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Dipeptidyl peptidase

W Michael Dismuke, Mikael Klingeborn, W Daniel Stamer
Exosomes are emerging as important mediators of cell-matrix interactions by means of specific adhesion proteins. Changes in the tissue-specific exosomal protein expression may underlie pathological conditions whereby extracellular matrix turnover and homeostasis is disrupted. Ocular hypertension due to extracellular matrix accumulation in the trabecular meshwork is a hallmark of glucocorticoid-induced glaucoma. In the trabecular meshwork, exosomal fibronectin mediates cell matrix interactions at cellular structures called "invadosomes"...
2016: PloS One
Shivani K Mhatre, Omar Serna, Shubhada Sansgiry, Marc L Fleming, E James Essien, Sujit S Sansgiry
BACKGROUND: Low adherence to oral antidiabetic drugs (OADs) in the Medicare population can greatly reduce Centers for Medicare & Medicaid Services (CMS) star ratings for managed care organizations (MCOs). OBJECTIVE: To develop and validate a risk assessment tool (Prescription Medication Adherence Prediction Tool for Diabetes Medications [RxAPT-D]) to predict nonadherence to OADs using Medicare claims data. METHODS: In this retrospective observational study, claims data for members enrolled in a Medicare Advantage Prescription Drug (MA-PD) program in Houston, Texas, were used...
November 2016: Journal of Managed Care & Specialty Pharmacy
Michael S Hu, Michael T Longaker
Scarring and fibrosis are an enormous public health concern, resulting in excessive morbidity and mortality in addition to countless lost health care dollars. Recent advances in cell and developmental biology promise a better understanding of scarring and fibrosis and may translate to new clinical therapies.
November 2016: Plastic and Reconstructive Surgery
Takeshi Osonoi, Miyoko Saito, Natsuyo Hariya, Moritaka Goto, Kazuki Mochizuki
Metformin, α-glucosidase inhibitors (α-GIs), and dipeptidyl peptidase 4 inhibitors (DPP-4Is) reduce hyperglycemia without excessive insulin secretion, and enhance postprandial plasma concentration of glucagon-like peptide-1 (GLP-1) in type-2 diabetes mellitus (T2DM) patients. We assessed add-on therapeutic effects of DPP-4I anagliptin in Japanese T2DM patients treated with metformin, an α-GI miglitol, or both drugs on postprandial responses of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), and on plasma concentration of the appetite-suppressing hormone leptin...
October 22, 2016: Peptides
J H M Driessen, F de Vries, H van Onzenoort, N C Harvey, C Neef, J van den Bergh, P Vestergaard, R M A Henry
The aim of the present study was to estimate the effect of incretins on fracture risk in the real world situation by meta-analysis of the available population-based cohort data. Pubmed and Embase were searched for original articles investigating use of incretin agents, and fracture risk up to December 2015. Adjusted results were extracted and results were pooled by use of generic inverse variance methods, assuming a random-effects model. Neither current dipeptidyl peptidase 4 - inhibitors use, nor current glucagon-like peptide 1 receptor agonists use was associated with a decreased risk of fracture: pooled relative risk [pooled RR (95% CI): 1...
October 25, 2016: British Journal of Clinical Pharmacology
Emuella M Flood, Kelly F Bell, Marie C de la Cruz, France M Ginchereau-Sowell
OBJECTIVE: To identify which treatment attributes are most influential in determining patient preferences for diabetes treatments and explore patient preferences for diabetes drug classes. RESEARCH DESIGN AND METHODS: U.S. adults with type 1 or type 2 diabetes completed an online adaptive conjoint analysis survey. The survey examined 14 attributes, including efficacy, regimen, and risk of common side effects and rare, but serious adverse events. Respondents selected between hypothetical treatments with different attributes...
October 25, 2016: Current Medical Research and Opinion
Guillermo Cásedas, Francisco Les, Maria Pilar Gómez-Serranillos, Carine Smith, Víctor López
Sour cherry juice (Prunus cerasus) is consumed as a nutritional supplement claiming health effects. The aim of the study was to evaluate the different properties of sour cherry juice in terms of antioxidant activity and inhibition of target enzymes in the central nervous system and diabetes. The content of polyphenols and anthocyanins was quantified. Different experiments were carried out to determine the radical scavenging properties of the juice. The activity of sour cherry juice was also tested in physiological relevant enzymes of the central nervous system (acetylcholinesterase, monoamine oxidase A, tyrosinase) and others involved in type 2 diabetes (α-glucosidase, dipeptidyl peptidase-4)...
October 24, 2016: Food & Function
Akihiko Sato, Akiomi Yoshihisa, Yuki Kanno, Mai Takiguchi, Shunsuke Miura, Takeshi Shimizu, Yuichi Nakamura, Hiroyuki Yamauchi, Takashi Owada, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Takayoshi Yamaki, Koichi Sugimoto, Hiroyuki Kunii, Kazuhiko Nakazato, Hitoshi Suzuki, Shu-Ichi Saitoh, Yasuchika Takeishi
BACKGROUND: Heart failure (HF) and diabetes mellitus (DM) often co-exist. Treatment of DM in HF patients is challenging because some therapies for DM are contraindicated in HF. Although previous experimental studies have reported that dipeptidyl peptidase-4 (DPP-4) inhibitors improve cardiovascular function, whether DPP-4 inhibition improves mortality of HF patients with DM remains unclear. Therefore, we examined the impact of DPP-4 inhibition on mortality in hospitalized HF patients using propensity score analyses...
June 2016: ESC Heart Failure
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
Xiaoqian Liu, Jingjing Wang, Yi Chu, Xiaoying Zhou
Dipeptidyl peptidase I (DPPI) is a lysosomal cysteine protease and derived from immune granule cells. It has been suggested playing an important role in the development of rheumatoid arthritis. In this study, a coumarin based fluorescent probe (GF-AFC) was designed and synthesized to evaluate DPPI activity in serum or tissue homogenates of collagen-induced arthritis (CIA) rats, an inflammatory arthropathy model. It was revealed that the fluorescent intensity was significantly increased in a very short time after specific substrate GF-AFC reacted with the DPPI...
October 19, 2016: Molecular and Cellular Probes
Michelangela Barbieri, Raffaele Marfella, Antonietta Esposito, Maria Rosaria Rizzo, Edith Angellotti, Ciro Mauro, Mario Siniscalchi, Fabio Chirico, Pasquale Caiazzo, Fulvio Furbatto, Alessandro Bellis, Nunzia D'Onofrio, Milena Vitiello, Franca Ferraraccio, Giuseppe Paolisso, Maria Luisa Balestrieri
AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated...
October 5, 2016: Journal of Diabetes and its Complications
Sung-Ho Kim, Jung-Hwa Yoo, Woo Je Lee, Cheol-Young Park
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of oral antidiabetic agent for the treatment of type 2 diabetes mellitus. They increase endogenous levels of incretin hormones, which stimulate glucose-dependent insulin secretion, decrease glucagon secretion, and contribute to reducing postprandial hyperglycemia. Although DPP-4 inhibitors have similar benefits, they can be differentiated in terms of their chemical structure, pharmacology, efficacy and safety profiles, and clinical considerations. Gemigliptin (brand name: Zemiglo), developed by LG Life Sciences, is a potent, selective, competitive, and long acting DPP-4 inhibitor...
October 2016: Diabetes & Metabolism Journal
Fumitaka Okajima, Tomoko Nagamine, Yuko Nakamura, Naomi Hattori, Hitoshi Sugihara, Naoya Emoto
The efficacy of the administration of sodium-glucose co-transporter 2 inhibitor (SGLT2I) or the co-administration of SGLT2I and dipeptidyl peptidase-4 inhibitor (DPP-4I) to insulin therapy is not well known. Fifty-eight patients with type 2 diabetes, admitted for glycemic control, were randomized to basal-bolus insulin therapy (BBT) alone or BBT plus 50 mg ipragliflozin and/or 20 mg teneligliptin. Insulin doses were adjusted to maintain normal blood glucose levels. Plasma glucose profiles were estimated by continuous glucose monitoring (CGM) before discharge...
October 20, 2016: Journal of Diabetes Investigation
Jaeseong Oh, Andrew HyoungJin Kim, SeungHwan Lee, Hyunjeong Cho, Yon Su Kim, Mi Young Bahng, Seo Hyun Yoon, Joo-Youn Cho, In-Jin Jang, Kyung-Sang Yu
Evogliptin is a novel potent and selective dipeptidyl peptidase-IV (DPP-IV) inhibitor. This study aimed to evaluate the pharmacokinetic and pharmacodynamic characteristics of evogliptin in renal impairment (RI) subjects. An open-label, parallel-group clinical study was conducted on mild, moderate, and severe RI subjects and matched normal renal function (NRF) subjects. A single oral 5 mg dose of evogliptin was administered and serial blood and urine samples were obtained to assess the pharmacokinetic and pharmacodynamic characteristics of evogliptin...
October 20, 2016: Diabetes, Obesity & Metabolism
Gunter Laux, Sarah Berger, Joachim Szecsenyi, Petra Kaufmann-Kolle, Rüdiger Leutgeb
BACKGROUND: The objective of this study was to analyze prescription decisions for family practice (FP) patients with Diabetes mellitus type 2 (DM2) using the case of the incretin mimetics Dipeptidyl peptidase-4 (DDP-4) inhibitors and Glucagon-like peptide-1 (GLP-1) agonists dependent on patients' health insurance status (statutory or private) in Germany. This study is important since the scientific debate is still open with regard to DPP-4-inhibitors and GLP-1-agonists, where some critics are raising questions on potential long-term risks for patients...
October 19, 2016: BMC Family Practice
Mitsutoshi Asakura, Fumika Karaki, Hideaki Fujii, Koichiro Atsuda, Tomoo Itoh, Ryoichi Fujiwara
Vildagliptin is a potent, orally active inhibitor of dipeptidyl peptidase-4 (DPP-4) for the treatment of type 2 diabetes mellitus. It has been reported that vildagliptin can cause hepatic dysfunction in patients. However, the molecular-mechanism of vildagliptin-induced liver dysfunction has not been elucidated. In this study, we employed an expression microarray to determine hepatic genes that were highly regulated by vildagliptin in mice. We found that pro-inflammatory S100 calcium-binding protein (S100) a8 and S100a9 were induced more than 5-fold by vildagliptin in the mouse liver...
October 19, 2016: Scientific Reports
Dejan Agić, Hrvoje Brkić, Sanja Tomić, Zrinka Karačić, Marija Špoljarević, Miroslav Lisjak, Drago Bešlo, Marija Abramić
Fifteen flavonoids were studied for their inhibitory activity against human dipeptidyl peptidase III (hDPP III) combining an in vitro assay with an in silico molecular modeling study. All analyzed flavonoids showed inhibitory effects against hDPP III with the IC50 values ranging from 22.0 to 437.2 μM. Our 3D QSAR studies indicate that the presence of hydrophilic regions at a flavonoid molecule increases its inhibitory activity while the higher percentage of hydrophobic surfaces have negative impact on enzyme inhibition...
October 18, 2016: Chemical Biology & Drug Design
Peter Mertens
Remarkable progress has been achieved in the field of diabetes with the development of incretin analogues, dipeptidyl peptidase IV inhibitors and novel insulin analogues; nevertheless, there is an unmet need for additional therapeutic options. The new generation of drugs, denoted gliflozines, that specifically interfere with sodium-glucose cotransporters (SGLT)-2 and exhibit a favourable impact on glucose metabolism in patients with type 2 diabetes are emerging as hopeful avenues. The resultant negative energy balance caused by glucosuria results in long-term weight losses, significantly reduced HbA1c levels approximating 0...
September 2016: Journal of Hypertension
Peter Hoffmann, Lori Martin, Michael Keselica, Diane Gunson, Elizabeth Skuba, Dan Lapadula, Michael Hayes, Phil Bentley, Steve Busch
This article describes acute toxicity data in cynomolgus monkeys following oral treatment with vildagliptin, a dipeptidyl peptidase-4 inhibitor. Acute toxicity symptoms in cynomolgus monkeys include edema formation of the extremities, tails, and face associated with skeletal muscle necrosis, and elevations of lactate dehydrogenase, creatine kinase, alanine transaminase, and aspartate aminotransferase activities in the serum; hypothermia; hypotension; tachycardia; moribundity; and death in a few isolated instances...
October 17, 2016: Toxicologic Pathology
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...
October 14, 2016: Virology
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