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  • modulate
  • Wootten D, Reynolds CA, Smith KJ, Mobarec JC, Furness SG, Miller LJ , Christopoulos A, Sexton PM. Key interactions by conserved polar amino acids located at the transmembrane helical boundaries in Class B GPCRs modulate activation, effector specificity and biased signalling in the glucagon-like peptide-1 receptor. (mayo.edu)
  • proteins
  • Instead, an alternative cAMP signaling mechanism has been described, one in which GLP-1 activates cAMP-binding proteins designated as cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs, also known as Epac ). (diabetesjournals.org)
  • GLP-1 is shown to stimulate cAMP production, and the action of cAMP is demonstrated to be mediated not only by PKA, but also by a newly recognized family of cAMP-binding proteins designated as cAMP-regulated guanine nucleotide exchange factors (cAMPGEFs, also known as Epac ) ( 13 , 14 ). (diabetesjournals.org)
  • G protein-coupled receptors (GPCRs) represent the largest family of receptor proteins encoded by the human genome and the biggest class of current drug targets. (monash.edu)
  • The interaction of the P2Y 12 receptor with proteins involved in its down-regulation is described by Margaret Cunningham [ 16 ]. (biochemsoctrans.org)
  • extracellular
  • Although insulin release downstream of GLP-1R activation is known to be critically dependent upon the formation of cAMP, there is also a role for mobilization of intracellular Ca 2+ and activation of mitogen-activated protein kinases such as extracellular signal-regulated kinase 1 and 2 (ERK1/2) in augmentation of insulin response ( Baggio and Drucker, 2007 ). (aspetjournals.org)
  • Particularly, the specific amino acid residues within the transmembrane helices and extracellular loops of the receptor that may confer ligand-induced receptor activation have been poorly investigated. (frontiersin.org)
  • At the extracellular surface, the organization of extracellular loop 3 and proximal transmembrane segments differs between our exendin-P5-bound structure and previous GLP-1-bound GLP-1 receptor structure 2 . (nature.com)
  • GPCRs
  • This may, in part, be due to technical difficulties associated with efficiently blocking the relatively large ligand/receptor-interacting pocket characteristic of the family B GPCRs. (aspetjournals.org)
  • adenosine
  • These can be quantified by determination of key parameters (left) and used to construct "Webs of Bias", an example of which is shown on the right for signalling of three different ligands at the adenosine A1 receptor. (monash.edu)
  • novel
  • Elena Borroni [ 11 ] describes a novel chemokine receptor which signals exclusively via β-arrestin and Nigel Bunnett [ 12 ] describes that targeting the internalized receptor in an endosome will alter the balance between G-protein and β-arrestin-mediated signalling. (biochemsoctrans.org)
  • vivo
  • in vivo, animals subjected to 1 week of bile duct ligation and to a single intraperitoneal injection of CCl 4 were treated with exendin-4 for 3 days. (bmj.com)
  • Physiological
  • For this to become a reality, however, will require a deepened understanding of the behavioral, neuronal, and physiological mechanisms by which the peripheral and central GLP-1 systems control for food intake and body weight regulation. (upenn.edu)
  • food intake
  • Intracellular signals mediating the food intake-suppressive effects of hindbrain glucagon-like peptide-1 receptor activation. (nih.gov)
  • Glucagon-like peptide-1 receptor (GLP-1R) activation within the nucleus tractus solitarius (NTS) suppresses food intake and body weight (BW), but the intracellular signals mediating these effects are unknown. (nih.gov)
  • The ability of the GLP-1 system to decrease food intake in rodents has been well described and parallels results from clinical trials. (sigmaaldrich.com)
  • muscarinic
  • movie showing molecular dynamics simulation of a negative allosteric modulator drug binding to the M2 muscarinic acetylcholine receptor. (monash.edu)
  • protein
  • G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms: A Biochemical Society Focused Meeting co-organized with Monash University held at Monash University Prato Centre, Prato, Italy, 12-14 September 2012. (biochemsoctrans.org)
  • Although GLP-1 is established to be a cAMP-elevating agent, these studies demonstrate that protein kinase A (PKA) is not the only cAMP-binding protein by which GLP-1 acts. (diabetesjournals.org)
  • Belongs to the G-protein coupled receptor 2 family. (mybiosource.com)
  • SCFAs act as a local nutrient source but can also trigger cell-specific signaling cascades by activation of the G-protein-coupled free fatty acid receptor (FFAR)2 (GPR43) and FFAR3 (GPR41) ( 17 , 18 ). (diabetesjournals.org)
  • tumor invasion and migration, including platelet-derived growth factor receptor beta (PDGFR), which was found to be the highest-ranking receptor protein genome-wide. (health-ground.com)
  • Gene Ontology (GO) annotations related to this gene include G-protein coupled receptor activity and glucagon receptor activity . (genecards.org)
  • Ramil CP, Dong M, An P, Lewandowski TM, Yu Z, Miller LJ , Lin Q. Spirohexene-Tetrazine Ligation Enables Bioorthogonal Labeling of Class B G Protein-Coupled Receptors in Live Cells. (mayo.edu)
  • Here we describe the structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a Gα s heterotrimer, determined at a global resolution of 3.3 Å. (nature.com)
  • The papers resulting from the recent Biochemical Society Focused Meeting 'G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms' held in Prato in September 2012 are introduced in the present overview. (biochemsoctrans.org)
  • The Biochemical Society/Monash University Focused Meeting 'G-Protein-Coupled Receptors: from Structural Insights to Functional Mechanisms' held in Prato in September 2012 has proved particularly timely. (biochemsoctrans.org)
  • effects
  • In conclusion, this review indicates that the effects on HR differ within the class of GLP-1 RAs: short-acting GLP-1 RAs are associated with a modest and transient HR increase before returning to baseline levels, while some long-acting GLP-1 RAs are associated with a more pronounced and sustained increase during the day and night. (biomedcentral.com)
  • In order to allow a more sensitive differentiation of GLP-1 RA-dependent HR effects, the current manuscript presents HR data derived from ECG measurements and ambulatory blood pressure monitoring at multiple time points over 24 h. (biomedcentral.com)
  • GLP-1 receptors mediate the effects of the incretin axis. (genecards.org)
  • Glucagon-like peptide 1 receptor (GLP-1R) expression by nerve fibres in inflammatory bowel disease and functional effects in cultured neurons. (abcam.com)
  • Glucagon-like peptide 1 (GLP-1) exhibits similar properties as amylin, with the exception of insulin secretory effects. (uptodate.com)
  • GLP-1 and amylin appear to have differing magnitudes of physiologic effects and bind to different receptors in the area postrema, the part of the brain that may be key for their effects on satiety [ 9,10 ]. (uptodate.com)