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dpp4 inhibitor

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https://www.readbyqxmd.com/read/28423178/head-to-head-comparison-of-structurally-unrelated-dpp4-inhibitors-in-the-setting-of-renal-ischemia-reperfusion-injury
#1
Christoph Reichetzeder, Karoline von Websky, Oleg Tsuprykov, Azadeh Mohagheghi Samarin, Luise Gabriele Falke, Sulistyo Emantoko Dwi Putra, Ahmed Abdallah Hasan, Viktoriia Antonenko, Caterina Curato, Jörg Rippman, Thomas Klein, Berthold Hocher
BACKGROUND AND PURPOSE: Results regarding protective effects of DPP4 inhibitors in renal ischemia-reperfusion-injury (IRI) are conflicting. The current study performed a head-to-head comparison of structurally unrelated DPP4 inhibitors in the setting of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 minutes. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p...
April 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28418203/effectiveness-of-vildagliptin-as-add-on-to-metformin-monotherapy-among-uncontrolled-type-2-diabetes-mellitus-patients-in-a-real-world-setting
#2
Cheli Melzer Cohen, Carla Davis, Varda Shalev, Gabriel Chodick
BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor (DPP4-i) commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized clinical trials but little evidence exists from observational studies. The aims of the present study were to evaluate the effectiveness of vildagliptin as an add-on therapy to metformin in reducing HbA1c as well as its influences on body weight and blood lipids in a real-life setting...
April 18, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28417296/dpp4-inhibitors-and-cardiovascular-outcomes-safety-on-heart-failure
#3
REVIEW
Chang Xia, Aditya Goud, Jason D'Souza, CHanukya Dahagam, Xiaoquan Rao, Sanjay Rajagopalan, Jixin Zhong
Diabetes is an important risk factor for cardiovascular disease. However, clinical data suggests intensive glycemic control significantly increase rather than decrease cardiovascular mortality, which is largely due to the fact that a majority of oral anti-diabetic drugs have adverse cardiovascular effect. There are several large-scale clinical trials evaluating the cardiovascular safety of DPP4 inhibitors, a novel class of oral anti-diabetic medications, which have been recently completed. They were proven to be safe with regard to cardiovascular outcomes...
April 18, 2017: Heart Failure Reviews
https://www.readbyqxmd.com/read/28393419/synthesis-and-evaluation-of-novel-1-2-4-triazolo-5-1-c-1-2-4-triazines-and-pyrazolo-5-1-c-1-2-4-triazines-as-potential-antidiabetic-agents
#4
Vladimir L Rusinov, Irina M Sapozhnikova, Anastasiya M Bliznik, Oleg N Chupakhin, Valery N Charushin, Alexander A Spasov, Pavel M Vassiliev, Valentina A Kuznetsova, Andrey I Rashchenko, Denis A Babkov
Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers...
April 10, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28376584/a-novel-multi-epitope-vaccine-based-on-dipeptidyl-peptidase-4-prevents-streptozotocin-induced-diabetes-by-producing-anti-dpp4-antibody-and-immunomodulatory-effect-in-c57bl-6j-mice
#5
Zhixin Li, Jinzhi Fang, Rui Jiao, Xiaomin Wei, Yanjie Ma, Xiaoran Liu, Peng Cheng, Taiming Li
Type 1 diabetes is a chronic organ-specific autoimmune disease in which selective destruction of insulin-producing β-cells leads to impaired glucose metabolism and its attendant complications. A series of Dipeptidyl peptidase 4 (DPP4) inhibitors have been developed and granted approval in the treatment of type 2 diabetes mellitus by inhibiting the enzymatic degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). An increasing number of studies have shown the potential benefits of DPP4 inhibitors for type 1 diabetes...
March 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28372289/dpp4-regulates-the-inflammatory-response-in-a-rat-model-of-febrile-seizures
#6
Qi Sun, Yusong Zhang, Jie Huang, Fang Yu, Jian Xu, Biwen Peng, Wanhong Liu, Song Han, Jun Yin, Xiaohua He
Febrile seizures (FS) are the most common seizure disorders in children aged 6 months to 5 years. Children suffering from complex FS have a high risk of developing subsequent temporal lobe epilepsy (TLE). Neuroinflammation is involved in the pathogenesis of FS although the mechanism remains unknown. Our previous study using the Whole Rat Genome Oligo Microarray determined that Dipeptidyl peptidase IV (DPP4) is potentially a related gene in FS rats. In this study, we demonstrated that DPP4 expression was significantly increased at both the protein and mRNA levels after hyperthermia induction...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28370279/sensitive-and-specific-lc-esi-ms-ms-method-for-determination-of-zydpla1-a-novel-long-acting-dpp4-inhibitor-in-rat-plasma-an-application-for-toxicokinetics-study-in-rats
#7
Poonam Giri, Nirmal Patel, Bharat Patel, Harilal Patel, Rajesh Bahekar, Nuggehally R Srinivas, Pankaj R Patel, Ranjit Desai
A rapid and highly specific assay was developed and validated for estimation ofZYDPLA1 in rat plasma using liquid chromatography coupled to tandem mass spectrometry with positive electrospray ionization. Method validation comprised of parameters such as: specificity, matrix effect, precision, accuracy, recovery, stability etc. The assay procedure involved a simple protein precipitation of ZYDPLA1 and alprazolam (internal standard, IS) from rat plasma using acetonitrile. Chromatographic separation was achieved with a gradient mobile phase comprising of (A) 0...
March 31, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28334048/hepatoprotective-effect-of-sitagliptin-against-methotrexate-induced-liver-toxicity
#8
Hany M Abo-Haded, Mohamed A Elkablawy, Zeyad Al-Johani, Osama Al-Ahmadi, Dina S El-Agamy
Sitagliptin is selective dipeptidyl peptidase-4 inhibitor (DPP4-I), used clinically as a new oral anti-diabetic agent. This study explored the underlying mechanisms of the hepatoprotective role of sitagliptin pretreatment against methotrexate (MTX) induced hepatotoxicity in mice. Forty mice were divided into four groups (10 mice each); control, MTX, and two sitagliptin groups (pretreated with sitagliptin 10 and 20 mg/kg/day, respectively) for five consecutive days prior to MTX injection. Results showed that MTX induced marked hepatic injury in the form of cloudy swelling, hydropic degeneration, apoptosis and focal necrosis in all hepatic zones...
2017: PloS One
https://www.readbyqxmd.com/read/28285800/perspectives-on-cardiovascular-effects-of-incretin-based-drugs-from-bedside-to-bench-return-trip
#9
Michaela Luconi, Giulia Cantini, Antonio Ceriello, Edoardo Mannucci
Recently, cardiovascular outcome trials with glucose-lowering drugs used in type 2 diabetes mellitus, namely glucagon-like peptide-1 receptor agonists (GLP-1RA), liraglutide and semaglutide, showed a reduction in cardiovascular events, which had not been observed in trials with other incretin-based drugs, such as lixisenatide or with dipeptidyl peptidase-4 inhibitors (DPP4i). Mechanisms underlying the observed cardiovascular differences between DPP4i and GLP1-RA, and across individual GLP1-RA are poorly understood...
March 2, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28250448/valvular-disease-dpp4-inhibitors-to-prevent-aortic-valve-calcification
#10
Irene Fernández-Ruiz
No abstract text is available yet for this article.
April 2017: Nature Reviews. Cardiology
https://www.readbyqxmd.com/read/28239939/combining-the-g-protein-coupled-receptor-40-agonist-fasiglifam-with-sitagliptin-improves-glycaemic-control-in-patients-with-type-2-diabetes-with-or-without-metformin-a-randomized-12-week-trial
#11
Xuejun V Peng, John F Marcinak, Marsha G Raanan, Charlie Cao
AIMS: To evaluate the efficacy and safety of fasiglifam, an orally active G-protein-coupled receptor 40 agonist, in combination with the dipeptidyl peptidase-4 inhibitor sitagliptin, in patients with type 2 diabetes inadequately controlled with diet/exercise (± metformin). MATERIALS AND METHODS: In this randomized, double-blind, phase II study, 368 patients received once-daily placebo, sitagliptin 100 mg, fasiglifam 25 or 50 mg, or the combination of sitagliptin 100 mg plus fasiglifam 25 or 50 mg...
February 27, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28238223/glucose-lowering-agents-for-treating-pre-existing-and-new-onset-diabetes-in-kidney-transplant-recipients
#12
REVIEW
Clement Lo, Min Jun, Sunil V Badve, Helen Pilmore, Sarah L White, Carmel Hawley, Alan Cass, Vlado Perkovic, Sophia Zoungas
BACKGROUND: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. OBJECTIVES: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes...
February 27, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28222401/combination-of-sitagliptin-and-silymarin-ameliorates-liver-fibrosis-induced-by-carbon-tetrachloride-in-rats
#13
Samia Salem Sokar, Magda El-Sayed El-Sayad, Mai El-Sayed Ghoneim, Abdelhadi Mohamed Shebl
Liver fibrosis is a common pathological condition that occurs in most conditions associated with chronic liver injury. Silymarin is a herbal product widely used for its hepatoprotective effect. Sitagliptin, a dipeptidyl peptidase-4 inhibitor (DPP4-I), is clinically used as an oral antidiabetic agent. This study was designed to investigate the effects of Sitagliptin, Silymarin, and their combination on established liver fibrosis in carbon tetrachloride (CCl4) rat model. Male albino rats received intraperitoneal injections of CCl4 three times a week for 7 weeks, as well as daily oral treatments of Sitagliptin (100mg/kg) or Silymarin (100mg/kg) or their combination during the 7 weeks of intoxication...
February 18, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28216506/-role-of-dipeptidyl-peptidase-4-and-its-inhibitor-in-the-respiratory-diseases
#14
Yabing Sun, Libing Ma
Dipeptidyl peptidase-4 (DPP-4) is known as a highly conserved type II transmembraneous glycoprotein widely distributed in a variety of tissues and cells, and expressed in the peripheral blood as a soluble form. It has been reported that DPP4 play a distinct role in the physiological and pathological processes, such as immune regulation, inflammatory reaction, cell adhesion, and cell apoptosis. DPP4 inhibitor showes an incredible effect on the control of blood glucose and it is thought as a newly-developed drug for diabetes, especially in regulation of post-prandial glycemia...
January 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/28194113/cardiovascular-benefits-of-native-glp-1-and-its-metabolites-an-indicator-for-glp-1-therapy-strategies
#15
REVIEW
Junfeng Li, Juan Zheng, Susanne Wang, Harry K Lau, Ali Fathi, Qinghua Wang
Cardiovascular disease is a common co-morbidity and leading cause of death in patients with type 2 diabetes mellitus (T2DM). Glucagon-like peptide 1 (GLP-1) is a peptide hormone produced by intestinal L cells in response to feeding. Native GLP-1 (7-36) amide is rapidly degraded by diaminopeptidyl peptidase-4 (DPP4) to GLP-1 (9-36) amide, making 9-36a the major circulating form. While it is 7-36a, and not its metabolites, which exerts trophic effects on islet β-cells, recent studies suggest that both 7-36a and its metabolites have direct cardiovascular effects, including preserving cardiomyocyte viability, ameliorating cardiac function, and vasodilation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28183314/dpp-4-inhibition-has-no-acute-effect-on-bnp-and-its-n-terminal-pro-hormone-measured-by-commercial-immune-assays-a-randomized-cross-over-trial-in-patients-with-type-2-diabetes
#16
Gian Paolo Fadini, Benedetta Maria Bonora, Mattia Albiero, Martina Zaninotto, Mario Plebani, Angelo Avogaro
BACKGROUND: Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD)...
February 10, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#17
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase 4 (DPP4) is expressed by resident renal cells, including glomerular cells. DPP4 inhibitors (gliptins) exert albuminuria lowering effects, but the role of renal DPP4 as a pharmacological target has not been elucidated. To better understand the actions of gliptins, the effects of linagliptin on the behaviour of immortalized human podocytes and mesangial cells were evaluated. EXPERIMENTAL APPROACH: The expression of DPP4 was measured at both the mRNA and protein levels...
May 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28122713/diabetes-hypertension-and-chronic-kidney-disease-progression-role-of-dpp4
#18
Ravi Nistala, Virginia Savin
The protein dipeptidyl peptidase 4 (DPP4) is a target in diabetes management and reduction of associated cardiovascular risk. Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications. The recently concluded, "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53" trial revealed a reduction in proteinuria in chronic kidney disease patients (stages 1-3)...
April 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28118607/middle-east-respiratory-syndrome-corona-virus-spike-glycoprotein-suppresses-macrophage-responses-via-dpp4-mediated-induction-of-irak-m-and-ppar%C3%AE
#19
Ahmed A Al-Qahtani, Konstantina Lyroni, Marina Aznaourova, Melpomeni Tseliou, Mashael R Al-Anazi, Mohammed N Al-Ahdal, Saad Alkahtani, George Sourvinos, Christos Tsatsanis
Middle East Respiratory Syndrome Corona Virus (MERS-CoV) is transmitted via the respiratory tract and causes severe Acute Respiratory Distress Syndrome by infecting lung epithelial cells and macrophages. Macrophages can readily recognize the virus and eliminate it. MERS-CoV infects cells via its Spike (S) glycoprotein that binds on Dipeptidyl-Peptidase 4 (DPP4) receptor present on macrophages. Whether this Spike/DPP4 association affects macrophage responses remains unknown. Herein we demonstrated that infection of macrophages with lentiviral particles pseudotyped with MERS-CoV S glycoprotein results in suppression of macrophage responses since it reduced the capacity of macrophages to produce TNFα and IL-6 in naive and LPS-activated THP-1 macrophages and augmented LPS-induced production of the immunosuppressive cytokine IL-10...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#20
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
March 30, 2017: European Journal of Pharmaceutical Sciences
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