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Glp 1 agonist

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https://www.readbyqxmd.com/read/29782892/a-glp-1-cck-fusion-peptide-harnesses-the-synergistic-effects-on-metabolism-of-cck-1-and-glp-1-receptor-agonism-in-mice
#1
David C Hornigold, Emma Roth, Victor Howard, Sarah Will, Stephanie Oldham, Matthew P Coghlan, Clemence Blouet, James L Trevaskis
Combination approaches for the treatment of metabolic diseases such as obesity and diabetes are becoming increasingly relevant. Co-administration of a glucagon-like peptide-1 receptor (GLP-1R) agonist with a cholecystokinin receptor-1 (CCKR1) agonist exert synergistic effects on weight loss in obese rodents. Here, we report on the effects of a novel fusion peptide (C2816) comprised of a stabilized GLP-1R agonist, AC3174, and a CCKR1-selective agonist, AC170222. C2816 was constructed such that AC3174 was linked to the N-terminus of AC170222, thus preserving the C-terminal amide of the CCK moiety...
May 18, 2018: Appetite
https://www.readbyqxmd.com/read/29779196/retrospective-analysis-of-an-insulin-to-liraglutide-switch-in-patients-with-type-2-diabetes-mellitus
#2
Eveline Bruinstroop, Laura Meyer, Catherine B Brouwer, Diana E van Rooijen, P Sytze van Dam
INTRODUCTION: Insulin and the GLP-1 receptor agonist liraglutide are both effective in reaching glycemic targets. The efficacy of an insulin-to-liraglutide switch in an obese population with concurrent use of sulfonylurea and metformin is unknown. We assessed the efficacy and determinants of success of an insulin-to-liraglutide switch in these patients. METHODS: In a retrospective study we analyzed all patients that underwent an insulin-to-liraglutide switch during routine medical care (January 2009-February 2015)...
May 19, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29778663/glp-1-receptor-agonists-and-reduction-of-cardiometabolic-risk-potential-underlying-mechanisms
#3
REVIEW
Manfredi Rizzo, Dragana Nikolic, Angelo Maria Patti, Carlo Mannina, Giuseppe Montalto, Brooke S McAdams, Ali A Rizvi, Francesco Cosentino
Type 2 diabetes mellitus (T2DM) is a metabolic condition with an elevated impact on cardiovascular (CV) risk. The innovative therapeutic approaches for T2DM - incretin-based therapies (IBTs), including glucagon-like peptide 1 (GLP-1) receptor agonists, have become popular and more widely used in recent years. The available scientific data from clinical studies and clinical practice highlights their beyond glucose-lowering effects, which is achieved without any increase in hypoglycaemia. The former effects include reduction in body weight, lipids, blood pressure, inflammatory markers, oxidative stress, endothelial dysfunction, and subclinical atherosclerosis, thus reducing and potentially preventing CV events...
May 17, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29777582/comparative-study-of-liraglutide-and-insulin-glargine-on-glycemic-control-and-pancreatic-%C3%AE-cell-function-in-db-db-mice
#4
Yanli Li, Jia Zheng, Yunfeng Shen, Wangen Li, Meimei Liu, Jun Wang, Surong Zhu, Meihua Wu
BACKGROUND The aim of this study was to compare the effects of liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, and insulin glargine, a long-acting insulin analog, on glycemic control and pancreatic β-cell function in db/db mice. MATERIAL AND METHODS Eight-week-old male db/db mice (n=40) were divided into five groups: the vehicle-treated group (VG) (n=8); the insulin glargine-treated group (GG) (dose, 450 mg/kg) (n=8), the low-dose liraglutide-treated group (LLG) (dose, 75 μg/kg) (n=8), the mid-dose liraglutide-treated group (MLG) (150 μg/kg) (n=8), and the high-dose liraglutide-treated group (HLG) (300 μg/kg) (n=8), treated with subcutaneous injection once daily, from 8-14 weeks-of-age...
May 19, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29776968/liraglutide-modulates-appetite-and-body-weight-via-glp-1r-expressing-glutamatergic-neurons
#5
Jessica M Adams, Hongjuan Pei, Darleen A Sandoval, Randy J Seeley, Rui B Chang, Stephen D Liberles, David P Olson
Glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved weight loss drugs. Despite their widespread use, the sites of action through which GLP-1R agonists (GLP1RAs) impact appetite and body weight are still not fully understood. Here, we determined whether GLP-1Rs in either GABAergic or glutamatergic neurons are necessary for the acute and chronic effects of the GLP1RA liraglutide on food intake, visceral illness, body weight and neural network activation. We found that mice lacking GLP-1Rs in vGAT -expressing GABAergic neurons responded identically to controls in all parameters measured, whereas deletion of GLP-1Rs in vGlut2 -expressing glutamatergic neurons eliminated liraglutide-induced weight loss and visceral illness and severely attenuated its effects on feeding...
May 18, 2018: Diabetes
https://www.readbyqxmd.com/read/29776406/the-effect-of-dpp-4-inhibition-to-improve-functional-outcome-after-stroke-is-mediated-by-the-sdf-1%C3%AE-cxcr4-pathway
#6
Fausto Chiazza, Harald Tammen, Hiranya Pintana, Grazyna Lietzau, Massimo Collino, Thomas Nyström, Thomas Klein, Vladimer Darsalia, Cesare Patrone
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors (gliptins) are approved drugs for the treatment of hyperglycemia in patients with type 2 diabetes. These effects are mainly mediated by inhibiting endogenous glucagon-like peptide-1 (GLP-1) cleavage. Interestingly, gliptins can also improve stroke outcome in rodents independently from GLP1. However, the underlying mechanisms are unknown. Stromal cell-derived factor-1α (SDF-1α) is a DPP-4 substrate and CXCR4 agonist promoting beneficial effects in injured brains...
May 19, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29773934/iglarlixi-a-new-once-daily-fixed-ratio-combination-of-basal-insulin-glargine-and-lixisenatide-for-the-management-of-type-2-diabetes
#7
Debbie Hinnen, Jodi Strong
Background: Patients with type 2 diabetes require treatment intensification to maintain glycemic control. Clinician reluctance, patient injection fears, hypoglycemia, weight gain, or other objections may lead to clinical inertia, whereby therapy is not intensified and patients live with uncontrolled hyperglycemia and increased risk for complications. Initiation of injectable therapy with a glucagon-like peptide (GLP)-1 receptor agonist and/or basal insulin is a recommended option for patients with type 2 diabetes inadequately controlled on one or more oral agents...
May 2018: Diabetes Spectrum: a Publication of the American Diabetes Association
https://www.readbyqxmd.com/read/29772784/capsaicin-in-metabolic-syndrome
#8
REVIEW
Sunil K Panchal, Edward Bliss, Lindsay Brown
Capsaicin, the major active constituent of chilli, is an agonist on transient receptor potential vanilloid channel 1 (TRPV1). TRPV1 is present on many metabolically active tissues, making it a potentially relevant target for metabolic interventions. Insulin resistance and obesity, being the major components of metabolic syndrome, increase the risk for the development of cardiovascular disease, type 2 diabetes, and non-alcoholic fatty liver disease. In vitro and pre-clinical studies have established the effectiveness of low-dose dietary capsaicin in attenuating metabolic disorders...
May 17, 2018: Nutrients
https://www.readbyqxmd.com/read/29768476/treatment-with-specific-soluble-factors-promotes-the-functional-maturation-of-transcription-factor-mediated-pancreatic-transdifferentiated-cells
#9
Hiroaki Motoyama, Akira Kobayashi, Takahide Yokoyama, Akira Shimizu, Hiroshi Sakai, Tsuyoshi Notake, Kentaro Fukushima, Shin-Ichi Miyagawa
Pancreatic lineage-specific transcription factors (TFs) display instructive roles in converting adult cells to endocrine pancreatic cells through a process known as transdifferentiation. However, little is known about potential factors capable of accelerating transdifferentiation following transduction to achieve the functional maturation of transdifferentiated cells. In this study, we demonstrated, using adult liver-derived progenitor cells, that soluble factors utilized in pancreatic differentiation protocols of pluripotent stem cells promote functional maturation of TFs-mediated transdifferentiated cells...
2018: PloS One
https://www.readbyqxmd.com/read/29760945/liraglutide-and-dulaglutide-therapy-in-addition-to-sglt-2-inhibitor-and-metformin-treatment-in-indian-type-2-diabetics-a-real-world-retrospective-observational-study
#10
S Ghosal, B Sinha
Background: Therapy for Type 2 diabetes (T2D) has been transformed by the introduction of newer agents like Glucagon like Peptide Receptor Agonists (GLP-1RA) and Sodium-glucose linked transporter inhibitors (SGLT2i). However with co-initiation of SGLT2i and GLP-1RA in the DURATION 8 trial an improvement in HbA1c was noted but the beneficial effect was not equal to the sum of its parts. In view of this we proceeded to test the hypothesis that sequential addition of GLP-1RA therapy to metformin and SGLT-2i may be more beneficial...
2018: Clinical Diabetes and Endocrinology
https://www.readbyqxmd.com/read/29756388/semaglutide-for-type-2-diabetes-mellitus-a-systematic-review-and-meta-analysis
#11
Panagiotis Andreadis, Thomas Karagiannis, Konstantinos Malandris, Ioannis Avgerinos, Aris Liakos, Apostolos Manolopoulos, Eleni Bekiari, David R Matthews, Apostolos Tsapas
AIM: To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes. METHODS: We searched major electronic databases and grey literature sources for randomised controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c . Secondary endpoints included change from baseline in body weight, blood pressure, heart rate, and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy...
May 13, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29752762/feeding-and-glp-1-receptor-activation-stabilize-%C3%AE-catenin-in-specific-hypothalamic-nuclei-in-male-rats
#12
Hayden J L McEwen, Emmanuelle Cognard, Sharon R Ladyman, Zin Khant-Aung, Alexander Tups, Peter R Shepherd, David R Grattan
β-catenin is a multifunctional protein that can act in the canonical Wnt/β-catenin pathway to regulate gene expression but can also bind to cadherin proteins in adherens junctions where it plays a key role in regulating cytoskeleton linked with these junctions. Recently, evidence has been presented indicating an essential role for β-catenin in regulating trafficking of insulin vesicles in β-cells and showing that changes in nutrient levels rapidly alter levels of β-catenin in these cells. Given the importance of neuroendocrine hormone secretion in the regulation of whole body glucose homeostasis, the objective of this study was to investigate whether β-catenin signalling is regulated in the hypothalamus during the normal physiological response to food intake...
May 11, 2018: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29744819/comparison-of-glycemic-variability-in-chinese-t2dm-patients-treated-with-exenatide-or-insulin-glargine-a-randomized-controlled-trial
#13
Ting-Ting Yin, Yan Bi, Ping Li, Shan-Mei Shen, Xiao-Lu Xiong, Li-Jun Gao, Can Jiang, Yan Wang, Wen-Huan Feng, Da-Long Zhu
INTRODUCTION: Increasing the frequency of blood glucose monitoring aids the evaluation of glycemic variability and blood glucose control by antidiabetic drugs. It remains unclear, however, whether GLP-1 receptor agonists or basal insulin has a better effect on glycemic variability in type 2 diabetes mellitus (T2DM) patients who are inadequately controlled by metformin. We used a continuous glucose monitoring system (CGMS) to compare patients on a GLP-1 receptor agonist with patients on basal insulin in terms of glycemic variability...
May 9, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29744272/antidiabetic-activity-of-mefloquine-via-glp-1-receptor-modulation-against-stz-na-induced-diabetes-in-albino-wistar-rats
#14
Rajnish Kumar Yadav, Jitendra K Rawat, Swetlana Gautam, Manjari Singh, Manish Kumar, Mohd Nazam Ansari, Subhadeep Roy, Abdulaziz S Saeedan, Gaurav Kaithwas
Mefloquine was retrieved as a glucagon -like peptide-1 receptor agonist and, therefore, evaluated for its antidiabetic potential against non-insulin-dependent diabetes mellitus (NIDDM) in experimental animals. NIDDM was induced by single intraperitoneal injection of streptozotocin and nicotinamide (60 + 110 mg/kg) in albino wistar rats. The experimental animals were scrutinised for electrocardiographic (ECG) and heart rate variability (HRV) factors to study the autonomic dysfunction along with blood glucose, serum insulin, and liver glycogen levels for glycemic control...
May 2018: 3 Biotech
https://www.readbyqxmd.com/read/29737256/cardiovascular-effects-of-liraglutide
#15
Nasser Mikhail
BACKGROUND: Liraglutide is a glucagon-like 1 (GLP-1) agonist approved for treatment of type 2 diabetes and obesity. OBJECTIVE: To review the cardiovascular effects of liraglutide including macrovascular and microvascular events, its use in heart failure, and its effects on heart rate and blood pressure. RESULTS: The impact of liraglutide on cardiovascular outcomes was examined in a large well-designed study published in 2016, the LEADER trial...
May 7, 2018: Current Hypertension Reviews
https://www.readbyqxmd.com/read/29732679/free-and-fixed-ratio-combinations-of-basal-insulin-and-glp-1-receptor-agonists-versus-basal-insulin-intensification-in-type-2-diabetes-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials
#16
Maria Ida Maiorino, Paolo Chiodini, Giuseppe Bellastella, Lorenzo Scappaticcio, Miriam Longo, Katherine Esposito, Dario Giugliano
We provide a meta-analysis of randomized controlled trials (RCTs) comparing free or fixed combination of a GLP-1RA plus basal insulin versus insulin intensification on metabolic control in patients with type 2 diabetes. We searched electronic databases for RCTs assessing changes in HbA1c, proportion of patients at HbA1c target of <7% (53 mmol/mol), hypoglycaemia, and weight change. We used a random-effect model to calculate the weighted mean difference (WMD) or relative risk (RR) with the 95% CI. We identified 11 RCTs, lasting 24-30 weeks, and involving 6176 patients...
May 7, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29729352/pegylated-prodrugs-of-antidiabetic-peptides-amylin-and-glp-1
#17
Roland Böttger, Daniel Knappe, Ralf Hoffmann
Agonists of the glucagon-like peptide-1 (GLP-1) receptor and analogs of human amylin have been studied for almost two decades due to their therapeutic potential to treat diabetes mellitus and obesity. Both native peptides exhibit unfavorable pharmacokinetics. Even optimized analogs less prone to proteolysis have to be applied at least daily or once-weekly utilizing microsphere formulations or fusion to proteins. Thus, innovative approaches allowing tuning the drug levels to achieve beneficial therapeutic responses and prolonged application intervals are demanded...
May 2, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/29725604/the-glucagon-like-peptide-1-receptor-agonist-exendin-4-inhibits-lipopolysaccharide-induced-osteoclast-formation-and-bone-resorption-via-inhibition-of-tnf-%C3%AE-expression-in-macrophages
#18
Wei-Ren Shen, Keisuke Kimura, Masahiko Ishida, Haruki Sugisawa, Akiko Kishikawa, Kazuhiro Shima, Saika Ogawa, Jiawei Qi, Hideki Kitaura
Glucagon-like peptide-1 (GLP-1) receptor agonists are an effective treatment approach for type 2 diabetes. Recently, anti-inflammatory effects of GLP-1 receptor agonists have also been reported. Lipopolysaccharide (LPS) induces inflammation and osteoclast formation. In this study, we investigated the effect of exendin-4, a widely used GLP-1 receptor agonist, in LPS-induced osteoclast formation and bone resorption. LPS with or without exendin-4 was administered on mouse calvariae by daily subcutaneous injection...
2018: Journal of Immunology Research
https://www.readbyqxmd.com/read/29725251/glucagon-like-peptide-1-receptor-agonist-and-glucagon-increase-glucose-stimulated-insulin-secretion-in-beta-cells-via-distinct-adenylyl-cyclases
#19
Young-Sun Lee, Hee-Sook Jun
Diabetes mellitus is a chronic disease in which the pancreas no longer produces enough insulin. Pancreatic alpha cell mass increases in response to insufficient insulin secretion. However, the reason for this increase is not clear. It is possible that the increased alpha-cells may stimulate compensatory insulin release in response to the insufficient insulin such as insulin resistance. In 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...
2018: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/29717000/two-distinct-domains-of-the-glucagon-like-peptide-1-receptor-control-peptide-mediated-biased-agonism
#20
Saifei Lei, Lachlan Clydesdale, Antao Dai, Xiaoqing Cai, Yang Feng, Dehua Yang, Yi-Lynn Liang, Cassandra Koole, Peishen Zhao, Thomas Coudrat, Arthur Christopoulos, Ming-Wei Wang, Denise Wootten, Patrick M Sexton
G protein-coupled receptors (GPCRs) can be differentially activated by ligands to generate multiple and distinct, downstream signaling profiles, a phenomenon termed biased agonism. The glucagon-like peptide-1 receptor (GLP-1R) is a class B GPCR and a key drug target for managing metabolic disorders; however, its peptide agonists display biased signaling that affect their relative efficacies. In this study, we 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...
May 1, 2018: Journal of Biological Chemistry
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