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Peptidase inhibitor

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https://www.readbyqxmd.com/read/28931178/the-oral-dipeptidyl-peptidase-4-inhibitor-sitagliptin-increases-circulating-levels-of-stromal-derived-factor-1-alpha
#1
Athanasia K Papazafiropoulou, Nikolaos Papanas, Aikaterini Trikkalinou, Evaggelos Fousteris, Andreas Melidonis
Recent studies have demonstrated that stromal derived factor-1α (SDF-1α) is a substrate of dipeptidyl-peptidase-4 (DPP-4) inhibitors. It has also been shown that SDF-1α shares anti-apoptotic as well as nephroprotective properties and exerts a beneficial effect in the cardiovascular system. Therefore, the aim of this study was to estimate the effect of treatment with the DDP-4 inhibitor sitagliptin on SDF-1α levels in subjects with type 2 diabetes mellitus (T2D). Overall, 32 patients (16 males) with T2D, mean age (±SD) 67...
September 20, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28929327/possible-long-term-efficacy-of-sitagliptin-a-dipeptidyl-peptidase-4-inhibitor-for-slowly-progressive-type-1-diabetes-spiddm-in-the-stage-of-non-insulin-dependency-an-open-label-randomized-controlled-pilot-trial-span-s
#2
Takuya Awata, Akira Shimada, Taro Maruyama, Yoichi Oikawa, Nobuyuki Yasukawa, Susumu Kurihara, Yumi Miyashita, Masako Hatano, Yuichi Ikegami, Masafumi Matsuda, Masataka Niwa, Youichiro Kazama, Shoichiro Tanaka, Tetsuro Kobayashi
INTRODUCTION: We tested the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in preserving the β-cell function for long-term periods in patients with slowly progressive type 1 diabetes (SPIDDM) or latent autoimmune diabetes in adults (LADA). METHODS: In the present open-label, randomized, controlled trial, 14 non-insulin-requiring diabetic patients with glutamic acid decarboxylase autoantibodies (GADAb) were randomly assigned to receive either sitagliptin (S group) or pioglitazone (P group)...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28929319/a-practical-approach-to-hypertension-management-in-diabetes
#3
REVIEW
Altamash Shaikh
Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and disability and leads to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. Practical approaches to hypertension in diabetes, including individualized targets are discussed, as per stage and complication of diabetes, according to current studies and guidelines. Angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs) are the most effective drugs for treating hypertension in diabetes, in the absence of contraindications...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#4
Sangchul Lee, Kwangtaek Kim, Jin-Nyoung Ho, Hyunjin Jin, Seok-Soo Byun, Eunsik Lee
Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923291/use-of-prohibited-medication-a-potentially-overlooked-confounder-in-clinical-trials-omarigliptin-once-weekly-dpp-4-inhibitor-monotherapy-trial-in-18-to-45-year-olds
#5
Ira Gantz, Liubov Sokolova, Lokesh Jain, Carol Iredale, Edward A O'Neill, Ziwen Wei, Raymond Lam, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
PURPOSE: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. METHODS: Patients with T2DM who were ≥18 to <45 years of age and either drug-naive or not on an antihyperglycemic agent for ≥12 weeks with inadequate glycemic control were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 102) or placebo once weekly (n = 101) for 24 weeks...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28923269/dpp-4-inhibition-protects-human-umbilical-vein-endothelial-cells-from-hypoxia-induced-vascular-barrier-impairment
#6
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28921919/oral-glucose-lowering-with-linagliptin-and-metformin-compared-with-linagliptin-alone-as-initial-treatment-in-asian-patients-with-newly-diagnosed-type-2-diabetes-and-marked-hyperglycemia-subgroup-analysis-of-a-randomized-clinical-trial
#7
Ronald Cw Ma, Stefano Del Prato, Baptist Gallwitz, Vyankatesh K Shivane, Diane Lewis-D'Agostino, Zelie Bailes, Sanjay Patel, Jisoo Lee, Maximilian von Eynatten, Maximiliano Di Domenico, Stuart A Ross
AIMS/INTRODUCTION: Type 2 diabetes mellitus (T2DM) is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enrol predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed T2DM patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed T2DM patients with glycated hemoglobin A1c (HbA1c) 8...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#8
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28904354/identification-and-characterization-of-the-novel-reversible-and-selective-cathepsin-x-inhibitors
#9
Urša Pečar Fonović, Ana Mitrović, Damijan Knez, Tanja Jakoš, Anja Pišlar, Boris Brus, Bojan Doljak, Jure Stojan, Simon Žakelj, Jurij Trontelj, Stanislav Gobec, Janko Kos
Cathepsin X is a cysteine peptidase involved in the progression of cancer and neurodegenerative diseases. Targeting this enzyme with selective inhibitors opens a new possibility for intervention in several therapeutic areas. In this study triazole-based reversible and selective inhibitors of cathepsin X have been identified. Their selectivity and binding is enhanced when the 2,3-dihydrobenzo[b][1,4]dioxine moiety is present as the R(1) substituent. Of a series of selected triazole-benzodioxine derivatives, compound 22 is the most potent inhibitor of cathepsin X carboxypeptidase activity (Ki = 2...
September 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28899989/dipeptidyl-peptidase-4-inhibitors-and-risk-of-heart-failure-in-patients-with-type-2-diabetes-mellitus-a-population-based-cohort-study
#10
Young-Gun Kim, Dukyong Yoon, Sooyoung Park, Seung Jin Han, Dae Jung Kim, Kwan-Woo Lee, Rae Woong Park, Hae Jin Kim
BACKGROUND: The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015...
September 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28895067/a-gc-ms-untargeted-metabolomics-analysis-in-the-plasma-and-liver-of-rats-lacking-dipeptidyl-peptidase-type-iv-enzyme-activity
#11
Antonio Murgia, Pierluigi Caboni, Erika Cadoni, Monica Serra, Fabio Marongiu, Ezio Laconi
This study was achieved with the aim to find metabolic changes between Fischer rats with different dipeptidyl peptidase-type 4 (DPPIV) expression. The DPPIV is an enzyme expressed in several tissues and is critically involved in the regulation of meal-related insulin secretion in healthy individuals. The metabolic consequences of chronic DPPIV inhibition were analyzed in a surrogate animal model of genetic enzyme deficiency. Hyphenated gas chromatography-mass spectrometry (GC-MS) and multivariate data analysis techniques were used to study the metabolic aqueous fraction profile of 18 plasma and liver samples in two syngeneic rat strains differing in DPPIV activity (DPPIV(+) vs...
September 11, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#12
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#13
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28891142/network-meta-analysis-of-lorcaserin-and-oral-hypoglycaemics-for-patients-with-type-2-diabetes-mellitus-and-obesity
#14
L M Neff, M S Broder, D Beenhouwer, E Chang, E Papoyan, Z W Wang
In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments...
September 10, 2017: Clinical Obesity
https://www.readbyqxmd.com/read/28885325/combination-therapy-of-metformin-plus-dipeptidyl-peptidase-4-inhibitor-versus-metformin-plus-sulfonylurea-and-their-association-with-a-decreased-risk-of-cardiovascular-disease-in-type-2-diabetes-mellitus-patients
#15
Fei Wang, Yuan He, Rong Zhang, Qiang Zeng, Xiaolan Zhao
BACKGROUND: Clinical trials assessing the combination therapy of metformin plus dipeptidyl peptidase-4 inhibitors versus metformin plus Sulfonylureas on risk of cardiovascular disease, cardiovascular mortality and/or all-cause mortality in type 2 diabetes have shown conflicting results. We therefore evaluated the combination therapy on the risk of cardiovascular disease, cardiovascular mortality and/or all-cause mortality in type 2 diabetes. METHODS: A systematic search of Medline/PubMed (from 2000 to September 2015), EMBASE (from 2000 to September 2015), and Web of Knowledge (from 2000 to September 2015) for research articles published in English was carried out to examine how combination therapy affects the risk of CVD mortality and/or all-cause mortality in T2DM patients...
September 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28883483/serpinb2-is-a-novel-tgf%C3%AE-responsive-lineage-fate-determinant-of-human-bone-marrow-stromal-cells
#16
Mona Elsafadi, Muthurangan Manikandan, Muhammad Atteya, Raed Abu Dawud, Sami Almalki, Zahid Ali Kaimkhani, Abdullah Aldahmash, Nehad M Alajez, Musaad Alfayez, Moustapha Kassem, Amer Mahmood
TGF-β1, a multifunctional regulator of cell growth and differentiation, is the most abundant bone matrix growth factor. During differentiation of human bone stromal cells (hBMSCs), which constitute bone marrow osteoblast (OS) and adipocyte (AD) progenitor cells, continuous TGF-β1 (10 ng/ml) treatment enhanced OS differentiation as evidenced by increased mineralised matrix production. Conversely, pulsed TGF-β1 administration during the commitment phase increased mature lipid-filled adipocyte numbers. Global gene expression analysis using DNA microarrays in hBMSCs treated with TGF-β1 identified 1587 up- and 1716 down-regulated genes in OS-induced, TGF-β1-treated compared to OS-induced hBMSCs (2...
September 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28883231/the-assessment-of-the-efficacy-of-dipeptidyl-peptidase-4-inhibitors-in-patients-with-glucocorticoid-induced-diabetes-by-continuous-glucose-monitoring
#17
Yusuke Yata, Michihiro Hosojima, Hideyuki Kabasawa, Tomomi Ishikawa, Ryohei Kaseda, Noriaki Iino, Yoshiki Suzuki, Akihiko Saito, Ichiei Narita
Objective The administration of glucocorticoids usually causes a mild increase in fasting glucose levels and a greater dose-dependent increase in postprandial values in patients without pre-existing diabetes mellitus. Patients with persistent hyperglycemia due to glucocorticoid therapy sometimes require insulin therapy, which might result in increased weight gain and more episodes of hypoglycemia, some of which are severe. On the other hand, scant evidence is available on the efficacy of oral hypoglycemic agents in treating glucocorticoid-induced diabetes...
September 6, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28881791/dipeptidyl-peptidase-4-inhibitor-use-is-associated-with-a-lower-risk-of-incident-acute-kidney-injury-in-patients-with-diabetes
#18
Chia-Ter Chao, Jui Wang, Hon-Yen Wu, Kuo-Liong Chien, Kuan-Yu Hung
OBJECTIVES: Dipeptidyl peptidase 4 inhibitor (DPP4i) use potentially slows the progression of diabetic kidney disease, but its effects on the risk of acute kidney injury (AKI) are unclear. We aimed to assess the association between DPP4i use and incident AKI episodes from a nationally representative cohort in Taiwan. MATERIALS AND METHODS: All patients newly diagnosed with diabetes mellitus (DM) between 2008, when DPP4i use was first approved in Taiwan, and mid-2013 were enrolled...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28880474/%C3%AE-cell-signalling-and-insulin-secretagogues-a-path-for-improved-diabetes-therapy
#19
REVIEW
Susumu Seino, Kenji Sugawara, Norihide Yokoi, Harumi Takahashi
Insulin secretagogues including sulfonylureas, glinides and incretin-related drugs such as dipeptidyl peptidase 4 (DPP-4) inhibitors and glucagon-like peptide-1 receptor agonists are widely used for treatment of type 2 diabetes. In addition, glucokinase activators and G-protein-coupled receptor 40 (GPR40) agonists also have been developed, although the drugs are not clinically usable. These different drugs exert their effects on insulin secretion by different mechanisms. Recent advances in β-cell signalling studies have not only deepened our understanding of insulin secretion but also revealed novel mechanisms of insulin secretagogues...
September 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28878934/postauthorization-safety-study-of-the-dpp-4-inhibitor-saxagliptin-a-large-scale-multinational-family-of-cohort-studies-of-five-outcomes
#20
Vincent Lo Re, Dena M Carbonari, M Elle Saine, Craig W Newcomb, Jason A Roy, Qing Liu, Qufei Wu, Serena Cardillo, Kevin Haynes, Stephen E Kimmel, Peter P Reese, David J Margolis, Andrea J Apter, K Rajender Reddy, Sean Hennessy, Harshvinder Bhullar, Arlene M Gallagher, Daina B Esposito, Brian L Strom
OBJECTIVE: To evaluate the risk of serious adverse events among patients with type 2 diabetes mellitus initiating saxagliptin compared with oral antidiabetic drugs (OADs) in classes other than dipeptidyl peptidase-4 (DPP-4) inhibitors. RESEARCH DESIGN AND METHODS: Cohort studies using 2009-2014 data from two UK medical record data sources (Clinical Practice Research Datalink, The Health Improvement Network) and two USA claims-based data sources (HealthCore Integrated Research Database, Medicare)...
2017: BMJ Open Diabetes Research & Care
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