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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/28819835/efficacy-and-safety-of-linagliptin-in-2681-asian-patients-stratified-by-age-obesity-and-renal-function-a-pooled-analysis-of-randomized-clinical-trials
#1
Guang Ning, Tushar Bandgar, Uwe Hehnke, Jisoo Lee, Juliana C N Chan
INTRODUCTION: Asian patients with type 2 diabetes (T2D) are younger, leaner, and more likely to develop renal dysfunction than White populations. In this multiethnic analysis of data from phase 3 trials, we investigated the efficacy and safety of the dipeptidyl peptidase-4 inhibitor linagliptin in Asians stratified by these subphenotypes. METHODS: Data from randomized, double-blind, placebo-controlled trials evaluating linagliptin (as monotherapy, add-on therapy to metformin ± sulfonylurea, combined with pioglitazone or added to insulin) were pooled with efficacy data from 11 randomized trials of at least 24 weeks and safety data from 15 trials of various durations...
August 17, 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28815568/gliptin-therapy-reduces-hepatic-and-myocardial-fat-in-type-2-diabetic-patients-gliptins-and-cardiometabolic-risk
#2
Lana Kosi-Trebotic, Jürgen Harreiter, Marek Chmelik, Anita Thomas, Ivica Just-Kukurova, Siegfried Trattnig, Alexandra Kautzky-Willer
AIMS: Increased hepatic and cardiac fat are common in patients with Type 2 diabetes mellitus (T2DM) and associated with greater risk of liver fibrosis and cardiovascular (CV) events. Sex-specific differences of Dipeptidyl peptidase-four (DPP-4) inhibitor effects on hepatic (HCL) and myocardial fat content (MYCL) have not been evaluated yet. METHODS: 41 T2DM patients received a gliptin add-on therapy when not reaching HbA1c goals under metformin monotherapy. They underwent cardiac and liver magnetic resonance tomography and spectroscopy before and 6 months after therapy initiation...
August 16, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28813679/the-tumor-suppressor-p53-limits-ferroptosis-by-blocking-dpp4-activity
#3
Yangchun Xie, Shan Zhu, Xinxin Song, Xiaofang Sun, Yong Fan, Jinbao Liu, Meizuo Zhong, Hua Yuan, Lin Zhang, Timothy R Billiar, Michael T Lotze, Herbert J Zeh, Rui Kang, Guido Kroemer, Daolin Tang
Ferroptosis is a form of regulated cell death that may facilitate the selective elimination of tumor cells. The tumor suppressor p53 (TP53) has been demonstrated to promote ferroptosis via a transcription-dependent mechanism. Here, we show that TP53 limits erastin-induced ferroptosis by blocking dipeptidyl-peptidase-4 (DPP4) activity in a transcription-independent manner. Loss of TP53 prevents nuclear accumulation of DPP4 and thus facilitates plasma-membrane-associated DPP4-dependent lipid peroxidation, which finally results in ferroptosis...
August 15, 2017: Cell Reports
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
#4
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/28811708/involvement-of-crf2-signaling-in-enterocyte-differentiation
#5
Benjamin Ducarouge, Marjolaine Pelissier-Rota, Rebecca Powell, Alain Buisson, Bruno Bonaz, Muriel Jacquier-Sarlin
AIM: To determine the role of corticotropin releasing factor receptor (CRF2) in epithelial permeability and enterocyte cell differentiation. METHODS: For this purpose, we used rat Sprague Dawley and various colon carcinoma cell lines (SW620, HCT8R, HT-29 and Caco-2 cell lines). Expression of CRF2 protein was analyzed by fluorescent immunolabeling in normal rat colon and then by western blot in dissociated colonic epithelial cells and in the lysates of colon carcinoma cell lines or during the early differentiation of HT-29 cells (ten first days)...
July 28, 2017: World Journal of Gastroenterology: WJG
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
#6
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
#7
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
#8
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/28801559/differential-effects-of-linagliptin-on-the-function-of-human-islets-isolated-from-non-diabetic-and-diabetic-donors
#9
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
#10
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/28799235/dipeptidyl-peptidase-4-serum-activity-and-concentration-are-increased-in-women-with-polycystic-ovary-syndrome
#11
Sindy Blauschmidt, Thomas Greither, Katharina Lampe, Solveig Köller, Petra Kaltwaßer, Hermann M Behre
OBJECTIVE: Polycystic ovary syndrome (PCOS) is a complex disease, the etiology of which is not well understood. Alterations in potential candidate genes involved in the biosynthesis and metabolism of androgens, folliculogenesis, and insulin and glucose metabolism have been suggested as possible etiologies. Dipeptidyl peptidase-4 (DPP4) plays a key role in glucose homeostasis and, thus, in the regulation of insulin secretion. The aim of our study was to analyze the DPP4 activity and concentrations in the serum of PCOS and non-PCOS patients and, additionally, study the activation of the DPP4 promoter by androgens in vitro...
August 11, 2017: Clinical Endocrinology
https://www.readbyqxmd.com/read/28799229/sitagliptin-mediated-preservation-of-endothelial-progenitor-cell-function-via-augmenting-autophagy-enhances-ischaemic-angiogenesis-in-diabetes
#12
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/28798686/strong-association-between-plasma-dipeptidyl-peptidase-4-activity-and-impaired-cognitive-function-in-elderly-population-with-normal-glucose-tolerance
#13
Bo Chen, Tianpeng Zheng, Linyuan Qin, Xueping Hu, Xiaoxi Zhang, Yihong Liu, Hongbo Liu, Shenghua Qin, Gang Li, Qinghua Li
Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT). Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28794822/overview-of-glucagon-like-peptide-1-receptor-agonists-for-the-treatment-of-patients-with-type-2-diabetes
#14
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
#15
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/28777292/influence-of-a-virgin-olive-oil-versus-butter-plus-cholesterol-enriched-diet-on-testicular-enzymatic-activities-in-adult-male-rats
#16
Germán Domínguez-Vías, Ana Belén Segarra, Magdalena Martínez-Cañamero, Manuel Ramírez-Sánchez, Isabel Prieto
The aim of the present work was to improve our knowledge on the mechanisms underlying the beneficial or deleterious effects on testicular function of the so-called Mediterranean and Western diet by analyzing glutamyl aminopeptidase (GluAP), gamma glutamyl transpeptidase (GGT) and dipeptidyl peptidase IV (DPP IV) activities in testis, as enzymes involved in testicular function. Male Wistar rats (6 months old) were fed for 24 weeks with three different diets: standard (S), an S diet supplemented with virgin-olive-oil (20%) (VOO), or a S diet enriched with butter (20%) plus cholesterol (0...
August 4, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28774208/moving-beyond-subcutaneous-insulin-the-application-of-adjunctive-therapies-to-the-treatment-of-type-1-diabetes
#17
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
#18
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
#19
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
#20
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
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