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https://www.readbyqxmd.com/read/27922176/dipeptidyl-peptidase-4-inhibitor-sitagliptin-reduces-inflammation-fibrosis-and-preserves-diastolic-function-in-a-rat-model-of-heart-failure-with-preserved-ejection-fraction
#1
Grazia Esposito, Donato Cappetta, Rosa Russo, Alessia Rivellino, Loreta Pia Ciuffreda, Fiorentina Roviezzo, Elena Piegari, L Liberato Berrino, Francesco Rossi, Antonella De Angelis, Konrad Urbanek
BACKGROUND AND PURPOSE: Heart failure with preserved ejection fraction (HFpEF) is a systemic syndrome driven by co-morbidities and its pathophysiology is poorly understood. Several studies suggesting that dipeptidyl peptidase 4 (DPP4) might be involved in the pathophysiology of heart failure prompted experimental and clinical investigations of DPP4 inhibitors on cardiovascular system. The aim of our study was to determine whether DPP4 inhibitor sitagliptin (SITA) affects the progression of HFpEF independently from the effects on glycaemia...
December 6, 2016: British Journal of Pharmacology
https://www.readbyqxmd.com/read/27899813/the-pro-fibrotic-role-of-dipeptidyl-peptidase-4-in-carbon-tetrachloride-induced-experimental-liver-injury
#2
Xin M Wang, Lauren E Holz, Sumaiya Chowdhury, Shaun P Cordoba, Kathryn A Evans, Margaret G Gall, Ana Júlia Vieira de Ribeiro, Yuan Zhou Zheng, Miriam T Levy, Denise M T Yu, Tsun-Wen Yao, Natasa Polak, Christopher J Jolly, Patrick Bertolino, Geoffrey W McCaughan, Mark D Gorrell
Liver fibrosis is a progressive pathological process involving inflammation and extracellular matrix deposition. Dipeptidyl peptidase 4 (DPP4), also known as CD26, is a cell surface glycoprotein and serine protease. DPP4 binds to fibronectin, can inactivate specific chemokines, incretin hormone and neuropeptides, and influences cell adhesion and migration. Such properties suggest a pro-fibrotic role for this peptidase but this hypothesis needs in vivo examination. Experimental liver injury was induced with carbon tetrachloride (CCl4) in DPP4 gene knockout (gko) mice...
November 30, 2016: Immunology and Cell Biology
https://www.readbyqxmd.com/read/27899228/the-recombinant-n-terminal-domain-of-spike-proteins-is-a-potential-vaccine-against-middle-east-respiratory-syndrome-coronavirus-mers-cov-infection
#3
Lan Jiaming, Yao Yanfeng, Deng Yao, Hu Yawei, Bao Linlin, Huang Baoying, Yan Jinghua, George F Gao, Qin Chuan, Tan Wenjie
The persistent public health threat of infection with the Middle East respiratory syndrome coronavirus (MERS-CoV) highlights the need for an effective MERS-CoV vaccine. Previous studies have focused mainly on the receptor-binding domain (RBD) on the spike protein of MERS-CoV. Herein, we investigated the immunogenicity and protective potential of the recombinant N-terminal domain (rNTD) of spike proteins as a vaccine candidate. BALB/c mice vaccinated with 5 or 10μg of rNTD protein demonstrated a significant humoral immune response (serum IgG and neutralizing activity)...
November 26, 2016: Vaccine
https://www.readbyqxmd.com/read/27898522/context-dependent-effects-of-dipeptidyl-peptidase-4-inhibitors
#4
Edwin K Jackson
PURPOSE OF REVIEW: The antidiabetic mechanism of dipeptidyl peptidase 4 (DPP4) inhibitors is attributed to attenuation of incretin metabolism. Because DPP4 has at least 45 substrates, context-dependent off-target effects of DPP4 inhibitors are likely. Here, we consider the clinical ramifications of the context-dependent effects of DPP4 inhibitors. RECENT FINDINGS: Although incretins protect organs from diabetic injury, nonincretin DPP4 substrates also accumulate when DPP4 is inhibited...
November 24, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27895822/linagliptin-alleviates-fatty-liver-disease-in-diabetic-db-db-mice
#5
Svetlana V Michurina, Irina Ju Ishenko, Vadim V Klimontov, Sergey A Archipov, Natalia E Myakina, Marina A Cherepanova, Eugenii L Zavjalov, Galina V Koncevaya, Vladimir I Konenkov
AIM: To study the effects of linagliptin on the structural signs of non-alcoholic fatty liver disease (NAFLD) in db/db mice. METHODS: Male diabetic db/db mice (BKS.Cg-Dock7(m+)/(+)Lepr(db)/J) aged 10 wk received the dipeptidyl peptidase 4 (DPP4) inhibitor linagliptin (10 mg/kg) or saline as a placebo once per day by gavage for 8 wk. Intact db/db mice served as controls. Structural changes in the liver were analyzed from light and electron microscopic images of sections from intact, placebo-treated and linagliptin-treated animals...
November 15, 2016: World Journal of Diabetes
https://www.readbyqxmd.com/read/27889414/changes-in-glucose-induced-plasma-active-glucagon-like-peptide-1-levels-by-co-administration-of-sodium-glucose-cotransporter-inhibitors-with-dipeptidyl-peptidase-4-inhibitors-in-rodents
#6
Takahiro Oguma, Chiaki Kuriyama, Keiko Nakayama, Yasuaki Matsushita, Kumiko Hikida, Minoru Tsuda-Tsukimoto, Akira Saito, Kenji Arakawa, Kiichiro Ueta, Masabumi Minami, Masaharu Shiotani
We investigated whether structurally different sodium-glucose cotransporter (SGLT) 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4) inhibitors, could enhance glucagon-like peptide-1 (GLP-1) secretion during oral glucose tolerance tests (OGTTs) in rodents. Three different SGLT inhibitors-1-(β-d-Glucopyranosyl)-4-chloro-3-[5-(6-fluoro-2-pyridyl)-2-thienylmethyl]benzene (GTB), TA-1887, and canagliflozin-were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1) elevation and suppressed glucose excursions in both normal and diabetic rodents...
October 28, 2016: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/27885461/prevention-and-treatment-effect-of-evogliptin-on-hepatic-steatosis-in-high-fat-fed-animal-models
#7
Mi-Kyung Kim, Yu Na Chae, Gook-Jun Ahn, Chang Yell Shin, Song-Hyen Choi, Eun Kyoung Yang, Yong Sung Sohn, Moon-Ho Son
Dipeptidyl peptidase 4 (DPP4) is an adipokine that interrupts insulin signaling. The resulting insulin resistance exacerbates hepatic steatosis. We previously reported that the novel DPP4 inhibitor evogliptin improves insulin resistance. This study aimed to verify the therapeutic potential of evogliptin for fatty liver. Evogliptin treatment was initiated simultaneously with a high-fat diet (HFD) feeding in normal mice and in a post-24 week HFD-fed rats. In a prevention study, insulin sensitivity was preserved in evogliptin-treated mice after a 16-week treatment...
November 24, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27881129/impact-of-dipeptidyl-peptidase-4-inhibitors-on-serum-adiponectin-a-meta-analysis
#8
Xin Liu, Peng Men, Yuhui Wang, Suodi Zhai, George Liu
BACKGROUND: Adiponectin, an adipose-specific protein, is negatively correlated with pro-atherogenic low-density lipoprotein cholesterol (LDL-C) and other cardiovascular risk factors such as insulin resistance. Therefore, low levels of adiponectin are associated with a higher risk for diabetes and cardiovascular disease. Dipeptidyl peptidase-4 inhibitors (DPP4i) have been used for the treatment of type 2 diabetes mellitus (T2DM) as reversible inhibitors through interacting with DPP4 substrate and increase serum incretins such as glucagon-like peptide-1 (GLP-1)...
November 23, 2016: Lipids in Health and Disease
https://www.readbyqxmd.com/read/27866216/association-of-circulating-dipeptidyl-peptidase-4-levels-with-osteoporotic-fracture-in-postmenopausal-women
#9
H Kim, K H Baek, S-Y Lee, S H Ahn, S H Lee, J-M Koh, Y Rhee, C H Kim, D-Y Kim, M-I Kang, B-J Kim, Y-K Min
: Postmenopausal women with osteoporotic fracture (OF) had higher plasma dipeptidyl-peptidase 4 (DPP4) levels than those without. Furthermore, higher plasma DPP4 levels were significantly associated with higher bone turnover and a higher prevalence of OF. These results indicated that DPP4 may be associated with OF by mediating bone turnover rate. INTRODUCTION: Evidence indicates that dipeptidyl-peptidase 4 (DPP4) plays a distinct role in bone metabolism. However, there has been no report on the association, if any, between circulating DPP4 levels and osteoporosis-related phenotypes, including osteoporotic fracture (OF)...
November 19, 2016: Osteoporosis International
https://www.readbyqxmd.com/read/27815838/decreased-methylation-level-of-h3k27me3-increases-seizure-susceptibility
#10
Zhongcheng Wang, Yusong Zhang, Jian Fang, Fang Yu, Duanhe Heng, Yuanteng Fan, Jian Xu, Biwen Peng, Wanhong Liu, Song Han, Xiaohua He
Epigenetic modifications including histone modifications are associated with seizure development and epileptogenesis; however, its underlying mechanism remains to be elucidated. Dipeptidyl peptidase 4 (DPP4) and IL6 are identified as febrile seizure (FS)-related genes using gene microarray analysis in hyperthermia prone (HP) rats. This purpose of the study focused on exploring whether epigenetic modifications marker histone H3 lysine 27 trimethylation (H3K27me3)-regulated DPP4 and IL6 expression further affected seizures development...
November 5, 2016: Molecular Neurobiology
https://www.readbyqxmd.com/read/27798350/the-effect-of-endurance-exercise-on-intestinal-integrity-in-well-trained-healthy-men
#11
Lonneke M JanssenDuijghuijsen, Marco Mensink, Kaatje Lenaerts, Ewa Fiedorowicz, Dorien A M van Dartel, Jurriaan J Mes, Yvette C Luiking, Jaap Keijer, Harry J Wichers, Renger F Witkamp, Klaske van Norren
Exercise is one of the external factors associated with impairment of intestinal integrity, possibly leading to increased permeability and altered absorption. Here, we aimed to examine to what extent endurance exercise in the glycogen-depleted state can affect intestinal permeability toward small molecules and protein-derived peptides in relation to markers of intestinal function. Eleven well-trained male volunteers (27 ± 4 years) ingested 40 g of casein protein and a lactulose/rhamnose (L/R) solution after an overnight fast in resting conditions (control) and after completing a dual - glycogen depletion and endurance - exercise protocol (first protocol execution)...
October 2016: Physiological Reports
https://www.readbyqxmd.com/read/27795435/cd8-t-cells-and-macrophages-regulate-pathogenesis-in-a-mouse-model-of-mers-cov-disease
#12
Christopher M Coleman, Jeanne M Sisk, Gabor Halasz, Jixin Zhong, Sarah E Beck, Krystal L Matthews, Thiagarajan Venkataraman, Sanjay Rajagopalan, Christos A Kyratsous, Matthew B Frieman
: Middle East respiratory syndrome coronavirus (MERS-CoV) is an important emerging pathogen that was first described in 2012. While the cell surface receptor for MERS-CoV has been identified as dipeptidyl peptidase IV (DPP4), the mouse DPP4 homologue does not allow for virus entry into cells. Therefore, development of mouse models of MERS-CoV has been hampered by the fact that MERS-CoV does not replicate in commonly available mouse strains. We have previously described a mouse model in which mDPP4 was replaced with hDPP4 such that hDPP4 is expressed under the endogenous mDPP4 promoter...
October 26, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27795425/recombinant-receptor-binding-domains-of-multiple-mers-coronaviruses-induce-cross-neutralizing-antibodies-against-divergent-human-and-camel-mers-coronaviruses-and-antibody-escape-mutants
#13
Wanbo Tai, Yufei Wang, Craig A Fett, Guangyu Zhao, Fang Li, Stanley Perlman, Shibo Jiang, Yusen Zhou, Lanying Du
: Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody-escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014 and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains...
October 19, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27776138/classification-of-benign-and-malignant-thyroid-nodules-using-a-combined-clinical-information-and-gene-expression-signatures
#14
Bing Zheng, Jun Liu, Jianlei Gu, Jing Du, Lin Wang, Shengli Gu, Juan Cheng, Jun Yang, Hui Lu
BACKGROUND: A key challenge in thyroid carcinoma is preoperatively diagnosing malignant thyroid nodules. A novel diagnostic test that measures the expression of a 3-gene signature (DPP4, SCG5 and CA12) has demonstrated promise in thyroid carcinoma assessment. However, more reliable prediction methods combining clinical features with genomic signatures with high accuracy, good stability and low cost are needed. METHODOLOGY/PRINCIPAL FINDINGS: 25 clinical information were recorded in 771 patients...
2016: PloS One
https://www.readbyqxmd.com/read/27773844/a-murine-model-of-type-2-diabetes-mellitus-developed-using-a-combination-of-high-fat-diet-and-multiple-low-doses-of-streptozotocin-treatment-mimics-the-metabolic-characteristics-of-type-2-diabetes-mellitus-in-humans
#15
Sayantan Nath, Sankar Kumar Ghosh, Yashmin Choudhury
INTRODUCTION: A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS: Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day...
October 20, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27762514/a-prospective-analysis-of-the-efficacy-and-safety-of-sodium-glucose-cotransporter-2-inhibitors-real-world-evidence-from-clinical-practice-in-india
#16
Bhavana Sosale, Aravind R Sosale, Prassanna M Kumar, Shashank R Joshi
BACKGROUND AND AIM: The number of patients with type 2 diabetes (T2DM) is increasing. Most patients with T2DM are uncontrolled and fail to achieve their target Hba1c. In recent years, newer agents such as SGLT2 inhibitors (SGLT2i) have been approved for clinical use. Though data from clinical trials and sub set analysis of Indian patients in global studies are promising, real world evidence from standard clinical practice in India is lacking. The aim of this study was to analyze the metabolic parameters in patients with T2DM on SGLT2i in real world clinical practice...
September 2016: Journal of the Association of Physicians of India
https://www.readbyqxmd.com/read/27750111/a-recombinant-receptor-binding-domain-of-mers-cov-in-trimeric-form-protects-human-dipeptidyl-peptidase-4-hdpp4-transgenic-mice-from-mers-cov-infection
#17
Wanbo Tai, Guangyu Zhao, Shihun Sun, Yan Guo, Yufei Wang, Xinrong Tao, Chien-Te K Tseng, Fang Li, Shibo Jiang, Lanying Du, Yusen Zhou
Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) was first identified in 2012, and it continues to threaten human health worldwide. No MERS vaccines are licensed for human use, reinforcing the urgency to develop safe and efficacious vaccines to prevent MERS. MERS-CoV spike protein forms a trimer, and its receptor-binding domain (RBD) serves as a vaccine target. Nevertheless, the protective efficacy of RBD in its native trimeric form has never been evaluated. In this study, a trimeric protein, RBD-Fd, was generated by fusing RBD with foldon trimerization motif...
December 2016: Virology
https://www.readbyqxmd.com/read/27746194/is-cleaved-glucagon-like-peptide-1-really-inactive-effects-of-glp-1-9-36-on-human-adipose-stem-cells
#18
Giulia Cantini, Alessandra Di Franco, Edoardo Mannucci, Michaela Luconi
Glucagon-like peptide 1(9-36) [GLP-1(9-36)] is generated by dipeptidyl peptidase-4 (DPP4) cleavage of the gut incretin hormone, GLP-1(7-36). Since GLP-1(9-36) has a very low affinity for the GLP-1 receptor (GLP-1R), it has so far been considered an inactive form of GLP-1. Here we show GLP-1(9-36) activity in human adipose stem cells (ASC) in vitro. GLP-1(9-36) inhibits human ASC proliferation, glucose uptake and adipogenesis, as well as induces cell apoptosis, to a similar extent as GLP-1(7-36) and liraglutide...
October 13, 2016: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/27744054/gliptins-in-managing-diabetes-reviewing-computational-strategy
#19
REVIEW
P Sneha, C George Priya Doss
The pace of anti-diabetic drug discovery is very slow in spite of increasing rate of prevalence of Type 2 Diabetes which remains a major public health concern. Though extensive research steps are taken in the past decade, yet craves for better new treatment strategies to overcome the current scenario. One such general finding is the evolution of gliptins which discriminately inhibits DPP4 (Dipeptidyl peptidase-4) enzyme. Although the mechanism of action of gliptin is highly target oriented and accurate, still its long-term use stands unknown...
December 1, 2016: Life Sciences
https://www.readbyqxmd.com/read/27741478/the-efficacy-and-safety-of-dpp4-inhibitors-in-patients-with-type-1-diabetes-a-systematic-review-and-meta-analysis
#20
Heming Guo, Chen Fang, Yun Huang, Yufang Pei, Linqi Chen, Ji Hu
AIMS: Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel class of antidiabetic medication in the treatment of type 2 diabetes mellitus. Several studies have indicated that DPP4 inhibitors could be used for type 1diabetes (T1DM). Here, we performed a meta-analysis to assess the efficacy and safety of DPP4 inhibitor therapy in patients with T1DM. METHODS: We conducted searches on Medline, Cochrane Library, Web of Science, and EMBASE for relevant studies published before November 21, 2015...
September 28, 2016: Diabetes Research and Clinical Practice
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