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DPP4 inhibitors

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https://www.readbyqxmd.com/read/28630069/degradation-of-incretins-and-modulation-of-blood-glucose-levels-by-periodontopathic-bacterial-dipeptidyl-peptidase-4
#1
Yuko Ohara-Nemoto, Manami Nakasato, Yu Shimoyama, Tomomi T Baba, Takeshi Kobayakawa, Toshio Ono, Takashi Yaegashi, Shigenobu Kimura, Takayuki K Nemoto
Severe periodontitis is known to aggravate diabetes mellitus, though molecular events related to that link have not been fully elucidated. Porphyromonas gingivalis, a major pathogen of periodontitis, expresses dipeptidyl peptidase 4 (DPP4), which is involved in regulation of blood glucose levels by cleaving incretins in humans. We examined the enzymatic characteristics of DPP4 from P. gingivalis as well as two other periodontopathic bacteria, Tannerella forsythia and Prevotella intermedia, and determined whether it is capable of regulating blood glucose levels...
June 19, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28585374/svmdlf-a-novel-r-based-web-application-for-prediction-of-dipeptidyl-peptidase-4-inhibitors
#2
Sharat Chandra, Jyotsana Pandey, Akhilesh K Tamrakar, Mohammad Imran Siddiqi
Dipeptidyl peptidase 4 (DPP4) is a well-known target for the antidiabetic drugs. However, currently available DPP4 inhibitor screening assays are costly and labor-intensive. It is important to create a robust in-silico method to predict the activity of DPP4 inhibitor for the new lead finding. Here, we introduce a R based web application SVMDLF (SVM based DPP4 Lead Finder) to predict the inhibitor of DPP4; based on support vector machine (SVM) model, predictions of which are confirmed by in-vitro biological evaluation...
June 6, 2017: Chemical Biology & Drug Design
https://www.readbyqxmd.com/read/28575350/dipeptidyl-peptidase-iv-as-a-prognostic-marker-and-therapeutic-target-in-papillary-thyroid-carcinoma
#3
Jie-Jen Lee, Tao-Yeuan Wang, Chien-Liang Liu, Ming-Nan Chien, Ming-Jen Chen, Yi-Chiung Hsu, Ching-Hsiang Leung, Shih-Ping Cheng
Context: Dipeptidyl peptidase IV (DPP4) is overexpressed in thyroid cancer and certain malignancies. Furthermore, DPP4 has been identified as a discriminatory marker for thyroid cancer. However, it remains unclear whether DPP4 expression plays a prognostic role. Objective: The aim of this study was to investigate the expression and function of DPP4 in thyroid cancer and the mechanisms involved. Design: We determined the expression of DPP4 by immunohistochemistry in tissue microarrays of thyroid tumors...
May 26, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28542373/comparative-effectiveness-of-oral-antidiabetic-drugs-in-preventing-cardiovascular-mortality-and-morbidity-a-network-meta-analysis
#4
Gyeongsil Lee, Seung-Won Oh, Seung-Sik Hwang, Ji Won Yoon, Sungchan Kang, Hee-Kyung Joh, Hyuktae Kwon, Jeehyun Kim, Danbee Park
In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors...
2017: PloS One
https://www.readbyqxmd.com/read/28539088/prescription-patterns-and-disease-control-in-type-2-diabetes-mellitus-patients-in-nursing-home-and-home-care-settings-a-retrospective-analysis-in-germany
#5
Karel Kostev, Timo Rockel, Louis Jacob
AIM: The aim of this study was to analyze prescription patterns and disease control in patients with type 2 diabetes mellitus (T2DM) in nursing home and home care settings in Germany. METHODS: The present study is based on data from the Disease Analyzer database (QuintilesIMS). Patients with an initial diagnosis of T2DM and documented HbA1c values between January 2011 and December 2015 were included in the analysis. The index date corresponded to the last documented HbA1c value...
May 1, 2017: Journal of Diabetes Science and Technology
https://www.readbyqxmd.com/read/28534682/diabetic-ketoacidosis-a-common-debut-of-diabetes-among-african-americans-with-type-2-diabetes
#6
Priyathama Vellanki, Guillermo E Umpierrez
OBJECTIVE: More than half of African Americans (AA) with a new diagnosis of diabetic ketoacidosis have clinical and metabolic features of type 2 diabetes during follow-up. This particular presentation of diabetes has been termed as ketosis-prone type 2 diabetes (KPDM) or atypical diabetes. METHODS: We review the epidemiology, diagnosis, pathophysiology and acute and long-term management of AA with KPDM and compare these similarities to patients with type 2 diabetes...
May 23, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/28514822/-cardiovascular-effects-of-antidiabetic-therapies
#7
Katharina Laubner, Jochen Seufert
Type 2- diabetes mellitus (T2DM) represents a major risk factor for cardiovascular complications and mortality. Strict glucose control in the early course of the disease prevents cardiovascular complications only in the long run. Non-medical therapies (diet, exercise, body weight reduction) bear little evidence for positive cardiovascular effects.Bariatric surgery is not number one choice in therapy of T2DM. Metformin seems to provide positive cardiovascular effects. Insulin seems to be cardiovascular neutral, as well as the DPP4-inhibitors Saxagliptin, Sitagliptin and Alogliptin...
May 2017: Deutsche Medizinische Wochenschrift
https://www.readbyqxmd.com/read/28502212/-trends-in-antidiabetic-treatment-prescribed-for-patients-with-type-2-diabetes-in-hungary-between-2001-and-2014-results-from-the-database-analysis-of-the-national-health-insurance-fund
#8
György Jermendy, Zoltán Kiss, György Rokszin, Zsolt Abonyi-Tóth, István Wittmann, Péter Kempler
In the last couple of years, significant developments in antidiabetic treatment have influenced the pharmacological treatment of type 2 diabetes mellitus (T2DM). The aim of this study was to analyze the changes in prescribing patterns of glucose-lowering drugs for T2DM patients in Hungary between 2001 and 2014. The number of patients with newly diagnosed T2DM decreased from 75,700 (2001) to 33,700 (2014), while prevalent T2DM cases continuously increased and plateaued in 2014 with a number of registered patients of 727,000...
May 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28498352/encapsulation-of-16-hydroxycleroda-3-13-dine-16-15-olide-in-mesoporous-silica-nanoparticles-as-a-natural-dipeptidyl-peptidase-4-inhibitor-potentiated-hypoglycemia-in-diabetic-mice
#9
Po-Kai Huang, Shi-Xiang Lin, May-Jywan Tsai, Max K Leong, Shian-Ren Lin, Ranjith Kumar Kankala, Chia-Hung Lee, Ching-Feng Weng
Natural supplements comprise good efficacy with less adverse effects as against diabetic therapy, but their advancement as anti-diabetic agents is unsatisfactory with regard to the delivery system. Dipeptidyl peptidase-4 (DPP4)/CD26) can degrade glucagon-like pepetide-1 (GLP-1) which renders a decrease of blood glucose levels. 16-hydroxycleroda-3,13-dine-16,15-olide (HCD) extracted from Polyalthia longifolia, exhibits numerous medicinal potentials including hypoglycemic potential. On consideration of HCD application, the bioavailability is affected by low solubility...
May 12, 2017: Nanomaterials
https://www.readbyqxmd.com/read/28447181/sglt-2-inhibition-with-dapagliflozin-reduces-the-activation-of-the-nlrp3-asc-inflammasome-and-attenuates-the-development-of-diabetic-cardiomyopathy-in-mice-with-type-2-diabetes-further-augmentation-of-the-effects-with-saxagliptin-a-dpp4-inhibitor
#10
Yumei Ye, Mandeep Bajaj, Hsiu-Chiung Yang, Jose R Perez-Polo, Yochai Birnbaum
PURPOSE: We assessed whether (1) dapagliflozin (Dapa, an SGLT2-inhibitor) attenuates the deterioration of heart function Nlrp3 and inflammasome activation in diabetic mice. (2) The effects can be augmented with saxagliptin (Saxa), a DDP4-inhibitor. (3) Dapa effect is possibly SGLT2-independent on cardiofibroblasts in vitro. METHODS: Type 2 diabetic (BTBR ob/ob) and wild-type (WT) mice received vehicle, Dapa, or Dapa+Saxa for 8 weeks. Glucose tolerance test and echocardiogram were performed...
April 2017: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/28442252/approaches-towards-the-development-of-chimeric-dpp4-ace-inhibitors-for-treating-metabolic-syndrome
#11
Jitendra A Sattigeri, Sachin Sethi, Joseph A Davis, Shahadat Ahmed, Geeta V Rayasam, Balasaheb G Jadhav, Satya M Chilla, Dhrubajyoti Datta, A Gadhave, Vamshi K Tulasi, Tarun Jain, Sreedhara Voleti, Biju Benjamin, Sunitha Udupa, Garima Jain, Yogender Singh, Kona Srinivas, Vinay S Bansal, Abhijit Ray, Pradip K Bhatnagar, Ian A Cliffe
Designing drug candidates exhibiting polypharmacology is one of the strategies adopted by medicinal chemists to address multifactorial diseases. Metabolic disease is one such multifactorial disorder characterized by hyperglycaemia, hypertension and dyslipidaemia among others. In this paper we report a new class of molecular framework combining the pharmacophoric features of DPP4 inhibitors with those of ACE inhibitors to afford potent dual inhibitors of DPP4 and ACE.
June 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28423178/head-to-head-comparison-of-structurally-unrelated-dipeptidyl-peptidase-4-inhibitors-in-the-setting-of-renal-ischemia-reperfusion-injury
#12
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 Rippmann, Thomas Klein, Berthold Hocher
BACKGROUND AND PURPOSE: Results regarding protective effects of dipeptidyl peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a model of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 min. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p.o. once daily on three consecutive days prior to IRI: linagliptin (1...
July 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
#13
Cheli Melzer Cohen, Carla Davis, Varda Shalev, Gabriel Chodick
BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the treatment of type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized controlled trials, but there is little evidence 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 and its affects 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
#14
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...
May 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
#15
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
#16
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...
May 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28372289/dpp4-regulates-the-inflammatory-response-in-a-rat-model-of-febrile-seizures
#17
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
#18
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
#19
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
#20
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
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