scholarly journals Not to be ignored: The involvement of the G-protein coupled formylpeptide receptors in high glucose-promoted progression of metabolic diseases and glioblastoma

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Yin Yu ◽  
Zhiyao Bao ◽  
Wanghua Gong ◽  
Keqiang Chen ◽  
Yingying Le ◽  
...  
Keyword(s):  
G Protein ◽  
High Glucose ◽  
Metabolic Diseases ◽  
G Protein Coupled

scholarly journals The relevance of adhesion G protein-coupled receptors in metabolic functions

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Isabell Kaczmarek ◽  
Tomáš Suchý ◽  
Simone Prömel ◽  
Torsten Schöneberg ◽  
Ines Liebscher ◽  
...  
Keyword(s):  
G Protein ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Specific Expression ◽  
Physiological Functions ◽  
Metabolic Functions ◽  
Central Nervous Systems ◽  
G Protein Coupled

Abstract G protein-coupled receptors (GPCRs) modulate a variety of physiological functions and have been proven to be outstanding drug targets. However, approximately one-third of all non-olfactory GPCRs are still orphans in respect to their signal transduction and physiological functions. Receptors of the class of Adhesion GPCRs (aGPCRs) are among these orphan receptors. They are characterized by unique features in their structure and tissue-specific expression, which yields them interesting candidates for deorphanization and testing as potential therapeutic targets. Capable of G-protein coupling and non-G protein-mediated function, aGPCRs may extend our repertoire of influencing physiological function. Besides their described significance in the immune and central nervous systems, growing evidence indicates a high importance of these receptors in metabolic tissue. RNAseq analyses revealed high expression of several aGPCRs in pancreatic islets, adipose tissue, liver, and intestine but also in neurons governing food intake. In this review, we focus on aGPCRs and their function in regulating metabolic pathways. Based on current knowledge, this receptor class represents high potential for future pharmacological approaches addressing obesity and other metabolic diseases.

Carbon source induced yeast-to-hypha transition in Candida albicans is dependent on the presence of amino acids and on the G-protein-coupled receptor Gpr1

2005 ◽  
Vol 33 (1) ◽  
pp. 291-293 ◽  
Author(s):  
M.M. Maidan ◽  
J.M. Thevelein ◽  
P. Van Dijck
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Amino Acids ◽  
Candida Albicans ◽  
Carbon Source ◽  
G Protein ◽  
High Glucose ◽  
Glucose Concentration ◽  
G Protein Coupled Receptor ◽  
Hypha Formation ◽  
G Protein Coupled

Yeast-to-hypha transition in Candida albicans can be induced by a wide variety of factors, including specific nutrients. We have started to investigate the mechanism by which some of these nutrients may be sensed. The G-protein-coupled receptor Gpr1 is required for yeast-to-hypha transition on various solid hypha-inducing media. Recently we have shown induction of Gpr1 internalization by specific amino acids, e.g. methionine. This suggests a possible role for methionine as a ligand of CaGpr1. Here we show that there is a big variation in methionine-induced hypha formation depending on the type of carbon source present in the medium. In addition high glucose concentrations repress hypha formation whereas a concentration of 0.1%, which mimics the glucose concentration present in the bloodstream, results in maximal hypha formation. Hence, it remains unclear whether Gpr1 senses sugars, as in Saccharomyces cerevisiae, or specific amino acids like methionine.

scholarly journals SAT-LB035 The G Protein-Coupled Estrogen Receptor GPER Plays a Dominant Role in Human Islet Cell Proliferation upon High Glucose

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Sigal Shaklai ◽  
Meital Grafi-Cohen ◽  
Orli Sharon ◽  
Gabi Shefer ◽  
Dalia Somjen ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Estrogen Receptor ◽  
G Protein ◽  
High Glucose ◽  
Islet Cell ◽  
Dominant Role ◽  
Human Islet ◽  
G Protein Coupled

scholarly journals Bile acid receptors FXR and TGR5 signaling in fatty liver diseases and therapy

2020 ◽  
Vol 318 (3) ◽  
pp. G554-G573 ◽  
Author(s):  
John Y. L. Chiang ◽  
Jessica M. Ferrell
Keyword(s):  
Bile Acid ◽  
Fatty Liver ◽  
Bile Acids ◽  
G Protein ◽  
Liver Diseases ◽  
Metabolic Diseases ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Receptors ◽  
G Protein Coupled

Bile acid synthesis is the most significant pathway for catabolism of cholesterol and for maintenance of whole body cholesterol homeostasis. Bile acids are physiological detergents that absorb, distribute, metabolize, and excrete nutrients, drugs, and xenobiotics. Bile acids also are signal molecules and metabolic integrators that activate nuclear farnesoid X receptor (FXR) and membrane Takeda G protein-coupled receptor 5 (TGR5; i.e., G protein-coupled bile acid receptor 1) to regulate glucose, lipid, and energy metabolism. The gut-to-liver axis plays a critical role in the transformation of primary bile acids to secondary bile acids, in the regulation of bile acid synthesis to maintain composition within the bile acid pool, and in the regulation of metabolic homeostasis to prevent hyperglycemia, dyslipidemia, obesity, and diabetes. High-fat and high-calorie diets, dysbiosis, alcohol, drugs, and disruption of sleep and circadian rhythms cause metabolic diseases, including alcoholic and nonalcoholic fatty liver diseases, obesity, diabetes, and cardiovascular disease. Bile acid-based drugs that target bile acid receptors are being developed for the treatment of metabolic diseases of the liver.

scholarly journals Ligand recognition and G-protein coupling selectivity of cholecystokinin A receptor

2021 ◽  
Author(s):  
Qiufeng Liu ◽  
Dehua Yang ◽  
Youwen Zhuang ◽  
Tristan I. Croll ◽  
Xiaoqing Cai ◽  
...  
Keyword(s):  
G Protein ◽  
Metabolic Diseases ◽  
Ligand Recognition ◽  
G Protein Coupling ◽  
Protein Coupling ◽  
Cryo Electron Microscopy ◽  
Receptor Recognition ◽  
G Protein Coupled ◽  
Nutrient Homeostasis ◽  
Similar Conformation

AbstractCholecystokinin A receptor (CCKAR) belongs to family A G-protein-coupled receptors and regulates nutrient homeostasis upon stimulation by cholecystokinin (CCK). It is an attractive drug target for gastrointestinal and metabolic diseases. One distinguishing feature of CCKAR is its ability to interact with a sulfated ligand and to couple with divergent G-protein subtypes, including Gs, Gi and Gq. However, the basis for G-protein coupling promiscuity and ligand recognition by CCKAR remains unknown. Here, we present three cryo-electron microscopy structures of sulfated CCK-8-activated CCKAR in complex with Gs, Gi and Gq heterotrimers, respectively. CCKAR presents a similar conformation in the three structures, whereas conformational differences in the ‘wavy hook’ of the Gα subunits and ICL3 of the receptor serve as determinants in G-protein coupling selectivity. Our findings provide a framework for understanding G-protein coupling promiscuity by CCKAR and uncover the mechanism of receptor recognition by sulfated CCK-8.

scholarly journals Metabolite G-Protein Coupled Receptors in Cardio-Metabolic Diseases

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3347
Author(s):  
Derek Strassheim ◽  
Timothy Sullivan ◽  
David C. Irwin ◽  
Evgenia Gerasimovskaya ◽  
Tim Lahm ◽  
...  
Keyword(s):  
G Protein ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Ketone Bodies ◽  
G Protein Coupled Receptors ◽  
Potential Drug ◽  
Pathological Conditions ◽  
Endogenous Metabolites ◽  
G Protein Coupled ◽  
Potential Drug Targets

G protein-coupled receptors (GPCRs) have originally been described as a family of receptors activated by hormones, neurotransmitters, and other mediators. However, in recent years GPCRs have shown to bind endogenous metabolites, which serve functions other than as signaling mediators. These receptors respond to fatty acids, mono- and disaccharides, amino acids, or various intermediates and products of metabolism, including ketone bodies, lactate, succinate, or bile acids. Given that many of these metabolic processes are dysregulated under pathological conditions, including diabetes, dyslipidemia, and obesity, receptors of endogenous metabolites have also been recognized as potential drug targets to prevent and/or treat metabolic and cardiovascular diseases. This review describes G protein-coupled receptors activated by endogenous metabolites and summarizes their physiological, pathophysiological, and potential pharmacological roles.

The G-protein-coupled receptor 40 family (GPR40–GPR43) and its role in nutrient sensing

2006 ◽  
Vol 34 (5) ◽  
pp. 770-773 ◽  
Author(s):  
D.K. Covington ◽  
C.A. Briscoe ◽  
A.J. Brown ◽  
C.K. Jayawickreme
Keyword(s):  
Fatty Acids ◽  
G Protein ◽  
Metabolic Diseases ◽  
Cell Function ◽  
Expression Patterns ◽  
Nutrient Sensing ◽  
Β Cell ◽  
The Metabolic Syndrome ◽  
G Protein Coupled ◽  
Chain Fatty Acids

Recent deorphanization efforts have paired the G-protein-coupled receptors GPR40, GPR41 and GPR43 with fatty acids as endogenous ligands. While carboxylic acids have been historically known to serve as fuel sources and biomarkers of disease, these studies demonstrate that fatty acids can act as signalling molecules at the cell-surface level. This receptor subfamily shares approx. 30% identity among members, with some limited cross-over between ligand activities. Generalized expression patterns within the pancreatic β-cell, adipose depots and the gastrointestinal tract infer involvement in energy source recognition, absorption, storage and/or metabolism. GPR40, activated by medium and long-chain fatty acids, has been shown to potentiate insulin secretion at the β-cell, and has been hypothesized to participate in the detrimental effects of chronic fatty acid exposure on β-cell function. GPR41 and GPR43 have been reported to stimulate leptin release and adipogenesis respectively via activation by short-chain fatty acids. These common themes implicate GPR40, GPR41 and GPR43 in playing significant roles in metabolic diseases, such as diabetes, obesity and the metabolic syndrome.

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