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https://www.readbyqxmd.com/read/29152780/6-nitroazolo-1-5-a-pyrimidin-7-4h-ones-as-antidiabetic-agents
#1
Alexander A Spasov, Denis A Babkov, Valentina A Sysoeva, Roman A Litvinov, Darya D Shamshina, Evgeny N Ulomsky, Konstantin V Savateev, Viktor V Fedotov, Pavel A Slepukhin, Oleg N Chupakhin, Valery N Charushin, Vladimir L Rusinov
Prevention of the formation of advanced glycation end-products (AGEs) is a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In these terms, new synthetic approaches to 6-nitroazolo[1,5-a]pyrimidines have been developed on the basis of the promising antiglycation activity of their structural analogues, such as azolo[5,1-c][1,2,4]triazine-4(1H)-ones. A number of nitroazolopyrimidines were obtained by using nitration, chlorodeoxygenation, and amination reactions, and their antidiabetic properties were elucidated in vitro...
November 20, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29152574/human-intestinal-tract-serves-as-an-alternative-infection-route-for-middle-east-respiratory-syndrome-coronavirus
#2
Jie Zhou, Cun Li, Guangyu Zhao, Hin Chu, Dong Wang, Helen Hoi-Ning Yan, Vincent Kwok-Man Poon, Lei Wen, Bosco Ho-Yin Wong, Xiaoyu Zhao, Man Chun Chiu, Dong Yang, Yixin Wang, Rex K H Au-Yeung, Ivy Hau-Yee Chan, Shihui Sun, Jasper Fuk-Woo Chan, Kelvin Kai-Wang To, Ziad A Memish, Victor M Corman, Christian Drosten, Ivan Fan-Ngai Hung, Yusen Zhou, Suet Yi Leung, Kwok-Yung Yuen
Middle East respiratory syndrome coronavirus (MERS-CoV) has caused human respiratory infections with a high case fatality rate since 2012. However, the mode of virus transmission is not well understood. The findings of epidemiological and virological studies prompted us to hypothesize that the human gastrointestinal tract could serve as an alternative route to acquire MERS-CoV infection. We demonstrated that human primary intestinal epithelial cells, small intestine explants, and intestinal organoids were highly susceptible to MERS-CoV and can sustain robust viral replication...
November 2017: Science Advances
https://www.readbyqxmd.com/read/29144805/dpp4-inhibitor-sitagliptin-as-a-potential-treatment-option-in-metformin-intolerant-obese-women-with-polycystic-ovary-syndrome-a-pilot-randomized-study
#3
Simona Ferjan, Andrej Janez, Mojca Jensterle
OBJECTIVE: Metformin has an established role in the management of polycystic ovary syndrome (PCOS). Some patients cannot tolerate it due to associated gastrointestinal adverse events. The present study evaluated DPP4 inhibitor sitagliptin as a potential treatment option in metformin intolerant PCOS. DESIGN: We conducted a 12-week prospective randomized open-label study with 30 obese metformin intolerant women with PCOS (aged 35.0±7.2 years, BMI 36.9±5.5 kg/m(2))...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29142025/cardioprotection-of-dapagliflozin-and-vildagliptin-in-cardiac-reperfusion-injury-rats
#4
Pongpan Tanajak, Piangkwan Sa-Nguanmoo, Sivaporn Sivasinprasan, Savitree Thummasorn, Natthaphat Siri-Angkul, Siriporn Chattipakorn, Nipon Chattipakorn
Sodium-glucose cotransporter 2 inhibitor (SGLT2-i) effects on cardiac ischemia/reperfusion (I/R) injury are unclear. Unlike SGLT2-i, dipeptidyl peptidase 4 inhibitors (DPP4-i) have shown effective cardioprotection in cardiac I/R injury. We aimed to investigate whether SGLT2-i reduces myocardial dysfunction and myocardial injury to a greater extent than DPP4-i in obese-insulin resistant rats with/without cardiac I/R injury. The high fat (HF) diet induced obese-insulin resistant rats were divided into 4 groups and received the following treatments for 28 days: vehicle (HFV); vildagliptin at a dosage of 3 mg/kg/day (HFVil); dapagliflozin at a dosage of 1 mg/kg/day (HFDa); and combination drugs (HFDaVil)...
November 15, 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/29140125/diabetes-area-patent-participation-analysis-part-ii-years-2011-2016
#5
Markus Boehm, Matthew Crawford, Jamie E Moscovitz, Philip A Carpino
Diabetes is a metabolic disease characterized by elevated levels of plasma glucose. When untreated, diabetes increases the risk of developing co-morbidities such as cardiovascular disease. Several drugs, often used as part of combination therapies, have been approved to treat the disease, but these drugs will eventually fail to effectively control blood glucose levels, at which point insulin replacement therapy is required. A medical need exists for new anti-diabetic drugs that exhibit good efficacy with improved safety/toleration profiles and can be added on top of existing therapies, or that can provide additional benefits beyond glucose lowering such as pancreatic beta (β)-cell protection...
November 15, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/29135080/a-comparison-of-adherence-and-persistence-by-medication-class-in-type-2-diabetes-a-systematic-review-and-meta-analysis
#6
Andrew McGovern, Zayd Tippu, William Hinton, Neil Munro, Martin Whyte, Simon de Lusignan
Limited medication adherence and persistence are barriers to successful treatment in type 2 diabetes (T2D). We searched MEDLINE, EMBASE, The Cochrane Library, The Register of Controlled Trials, PsychINFO, and CINAHL for observational and interventional studies comparing medication adherence or persistence between two or more glucose lowering medications in people with T2D. Where several studies (n≥5) provided the same comparison a random effects meta-analysis was performed reporting mean difference (MD), odds ratio (OR), or hazard ratio (HR) depending on the pooled study outcomes...
November 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29130940/neuropeptide-y-regulates-a-vascular-gateway-for-hematopoietic-stem-and-progenitor-cells
#7
Pratibha Singh, Jonathan Hoggatt, Malgorzata M Kamocka, Khalid S Mohammad, Mary R Saunders, Hongge Li, Jennifer Speth, Nadia Carlesso, Theresa A Guise, Louis M Pelus
Endothelial cells (ECs) are components of the hematopoietic microenvironment and regulate hematopoietic stem and progenitor cell (HSPC) homeostasis. Cytokine treatments that cause HSPC trafficking to peripheral blood are associated with an increase in dipeptidylpeptidase 4/CD26 (DPP4/CD26), an enzyme that truncates the neurotransmitter neuropeptide Y (NPY). Here, we show that enzymatically altered NPY signaling in ECs caused reduced VE-cadherin and CD31 expression along EC junctions, resulting in increased vascular permeability and HSPC egress...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29130939/open-the-gates-vascular-neurocrine-signaling-mobilizes-hematopoietic-stem-and-progenitor-cells
#8
Tomer Itkin, Jésus María Gómez-Salinero, Shahin Rafii
Mobilization of hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) into the peripheral blood is a complex process that is enhanced dramatically under stress-induced conditions. A better understanding of how the mobilization process is regulated will likely facilitate the development of improved clinical protocols for stem cell harvesting and transplantation. In this issue of the JCI, Singh et al. (1) showed that the truncated cleaved form of neurotransmitter neuropeptide Y (NPY) actively promotes a breach of BM vascular sinusoidal portals, thereby augmenting HSPC trafficking to the circulation...
November 13, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/29114002/sdf-1%C3%AE-stromal-cell-derived-factor-1%C3%AE-induces-cardiac-fibroblasts-renal-microvascular-smooth-muscle-cells-and-glomerular-mesangial-cells-to-proliferate-cause-hypertrophy-and-produce-collagen
#9
Edwin K Jackson, Yumeng Zhang, Delbert D Gillespie, Xiao Zhu, Dongmei Cheng, Travis C Jackson
BACKGROUND: Activated cardiac fibroblasts (CFs), preglomerular vascular smooth muscle cells (PGVSMCs), and glomerular mesangial cells (GMCs) proliferate, cause hypertrophy, and produce collagen; in this way, activated CFs contribute to cardiac fibrosis, and activated PGVSMCs and GMCs promote renal fibrosis. In heart and kidney diseases, SDF-1α (stromal cell-derived factor 1α; endogenous CXCR4 [C-X-C motif chemokine receptor 4] receptor agonist) levels are often elevated; therefore, it is important to know whether and how the SDF-1α/CXCR4 axis activates CFs, PGVSMCs, or GMCs...
November 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29107298/klk5-induces-shedding-of-dpp4-from-circulatory-th17-cells-in-type-2-diabetes
#10
Titli Nargis, Krishna Kumar, Amrit Raj Ghosh, Amit Sharma, Dipayan Rudra, Debrup Sen, Saikat Chakrabarti, Satinath Mukhopadhyay, Dipyaman Ganguly, Partha Chakrabarti
OBJECTIVE: Increasing plasma levels and activity of dipeptidyl peptidase-4 (DPP4 or CD26) are associated with rapid progression of metabolic syndrome to overt type 2 diabetes mellitus (T2DM). While DPP4 inhibitors are increasingly used as anti-hyperglycemic agents, the reason for the increase in plasma DPP4 activity in T2DM patients remains elusive. METHODS: We looked into the source of plasma DPP4 activity in a cohort of 135 treatment naive nonobese (BMI < 30) T2DM patients...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29095568/direct-head-to-head-comparison-of-glycemic-durability-of-dipeptidyl-peptidase-4-inhibitors-and-sulphonylureas-in-patients-with-type-2-diabetes-mellitus-a-meta-analysis-of-long-term-randomized-controlled-trials
#11
Kang Chen, Deying Kang, Miao Yu, Ruya Zhang, Ye Zhang, Guojuan Chen, Yiming Mu
We performed a meta-analysis of randomized controlled trials (RCTs) to compare the long-term glycemic durability between dipeptidyl-peptidase 4 (DPP4) inhibitors and sulfonylureas (SUs) in patients with type 2 diabetes mellitus (T2DM), in terms of the changes in glycosylated hemoglobin (HbA1c) levels from an intermediate time point (26 weeks or 52 weeks) to 104 weeks of treatment. The Medline (PubMed), Embase (Ovid), and CENTER (Cochrane Library) databases were searched for relevant RCTs. Eight RCTs were included...
November 2, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/29093273/genetic-determinants-of-circulating-gip-and-glp-1-concentrations
#12
Peter Almgren, Andreas Lindqvist, Ulrika Krus, Liisa Hakaste, Emilia Ottosson-Laakso, Olof Asplund, Emily Sonestedt, Rashmi B Prasad, Esa Laurila, Marju Orho-Melander, Olle Melander, Tiinamaija Tuomi, Jens Juul Holst, Peter M Nilsson, Nils Wierup, Leif Groop, Emma Ahlqvist
The secretion of insulin and glucagon from the pancreas and the incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) from the gastrointestinal tract is essential for glucose homeostasis. Several novel treatment strategies for type 2 diabetes (T2D) mimic GLP-1 actions or inhibit incretin degradation (DPP4 inhibitors), but none is thus far aimed at increasing the secretion of endogenous incretins. In order to identify new potential therapeutic targets for treatment of T2D, we performed a meta-analysis of a GWAS and an exome-wide association study of circulating insulin, glucagon, GIP, and GLP-1 concentrations measured during an oral glucose tolerance test in up to 7,828 individuals...
November 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/29080679/sfrp2-dpp4-and-fmo1-lsp1-define-major-fibroblast-populations-in-human-skin
#13
Tracy Tabib, Christina Morse, Ting Wang, Wei Chen, Robert Lafyatis
Fibroblasts produce matrix, regulate inflammation, mediate reparative processes, and serve as pluripotent mesenchymal cells. Analyzing digested normal human skin by single cell RNA-seq (scRNA-seq), we explored different fibroblast populations. T-distributed stochastic neighbor embedding and clustering of scRNA-seq data from six biopsies revealed two major fibroblast populations, defined by distinct genes, including SFRP2 and FMO1, expressed exclusively by these two major fibroblast populations. Further subpopulations were defined within each of the SFRP2 and FMO1 populations, as well as five minor fibroblast populations, each expressing discrete genes: CRABP1, COL11A1, FMO2, PRG4 or C2ORF40...
October 25, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29071110/real-world-weight-change-among-patients-treated-with-glucagon-like-peptide-1-receptor-agonist-dipeptidyl-peptidase-4-inhibitor-and-sulfonylureas-for-type-2-diabetes-and-the-influence-of-medication-adherence
#14
G S Carls, R Tan, J Y Zhu, E Tuttle, J Yee, S V Edelman, W H Polonsky
AIMS: The study aims to examine real-world weight change and the role of medication adherence among patients with type 2 diabetes who initiated one of three drug classes: glucagon-like peptide-1 receptor agonist (GLP-1RA), dipeptidyl peptidase-4 inhibitor (DPP4) and sulfonylureas (SUs). MATERIALS AND METHODS: A cohort of patients initiating one of the three drug classes was selected from a large US database of integrated electronic medical record and administrative claims...
September 2017: Obesity Science & Practice
https://www.readbyqxmd.com/read/29061303/unique-binding-mode-of-evogliptin-with-human-dipeptidyl-peptidase-iv
#15
Hyung Ki Lee, Mi-Kyung Kim, Ha Dong Kim, Heung Jae Kim, Ji Won Kim, Jie-Oh Lee, Chan-Wha Kim, Eunice EunKyeong Kim
Evogliptin ((R)-4-((R)-3-amino-4-(2,4,5-trifluorophenyl)butanoyl)-3-(tert-butoxymethyl) piperazine-2-one)) is a highly potent selective inhibitor of dipeptidyl peptidase IV (DPP4) that was approved for the treatment of type 2 diabetes in South Korea. In this study, we report the crystal structures of Evogliptin, DA-12166, and DA-12228 (S,R diastereomer of Evogliptin) complexed to human DPP4. Analysis of both the structures and inhibitory activities suggests that the binding of the trifluorophenyl moiety in the S1 pocket and the piperazine-2-one moiety have hydrophobic interactions with Phe357 in the S2 extensive subsite, and that the multiple hydrogen bonds made by the (R)-β-amine group in the S2 pocket and the contacts made by the (R)-tert-butyl group with Arg125 contribute to the high potency observed for Evogliptin...
October 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29054111/dipeptidyl-peptidase-4-inhibitors-attenuates-the-decline-of-skeletal-muscle-mass-in-patients-with-type-2-diabetes
#16
Ryotaro Bouchi, Tatsuya Fukuda, Takato Takeuchi, Yujiro Nakano, Masanori Murakami, Isao Minami, Hajime Izumiyama, Koshi Hashimoto, Takanobu Yoshimoto, Yoshihiro Ogawa
BACKGROUND: Activation of dipeptidyl peptidase 4 (DPP4) has been reported to be associated with impairment of insulin signaling in skeletal muscle mass, presumably leading to loss of muscle function. This study was aimed to investigate whether the use of DPP4 inhibitors (DPP4i) could attenuate the progressive loss of muscle mass in patients with type 2 diabetes. METHODS: A total 105 patients with type 2 diabetes (mean age 62 ± 12 years; 39% female) were studied in this retrospective observational study...
October 20, 2017: Diabetes/metabolism Research and Reviews
https://www.readbyqxmd.com/read/29040423/title-therapeutic-strategies-utilising-sdf-1%C3%AE-in-ischaemic-cardiomyopathy
#17
Oliver J Ziff, Daniel I Bromage, Derek M Yellon, Sean M Davidson
Heart failure is rapidly increasing in prevalence and will redraw the global landscape for cardiovascular health. Alleviating and repairing cardiac injury associated with myocardial infarction (MI) is key to improving this burden. Homing signals mobilise and recruit stem cells to the ischaemic myocardium where they exert beneficial paracrine effects. The chemoattractant cytokine SDF-1α and its associated receptor CXCR4 are upregulated after MI and appear to be important in this context. Activation of CXCR4 promotes both cardiomyocyte survival and stem cell migration towards the infarcted myocardium...
October 13, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29035321/a-novel-multi-epitope-vaccine-based-on-urate-transporter-1-alleviates-streptozotocin-induced-diabetes-by-producing-anti-urat1-antibody-and-an-immunomodulatory-effect-in-c57bl-6j-mice
#18
Yanjie Ma, Huimin Cao, Zhixin Li, Jinzhi Fang, Xiaomin Wei, Peng Cheng, Rui Jiao, Xiaoran Liu, Ya Li, Yun Xing, Jiali Tang, Liang Jin, Taiming Li
Hyperuricemia (HUA) is related to diabetes. Uric acid-induced inflammation and oxidative stress are risk factors for diabetes and its complications. Human urate transporter 1 (URAT1) regulates the renal tubular reabsorption of uric acid. IA-2(5)-P2-1, a potent immunogenic carrier designed by our laboratory, can induce high-titer specific antibodies when it carries a B cell epitope, such as B cell epitopes of DPP4 (Dipeptidyl peptidase-4), xanthine oxidase. In this report, we describe a novel multi-epitope vaccine composing a peptide of URAT1, an anti-diabetic B epitope of insulinoma antigen-2(IA-2) and a Th2 epitope (P2:IPALDSLTPANED) of P277 peptide in human heat shock protein 60 (HSP60)...
October 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29031724/elevated-hepatic-dpp4-activity-promotes-insulin-resistance-and-non-alcoholic-fatty-liver-disease
#19
Christian Baumeier, Luisa Schlüter, Sophie Saussenthaler, Thomas Laeger, Maria Rödiger, Stella Amelie Alaze, Louise Fritsche, Hans-Ulrich Häring, Norbert Stefan, Andreas Fritsche, Robert Wolfgang Schwenk, Annette Schürmann
OBJECTIVE: Increased hepatic expression of dipeptidyl peptidase 4 (DPP4) is associated with non-alcoholic fatty liver disease (NAFLD). Whether this is causative for the development of NAFLD is not yet clarified. Here we investigate the effect of hepatic DPP4 overexpression on the development of liver steatosis in a mouse model of diet-induced obesity. METHODS: Plasma DPP4 activity of subjects with or without NAFLD was analyzed. Wild-type (WT) and liver-specific Dpp4 transgenic mice (Dpp4-Liv-Tg) were fed a high-fat diet and characterized for body weight, body composition, hepatic fat content and insulin sensitivity...
October 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29029383/dpp4-inhibition-prevents-aki
#20
EDITORIAL
Christoph Reichetzeder, Berthold Hocher
No abstract text is available yet for this article.
September 12, 2017: Oncotarget
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