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Peptidase inhibitor

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https://www.readbyqxmd.com/read/28812047/selected-missense-mutations-impair-frataxin-processing-in-friedreich-ataxia
#1
Elisia Clark, Jill S Butler, Charles J Isaacs, Marek Napierala, David R Lynch
OBJECTIVE: Frataxin (FXN) is a highly conserved mitochondrial protein. Reduced FXN levels cause Friedreich ataxia, a recessive neurodegenerative disease. Typical patients carry GAA repeat expansions on both alleles, while a subgroup of patients carry a missense mutation on one allele and a GAA repeat expansion on the other. Here, we report that selected disease-related FXN missense mutations impair FXN localization, interaction with mitochondria processing peptidase, and processing. METHODS: Immunocytochemical studies and subcellular fractionation were performed to study FXN import into the mitochondria and examine the mechanism by which mutations impair FXN processing...
August 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/28811850/effect-of-sodium-glucose-cotransporter-2-inhibitors-with-low-sglt2-sglt1-selectivity-on-circulating-glucagon-like-peptide-1-levels-in-type-2-diabetes-mellitus
#2
REVIEW
Kohzo Takebayashi, Toshihiko Inukai
Sodium glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs that improve glycemic control by inhibiting reabsorption of glucose filtered through the renal glomerulus. Use of drugs in this class has increased because of their effect of decreasing body weight and a low risk for hypoglycemia, in addition to a relatively strong glucose-lowering effect. SGLT2 inhibitors such as canagliflozin and sotagliflozin (a SGLT1/SGLT2 dual inhibitor) also have a mild or moderate intestinal and renal SGLT1 inhibitory effect because of their relatively weak selectivity for SGLT2 over SGLT1...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28811622/dipeptidyl-peptidase-4-inhibitors-and-cancer-risk-in-patients-with-type-2-diabetes-a-meta-analysis-of-randomized-clinical-trials
#3
Ming Zhao, Jiayi Chen, Yanyan Yuan, Zuquan Zou, Xiaolong Lai, Daud M Rahmani, Fuyan Wang, Yang Xi, Qin Huang, Shizhong Bu
Some recent studies have suggested that the use of dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with cancer development. However, some other studies suggest no such association. The aim of the present study was to evaluate the effect of DPP4i on the risk of developing cancers. The electronic databases PubMed, Medline, EMBASE, Web of Science and Cochrane Library and the clinical trial registry were searched for published and unpublished randomized clinical trials on humans. Eligible studies were RCTs conducted in patients with type 2 diabetes mellitus, comparing DPP4i with a placebo or other active drugs...
August 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28807765/sglt2-inhibitor-and-dpp-4-inhibitor-improve-brain-function-via-attenuating-mitochondrial-dysfunction-insulin-resistance-inflammation-and-apoptosis-in-hfd-induced-obese-rats
#4
Piangkwan Sa-Nguanmoo, Pongpan Tanajak, Sasiwan Kerdphoo, Thidarat Jaiwongkam, Wasana Pratchayasakul, Nipon Chattipakorn, Siriporn C Chattipakorn
Dipeptidyl peptidase-4 inhibitor (vildagliptin) has been shown to exert beneficial effects on insulin sensitivity and neuroprotection in obese-insulin resistance. Recent studies demonstrated the neuroprotection of the sodium-glucose co-transporter 2 inhibitor (dapagliflozin) in diabetes. However, the comparative effects of both drugs and a combination of two drugs on metabolic dysfunction and brain dysfunction impaired by the obese-insulin resistance have never been investigated. Forty male Wistar rats were divided into two groups, and received either a normal-diet (ND, n=8) or a high-fat diet (HFD, n=32) for 16weeks...
August 11, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28806472/effects-of-clarithromycin-on-the-pharmacokinetics-of-evogliptin-in-healthy-volunteers
#5
E S Oh, C Choi, C O Kim, K H Kim, Y N Kim, S J Kim, M S Park
WHAT IS KNOWN AND OBJECTIVE: Evogliptin (DA-1229), a novel dipeptidyl peptidase (DPP)-4 inhibitor with high potency and selectivity, was approved in Korea for the treatment of type 2 diabetes. Preclinical studies suggest that it is metabolized by cytochrome (CYP) P450 isozymes. Based on these findings, a clinical study was designed to investigate the pharmacokinetic (PK) interaction of evogliptin with a CYP inhibitor, clarithromycin. METHODS: An open-label, two-phase, crossover study was conducted with 12 healthy subjects...
August 14, 2017: Journal of Clinical Pharmacy and Therapeutics
https://www.readbyqxmd.com/read/28806402/multi-functional-mechanisms-of-immune-evasion-by-the-streptococcal-complement-inhibitor-c5a-peptidase
#6
Nicola N Lynskey, Mark Reglinski, Damien Calay, Matthew K Siggins, Justin C Mason, Marina Botto, Shiranee Sriskandan
The complement cascade is crucial for clearance and control of invading pathogens, and as such is a key target for pathogen mediated host modulation. C3 is the central molecule of the complement cascade, and plays a vital role in opsonization of bacteria and recruitment of neutrophils to the site of infection. Streptococcal species have evolved multiple mechanisms to disrupt complement-mediated innate immunity, among which ScpA (C5a peptidase), a C5a inactivating enzyme, is widely conserved. Here we demonstrate for the first time that pyogenic streptococcal species are capable of cleaving C3, and identify C3 and C3a as novel substrates for the streptococcal ScpA, which are functionally inactivated as a result of cleavage 7 amino acids upstream of the natural C3 convertase...
August 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28803047/puromycin-based-inhibitors-of-aminopeptidases-for-the-potential-treatment-of-hematologic-malignancies
#7
Rohit Singh, Jessica Williams, Robert Vince
Substantial progress has been described in the study of puromycin and its analogs for antibiotic properties. However, the peptidase inhibitory activity of related analogs has not been explored as extensively. Specifically, inhibiting aminopeptidases for achieving antitumor effect has been sparsely investigated. Herein, we address this challenge by reporting the synthesis of a series of analogs based on the structural template of puromycin. We also present exhaustive biochemical and in vitro analyses in support of our thesis...
July 26, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#8
Yanqing Zhang, Meifen Wu, Wynn Htun, Emily W Dong, Franck Mauvais-Jarvis, Vivian A Fonseca, Hongju Wu
Linagliptin is a dipeptidyl Peptidase-4 (DPP-4) inhibitor that inhibits the degradation of glucagon-like peptide 1 (GLP-1), and has been approved for the treatment of type 2 diabetes (T2D) in clinic. Previous studies have shown linagliptin improves β cell function using animal models and isolated islets from normal subjects. Since β cell dysfunction occurs during diabetes development, it was not clear how human islets of T2D patients would respond to linagliptin treatment. Therefore, in this study we employed human islets isolated from donors with and without T2D and evaluated how they responded to linagliptin treatment...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801475/understanding-the-gap-between-efficacy-in-randomized-controlled-trials-and-effectiveness-in-real-world-use-of-glp-1ra-and-dpp4-therapies-in-patients-with-type-2-diabetes
#9
Ginger S Carls, Edward Tuttle, Ruo-Ding Tan, Johnny Huynh, John Yee, Steven V Edelman, William H Polonsky
OBJECTIVE: This objective of this study was to estimate and explain the gap between clinical efficacy and real-world (RW) effectiveness of type 2 diabetes medications. RESEARCH DESIGN AND METHODS: This mixed-methods quasi-experimental study used retrospective claims (Optum/Humedica) to compare the change in HbA1c of RW patients with type 2 diabetes 12 months after starting a glucagon-like peptide-1 receptor agonist (GLP-1RA) or dipeptidyl peptidase-4 inhibitor (DPP4) with published findings from randomized controlled trials (RCTs) evaluating these drugs...
August 11, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28799229/sitagliptin-mediated-preservation-of-endothelial-progenitor-cell-function-via-augmenting-autophagy-enhances-ischaemic-angiogenesis-in-diabetes
#10
Xiaozhen Dai, Jun Zeng, Xiaoqing Yan, Qian Lin, Kai Wang, Jing Chen, Feixia Shen, Xuemei Gu, Yuehui Wang, Jun Chen, Kejian Pan, Lu Cai, Kupper A Wintergerst, Yi Tan
Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs). However, the direct effects of sitagliptin on EPC function remain elusive. In this study, we evaluated the proangiogenic effects of sitagliptin on a diabetic hind limb ischaemia (HLI) model in vivo and on EPC culture in vitro. Treatment of db/db mice with sitagliptin (Januvia) after HLI surgery efficiently enhanced ischaemic angiogenesis and blood perfusion, which was accompanied by significant increases in circulating EPC numbers...
August 10, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#11
Kelvin Lingjet Tran, Young In Park, Shalin Pandya, Navin John Muliyil, Brandon David Jensen, Kovin Huynh, Quang T Nguyen
BACKGROUND: It is estimated that 29.1 million people or 9.3% of the US population have diabetes, which contributes to considerable medical and financial burden. Type 2 diabetes mellitus is characterized by insulin resistance and insulin secretion impairment leading to hyperglycemia. The presence of insulin resistance is strongly correlated with obesity. OBJECTIVE: This article reviews the available glucagon-like peptide-1 (GLP-1) receptor agonists and their role in the management of patients with diabetes, to help guide the selection of the most suitable agent for the individualized treatment of patients with type 2 diabetes...
June 2017: American Health & Drug Benefits
https://www.readbyqxmd.com/read/28790917/effect-of-dipeptidyl-peptidase-4-inhibitors-on-bone-metabolism-and-the-possible-underlying-mechanisms
#12
REVIEW
Yinqiu Yang, Chenhe Zhao, Jing Liang, Mingxiang Yu, Xinhua Qu
Diabetes mellitus has been demonstrated to be closely associated with osteoporosis. Accordingly, hypoglycemic therapy is considered effective in treating metabolic bone disease. Recently, the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors, a new type of antidiabetic drug, on bone metabolism have been widely studied. This review mainly describes the effects of DPP-4 inhibitors on bone metabolism, including their effects on bone mineral density, bone quality, and fracture risk. In addition, the potential underlying mechanisms are discussed...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28790846/the-association-between-spink1-and-clinical-outcomes-in-patients-with-prostate-cancer-a-systematic-review-and-meta-analysis
#13
Xingming Zhang, Xiaoxue Yin, Pengfei Shen, Guangxi Sun, Yaojing Yang, Jiandong Liu, Ni Chen, Hao Zeng
Evidence of the prognostic role of serine peptidase inhibitor Kazal type 1 (SPINK1) in prostate cancer (PCa) is controversial. The aim of this study was, therefore, to evaluate the association between SPINK1 and clinical outcomes in PCa. Searches were made of PubMed, Medline, Embase, and the China Biology Medicine disc (CBMdisc) up to January 2017. The Newcastle-Ottawa Scale was used to assess the risk of bias of included studies. RevMan software was used to perform meta-analysis, and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was employed for assessing the quality of the evidence...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28782363/transport-study-of-egg-derived-antihypertensive-peptides-lkp-and-iqw-using-caco-2-and-ht29-co-culture-monolayers
#14
Qingbiao Xu, Hongbing Fan, Wenlin Yu, Hui Hong, Jianping Wu
The objective of this study was to investigate the mechanisms of the transport of antihypertensive tripeptides LKP (Leu-Lys-Pro) and IQW (Ile-Gln-Trp) derived from egg white using a co-culture system of Caco-2 and HT29 cell monolayers. The results revealed that LKP and IQW have no cytotoxicity to the cell viability after 2 h-incubation, and could be transported intact across co-culture monolayers (apparent permeability coefficient: (18.11 ± 1.57) × 10-8 and (13.21 ± 1.12) × 10-8 cm/s, respectively), and were resistant to peptidase secreted by enterocytes...
August 7, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28774208/moving-beyond-subcutaneous-insulin-the-application-of-adjunctive-therapies-to-the-treatment-of-type-1-diabetes
#15
Kathleen H Ang, Jennifer L Sherr
With the discovery of insulin nearly a century ago, the diagnosis of Type 1 Diabetes (T1D) transformed from a death sentence to a chronic medical condition. Despite the advances that have been made, the vast majority of those living with T1D still struggle to achieve targeted control. Yet, a plethora of agents have been developed to treat those with Type 2 Diabetes. Exploration of how these agents may benefit those with T1D has been an area of intense investigation, especially due to the overweight/obesity epidemic, which now afflicts more than 60% of those living with T1D...
August 3, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28773977/gold-nanoparticle-based-colorimetric-and-electrochemical-methods-for-dipeptidyl-peptidase-iv-activity-assay-and-inhibitor-screening
#16
Ning Xia, Xin Wang, Xiaojin Wang, Binbin Zhou
We presented the colorimetric and electrochemical methods for determination of the dipeptidyl peptidase-IV (DPP-IV) activity and screening of its inhibitor using gold nanoparticle (AuNP) as the probe. In the colorimetric assay, the substrate peptide with a sequence of Arg-Pro-Arg induced the aggregation and color change of AuNPs, whereas cleavage of the peptide by DPP-IV prevented the aggregation of AuNPs. Furthermore, the aggregation of AuNPs in the solution was easily initiated on a solid/liquid (electrode/electrolyte) surface, which induced a decrease in the electron-transfer resistance...
October 21, 2016: Materials
https://www.readbyqxmd.com/read/28771933/impact-of-clinical-evidence-communications-and-drug-regulation-changes-concerning-rosiglitazone-on-prescribing-patterns-of-antidiabetic-therapies
#17
Yoojin Noh, Dae Ryong Kang, Dae Jung Kim, Kwang Jae Lee, Sukhyang Lee, Sooyoung Shin
PURPOSE: Cardiovascular safety alerts about rosiglitazone resulted in regulatory actions in several countries in 2010, but the Food and Drug Administration eliminated access restrictions in 2013, reflecting new evidence concerning the drug safety. We investigated the effects of safety signals and regulation shifts concerning rosiglitazone on prescribing of antidiabetic drugs (ADs). METHODS: Patient data were extracted from the Korean health insurance claims database for 2007 to 2015...
August 3, 2017: Pharmacoepidemiology and Drug Safety
https://www.readbyqxmd.com/read/28771923/dapagliflozin-compared-to-dpp-4-inhibitors-is-associated-with-lower-risk-of-cardiovascular-events-and-all-cause-mortality-in-type-2-diabetes-patients-cvd-real-nordic-a-multinational-observational-study
#18
F Persson, T Nyström, M E Jørgensen, B Carstensen, H L Gulseth, M Thuresson, P Fenici, D Nathanson, J W Eriksson, A Norhammar, J Bodegard, K I Birkeland
AIMS: To compare the sodium glucose-cotransporter-2-inhibitor (SGLT-2i) dapagliflozin versus dipeptidyl peptidase-4 inhibitors (DPP-4i) regarding risk associations of MACE (nonfatal myocardial infarction, nonfatal stroke or cardiovascular [CV] mortality), hospital events for heart failure (HHF), atrial fibrillation, and severe hypoglycemia for type 2 diabetes (T2D) patients in a real-world setting. METHODS: All T2D patients dispensed with glucose lowering drugs (GLDs) during 2012-2015 were identified in nationwide registries in Denmark, Norway and Sweden...
August 3, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28771625/inhibition-of-dipeptidyl-peptidase-4-ameliorates-cardiac-ischemia-and-systolic-dysfunction-by-up-regulating-the-fgf-2-egr-1-pathway
#19
Masayoshi Suda, Ippei Shimizu, Yohko Yoshida, Yuka Hayashi, Ryutaro Ikegami, Goro Katsuumi, Takayuki Wakasugi, Yutaka Yoshida, Shujiro Okuda, Tomoyoshi Soga, Tohru Minamino
Dipeptidyl peptidase 4 inhibitors are used worldwide in the management of diabetes, but their role in the prevention or treatment of cardiovascular disorders has yet to be defined. We found that linagliptin, a DPP-4 inhibitor, suppressed capillary rarefaction in the hearts of mice with dietary obesity. Metabolomic analysis performed with capillary electrophoresis/mass spectrometry (LC-MS/MS) showed that linagliptin promoted favorable metabolic remodeling in cardiac tissue, which was characterized by high levels of citrulline and creatine...
2017: PloS One
https://www.readbyqxmd.com/read/28771387/minimizing-glycemic-fluctuations-in-patients-with-type-2-diabetes-approaches-and-importance
#20
Paresh Dandona
Glycemic fluctuations, characterized by short-term oscillations in plasma glucose, are important when managing type 2 diabetes (T2D) and may be considered a target of glucose-lowering therapies. Continuous glucose monitoring (CGM) has been used to evaluate the effects of different treatments on glycemic fluctuations. This review examines approaches to and the importance of minimizing glycemic fluctuations among patients with T2D. Measures of HbA1c, fructosamine, and glycated albumin reflect a long-term average of plasma glucose, and are therefore unable to provide an accurate measure of short-term glycemic oscillations...
August 3, 2017: Diabetes Technology & Therapeutics
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