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Role of cysteine 341 and arginine 348 of GLP-1 receptor in G-protein coupling.
cryo-electron microscopy structure of the peptide-activated GLP-1R-Gs complex at near atomic resolution
The simulated results show that the extracellular domain of GLP-1R closes in the GLP-1 bound state and opens in the GLP-1 unbound state.
Peripheral blood mononuclear cells (PBMCs) of COPD patients showed defective GLP-1R signaling and functional T-lymphocyte abnormalities.GLP-1R expression decreased in circulating PBMCs of COPD patients.
A missense variant (rs10305492) in the glucagon-like peptide-1 receptor (GLP1R) gene-coding region was associated with lower fasting glucose levels and a reduced risk of both Diabetes and Cardiovascular Disease.
higher GLP-1R expression may be associated with better prognosis in endometrial cancer patients
This study combined mutagenesis experiments and mapping of surface mutations onto recently described GLP-1R structures, which revealed two major domains in the GLP-1/GLP-1R/Gs protein active structure that are differentially important for both receptor quiescence and ligand-specific initiation and propagation of biased agonism.
review studies that have focused on GLP-1 and the spinal cord, and summarize the expression of GLP-1R and the innervation of PPG neurons in the spinal cord, as well as the potential therapeutic benefits of GLP-1R activation.
The study provides evidence that the insulinotropic action of zfGIP in mammalian systems involves activation of both the GLP-1 and the GIP receptors but not the glucagon receptor
Clinical studies in non-diabetic patients with neurodegenerative disorders showed neuroprotective effects following administration with GLP-1 receptor agonists, demonstrating that neuroprotective effects are independent of blood glucose levels.
Some GLP-1 receptor agonist (GLP-1RA) have been approved for the treatment of type 2 diabetes mellitus(T2DM) and although clinical trials may not have been designed to investigate bone fracture, first results suggest that GLP-1RA may not exacerbate abnormal bone quality observed in T2DM
Here, we discuss recent findings concerning the signalling and trafficking of the GLP-1R in pancreatic beta cells. Leveraging "bias" at the receptor towards cAMP generation versus the recruitment of beta-arrestins and extracellular signal-regulated kinases (ERK1/2) activation may allow the development of new analogues with significantly improved clinical efficacy.
This may represent a potential mechanism for GLP-1R agonist-induced cardioprotection in type 2 diabetes , as increases in fatty acid oxidation and decreases in glucose oxidation are frequently observed in the hearts of animals and human subjects with T2D.
In type 2 diabetic patients from a Han Chinese population, some variations in the GLP-1R gene were associated with a lower risk of developing coronary artery disease.
Activation of endogenous GLP-1 is associated with sepsis in patients with type 2 diabetes.
increased GLP-1R innervation in IBD bowel could mediate enhanced visceral afferent signalling, and provide a peripheral target for therapeutic intervention
GLP1R mRNA transcripts, encompassing the entire open reading frame, were detected in all four cardiac chambers from 15 hearts at levels approximating those detected in human pancreas.
Low active GLP-1 secretion is associated with hypertriglyceridaemia.
this study, we investigated whether glucagon and glucagon-like peptide-1 (GLP-1), hormones produced by alpha cells, contribute to insulin secretion in INS-1 cells, a beta cell line. Co-treatment with glucagon and exendin-4 (Ex-4), a GLP-1 receptor agonist, additively increased glucose-stimulated insulin secretion in INS-1 cells
genetic association studies in population in Republic of Korea: Data suggest that SNPs in PAX4 and GLP1R are associated with type 2 diabetes (T2D) in the population studied. In genome-wide associations, PAX4 Arg192His increased risk of T2D; GLP1R Arg131Gln decreased risk of T2D. (PAX4 = paired box 4 protein; GLP1R = glucagon-like peptide 1 receptor)
LINC01121 functions as a tumor promoter by means of its involvement in the process of translational repression of the GLP1R and inhibition of the cAMP/PKA signaling pathway.
cryo-EM structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a Galphas heterotrimer, determined at a global resolution of 3.3 A
The GLP1 receptor agonist exendin4 may be a potential therapeutic agent for hIAPPinduced betacell damage.
The results demonstrate that lymphatic GLP-1 and the GLP-1 receptor (GLP-1r) mediate bile acid-induced glucoregulatory effects.
Upon challenge by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, the mRNA expression of both GLP-1 and GLP-1R was markedly downregulated in EAE-symptomatic spinal cords, indicating attenuated activity of GLP-1/GLP-1R signaling in EAE.
activation of the GLP-1 receptor signal may alleviate insulin insufficiency and aid glycaemic control in Wolfram syndrome
GLP-1R agonists increase HR regulation of autonomic nervous system function and activation of the atrial GLP-1R. Isolated atrial GLP-1R does not transduce a direct chronotropic effect following exposure to GLP-1R agonists in the intact heart, or isolated atrium, ex vivo. Hence, cardiac GLP-1R circuits controlling HR require neural inputs and do not function in a heart-autonomous manner.
Glp1r/gipr double knockout mice have higher insulin clearance than WT mice, following intravenous injection of glucose. This suggests that incretin hormones reduce insulin clearance at physiological, nonstimulated levels.
Study shows that GLP-1 receptor signalling promotes beta-cell glucose metabolism via mTOR-dependent HIF-1alpha activation. findings suggest that chronic GLP-1 actions on insulin secretion include elevated beta-cell glucose metabolism. Moreover, our data reveal novel aspects of GLP-1 stimulated insulin secretion involving de novo gene expression.
chronotherapeutic modulation of vagal afferent GLP-1R signaling may aid in treating metabolic disorders.
Presynaptic GLP-1 receptors enhance the depolarization-evoked release of glutamate and GABA in the mouse cortex and hippocampus.
This study presents an unexpected proinflammatory switch from Galphas to GalphaI glp1r signaling in burn monocytes which promotes ERK1/2 and NF-kappaB activation
Glucagon-like peptide (GLP)-1 modulates epithelial ion transport indirectly by activating calcitonin gene-related peptide (CGRP)-containing submucosal enteric neurons in the mouse colon. This GLP-1-CGRP response was area-specific and could potentially contribute to the diarrheal side effect of certain GLP-1 receptor therapeutics.
Data (including data from studies using transgenic and knockout mice) suggest that Glp1/Glp1r signaling in insulin-secreting cells plays important role in development of glucose intolerance in obesity; however, Glp1r is not required in insulin-secreting cells for improvement in glucose intolerance after weight loss due to bariatric surgery (here, vertical sleeve gastrectomy).
GLP-1R signaling in paraventricular thalamic nucleus plays a role in food intake control.
GLP-1 receptor agonists suppress the progression of atherosclerosis by inhibiting vascular smooth muscle cell proliferation and enhancing AMP-activated protein kinase and cell cycle regulation in ApoE deficient mice.
IL-33, GLP-1R, and CCL20 are deregulated in human inflammatory bowel disease. GLP-1 receptor agonists upregulate IL-33, mucin 5b, and CCL20 in murine Brunner's glands. GLP-1 receptor agonists affect gut homeostasis in both proximal and distal parts of the gut.
findings identify a group of proteins that interact with GLP-1R and show that one specific interacting protein, SERP1, has an important role in facilitating the glycosylation of GLP-1R and rescuing its activities after ER stress induced by tunicamycin.
Suggest transcription factor 7-like 2 is a possible regulator of glucagon-like peptide 1 receptor expression in endothelial/smooth muscle cells in diabetic mice.
ventromedial hypothalamus GLP-1R regulates food intake by engaging key nutrient sensors but is dispensable for the effects of GLP-1RA on nutrient homeostasis
GLP-1R is highly expressed within the lateral septum.
Study showe that GLP-producing fibers interact with hypothalamic arcuate nucleus (ARC) Kiss1 cells that express GLP-1R, and GLP-1R signaling directly activates ARC Kiss1 function in an estradiol-independent manner. Pharmacological activation of GLP-1R signaling during fasting or pharmacological inhibition of CNS GLP-1R signaling during normal feeding does not alter circulating luteinizing hormone levels.
induces insulin secretion\; mediates neuroendocrine signaling of feeding behavior\; mediates cardiovascular response and increased blood pressure
glucagon-like peptide 1 receptor
, glucagon-like peptide 1 receptor-like
, GLP-1 receptor
, pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1