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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/29345066/protease-activated-receptor-2-is-necessary-for-neutrophil-chemorepulsion-induced-by-trypsin-tryptase-or-dipeptidyl-peptidase-iv
#1
Michael J V White, Luis E Chinea, Darrell Pilling, Richard H Gomer
Compared to neutrophil chemoattractants, relatively little is known about the mechanism neutrophils use to respond to chemorepellents. We previously found that the soluble extracellular protein dipeptidyl peptidase IV (DPPIV) is a neutrophil chemorepellent. In this report, we show that an inhibitor of the protease activated receptor 2 (PAR2) blocks DPPIV-induced human neutrophil chemorepulsion, and that PAR2 agonists such as trypsin, tryptase, 2f-LIGRL, SLIGKV, and AC55541 induce human neutrophil chemorepulsion...
January 2018: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/29345029/high-prevalence-and-functional-effects-of-serum-antineuronal-antibodies-in-patients-with-gastrointestinal-disorders
#2
A Lütt, K Michel, D Krüger, M S Volz, M Nassir, E Schulz, L Poralla, P Tangermann, C Bojarski, M Höltje, B Teegen, W Stöcker, M Schemann, B Siegmund, H Prüss
BACKGROUND: Antineuronal antibodies can be associated with both gastrointestinal (GI) and brain disorders. For example, antibodies against the potassium channel subunit dipeptidyl-peptidase-like protein-6 (DPPX) bind to neurons in the central nervous system (CNS) and myenteric plexus and cause encephalitis, commonly preceded by severe unspecific GI symptoms. We therefore investigated the prevalence of antineuronal antibodies indicative of treatable autoimmune CNS etiologies in GI patients...
January 18, 2018: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/29344085/synthesis-secretion-function-metabolism-and-application-of-natriuretic-peptides-in-heart-failure
#3
REVIEW
Shihui Fu, Ping Ping, Fengqi Wang, Leiming Luo
As a family of hormones with pleiotropic effects, natriuretic peptide (NP) system includes atrial NP (ANP), B-type NP (BNP), C-type NP (CNP), dendroaspis NP and urodilatin, with NP receptor-A (guanylate cyclase-A), NP receptor-B (guanylate cyclase-B) and NP receptor-C (clearance receptor). These peptides are genetically distinct, but structurally and functionally related for regulating circulatory homeostasis in vertebrates. In humans, ANP and BNP are encoded by NP precursor A (NPPA) and NPPB genes on chromosome 1, whereas CNP is encoded by NPPC on chromosome 2...
2018: Journal of Biological Engineering
https://www.readbyqxmd.com/read/29343445/development-regulation-metabolism-and-function-of-bone-marrow-adipose-tissues
#4
Ziru Li, Julie Hardij, Devika P Bagchi, Erica L Scheller, Ormond A MacDougald
Most adipocytes exist in discrete depots throughout the body, notably in well-defined white and brown adipose tissues. However, adipocytes also reside within specialized niches, of which the most abundant is within bone marrow. Whereas bone marrow adipose tissue (BMAT) shares many properties in common with white adipose tissue, the distinct functions of BMAT are reflected by its development, regulation, protein secretion, and lipid composition. In addition to its potential role as a local energy reservoir, BMAT also secretes proteins, including adiponectin, RANK ligand, dipeptidyl peptidase-4, and stem cell factor, which contribute to local marrow niche functions and which may also influence global metabolism...
January 14, 2018: Bone
https://www.readbyqxmd.com/read/29335646/dipeptidyl-peptidase-4-inhibitors-pancreatic-cancer-and-acute-pancreatitis-a-meta-analysis-with-trial-sequential-analysis
#5
Lana C Pinto, Dimitris V Rados, Sabrina S Barkan, Cristiane B Leitão, Jorge L Gross
The use of dipeptidyl peptidase-4 (DPP-4) inhibitors may be associated with pancreatic cancer and acute pancreatitis. Recent meta-analyses have reported conflicting findings. Therefore, we performed a meta-analysis to assess the risk of both pancreatic cancer and acute pancreatitis associated with the use of DPP-4 inhibitors. We also used trial sequential analysis to evaluate whether the number of patients included was enough to reach conclusions. We included randomised controlled trials lasting 24 weeks or more that compared DPP-4 inhibitors with placebo or other antihyperglycaemic agents...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334906/rationale-and-design-of-the-carolina%C3%A2-cognition-substudy-a-randomised-controlled-trial-on-cognitive-outcomes-of-linagliptin-versus-glimepiride-in-patients-with-type-2-diabetes-mellitus
#6
Geert Jan Biessels, Jolien Janssen, Esther van den Berg, Bernard Zinman, Mark A Espeland, Michaela Mattheus, Odd Erik Johansen
BACKGROUND: Type 2 diabetes mellitus is associated with cognitive dysfunction and an increased risk of dementia. Linagliptin is a glucose-lowering agent of the dipeptidyl peptidase-IV (DPP-IV) inhibitor class that is of particular interest for the prevention of accelerated cognitive decline, because it may potentially benefit the brain through pleiotropic effects, beyond glucose lowering. This paper presents the design of a study that aims to establish if linagliptin is superior to the sulfonylurea glimepiride in the prevention of accelerated cognitive decline in patients with type 2 diabetes mellitus...
January 15, 2018: BMC Neurology
https://www.readbyqxmd.com/read/29331088/significance-of-circulatory-dpp4-activity-in-metabolic-diseases
#7
REVIEW
Titli Nargis, Partha Chakrabarti
Dipeptidyl peptidase 4 (DPP4), also known as CD26 is a type II transmembrane protein that is released from the cell membrane in a nonclassical secretory mechanism. This exopeptidase selectively degrades varieties of substrates including incretin hormones, growth factors, and cytokines. A significant detectable amount of DPP4 activity can be measured in plasma as well as in different tissues such as intestinal epithelium, vascular endothelium, lymphocytes, monocytes, kidney, liver, adipose, lung, thymus, spleen, prostate, etc...
January 13, 2018: IUBMB Life
https://www.readbyqxmd.com/read/29330812/evaluation-of-the-effect-of-alogliptin-on-tissue-characteristics-of-the-carotid-wall-subanalysis-of-the-spead-a-trial
#8
Yoko Irie, Naoto Katakami, Tomoya Mita, Mitsuyoshi Takahara, Taka-Aki Matsuoka, Masahiko Gosho, Hirotaka Watada, Iichiro Shimomura
INTRODUCTION: Ultrasonic tissue characterization of the carotid wall using gray-scale median (GSM) reflects its composition and low-GSM plaque is considered to be unstable. The present study evaluated the effect of alogliptin, a dipeptidyl peptidase-4 inhibitor, on the longitudinal change in GSM, an index of the tissue characteristics of the carotid wall, in patients with type 2 diabetes (T2DM). METHODS: This is a post hoc subanalysis using data obtained from the SPEAD-A trial, a randomized controlled trial that demonstrated the beneficial effect of alogliptin treatment on the progression of carotid intima-media thickness in patients with T2DM with no past history of apparent cardiovascular disease...
January 12, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/29330364/polypharmacy-through-phage-display-selection-of-glucagon-and-glp-1-receptor-co-agonists-from-a-phage-displayed-peptide-library
#9
Anna Demartis, Armin Lahm, Licia Tomei, Elisa Beghetto, Valentina Di Biasio, Federica Orvieto, Francesco Frattolillo, Paul E Carrington, Sheena Mumick, Brian Hawes, Elisabetta Bianchi, Anandan Palani, Antonello Pessi
A promising emerging area for the treatment of obesity and diabetes is combinatorial hormone therapy, where single-molecule peptides are rationally designed to integrate the complementary actions of multiple endogenous metabolically-related hormones. We describe here a proof-of-concept study on developing unimolecular polypharmacy agents through the use of selection methods based on phage-displayed peptide libraries (PDL). Co-agonists of the glucagon (GCG) and GLP-1 receptors were identified from a PDL sequentially selected on GCGR- and GLP1R-overexpressing cells...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29327406/short-and-medium-term-efficacy-of-sodium-glucose-co-transporter-2-sglt-2-inhibitors-a-meta-analysis-of-randomized-clinical-trials
#10
Matteo Monami, Francesco Liistro, Alessia Scatena, Besmir Nreu, Edoardo Mannucci
AIMS: Sodium glucose co-transport-2 (SGLT-2) inhibitors reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. Aim of this meta-analysis is the systematic collection of available data from randomized trials, in order to establish the durability of the efficacy of SGLT-2 inhibitors on glycemic control and body mass index. METHODS: A meta-analysis was performed including all trials with a duration of at least 12 weeks, comparing SGLT-2 inhibitors with a non-SGLT-2 inhibitor agents in type 2 diabetes...
January 12, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29324356/inflammation-induced-er-stress-affects-absorptive-intestinal-epithelial-cells-function-and-integrity
#11
Sucheera Chotikatum, Hassan Y Naim, Nahed El-Najjar
Recent studies have linked impairment of intestinal epithelial function in inflammatory bowel disease to the disturbance of endoplasmic reticulum homeostasis (ER) in response to stress. Most studies are on goblet and Paneth cells, which are considered more susceptible to stress due to their role in the protection of intestinal epithelium against microbes and harmful substances. However, studies on the role of inflammation-induced ER stress in absorptive intestinal cells are scarce. In this study, we show, using Caco-2 cells as a model of intestinal epithelial barrier, that inducing ER stress using a cocktail mixture of pro-inflammatory mediators [TNFα (50ng/ml), MCP1 (50ng/ml), and IL-1β (25ng/ml)] as observed in IBD patients induces ER stress and leads to significant changes in key proteins of the apical (sucrase-isomaltase (SI), dipeptidyl-peptidase (DPPIV), and ezrin) and basolateral (E-cadherin, zonula occludens (ZO-1), and connexin-43) membranes...
January 8, 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29322610/safety-and-efficacy-of-once-weekly-semaglutide-versus-additional-oral-antidiabetic-drugs-in-japanese-subjects-with-inadequately-controlled-t2d-a-randomised-trial
#12
Kohei Kaku, Yuichiro Yamada, Hirotaka Watada, Atsuko Abiko, Tomoyuki Nishida, Jeppe Zacho, Arihiro Kiyosue
AIMS: Semaglutide is a glucagon-like peptide 1 analogue in development for type 2 diabetes (T2D). Safety and efficacy of once-weekly subcutaneous semaglutide as monotherapy or combined with an oral antidiabetic drug (OAD) vs an additional OAD was evaluated in Japanese subjects with T2D inadequately controlled on diet/exercise or OAD monotherapy. METHODS: In this phase 3, open-label trial, adults with T2D were randomised 2:2:1 to semaglutide 0.5 mg or 1.0 mg, or one additional OAD (dipeptidyl peptidase-4 inhibitor, biguanide, sulphonylurea, glinide, α-glucosidase inhibitor or thiazolidinedione) with different modes of action...
January 11, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29321388/suppression-of-abdominal-aortic-aneurysm-formation-in-mice-by-teneligliptin-a-dipeptidyl-peptidase-4-inhibitor
#13
Yusuke Takahara, Tomotake Tokunou, Toshihiro Ichiki
AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors lower blood glucose levels through inhibition of incretin degradation, which stimulates insulin secretion. Recent studies reported that DPP-4 inhibitors suppressed atherogenesis in apolipoprotein E-knockout (ApoEKO) mice. In this study, we investigated whether teneligliptin, a DPP-4 inhibitor, affects the development of abdominal aortic aneurysms (AAA) in ApoEKO mice. METHODS: ApoEKO mice were fed a high-fat diet (HFD) and infused with angiotensin (Ang) II by osmotic mini pumps for 4 weeks to induce AAA with (DPP-4i group) or without (control group) teneligliptin administered orally from 1 week before HFD and Ang II infusion to the end of the experiment...
January 10, 2018: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/29320602/when-metformin-is-not-enough-pros-and-cons-of-sglt2-and-dpp-4-inhibitors-as-a-second-line-therapy
#14
REVIEW
Angelo Avogaro, Elías Delgado, Ildiko Lingvay
The newer oral therapies for type 2 diabetes (T2DM); dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have advantages over older agents. DPP-4 inhibitors are weight neutral, and have few adverse effects. SGLT2 inhibitors have additional benefits; weight loss, blood pressure reduction, cardiovascular risk reduction, and renoprotective effects. SGLT2 inhibitors, have increased risk of urogenital infections and possible risk of "euglycaemic" diabetic ketoacidosis...
January 10, 2018: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29316236/long-term-safety-and-efficacy-of-tofogliflozin-add-on-to-insulin-in-patients-with-type-2-diabetes-results-from-a-52-week-multicenter-randomized-double-blind-open-label-extension-phase-4-study-in-japan-j-step-ins
#15
Yasuo Terauchi, Masahiro Tamura, Masayuki Senda, Ryoji Gunji, Kohei Kaku
AIMS: To evaluate the long-term safety and efficacy of tofogliflozin as an add-on treatment to insulin over 52 weeks. MATERIALS AND METHODS: This 52-week, multicenter, Phase 4 study consisted of a 16-week, randomized, double-blind, placebo-controlled phase and a 36-week open label extension phase (NCT02201004). Japanese patients with type 2 diabetes mellitus aged 20-75 years with suboptimal glycemic control (7.5%-10.5%) on insulin monotherapy (basal-bolus, bolus, premix [low and high], and basal) or on combination therapy of basal insulin and dipeptidyl peptidase-4 inhibitor were eligible for participation...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29316197/tofogliflozin-decreases-body-fat-mass-and-improves-peripheral-insulin-resistance
#16
Ren Matsuba, Ikuro Matsuba, Mototsugu Shimokawa, Yoshio Nagai, Yasushi Tanaka
The impact of tofogliflozin, a sodium glucose transporter 2 inhibitor, on peripheral glucose uptake in patients with type 2 diabetes mellitus (T2DM) was investigated by the hyperinsulinemic-euglycemic clamp method in a single-arm, open-label study. The following parameters were compared between before and after tofogliflozin administration for 12 weeks in 16 T2DM patients using dipeptidyl peptidase 4 inhibitors: body weight, blood pressure, glucose metabolism, liver function, lipid profile, and body composition...
January 5, 2018: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29310647/have-dipeptidyl-peptidase-4-inhibitors-ameliorated-the-vascular-complications-of-type-2-diabetes-in-large-scale-trials-the-potential-confounding-effect-of-stem-cell-chemokines
#17
REVIEW
Milton Packer
Drugs that inhibit dipeptidyl peptidase-4 (DPP-4) are conventionally regarded as incretin-based agents that signal through the glucagon-like peptide-1 (GLP-1) receptor. However, inhibition of DPP-4 also potentiates the stem cell chemokine, stromal cell-derived factor-1 (SDF-1), which can promote inflammation, proliferative responses and neovascularization. In large-scale cardiovascular outcome trials, enhanced GLP-1 signaling has reduced the risk of atherosclerotic ischemic events, potentially because GLP-1 retards the growth and increases the stability of atherosclerotic plaques...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29310393/association-between-dipeptidyl-peptidase-4-inhibitor-drugs-and-risk-of-acute-pancreatitis-a-meta-analysis
#18
Shimin Chen, Enfa Zhao, Wenfei Li, Jiehong Wang
BACKGROUND: Previous studies have reported conflicting results for the relationship between dipeptidyl peptidase-4 (DPP-4) inhibitor drugs and acute pancreatitis. The aim of this study was to investigate the association between DPP-4 inhibitors and an increased risk of acute pancreatitis using meta-analysis. METHODS: We conducted a comprehensive search in PubMed, Embase, Web of Science, and Cochrane library from inception to March 4, 2017. Original articles with data on DPP-4 inhibitors and acute pancreatitis were included...
December 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/29304092/dipeptidyl-peptidase-3-a-novel-protease-from-leishmania-braziliensis
#19
Jenny R Diaz, Cesar A Ramírez, Paola A Nocua, Fanny Guzman, José M Requena, Concepción J Puerta
The increase of leishmaniasis cases worldwide and the emergence of Leishmania strains resistant to current treatments make necessary to find new therapeutic targets. Proteases are appealing drug targets because they play pivotal roles in facilitating parasite survival and promoting pathogenesis. Enzymes belonging to the dipeptidyl peptidase 3 (DPP3) group have been described in different organisms such as mammals, insects and yeast, in which these enzymes have been involved in both protein turnover and protection against oxidative damage...
2018: PloS One
https://www.readbyqxmd.com/read/29301579/linagliptin-and-cardiovascular-outcomes-in-type-2-diabetes-after-acute-coronary-syndrome-or-acute-ischemic-stroke
#20
Yan-Rong Li, Sung-Sheng Tsai, Dong-Yi Chen, Szu-Tah Chen, Jui-Hung Sun, Hung-Yu Chang, Miaw-Jene Liou, Tien-Hsing Chen
BACKGROUND: The cardiovascular safety and efficacy of linagliptin, a dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-world cohort study was to evaluate the cardiovascular outcomes of linagliptin in patients with T2DM after ACS or AIS. METHODS: An open observational noncrossover retrospective cohort study was conducted between June 1, 2012 and December 31, 2013 utilizing Taiwan National Health Insurance Research Database...
January 4, 2018: Cardiovascular Diabetology
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