers a signaling pathway leading to GLP-1 secretion, an incretin hormone. In metabolic diseases GLP-1 concentration and incretin effect are reduced while partly restored after Roux-en-Y gastric bypass (RYGB). We wondered if the decreased GLP-1 secretion in metabolic diseases is caused by an intestinal defect in sweet taste transduction pathway. In our RNA-sequencing of EEC GNAT3 expression is decreased in patients with obesity and type 2 diabetes compared to normoglycemic obese patients. This prompted us to explore sweet taste signaling pathway in mice with metabolic deteriorations. During obesity onset in mice Gnat3 expression was downregulated in EEC. After metabolic improvement with entero-gastro anastomosis surgery in mice (a surrogate of the RYGB in humans), the expression of Gnat3 increased in the new alimentary tract and glucose-induced GLP-1 secretion was improved. In order to evaluate if high-fat diet-induced dysbiotic intestinal microbiota could explain the changes in the expression of sweet taste a-subunit G protein, we performed a fecal microbiota transfer in mice. However, we could not conclude if dysbiotic microbiota impacted or not intestinal Gnat3 expression. Our data highlight that metabolic disorders were associated with altered gene expression of sweet taste signaling in intestine. This could contribute to impaired GLP-1 secretion that is partly rescued after metabolic improvement.

scholarly journals Activation of the sweet taste receptor, T1R3, by the artificial sweetener sucralose regulates the pulmonary endothelium

2018 ◽  
Vol 314 (1) ◽  
pp. L165-L176 ◽  
Author(s):  
Elizabeth O. Harrington ◽  
Alexander Vang ◽  
Julie Braza ◽  
Aparna Shil ◽  
Havovi Chichger
Keyword(s):  
G Protein ◽  
Barrier Function ◽  
Taste Receptor ◽  
Sweet Taste ◽  
Endothelial Barrier ◽  
Pulmonary Vasculature ◽  
Cell Contact ◽  
Actin Remodeling ◽  
Pulmonary Endothelium ◽  
Sweet Taste Receptor

A hallmark of acute respiratory distress syndrome (ARDS) is pulmonary vascular permeability. In these settings, loss of barrier integrity is mediated by cell-contact disassembly and actin remodeling. Studies into molecular mechanisms responsible for improving microvascular barrier function are therefore vital in the development of therapeutic targets for reducing vascular permeability in ARDS. The sweet taste receptor T1R3 is a G protein-coupled receptor, activated following exposure to sweet molecules, to trigger a gustducin-dependent signal cascade. In recent years, extraoral locations for T1R3 have been identified; however, no studies have focused on T1R3 within the vasculature. We hypothesize that activation of T1R3, in the pulmonary vasculature, plays a role in regulating endothelial barrier function in settings of ARDS. Our study demonstrated expression of T1R3 within the pulmonary vasculature, with a drop in expression levels following exposure to barrier-disruptive agents. Exposure of lung microvascular endothelial cells to the intensely sweet molecule sucralose attenuated LPS- and thrombin-induced endothelial barrier dysfunction. Likewise, sucralose exposure attenuated bacteria-induced lung edema formation in vivo. Inhibition of sweet taste signaling, through zinc sulfate, T1R3, or G-protein siRNA, blunted the protective effects of sucralose on the endothelium. Sucralose significantly reduced LPS-induced increased expression or phosphorylation of the key signaling molecules Src, p21-activated kinase (PAK), myosin light chain-2 (MLC2), heat shock protein 27 (HSP27), and p110α phosphatidylinositol 3-kinase (p110αPI3K). Activation of T1R3 by sucralose protects the pulmonary endothelium from edemagenic agent-induced barrier disruption, potentially through abrogation of Src/PAK/p110αPI3K-mediated cell-contact disassembly and Src/MLC2/HSP27-mediated actin remodeling. Identification of sweet taste sensing in the pulmonary vasculature may represent a novel therapeutic target to protect the endothelium in settings of ARDS.

Sign in / Sign up

Export Citation Format

Share Document