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https://www.readbyqxmd.com/read/29341461/effect-of-immediate-and-prolonged-glp-1-receptor-agonist-administration-on-uric-acid-and-its-kidney-clearance-post-hoc-analyses-of-four-clinical-trials
#1
Lennart Tonneijck, Marcel H A Muskiet, Mark M Smits, Petter Bjornstad, Mark H H Kramer, Michaela Diamant, Ewout J Hoorn, Jaap A Joles, Daniël H van Raalte
AIMS: To determine effects of glucagon-like peptide (GLP)-1 receptor agonists (RA) on uric acid (UA)-levels and kidney UA-clearance. MATERIAL AND METHODS: Post-hoc analyses of four controlled clinical trials, which assessed actions of GLP-1RA-administration on kidney physiology. Immediate effects of GLP-1RA exenatide-infusion versus placebo was determined in 9 healthy overweight males (Study-A) and in 52 overweight T2DM-patients (Study-B). Effects were also examined of 12-week long-acting GLP-1RA liraglutide versus placebo in 36 overweight T2DM-patients (Study-C) and of 8-week short-acting GLP-1RA lixisenatide versus once-daily titrated insulin-glulisine in 35 overweight T2DM-patients (Study-D)...
January 17, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29341370/real-world-clinical-outcomes-and-predictors-of-glycaemic-and-weight-response-to-exenatide-once-weekly-in-patients-with-type-2-diabetes-the-cibeles-project
#2
Juan José Gorgojo-Martínez, Manuel Angel Gargallo-Fernández, Miguel Brito-Sanfiel, Arturo Lisbona-Catalán
AIMS: To evaluate in a real-world setting the effectiveness of exenatide once-weekly (ExQW) in patients with T2D and to determine predictors of glycaemic and weight response to this drug at 6 months. METHODS: Observational, retrospective, multicenter study in adult patients with T2D and BMI ≥30 kg/m2 from 4 tertiary Spanish hospitals who started ExQW therapy at least 6 months before the inclusion and had not achieved adequate glycaemic control on oral therapies or other GLP-1 receptor agonists...
January 17, 2018: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/29337226/glp-1-signaling-and-alcohol-mediated-behaviors-preclinical-and-clinical-evidence
#3
REVIEW
Elisabet Jerlhag
Alcohol addiction, affecting approximately four percent of the population, contributes significantly to the global burden of diseases and is a substantial cost to the society. The neurochemical mechanisms regulating alcohol mediated behaviors is complex and in more recent years a new physiological role of the gut-brain peptides, traditionally known to regulate appetite and food intake, have been suggested. Indeed, regulators of alcohol-mediated behaviors. One of these gut-brain peptides is the annorexigenic peptide glucagon-like peptide-1 (GLP-1), Preclinical studies show that GLP-1 receptor activation, either by GLP-1 or analogues, attenuate the ability of alcohol to activate the mesolimbic dopamine system as well as decrease alcohol consumption and operant self-administration...
January 11, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29335890/effectiveness-of-sodium-glucose-cotransporter-2-inhibitor-as-an-add-on-drug-to-glp-1-receptor-agonists-for-glycemic-control-of-a-patient-with-prader-willi-syndrome-a-case-report
#4
Yukio Horikawa, Mayumi Enya, Makie Komagata, Ken-Ichi Hashimoto, Masayo Kagami, Maki Fukami, Jun Takeda
INTRODUCTION: Diabetes patients with Prader-Willi syndrome (PWS) are obese because of hyperphagia; weight control by dietary modification and medicine is required for glycemic control. There are several recent reports showing the effectiveness of GLP-1 receptor agonists (GLP-1RAs) for diabetes treatment in PWS. CASE REPORT: A 36-year-old Japanese male patient was diagnosed with PWS at 10 years of age. At age 16 years, he was diagnosed with diabetes and began to take several kinds of oral hypoglycemic agents...
January 15, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29334278/a-comparative-safety-review-between-glp-1-receptor-agonists-and-sglt2-inhibitors-for-diabetes-treatment
#5
Agostino Consoli, Gloria Formoso, Maria Pompea Antonia Baldassarre, Fabrizio Febo
Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose cotransporter 2 inhibitors (SGLT2i) are of particular interest in type 2 diabetes treatment strategies, due to their efficacy in reducing HbA1c with a low risk of hypoglycaemia, to their positive effects on body weight and blood pressure and in light of their effects on cardiovascular risk and on nephroprotection emerged from the most recent cardiovascular outcome trials. Since it is therefore very likely that GLP-1RA and SGLT2i use will become more and more common, it is more and more important to gather and discuss information about their safety profile...
January 15, 2018: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/29331643/glucagon-like-peptide-1-signaling-inhibits-allergen-induced-lung-il-33-release-and-reduces-group-2-innate-lymphoid-cell-ilc2-cytokine-production-in-vivo
#6
Shinji Toki, Kasia Goleniewska, Sara Reiss, Jian Zhang, Melissa H Bloodworth, Matthew T Stier, Weisong Zhou, Dawn C Newcomb, Lorraine B Ware, Gregg D Stanwood, Aurelio Galli, Kelli L Boyd, Kevin D Niswender, R Stokes Peebles
BACKGROUND: IL-33 is one of the most consistently associated gene candidates for asthma identified by GWAS. Studies in mice and in human cells have confirmed the importance of IL-33 in inducing type-2 cytokine production from both group 2 innate lymphoid cells (ILC2) and Th2 cells. However, there are no pharmacologic agents known to inhibit IL-33 release from airway cells. OBJECTIVE: To determine the effect of glucagon like peptide receptor-1 GLP-1R signaling on aeroallergen-induced airway IL-33 production and release and on innate type-2 airway inflammation...
January 10, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29330461/comparing-olive-oil-and-c4-dietary-oil-a-prodrug-for-the-gpr119-agonist-2-oleoyl-glycerol-less-energy-intake-of-the-latter-is-needed-to-stimulate-incretin-hormone-secretion-in-overweight-subjects-with-type-2-diabetes
#7
Mette Johannsen Mandøe, Katrine Bagge Hansen, Johanne Agerlin Windeløv, Filip Krag Knop, Jens Frederik Rehfeld, Mette Marie Rosenkilde, Jens Juul Holst, Harald Severin Hansen
BACKGROUND/OBJECTIVE: After digestion, dietary triacylglycerol stimulates incretin release in humans, mainly through generation of 2-monoacylglycerol, an agonist for the intestinal G protein-coupled receptor 119 (GPR119). Enhanced incretin release may have beneficial metabolic effects. However, dietary fat may promote weight gain and should therefore be restricted in obesity. We designed C4-dietary oil (1,3-di-butyryl-2-oleoyl glycerol) as a 2-oleoyl glycerol (2-OG)-generating fat type, which would stimulate incretin release to the same extent while providing less calories than equimolar amounts of common triglycerides, e...
January 12, 2018: Nutrition & Diabetes
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#8
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327400/a-vitamin-b12-conjugate-of-exendin-4-improves-glucose-tolerance-without-associated-nausea-or-hypophagia-in-rodents
#9
Elizabeth G Mietlicki-Baase, Claudia G Liberini, Jayme L Workinger, Ron L Bonaccorso, Tito Borner, David J Reiner, Kieran Koch-Laskowski, Lauren E McGrath, Rinzin Lhamo, Lauren M Stein, Bart C De Jonghe, George G Holz, Christian L Roth, Robert P Doyle, Matthew R Hayes
AIMS: While pharmacological glucagon-like peptide-1 receptor (GLP-1R) agonists are FDA-approved for treating type 2 diabetes mellitus (T2DM) and obesity, a major side effect is nausea/malaise. We recently developed a conjugate of vitamin B12 bound to the GLP-1R agonist exendin-4 (Ex4), which displays enhanced proteolytic stability and retention of GLP-1R agonism. Here, we evaluate whether the conjugate (B12-Ex4) can improve glucose tolerance without producing anorexia and malaise. MATERIALS AND METHODS: We evaluated the effects of systemic B12-Ex4 and unconjugated Ex4 on food intake and body weight change, oral glucose tolerance, and nausea/malaise in male rats, and on intraperitoneal glucose tolerance in mice...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29317623/glp-1-release-and-vagal-afferent-activation-mediate-the-beneficial-metabolic-and-chronotherapeutic-effects-of-d-allulose
#10
Yusaku Iwasaki, Mio Sendo, Katsuya Dezaki, Tohru Hira, Takehiro Sato, Masanori Nakata, Chayon Goswami, Ryohei Aoki, Takeshi Arai, Parmila Kumari, Masaki Hayakawa, Chiaki Masuda, Takashi Okada, Hiroshi Hara, Daniel J Drucker, Yuichiro Yamada, Masaaki Tokuda, Toshihiko Yada
Overeating and arrhythmic feeding promote obesity and diabetes. Glucagon-like peptide-1 receptor (GLP-1R) agonists are effective anti-obesity drugs but their use is limited by side effects. Here we show that oral administration of the non-calorie sweetener, rare sugar D-allulose (D-psicose), induces GLP-1 release, activates vagal afferent signaling, reduces food intake and promotes glucose tolerance in healthy and obese-diabetic animal models. Subchronic D-allulose administered at the light period (LP) onset ameliorates LP-specific hyperphagia, visceral obesity, and glucose intolerance...
January 9, 2018: Nature Communications
https://www.readbyqxmd.com/read/29316397/discovery-of-potent-and-orally-bioavailable-dihydropyrazole-gpr40-agonists
#11
Jun Shi, Zhengxiang Gu, Elizabeth Anne Jurica, Ximao Wu, Lauren E Haque, Kristin N Williams, Andres S Hernandez, Zhenqiu Hong, Qi Gao, Marta Dabros, Akin H Davulcu, Arvind Mathur, Richard A Rampulla, Arun Kumar Gupta, Ramya Jayaram, Atsu Apedo, Douglas B Moore, Heng Liu, Lori K Kunselman, Edward J Brady, Jason J Wilkes, Bradley A Zinker, Hong Cai, Yue-Zhong Shu, Qin Sun, Elizabeth A Dierks, Kimberly A Foster, Carrie Xu, Tao Wang, Reshma Panemangalore, Mary Ellen Cvijic, Chunshan Xie, Gary G Cao, Min Zhou, John Krupinski, Jean M Whaley, Jeffrey A Robl, William R Ewing, Bruce Alan Ellsworth
G protein-coupled receptor 40 (GPR40) has become an attractive target for the treatment of diabetes since it was shown clinically to promote glucose-stimulated insulin secretion. Herein, we report our efforts to develop highly selective and potent GPR40 agonists with a dual mechanism of action, promoting both glucose-dependent insulin and incretin secretion. Employing strategies to increase polarity and the ratio of sp3/sp2 character of the chemotype, we identified BMS-986118 (compound 4), which showed potent and selective GPR40 agonist activity in vitro...
January 9, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29310647/have-dipeptidyl-peptidase-4-inhibitors-ameliorated-the-vascular-complications-of-type-2-diabetes-in-large-scale-trials-the-potential-confounding-effect-of-stem-cell-chemokines
#12
REVIEW
Milton Packer
Drugs that inhibit dipeptidyl peptidase-4 (DPP-4) are conventionally regarded as incretin-based agents that signal through the glucagon-like peptide-1 (GLP-1) receptor. However, inhibition of DPP-4 also potentiates the stem cell chemokine, stromal cell-derived factor-1 (SDF-1), which can promote inflammation, proliferative responses and neovascularization. In large-scale cardiovascular outcome trials, enhanced GLP-1 signaling has reduced the risk of atherosclerotic ischemic events, potentially because GLP-1 retards the growth and increases the stability of atherosclerotic plaques...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29301824/clinical-impact-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-uncontrolled-type-2-diabetes-and-very-high-baseline-hba1c-the-freedom-1-hbl-study
#13
Robert R Henry, Julio Rosenstock, Douglas S Denham, Prakash Prabhakar, Lise Kjems, Michelle A Baron
OBJECTIVE: ITCA 650 is a subdermal osmotic mini-pump that continuously delivers exenatide subcutaneously for 3-6 months. The efficacy, safety, and tolerability of ITCA 650 added to diet and exercise alone or combined with metformin, sulfonylurea, or thiazolidinedione monotherapy or a combination of these drugs was evaluated in poorly controlled patients with type 2 diabetes (T2D) who were ineligible for participation in a placebo-controlled study (FREEDOM-1) because of severe hyperglycemia (HbA1c >10% [86 mmol/mol])...
January 4, 2018: Diabetes Care
https://www.readbyqxmd.com/read/29295870/effect-of-liraglutide-on-atrial-natriuretic-peptide-adrenomedullin-and-copeptin-in-pcos
#14
Signe Frøssing, Malin Nylander, Caroline Kistorp, Sven O Skouby, Jens Faber
CONTEXT: Women with polycystic ovary syndrome (PCOS) have an increased risk of cardiovascular disease (CVD), and biomarkers can be used to detect early subclinical CVD. Midregional-pro-adrenomedullin (MR-proADM), midregional-pro-atrial natriuretic peptide (MR-proANP) and copeptin are all associated with CVD and part of the delicate system controlling fluid and hemodynamic homeostasis through vascular tonus and diuresis. The GLP-1 receptor agonist liraglutide, developed for treatment of type 2 diabetes (T2D), improves cardiovascular outcomes in patients with T2D including a decrease in particular MR-proANP...
January 2018: Endocrine Connections
https://www.readbyqxmd.com/read/29284659/a-targeted-rnai-screen-identifies-endocytic-trafficking-factors-that-control-glp-1-receptor-signaling-in-pancreatic-beta-cells
#15
Teresa Buenaventura, Nisha Kanda, Phoebe C Douzenis, Ben Jones, Stephen R Bloom, Pauline Chabosseau, Ivan R Corrêa, Domenico Bosco, Lorenzo Piemonti, Piero Marchetti, Paul R Johnson, Am James Shapiro, Guy A Rutter, Alejandra Tomas
The GLP-1 receptor (GLP-1R) is a key target for type 2 diabetes (T2D) treatment. Since endocytic trafficking of agonist-bound receptors is one of the most important routes for regulation of receptor signaling, a better understanding of this process may facilitate the development of new T2D therapeutic strategies. Here, we have screened 29 proteins with known functions in G protein-coupled receptor trafficking for their role in GLP-1R potentiation of insulin secretion in pancreatic beta cells. We identify five (clathrin, dynamin1, AP2, SNX27 and SNX1) that increase and four (HIP1, HIP14, GASP-1 and Nedd4) that decrease insulin secretion from murine insulinoma MIN6B1 cells in response to the GLP-1 analogue exendin-4...
December 28, 2017: Diabetes
https://www.readbyqxmd.com/read/29283509/exenatide-exhibits-anti-inflammatory-properties-and-modulates-endothelial-response-to-tumor-necrosis-factor-%C3%AE-mediated-activation
#16
Wojciech Garczorz, Enrique Gallego-Colon, Agnieszka Kosowska, Agnieszka Kłych-Ratuszny, Michał Woźniak, Wiesław Marcol, K J Niesner, Tomasz Francuz
INTRODUCTION: Cardiovascular disease is the main cause of mortality and morbidity in the industrialized world. Incretin mimetic compounds such as exenatide are currently used in the treatment of type 2 diabetes. AIMS: We investigated the effects of incretin drugs on apoptosis, adhesion molecule expression, and concentration of extracellular matrix (ECM) metalloproteinases under inflammatory conditions within the context of atherosclerotic plaque formation of both human coronary artery endothelial cells (hCAECs) and human aortic endothelial cells (hAoECs)...
December 28, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/29277321/network-meta-analysis-of-cardiovascular-outcomes-in-randomized-controlled-trials-of-new-antidiabetic-drugs
#17
Yue Fei, Man-Fung Tsoi, Cyrus Rustam Kumana, Tommy Tsang Cheung, Bernard Man Yung Cheung
BACKGROUND: Randomized controlled trials (RCTs) directly comparing cardiovascular outcomes of new antidiabetic drugs are lacking. We used network meta-analysis to compare new antidiabetic drug classes with respect to major adverse cardiovascular events (MACE) and mortality. METHODS: We searched MEDLINE, EMBASE, the Cochrane database, and ClinicalTrials.gov up to 30 December 2016 for RCTs involving SGLT-2 inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dipeptidyl peptidase-4 (DPP-4) inhibitors in diabetic patients that reported MACE and deaths...
December 20, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/29259802/the-effect-of-the-glp-1-analogue-exenatide-on-functional-connectivity-within-an-nts-based-network-in-women-with-and-without-obesity
#18
K Coveleskie, L A Kilpatrick, A Gupta, J Stains, L Connolly, J S Labus, C Sanmiguel, E A Mayer
Objective: The differential effect of GLP-1 agonist Exenatide on functional connectivity of the nucleus tractus solitaries (NTS), a key region associated with homeostasis, and on appetite-related behaviours was investigated in women with normal weight compared with women with obesity. Methods: Following an 8-h fast, 19 female subjects (11 lean, 8 obese) participated in a 2-d double blind crossover study. Subjects underwent functional magnetic resonance imaging at fast and 30-min post subcutaneous injection of 5 μg of Exenatide or placebo...
December 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29249556/both-classic-gs-camp-pka-creb-and-alternative-gs-camp-pka-p38%C3%AE-creb-signal-pathways-mediate-exenatide-stimulated-expression-of-m2-microglial-markers
#19
Hai-Yun Wu, Xue-Qi Tang, Hao Liu, Xiao-Fang Mao, Yong-Xiang Wang
GLP-1 receptor agonists, exenatide and GLP-1, promoted M2 type polarization in monocytes/macrophages and microglial cells. This study explored the signal basis underlying exenatide-stimulated expression of M2 microglia-specific genes, including the cytoplasmic marker Arg 1, surface marker CD206, and secretion protein marker IL-4. Treatment with exenatide in cultured primary microglial cells concentration dependently stimulated the expression of Arg 1, CD206 and IL-4, but did not significantly alter LPS-stimulated expression of TNF-α, IL-1β and IL-6...
December 12, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29242349/efficacy-and-safety-of-itca-650-a-novel-drug-device-glp-1-receptor-agonist-in-type-2-diabetes-uncontrolled-with-oral-antidiabetes-drugs-the-freedom-1-trial
#20
Julio Rosenstock, John B Buse, Rehan Azeem, Prakash Prabhakar, Lise Kjems, Holly Huang, Michelle A Baron
OBJECTIVE: ITCA 650 (exenatide in osmotic mini-pump) continuously delivers exenatide subcutaneously for 3-6 months. Two doses of ITCA 650 were compared with placebo in patients with uncontrolled type 2 diabetes. RESEARCH DESIGN AND METHODS: This 39-week, phase 3, double-blind, placebo-controlled trial randomized 460 patients aged 18-80 years with glycated hemoglobin (HbA1c) 7.5-10% [58-86 mmol/mol] 1:1:1 to placebo, ITCA 650 40 μg/day, or ITCA 650 60 μg/day. Primary end point was change in HbA1c at 39 weeks...
December 14, 2017: Diabetes Care
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