1,356 results match your criteria glp-1r


Evaluation of glucagon-like peptide-1 receptor expression in non-diabetic and diabetic atherosclerotic mice using PET tracer Ga-NODAGA-exendin-4.

Am J Physiol Endocrinol Metab 2021 Apr 12. Epub 2021 Apr 12.

Turku PET Centre, University of Turku, Finland.

Activation of glucagon-like peptide-1 receptor (GLP-1R) signaling attenuates development of atherosclerosis and vascular inflammation. However, the expression of GLP-1R in atherosclerotic arteries remains uncertain. We evaluated whether a positron emission tomography (PET) tracer Ga-NODAGA-exendin-4 enables detection and imaging of GLP-1R expression in the mouse atherosclerotic aorta. Read More

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New antidiabetic therapy and HFpEF: light at the end of tunnel?

Heart Fail Rev 2021 Apr 11. Epub 2021 Apr 11.

Clinica Medica, University of Milan-Bicocca, Milan, Italy.

New antidiabetic therapy that includes sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 receptor (GLP-1R) agonists, and dipeptidyl peptidase 4 (DPP-4) inhibitors showed significant benefit on cardiovascular outcomes in patients with and without type 2 diabetes mellitus, and this was particularly confirmed for SGLT2 inhibitors in subjects with heart failure (HF) with reduced ejection fraction (HFrEF). Their role on patients with HF with preserved ejection fraction (HFpEF) is still not elucidated, but encouraging results coming from the clinical studies indicate their beneficial role. The role of GLP-1R agonists and particularly DPP-4 inhibitors is less clear and debatable. Read More

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GLP-1 peptide analogs for targeting pancreatic beta cells.

Drug Discov Today 2021 Apr 8. Epub 2021 Apr 8.

Department of Microbiology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran. Electronic address:

Loss or dysfunction of the pancreatic beta cells or insulin receptors leads to diabetes mellitus (DM). This usually occurs over many years; therefore, the development of methods for the timely detection and clinical intervention are vital to prevent the development of this disease. Glucagon-like peptide-1 receptor (GLP-1R) is the receptor of GLP-1, an incretin hormone that causes insulin secretion in a glucose-dependent manner. Read More

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Exenatide Adjunct to Nicotine Patch Facilitates Smoking Cessation and May Reduce Post-Cessation Weight Gain: a Pilot Randomized Controlled Trial.

Nicotine Tob Res 2021 Apr 8. Epub 2021 Apr 8.

Center for Neurobehavioral Research on Addiction, Louis A. Faillace, M.D., Department of Psychiatry and Behavioral Sciences, UTHealth, McGovern Medical School, Houston, TX.

Introduction: Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving and withdrawal symptoms, with post-cessation body weight as secondary outcome. Read More

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Exendin-4 Promotes Schwann Cell Survival/Migration and Myelination In Vitro.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Diabetic Neuropathy Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan.

Besides its insulinotropic actions on pancreatic β cells, neuroprotective activities of glucagon-like peptide-1 (GLP-1) have attracted attention. The efficacy of a GLP-1 receptor (GLP-1R) agonist exendin-4 (Ex-4) for functional repair after sciatic nerve injury and amelioration of diabetic peripheral neuropathy (DPN) has been reported; however, the underlying mechanisms remain unclear. In this study, the bioactivities of Ex-4 on immortalized adult rat Schwann cells IFRS1 and adult rat dorsal root ganglion (DRG) neuron-IFRS1 co-culture system were investigated. Read More

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Sitagliptin, a dipeptidyl peptidase-4 inhibitor, attenuates apoptosis of vascular smooth muscle cells and reduces atherosclerosis in diabetic apolipoprotein E-deficient mice.

Vascul Pharmacol 2021 Mar 26:106854. Epub 2021 Mar 26.

Department of Cardiology, Chinese Hainan Hospital of PLA General Hospital, Sanya, Hainan Province, China.

Sitagliptin, a dipeptidyl peptidase-4(DPP-4) Inhibitor, has been found to have an anti-atherosclerotic effect. Since apoptosis of vascular smooth muscle cells (VSMCs) contributes to the occurrence of diabetic atherosclerosis. This study aimed to examine whether sitagliptin suppresses the atherosclerosis progression to hyperglycemia in a low-dose streptozotocin (STZ)-induced diabetic mouse model, and then investigated the effect of sitagliptin on VSMCs apoptosis and its underlying mechanism. Read More

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A Potential Mechanism Underlying the Therapeutic Effects of Progesterone and Allopregnanolone on Ketamine-Induced Cognitive Deficits.

Front Pharmacol 2021 8;12:612083. Epub 2021 Mar 8.

Department of Pharmacy, Second Xiangya Hospital, Central South University, Changsha, China.

Ketamine exposure can model cognitive deficits associated with schizophrenia. Progesterone (PROG) and its active metabolite allopregnanolone (ALLO) have neuroprotective effects and the pathway involving progesterone receptor membrane component 1 (PGRMC1), epidermal growth factor receptor (EGFR), glucagon-like peptide-1 receptor (GLP-1R), phosphatidylinositol 3 kinase (PI3K), and protein kinase B (Akt) appears to play a key role in their neuroprotection. The present study aimed to investigate the effects of PROG (8,16 mg kg) and ALLO (8,16 mg kg) on the reversal of cognitive deficits induced by ketamine (30 mg kg) via the PGRMC1 pathway in rat brains, including hippocampus and prefrontal cortex (PFC). Read More

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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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GLP-1 receptor agonists and their cardiovascular benefits - the role of the GLP-1 receptor.

Br J Pharmacol 2021 Mar 25. Epub 2021 Mar 25.

Department of Cardiology, University Medical Center, Mainz, Germany.

Cardiovascular outcome trials (CVOT) revealed cardiovascular benefits for type 2 diabetes mellitus patients when treated with long-acting glucagon-like peptide-1 receptor (GLP-1R) agonists. In the last decade, major advances were made characterising the physiological effects of GLP-1 and its action on numerous target organs and tissues including brain, liver, kidney, heart, and blood vessels. However, the effects of GLP-1/GLP-1R agonists and the GLP-1 receptor on the cardiovascular system have not been fully elucidated. Read More

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Liraglutide Alleviates Hepatic Steatosis and Liver Injury in T2MD Rats via a GLP-1R Dependent AMPK Pathway.

Front Pharmacol 2020 4;11:600175. Epub 2021 Mar 4.

Department of Nutrition, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Non-alcoholic fatty liver disease (NAFLD), ranging from non-alcoholic fatty liver to non-alcoholic steatohepatitis, can be prevalent in patients with type 2 diabetes mellitus (T2DM). However, no antidiabetic drug has been approved for the treatment of NAFLD in T2DM patients. Multiple daily injections of basal-bolus insulin are often the final therapeutic option for T2DM. Read More

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Non-Peptide Agonists and Positive Allosteric Modulators of Glucagon-Like Peptide-1 Receptor: Alternative Approaches for Treatment of Type 2 Diabetes.

Br J Pharmacol 2021 Mar 16. Epub 2021 Mar 16.

Department of Chemistry & Biochemistry, University of the Sciences in Philadelphia, Philadelphia, PA, 19104, USA.

Glucagon-Like Peptide-1 Receptor (GLP-1R) belongs to the pharmaceutically important Class B family of GPCRs and is involved in multiple biologically significant signaling pathways. Its incretin peptide ligand GLP-1 analogs are effective drugs for the treatment of type 2 diabetes. Although developing non-peptide small molecule drugs targeting GLP-1R remains elusive, considerable progress has been made in discovering small molecule, non-peptide agonists and positive allosteric modulators (PAMs) of GLP-1R with demonstrated efficacy. Read More

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Discovery of an Orally Efficacious Positive Allosteric Modulator of the Glucagon-like Peptide-1 Receptor.

J Med Chem 2021 Mar 15;64(6):3439-3448. Epub 2021 Mar 15.

Discovery Chemistry Research and Technologies, Lilly, S.A., Avda. de la Industria 30, Alcobendas, Madrid 28108, Spain.

The identification of LSN3318839, a positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), is described. LSN3318839 increases the potency and efficacy of the weak metabolite GLP-1(9-36)NH to become a full agonist at the GLP-1R and modestly potentiates the activity of the highly potent full-length ligand, GLP-1(7-36)NH. LSN3318839 preferentially enhances G protein-coupled signaling by the GLP-1R over β-arrestin recruitment. Read More

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Functional GLP-1R antibodies identified from a synthetic GPCR-focused library demonstrate potent blood glucose control.

MAbs 2021 Jan-Dec;13(1):1893425

Twist Biopharma, South San Francisco, CA, USA.

G protein-coupled receptors (GPCRs) are a group of seven-transmembrane receptor proteins that have proven to be successful drug targets. Antibodies are becoming an increasingly promising modality to target these receptors due to their unique properties, such as exquisite specificity, long half-life, and fewer side effects, and their improved pharmacokinetic and pharmacodynamic profiles compared to peptides and small molecules, which results from their more favorable biodistribution. To date, there are only two US Food and Drug Administration-approved GPCR antibody drugs, namely erenumab and mogamulizumab, and this highlights the challenges encountered in identifying functional antibodies against GPCRs. 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

Combined treatment with bone marrow-derived mesenchymal stem cells and exendin-4 promotes islet regeneration in STZ-induced diabetic rats.

Stem Cells Dev 2021 Mar 7. Epub 2021 Mar 7.

Medical School of Chinese PLA, 104607, Beijing, Beijing, China;

This study was designed to assess whether the combination of the glucagon-like peptide-1 (GLP-1) analog exendin-4 (Ex4) and bone marrow-derived mesenchymal stem cell (BM-MSC) could enhance β-cell action in STZ-induced diabetic rats. Forty male SD rats were randomly assigned to five groups: the normal control group (Normal), diabetes group (DM), MSC-treated group (MSC), Ex4-treated group (Ex4) and MSC plus Ex4-treated group (MSC + Ex4). Body weight, blood glucose level, intraperitoneal glucose tolerance test (IPGTT) and in vitro glucose-stimulated insulin secretion (GSIS) were used to assess the treatment efficacy. Read More

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Synthesis, Optimization, and Biological Evaluation of Corrinated Conjugates of the GLP-1R Agonist Exendin-4.

J Med Chem 2021 Mar 6;64(6):3479-3492. Epub 2021 Mar 6.

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

Corrination is the conjugation of a corrin ring containing molecule, such as vitamin B (B12) or B12 biosynthetic precursor dicyanocobinamide (Cbi), to small molecules, peptides, or proteins with the goal of modifying pharmacology. Recently, a corrinated GLP-1R agonist (GLP-1RA) exendin-4 (Ex4) has been shown to have reduced penetration into the central nervous system relative to Ex4 alone, producing a glucoregulatory GLP-1RA devoid of anorexia and emesis. The study herein was designed to optimize the lead conjugate for GLP-1R agonism and binding. Read More

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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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GRK2 regulates GLP-1R-mediated early phase insulin secretion in vivo.

BMC Biol 2021 Mar 3;19(1):40. Epub 2021 Mar 3.

Departamento de Biología Molecular and Centro de Biología Molecular Severo Ochoa (CBMSO) UAM-CSIC; Instituto de Investigación Sanitaria Hospital Universitario La Princesa; CIBER de Enfermedades Cardiovasculares (CIBERCV), UNIVERSIDAD AUTONOMA DE MADRID and Instituto de Salud Carlos III, Madrid, Spain.

Background: Insulin secretion from the pancreatic β-cell is finely modulated by different signals to allow an adequate control of glucose homeostasis. Incretin hormones such as glucagon-like peptide-1 (GLP-1) act as key physiological potentiators of insulin release through binding to the G protein-coupled receptor GLP-1R. Another key regulator of insulin signaling is the Ser/Thr kinase G protein-coupled receptor kinase 2 (GRK2). Read More

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Exendin-4, a glucagon-like peptide receptor agonist, facilitates osteoblast differentiation via connexin43.

Endocrine 2021 Feb 27. Epub 2021 Feb 27.

Division of Endocrinology and Metabolism, Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea.

Purpose: To investigate whether exendin-4 (Ex-4), a glucagon-like peptide 1 receptor (GLP-1R) agonist, affects connexin 43 (Cx43) expression in osteoblasts, and determine the specific mechanism underlying Cx43 modulation by Ex-4.

Methods: Osteoblast-like MC3T3-E1 cells were treated with Ex-4 with or without GLP-1R antagonist. We assessed Cx43 expression using RT-PCR, western blotting, and confocal microscopy; visualized intercellular communication using Lucifer yellow dye transfer assay; evaluated osteoblast differentiation using alkaline phosphatase and Alizarin red S (ARS) staining. Read More

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February 2021

GLP-1 Val8: A Biased GLP-1R Agonist with Altered Binding Kinetics and Impaired Release of Pancreatic Hormones in Rats.

ACS Pharmacol Transl Sci 2021 Feb 19;4(1):296-313. Epub 2021 Jan 19.

Laboratory for Molecular Pharmacology, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark.

Biased ligands that selectively confer activity in one pathway over another are pharmacologically important because biased signaling may reduce on-target side effects and improve drug efficacy. Here, we describe an N-terminal modification in the incretin hormone glucagon-like peptide (GLP-1) that alters the signaling capabilities of the GLP-1 receptor (GLP-1R) by making it G protein biased over internalization but was originally designed to confer DPP-4 resistance and thereby prolong the half-life of GLP-1. Despite similar binding affinity, cAMP production, and calcium mobilization, substitution of a single amino acid (Ala8 to Val8) in the N-terminus of GLP-1(7-36)NH (GLP-1 Val8) severely impaired its ability to internalize GLP-1R compared to endogenous GLP-1. Read More

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February 2021

FXR-mediated epigenetic regulation of GLP-1R expression contributes to enhanced incretin effect in diabetes after RYGB.

J Cell Mol Med 2021 Feb 21. Epub 2021 Feb 21.

Shenzhen University Diabetes Institute, School of Medicine, Shenzhen University, Shenzhen, China.

In this study, we investigated how Roux-en-Y gastric bypass (RYGB) enhances glucagon-like peptide 1 (GLP-1) response in GK rats and explored the potential link between RYGB-stimulated BAs/FXR signalling and GLP-1R-linked signalling in β-cells, a key pathway that regulates glucose-stimulated insulin secretion (GSIS). Here we show that RYGB restores GLP-1R expression in GK rat islets. This involves increased total BAs as well as chenodeoxycholic acid (CDCA), leading to FXR activation, increasing FXR binding to the promoter of Glp-1r and enhancing occupancy of histone acetyltransferase steroid receptor coactivator-1 (SRC1), thus increasing histone H3 acetylation at the promoter. Read More

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February 2021

Glucagon-like peptide 1 receptor (GLP-1R) agonist relieved asthmatic airway inflammation via suppression of NLRP3 inflammasome activation in obese asthma mice model.

Pulm Pharmacol Ther 2021 Apr 12;67:102003. Epub 2021 Feb 12.

Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Background: Obesity is a correctable factor for uncontrolled bronchial asthma. However, the effects of glucagon-like peptide-1 receptor (GLP-1R) agonist, a recently approved antiobestic drug, on airway hyperresponsiveness (AHR) and immune responses are not known.

Methods: Mice were fed with high-fat diet (HFD, 60% fat) for 8 weeks to induce obesity. Read More

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Liraglutide to Improve corONary haemodynamics during Exercise streSS (LIONESS): a double-blind randomised placebo-controlled crossover trial.

Diabetol Metab Syndr 2021 Feb 12;13(1):17. Epub 2021 Feb 12.

King's College London British Heart Foundation Centre of Research Excellence, The Rayne Institute, Cardiovascular Division, St Thomas' Hospital, Westminster Bridge Road, London, SE1 7EH, UK.

Background: Glucagon-like peptide-1 receptor (GLP-1R) activation may improve myocardial performance in the context of ischaemia, independent of glycaemic control, in individuals with and without type 2 diabetes mellitus.

Methods: The LIONESS trial was a single-centre randomised double-blind placebo-controlled crossover study to determine whether prolonged GLP-1R activation could improve exercise haemodynamics in chronic stable angina patients. Eligibility criteria comprised angiographic evidence of obstructive coronary artery disease (CAD) and an abnormal baseline exercise tolerance test (ETT) demonstrating > 0. Read More

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February 2021

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

Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists.

Mol Metab 2021 Feb 6;49:101181. Epub 2021 Feb 6.

Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, Neuherberg, Germany; German Center for Diabetes Research (DZD), Neuherberg, Germany; Department of Pharmacology and Experimental Therapy, Institute of Experimental and Clinical Pharmacology and Toxicology, Eberhard Karls University Hospitals and Clinics, 72076 Tübingen, Germany. Electronic address:

Objective: We assessed the spatiotemporal GLP-1 and GIP receptor signaling, trafficking, and recycling dynamics of GIPR mono-agonists, GLP-1R mono-agonists including semaglutide, and GLP-1/GIP dual-agonists MAR709 and tirzepatide.

Methods: Receptor G protein recruitment and internalization/trafficking dynamics were assessed using bioluminescence resonance energy transfer (BRET)-based technology and live-cell HILO microscopy.

Results: Relative to native and acylated GLP-1 agonists, MAR709 and tirzepatide showed preserved maximal cAMP production despite partial Gα recruitment paralleled by diminished ligand-induced receptor internalization at both target receptors. Read More

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February 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