693 results match your criteria human glp-1r


A genetic map of the mouse dorsal vagal complex and its role in obesity.

Nat Metab 2021 Mar 25. Epub 2021 Mar 25.

Novo Nordisk Foundation Center for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

The brainstem dorsal vagal complex (DVC) is known to regulate energy balance and is the target of appetite-suppressing hormones, such as glucagon-like peptide 1 (GLP-1). Here we provide a comprehensive genetic map of the DVC and identify neuronal populations that control feeding. Combining bulk and single-nucleus gene expression and chromatin profiling of DVC cells, we reveal 25 neuronal populations with unique transcriptional and chromatin accessibility landscapes and peptide receptor expression profiles. Read More

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Feasibility of a scale-down production of [68Ga]Ga-NODAGA-Exendin-4 in a hospital based radiopharmacy.

Curr Radiopharm 2021 Mar 9. Epub 2021 Mar 9.

Nuclear Medicine and Molecular Imaging Department, University Hospital of Parma, via Gramsci 14, 43126 Parma. Italy.

Background: Glucagon-like peptide 1 receptor (GLP-1R) is preferentially expressed in β-cells, but it is highly expressed in human insulinomas and gastrinomas. Several GLP-1 receptor-avid radioligands have been developed to image insulin-secreting tumors or to provide a quantitative in vivo biomarker of pancreatic β-cell mass. Exendin-4 is a high affinity ligand of the GLP1-R, which is a candidate for being labeled with a PET isotope and used for imaging purposes. Read More

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Increased co-expression of PSMA2 and GLP-1 receptor in cervical cancer models in type 2 diabetes attenuated by Exendin-4: A translational case-control study.

EBioMedicine 2021 Mar 6;65:103242. Epub 2021 Mar 6.

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China; Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong SAR, China. Electronic address:

Background: Type 2 diabetes (T2D) increases the risk of many types of cancer. Dysregulation of proteasome-related protein degradation leads to tumorigenesis, while Exendin-4, a glucagon-like peptide 1 receptor (GLP-1R) agonist, possesses anti-cancer effects.

Methods: We explored the co-expression of proteasome alpha 2 subunit (PSMA2) and GLP-1R in the Cancer Genome Atlas (TCGA) database and human cervical cancer specimens, supplemented by in vivo and in vitro studies using multiple cervical cancer cell lines. Read More

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Liraglutide Protects Nucleus Pulposus Cells Against High-Glucose Induced Apoptosis by Activating PI3K/Akt/ mTOR/Caspase-3 and PI3K/Akt/GSK3β/Caspase-3 Signaling Pathways.

Front Med (Lausanne) 2021 19;8:630962. Epub 2021 Feb 19.

Department of Endocrinology, The Third Hospital of Hebei Medical University, Shijiazhuang, China.

Diabetes mellitus (DM) is reportedly a significant risk factor for intervertebral disc degeneration (IDD). Incretin system and particularly glucagon-like peptide 1 (GLP-1) because of its glucose-lowering effects has become an important target in therapeutic strategies of type 2 diabetes (T2D). Liraglutide is a GLP-1 receptor (GLP-1R) agonist with glucoregulatory and insulinotropic functions as well as regulatory functions on cell proliferation, differentiation, and apoptosis. Read More

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February 2021

Effect of C-terminus Conjugation via Different Conjugation Chemistries on In Vivo Activity of Albumin-Conjugated Recombinant GLP-1.

Pharmaceutics 2021 Feb 15;13(2). Epub 2021 Feb 15.

Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology (GIST), Gwangju 61005, Korea.

Glucagon-like peptide-1 (GLP-1) is a peptide hormone with tremendous therapeutic potential for treating type 2 diabetes mellitus. However, the short half-life of its native form is a significant drawback. We previously prolonged the plasma half-life of GLP-1 via site-specific conjugation of human serum albumin (HSA) at position 16 of recombinant GLP-1 using site-specific incorporation of p-azido-phenylalanine (AzF) and strain-promoted azide-alkyne cycloaddition (SPAAC). Read More

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February 2021

Novel XTENylated AWRK6 analog with hypoglycemic activity, and anti-HSV-2 potential in combination with double shRNA.

Life Sci 2021 Jun 2;274:119313. Epub 2021 Mar 2.

Department of Biochemistry and Molecular Biology, Zhuhai Campus of Zunyi Medical University, Zhuhai 519041, Guangdong, PR China. Electronic address:

Aims: To design and evaluate a novel AWRK6 peptide-based long-acting GLP-1 receptor agonist (GLP-1RA) conjugated a recombinant polyethylene glycol mimetic (XTEN protein) with significant therapeutic potential on type 2 diabetes mellitus (T2DM) alone as well as Herpes simplex virus type 2 (HSV-2) infection in combination with double shRNA.

Main Methods: First, four AWRK6 analogs (termed XA-1 to XA-4) were designed and produced by solid phase synthesis strategy. Further surface plasmon resonance (SPR) measurement and in vitro cAMP accumulation assay were performed to detect the GLP-1R binding affinities and GLP-1R activation, respectively. Read More

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Continuous stimulation of dual-function peptide PGLP-1-VP inhibits the morbidity and mortality of NOD mice through anti-inflammation and immunoregulation.

Sci Rep 2021 Feb 11;11(1):3593. Epub 2021 Feb 11.

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Drug Screening, School of Life Science and Technology, China Pharmaceutical University, Nanjing, China.

Multiple animal and human studies have shown that administration of GLP-1RA can enhance β-cell recovery, reduce insulin dosage, reduce HbA1c content in the blood, reduce the risk of hypoglycemia and reduce inflammation. In the NOD mouse model, peptide VP treatment can prevent and treat type 1 diabetes through immunomodulation. Therefore, we designed a new dual-functional PGLP-1-VP, which is expected to combine the anti-inflammatory effect of PGLP-1 and the immunomodulatory effect of VP peptide. Read More

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February 2021

Vagally Mediated Gut-Brain Relationships in Appetite Control-Insights from Porcine Studies.

Nutrients 2021 Jan 30;13(2). Epub 2021 Jan 30.

Aniscan Unit, INRAE, Saint-Gilles, 35590 Paris, France.

Signals arising from the upper part of the gut are essential for the regulation of food intake, particularly satiation. This information is supplied to the brain partly by vagal nervous afferents. The porcine model, because of its sizeable gyrencephalic brain, omnivorous regimen, and comparative anatomy of the proximal part of the gut to that of humans, has provided several important insights relating to the relevance of vagally mediated gut-brain relationships to the regulation of food intake. Read More

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January 2021

GLP-1 receptor signaling increases PCSK1 and β cell features in human α cells.

JCI Insight 2021 Feb 8;6(3). Epub 2021 Feb 8.

Department of Biomedical Sciences and.

Glucagon-like peptide-1 (GLP-1) is an incretin hormone that potentiates glucose-stimulated insulin secretion. GLP-1 is classically produced by gut L cells; however, under certain circumstances α cells can express the prohormone convertase required for proglucagon processing to GLP-1, prohormone convertase 1/3 (PC1/3), and can produce GLP-1. However, the mechanisms through which this occurs are poorly defined. Read More

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February 2021

Can GLP-1 Be a Target for Reward System Related Disorders? A Qualitative Synthesis and Systematic Review Analysis of Studies on Palatable Food, Drugs of Abuse, and Alcohol.

Front Behav Neurosci 2020 18;14:614884. Epub 2021 Jan 18.

Koç University, Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.

The role of glucagon-like peptide 1 (GLP-1) in insulin-dependent signaling is well-known; GLP-1 enhances glucose-dependent insulin secretion and lowers blood glucose in diabetes. GLP-1 receptors (GLP-1R) are also widely expressed in the brain, and in addition to its role in neuroprotection, it affects reward pathways. This systematic review aimed to analyze the studies on GLP-1 and reward pathways and its currently identified mechanisms. Read More

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January 2021

Glucagon-like peptide-1 receptor is expressed in human and rodent testis.

Andrology 2020 11 11;8(6):1935-1945. Epub 2020 Aug 11.

Department of Experimental and Clinical Medicine, University of Catania, Catania, Italy.

Background: The incretin hormone glucagon-like peptide-l (GLP-1) is an important regulator of post-prandial insulin secretion, acting through a G protein-coupled cell surface receptor (GLP-1R). In addition to its expression in pancreatic β-cells, several studies suggested that GLP-1R is located in extra-pancreatic tissues.

Objectives: In this study, we examined for the first time the testicular distribution of the GLP-1R, both in normal human and neoplastic testicular tissues as well as in rodent testis and rodent testicular cell lines. Read More

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November 2020

Design and Evaluation of Peptide Dual-Agonists of GLP-1 and NPY2 Receptors for Glucoregulation and Weight Loss with Mitigated Nausea and Emesis.

J Med Chem 2021 01 15;64(2):1127-1138. Epub 2021 Jan 15.

Department of Chemistry, Syracuse University, 111 College Place, Syracuse, New York 13244, United States.

There is a critical unmet need for therapeutics to treat the epidemic of comorbidities associated with obesity and type 2 diabetes, ideally devoid of nausea/emesis. This study developed monomeric peptide agonists of glucagon-like peptide 1 receptor (GLP-1R) and neuropeptide Y2 receptor (Y2-R) based on exendin-4 (Ex-4) and PYY. A novel peptide, GEP44, was obtained via receptor screens, insulin secretion in islets, stability assays, and rat and shrew studies of glucoregulation, weight loss, nausea, and emesis. Read More

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January 2021

Design and preparation of the class B G protein-coupled receptors GLP-1R and GCGR for F-NMR studies in solution.

FEBS J 2020 Dec 23. Epub 2020 Dec 23.

iHuman Institute, ShanghaiTech University, China.

The human glucagon-like peptide-1 receptor (GLP-1R) and the glucagon receptor (GCGR) are class B G protein-coupled receptors (GPCRs) that are activated by interactions with, respectively, the glucagon-like peptide-1 (GLP-1) and glucagon (GCG). These polypeptide hormones are involved in the regulation of lipid and cholic acid metabolism, and thus play an important role in the pathogenesis of glucose metabolism and diabetes mellitus, which attracts keen interest of these GPCRs as drug targets. GLP-1R and GCGR have therefore been extensively investigated by X-ray crystallography and cryo-electron microscopy (cryo-EM), so that their structures are well known. Read More

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December 2020

ι-Carrageenan Tetrasaccharide from ι-Carrageenan Inhibits Islet β Cell Apoptosis Via the Upregulation of GLP-1 to Inhibit the Mitochondrial Apoptosis Pathway.

J Agric Food Chem 2021 Jan 22;69(1):212-222. Epub 2020 Dec 22.

College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China.

ι-Carrageenan performs diversified biological activities but has low bioavailability. ι-Carrageenan tetrasaccharide (ιCTs), a novel marine oligosaccharide prepared by the marine enzyme , was investigated for its effects on insulin resistance in high-fat and high-sucrose diet mice. Oral administration of ιCTs (ιCTs-L 30. Read More

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January 2021

GLP-1 receptor signaling in the laterodorsal tegmental nucleus attenuates cocaine seeking by activating GABAergic circuits that project to the VTA.

Mol Psychiatry 2020 Nov 30. Epub 2020 Nov 30.

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

An emerging preclinical literature suggests that targeting central glucagon-like peptide-1 receptors (GLP-1Rs) may represent a novel approach to treating cocaine use disorder. However, the exact neural circuits and cell types that mediate the suppressive effects of GLP-1R agonists on cocaine-seeking behavior are largely unknown. The laterodorsal tegmental nucleus (LDTg) expresses GLP-1Rs and functions as a neuroanatomical hub connecting the nucleus tractus solitarius (NTS), the primary source of central GLP-1, with midbrain and forebrain nuclei known to regulate cocaine-seeking behavior. Read More

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November 2020

A unique hormonal recognition feature of the human glucagon-like peptide-2 receptor.

Cell Res 2020 12 25;30(12):1098-1108. Epub 2020 Nov 25.

The CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.

Glucagon-like peptides (GLP-1 and GLP-2) are two proglucagon-derived intestinal hormones that mediate distinct physiological functions through two related receptors (GLP-1R and GLP-2R) which are important drug targets for metabolic disorders and Crohn's disease, respectively. Despite great progress in GLP-1R structure determination, our understanding on the differences of peptide binding and signal transduction between these two receptors remains elusive. Here we report the electron microscopy structure of the human GLP-2R in complex with GLP-2 and a G heterotrimer. Read More

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December 2020

Glucagon-like peptide-1 receptor agonist, exendin-4, reduces reinstatement of heroin-seeking behavior in rats.

Behav Pharmacol 2020 Nov 20. Epub 2020 Nov 20.

Department of Neural and behavioral Sciences.

Opioid use disorder (OUD) causes the death of nearly 130 Americans daily. It is evident that new avenues for treatment are needed. To this end, studies have reported that 'satiety' agents such as the glucagon-like peptide-1 receptor (GLP-1R) agonist, exendin-4 (Ex-4), decreases responding for addictive drugs such as cocaine, nicotine, alcohol, and oxycodone, but no work has been done with heroin. Read More

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November 2020

GLP-1R activation alters performance in cognitive tasks in a sex-dependent manner.

Neurol Sci 2020 Nov 22. Epub 2020 Nov 22.

Department of Biomedical Sciences and Center for Brain Repair, Florida State University College of Medicine, Tallahassee, FL, 32306, USA.

Rationale: The activation of the glucagon-like peptide-1 receptor (GLP-1R) has been purported to have antidepressant-like and cognitive-enhancing effects. Many people suffering from major depressive disorder (MDD) also experience deficits in cognition. While currently approved antidepressant pharmacotherapies can alleviate the mood symptoms in some patients, they do not treat the cognitive ones. Read More

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November 2020

Ligand-Specific Factors Influencing GLP-1 Receptor Post-Endocytic Trafficking and Degradation in Pancreatic Beta Cells.

Int J Mol Sci 2020 Nov 9;21(21). Epub 2020 Nov 9.

Section of Endocrinology and Investigative Medicine, Imperial College London, London W12 0NN, UK.

The glucagon-like peptide-1 receptor (GLP-1R) is an important regulator of blood glucose homeostasis. Ligand-specific differences in membrane trafficking of the GLP-1R influence its signalling properties and therapeutic potential in type 2 diabetes. Here, we have evaluated how different factors combine to control the post-endocytic trafficking of GLP-1R to recycling versus degradative pathways. Read More

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November 2020

Structural basis for GLP-1 receptor activation by LY3502970, an orally active nonpeptide agonist.

Proc Natl Acad Sci U S A 2020 11 11;117(47):29959-29967. Epub 2020 Nov 11.

Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285

Glucagon-like peptide-1 receptor (GLP-1R) agonists are efficacious antidiabetic medications that work by enhancing glucose-dependent insulin secretion and improving energy balance. Currently approved GLP-1R agonists are peptide based, and it has proven difficult to obtain small-molecule activators possessing optimal pharmaceutical properties. We report the discovery and mechanism of action of LY3502970 (OWL833), a nonpeptide GLP-1R agonist. Read More

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November 2020

Pancreatic GLP-1r binding potential is reduced in insulin-resistant pigs.

BMJ Open Diabetes Res Care 2020 11;8(2)

Center of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia.

Introduction: The insulinotropic capacity of exogenous glucagon like peptide-1 (GLP-1) is reduced in type 2 diabetes and the insulin-resistant obese. We have tested the hypothesis that this response is the consequence of a reduced pancreatic GLP-1 receptor (GLP-1r) density in insulin-resistant obese animals.

Research Design And Methods: GLP-1r density was measured in lean and insulin-resistant adult miniature pigs after the administration of a Ga-labeled GLP-1r agonist. Read More

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November 2020

Glucagon-Like Peptide-1 (GLP-1) in the Integration of Neural and Endocrine Responses to Stress.

Nutrients 2020 Oct 28;12(11). Epub 2020 Oct 28.

Laboratory of Endocrinology, Biomedical Research Center (CINBIO), University of Vigo, 36310 Vigo, Spain.

Glucagon like-peptide 1 (GLP-1) within the brain is produced by a population of preproglucagon neurons located in the caudal nucleus of the solitary tract. These neurons project to the hypothalamus and another forebrain, hindbrain, and mesolimbic brain areas control the autonomic function, feeding, and the motivation to feed or regulate the stress response and the hypothalamic-pituitary-adrenal axis. GLP-1 receptor (GLP-1R) controls both food intake and feeding behavior (hunger-driven feeding, the hedonic value of food, and food motivation). Read More

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October 2020

Imaging of the glucagon receptor in subjects with type 2 diabetes.

J Nucl Med 2020 Oct 23. Epub 2020 Oct 23.

Sanofi.

Despite the importance of the Glucagon receptor (GCGR) in disease and in pharmaceutical drug development, there is a lack of specific and sensitive biomarkers of its activation in human. The Positron Emission Tomography (PET) radioligand Ga-DO3A-VS-Tuna-2 (Ga-Tuna-2) was developed to yield a non-invasive imaging marker for GCGR target distribution and drug target engagement in humans. The biodistribution and dosimetry of Ga-Tuna-2 was assessed by PET/Computed Tomography (CT) in = 13 individuals with Type 2 Diabetes (T2D) as part of a clinical study assessing the occupancy of dual GCGR/Glucagon Like Peptide-1 Receptor (GLP-1R) agonist SAR425899. Read More

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October 2020

Incretin drugs effect on epigenetic machinery: New potential therapeutic implications in preventing vascular diabetic complications.

FASEB J 2020 12 22;34(12):16489-16503. Epub 2020 Oct 22.

Department of Advanced Medical and Surgical Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.

The effect of GLP-1R agonists on DNA methylation levels of NF-κB and SOD2 genes in human aortic endothelial cells exposed to high glucose and in diabetic patients treated and not with incretin-based drugs, was evaluated. Methylation levels, mRNA and protein expression of NF-κB and SOD2 genes were measured in human endothelial cells exposed to high glucose for 7 days and treated with GLP-1R agonists. Methylation status of NF-κB and SOD2 promoter was also analyzed in 128 diabetics and 116 nondiabetics and correlated with intima media thickness (ITM), an early marker of atherosclerotic process. Read More

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December 2020

Glucose Sensing Mediated by Portal Glucagon-Like Peptide 1 Receptor Is Markedly Impaired in Insulin-Resistant Obese Animals.

Diabetes 2021 01 16;70(1):99-110. Epub 2020 Oct 16.

Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia.

The glucose portal sensor informs the brain of changes in glucose inflow through vagal afferents that require an activated glucagon-like peptide 1 receptor (GLP-1r). The GLP-1 system is known to be impaired in insulin-resistant conditions, and we sought to understand the consequences of GLP-1 resistance on glucose portal signaling. GLP-1-dependent portal glucose signaling was identified, in vivo, using a novel Ga-labeled GLP-1r positron-emitting probe that supplied a quantitative in situ tridimensional representation of the portal sensor with specific reference to the receptor density expressed in binding potential units. Read More

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January 2021

[Effects of Exenatide-4 on proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells].

Shanghai Kou Qiang Yi Xue 2020 Jun;29(3):225-230

National Shandong Provincial Key Laboratory of Oral Tissue Regeneration,Department of Periodontology, School of Stomatology, Shandong University. Jinan 250012, China.

Purpose: To investigate the effects of exendin-4(EX-4) on proliferation, migration and osteogenic differentiation of human periodontal ligament stem cells(PDLSCs).

Methods: PDLSCs were isolated and cultured using limited dilution method in vitro. Colony formation assay, osteogenic and adipogenic differentiation were applied to identify the stem cells. Read More

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Receptor occupancy of dual glucagon-like peptide 1/glucagon receptor agonist SAR425899 in individuals with type 2 diabetes.

Sci Rep 2020 10 7;10(1):16758. Epub 2020 Oct 7.

Translational Medicine, Sanofi, Frankfurt, Germany.

Unimolecular dual agonists for the glucagon-like peptide 1 receptor (GLP1R) and glucagon receptor (GCGR) are emerging as a potential new class of important therapeutics in type 2 diabetes (T2D). Reliable and quantitative assessments of in vivo occupancy on each receptor would improve the understanding of the efficacy of this class of drugs. In this study we investigated the target occupancy of the dual agonist SAR425899 at the GLP1R in pancreas and GCGR in liver by Positron Emission Tomography/Computed Tomography (PET/CT). Read More

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October 2020

Differential GLP-1R Binding and Activation by Peptide and Non-peptide Agonists.

Mol Cell 2020 11 6;80(3):485-500.e7. Epub 2020 Oct 6.

Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia. Electronic address:

Peptide drugs targeting class B1 G-protein-coupled receptors (GPCRs) can treat multiple diseases; however, there remains substantial interest in the development of orally delivered non-peptide drugs. Here, we reveal unexpected overlap between signaling and regulation of the glucagon-like peptide-1 (GLP-1) receptor by the non-peptide agonist PF 06882961 and GLP-1 that was not observed for another compound, CHU-128. Compounds from these patent series, including PF 06882961, are currently in clinical trials for treatment of type 2 diabetes. Read More

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November 2020

Glucagon-like peptide-1 receptor co-agonists for treating metabolic disease.

Mol Metab 2021 Apr 25;46:101090. Epub 2020 Sep 25.

Lunenfeld-Tanenbaum Research Institute, Department of Medicine, Mt. Sinai Hospital, Toronto, Ontario, M5G 1X5 Canada. Electronic address:

Background: Glucagon-like peptide-1 receptor (GLP-1R) agonists are approved to treat type 2 diabetes and obesity. They elicit robust improvements in glycemic control and weight loss, combined with cardioprotection in individuals at risk of or with pre-existing cardiovascular disease. These attributes make GLP-1 a preferred partner for next-generation therapies exhibiting improved efficacy yet retaining safety to treat diabetes, obesity, non-alcoholic steatohepatitis, and related cardiometabolic disorders. Read More

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Glucagon-like peptide-1 alleviates diabetic kidney disease through activation of autophagy by regulating AMP-activated protein kinase-mammalian target of rapamycin pathway.

Am J Physiol Endocrinol Metab 2020 12 28;319(6):E1019-E1030. Epub 2020 Sep 28.

Department of Endocrinology, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong, China.

Glucagon-like peptide-1 (GLP-1) is a novel antidiabetic agent used in clinical practice. Recently, it was reported to exert a renoprotective effect in the human kidney-2 cells and kidneys of diabetic rats, which was induced by one type of GLP-1 analog, liraglutide, in the presence of high glucose. However, most of the previous findings mainly focused on its indirect effect in inhibiting the advanced glycation end products. Read More

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December 2020