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Peptidase inhibitor

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https://www.readbyqxmd.com/read/27914297/long-term-efficacy-and-safety-of-vildagliptin-add-on-therapy-in-type-2-diabetes-mellitus-with-insulin-treatment
#1
Ippei Kanazawa, Ken-Ichiro Tanaka, Masakazu Notsu, Sayuri Tanaka, Nobuaki Kiyohara, Sayo Koike, Yuko Yamane, Yuko Tada, Motofumi Sasaki, Mika Yamauchi, Toshitsugu Sugimoto
BACKGROUND: The use of dipeptidyl peptidase (DPP)-4 inhibitors in patients with type 2 diabetes treated with insulin may be beneficial. However, the long-term efficacy and safety of vildagliptin add-on therapy in these patients remains unclear. SUBJECTS AND METHODS: A total of 73 patients with type 2 diabetes treated with insulin were randomly assigned to receive either add-on therapy of vildagliptin (n=37) or conventional therapy without DPP-4 inhibitors (n=36) for glucose control...
November 20, 2016: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/27905912/effect-of-sitagliptin-on-blood-glucose-control-in-patients-with-type-2-diabetes-mellitus-who-are-treatment-naive-or-poorly-responsive-to-existing-antidiabetic-drugs-the-jamp-study
#2
Hiroshi Sakura, Naotake Hashimoto, Kazuo Sasamoto, Hiroshi Ohashi, Sumiko Hasumi, Noriko Ujihara, Tadasu Kasahara, Osamu Tomonaga, Hideo Nunome, Masashi Honda, Yasuhiko Iwamoto
BACKGROUND: To investigate the ameliorating effect of sitagliptin, a dipeptidyl peptidase-4 inhibitor, on blood glucose control in patients with type 2 diabetes mellitus who were previously untreated with or who have a poor responsive to existing antidiabetic drugs. METHODS: Sitagliptin (50 mg/day) was added on to the pre-existing therapy for type 2 diabetes and changes in the glycated hemoglobin (HbA1c) level after 3 months of treatment were compared with the baseline and performed exploratory analysis...
December 1, 2016: BMC Endocrine Disorders
https://www.readbyqxmd.com/read/27899813/the-pro-fibrotic-role-of-dipeptidyl-peptidase-4-in-carbon-tetrachloride-induced-experimental-liver-injury
#3
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/27899793/bacterial-proteases-untapped-antimicrobial-drug-targets
#4
REVIEW
Elizabeth Culp, Gerard D Wright
Bacterial proteases are an extensive collection of enzymes that have vital roles in cell viability, stress response and pathogenicity. Although their perturbation clearly offers the potential for antimicrobial drug development, both as traditional antibiotics and anti-virulence drugs, they are not yet the target of any clinically used therapeutics. Here we describe the potential for and recent progress in the development of compounds targeting bacterial proteases with a focus on AAA+ family proteolytic complexes and signal peptidases (SPs)...
November 30, 2016: Journal of Antibiotics
https://www.readbyqxmd.com/read/27898522/context-dependent-effects-of-dipeptidyl-peptidase-4-inhibitors
#5
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
#6
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/27895112/hepatic-dipeptidyl-peptidase-4-controls-pharmacokinetics-of-vildagliptin-in-vivo
#7
Mitsutoshi Asakura, Tatsuki Fukami, Miki Nakajima, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
The major metabolic pathway of vildagliptin, which is an inhibitor of dipeptidyl peptidase-4 (DPP-4), in humans is hydrolysis at the cyano group to produce a carboxylic acid metabolite M20.7. Our in vitro study previously demonstrated that DPP-4 itself greatly contributed to the hydrolysis of vildagliptin in mouse, rat, and human livers. To investigate whether hepatic DPP-4 contributes to the hydrolysis of vildagliptin in vivo, in the present study, we conducted in vivo pharmacokinetics studies of vildagliptin in mice co-administered with vildagliptin and sitagliptin, which is another DPP-4 inhibitor, and also in streptozotocin (STZ)-induced diabetic mice...
November 28, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27894252/transcriptome-analysis-reveals-the-genetic-basis-underlying-the-seasonal-development-of-keratinized-nuptial-spines-in-leptobrachium-boringii
#8
Wei Zhang, Yue Guo, Jun Li, Li Huang, Eric Gilbert Kazitsa, Hua Wu
BACKGROUND: The expression of sexually selected traits often varies with populations' breeding cycles in many animals. The elucidation of mechanisms underlying the expression of such traits is a research topic in evolutionary biology; however, the genetic basis of the seasonal development of their expression remains unknown. Male Leptobrachium boringii develop keratinized nuptial spines on their upper jaw during the breeding season that fall off when the breeding season ends. To illuminate the genetic basis for the expression of this trait and its seasonal development, we assessed the de novo transcriptome for L...
November 28, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27892457/amplification-of-usp13-drives-ovarian-cancer-metabolism
#9
Cecil Han, Lifeng Yang, Hyun Ho Choi, Joelle Baddour, Abhinav Achreja, Yunhua Liu, Yujing Li, Jiada Li, Guohui Wan, Cheng Huang, Guang Ji, Xinna Zhang, Deepak Nagrath, Xiongbin Lu
Dysregulated energetic metabolism has been recently identified as a hallmark of cancer. Although mutations in metabolic enzymes hardwire metabolism to tumourigenesis, they are relatively infrequent in ovarian cancer. More often, cancer metabolism is re-engineered by altered abundance and activity of the metabolic enzymes. Here we identify ubiquitin-specific peptidase 13 (USP13) as a master regulator that drives ovarian cancer metabolism. USP13 specifically deubiquitinates and thus upregulates ATP citrate lyase and oxoglutarate dehydrogenase, two key enzymes that determine mitochondrial respiration, glutaminolysis and fatty acid synthesis...
November 28, 2016: Nature Communications
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
#10
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
#11
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/27885251/postprandial-and-orthostatic-hypotension-treated-by-sitagliptin-in-a-patient-with-dementia-with-lewy-bodies
#12
Yoshihiro Saito, Joji Ishikawa, Kazumasa Harada
BACKGROUND Postprandial hypotension, induced by an absorption of glucose from intestine, could be treated by acarbose; however, it was unclear whether dipeptidyl peptidase-4 inhibitor reduced postprandial hypotension. CASE REPORT A 78-year-old woman who had experienced episodes of dizziness and hypotension after eating was admitted to our hospital. During 24-hour ambulatory blood pressure monitoring, there were repeated episodes of marked postprandial hypotension; i.e., a significant systolic blood pressure reduction within two hours after eating (from -58 to -64 mm Hg after meals)...
November 25, 2016: American Journal of Case Reports
https://www.readbyqxmd.com/read/27884648/dipeptidyl-peptidase-4-inhibitors-peripheral-arterial-disease-and-lower-extremity-amputation-risk-in-diabetic-patients
#13
Chun-Chin Chang, Yung-Tai Chen, Chien-Yi Hsu, Yu-Wen Su, Chun-Chih Chiu, Hsin-Bang Leu, Po-Hsun Huang, Jaw-Wen Chen, Shing-Jong Lin
BACKGROUND: Recent studies have elucidated the vascular protective effects of dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors). However, to date no large-scale studies have been carried out to determine the impact of DPP-4 inhibitors on the occurrence of peripheral arterial disease, and lower extremity amputation risk in patients with type 2 diabetes mellitus. METHODS: We conducted a retrospective registry analysis using Taiwan's National Health Insurance Research Database to investigate the correlation between the use of DPP-4 inhibitors and risk of peripheral arterial disease in patients with type 2 diabetes mellitus...
November 21, 2016: American Journal of Medicine
https://www.readbyqxmd.com/read/27884496/glucagon-like-peptide-1-and-its-receptor-agonists-their-roles-in-management-of-type-2-diabetes-mellitus
#14
REVIEW
Ankit Gupta, Herbert F Jelinek, Hayder Al-Aubaidy
This study summarizes major work which investigated the roles of glucagon like peptide-1 (GLP-1) and its receptor (GLP-1R); the use of GLP-1-R agonists and dipeptidyl peptidase 4 inhibitor in the management of type 2 diabetes mellitus. It focuses on the recent therapeutic development which has occurred in this field, and also discusses the potential treatments which can be discovered and implemented in the near future to design an effective therapy for type 2 diabetes mellitus.
September 15, 2016: Diabetes & Metabolic Syndrome
https://www.readbyqxmd.com/read/27884201/nickel-pyrithione-induces-apoptosis-in-chronic-myeloid-leukemia-cells-resistant-to-imatinib-via-both-bcr-abl-dependent-and-bcr-abl-independent-mechanisms
#15
Xiaoying Lan, Chong Zhao, Xin Chen, Peiquan Zhang, Dan Zang, Jinjie Wu, Jinghong Chen, Huidan Long, Li Yang, Hongbiao Huang, Bing Z Carter, Xuejun Wang, Xianping Shi, Jinbao Liu
BACKGROUND: Acquired imatinib (IM) resistance is frequently characterized by Bcr-Abl mutations that affect IM binding and kinase inhibition in patients with chronic myelogenous leukemia (CML). Bcr-Abl-T315I mutation is the predominant mechanism of the acquired resistance to IM. Therefore, it is urgent to search for additional approaches and targeting strategies to overcome IM resistance. We recently reported that nickel pyrithione (NiPT) potently inhibits the ubiquitin proteasome system via targeting the 19S proteasome-associated deubiquitinases (UCHL5 and USP14), without effecting on the 20S proteasome...
November 25, 2016: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/27883260/the-use-of-incretin-agents-and-risk-of-acute-and-chronic-pancreatitis-a-population-based-cohort-study
#16
Lotte M Knapen, Roy G P J de Jong, Johanna H M Driessen, Yolande C Keulemans, Nielka P van Erp, Marie L De Bruin, Hubert G M Leufkens, Sander Croes, Frank de Vries
BACKGROUND: Incretin-based therapies (Dipeptidyl Peptidase 4 inhibitors and Glucagon-Like Peptide-1 Receptor Agonists) are effective new agents for the treatment of Type 2 Diabetes Mellitus (T2DM). While incretin-based therapies have been associated with pancreatitis, evidence is conflicting for acute pancreatitis and lacks for chronic pancreatitis. OBJECTIVE: To determine the association between the use of incretin agents and the risk of any, acute and chronic pancreatitis...
November 24, 2016: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/27882332/c-peptide-levels-predict-the-effectiveness-of-dipeptidyl-peptidase-4-inhibitor-therapy
#17
Sevin Demir, Sule Temizkan, Mehmet Sargin
Background. Our aim was to define the conditions that affect therapeutic success when dipeptidyl peptidase-4 (DPP-4) inhibitor is added to metformin monotherapy. Materials and Methods. We reviewed the medical records of 56 patients who had received DPP-4 inhibitor as an add-on to metformin monotherapy and evaluated their response in the first year of therapy. Fasting blood glucose (FBG), HbA1c, C-peptide, and weight of the patients were recorded at 3-month intervals during the first year of treatment. Results...
2016: Journal of Diabetes Research
https://www.readbyqxmd.com/read/27881129/impact-of-dipeptidyl-peptidase-4-inhibitors-on-serum-adiponectin-a-meta-analysis
#18
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/27875385/effects-of-linagliptin-on-vessel-wall-healing-in-the-rat-model-of-arterial-injury-under-normal-and-diabetic-conditions
#19
Linnea Eriksson, Samuel Röhl, Robert Saxelin, Mariette Lengquist, Malin Kronqvist, Kenneth Caidahl, Claes-Göran Östenson, Anton Razuvaev
Diabetic patients suffer an increased risk of restenosis and late stent thrombosis after angioplasty, complications that are related to a defective re-endothelialization. Dipeptidyl peptidase-4 inhibitors have been suggested to exert direct effect on endothelial and smooth muscle cells (SMCs). Therefore the objective was to study if the dipeptidyl peptidase-4 inhibitor linagliptin could influence vascular repair and accelerate re-endothelialization after arterial injury in healthy and diabetic animals. Diabetic Goto-Kakizaki and healthy Wistar rats were subjected to arterial injury and treated with linagliptin or vehicle...
November 17, 2016: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/27873238/cardiovascular-safety-of-dipeptidyl-peptidase-iv-inhibitors-a-meta-analysis-of-placebo-controlled-randomized-trials
#20
Islam Y Elgendy, Ahmed N Mahmoud, Amr F Barakat, Akram Y Elgendy, Marwan Saad, Ahmed Abuzaid, Siddarth A Wayangankar, Anthony A Bavry
BACKGROUND: Large randomized trials have shown conflicting evidence regarding the cardiovascular safety of dipeptidyl-peptidase 4 (DPP-4) inhibitors. Systematic reviews have been limited by incomplete data and inclusion of observational studies. This study aimed to systematically evaluate the cardiovascular safety of DPP-4 inhibitors in patients with type 2 diabetes. METHODS: Electronic databases were searched for randomized trials that compared DPP-4 inhibitors versus placebo and reported cardiovascular outcomes...
November 21, 2016: American Journal of Cardiovascular Drugs: Drugs, Devices, and Other Interventions
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