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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/28442582/lx2761-a-sodium-glucose-cotransporter-1-inhibitor-restricted-to-the-intestine-improves-glycemic-control-in-mice
#1
David R Powell, Melinda G Smith, Deon D Doree, Angela L Harris, Jennifer Greer, Christopher M DaCosta, Andrea Thompson, Sabrina Jeter-Jones, Wendy Xiong, Kenneth G Carson, Nicole C Goodwin, Bryce A Harrison, David B Rawlins, Eric D Strobel, Suma Gopinathan, Alan Wilson, Faika Mseeh, Brian Zambrowicz, Zhi-Ming Ding
LX2761 is a potent sodium/glucose cotransporter 1 inhibitor restricted to the intestinal lumen after oral administration. Studies presented here evaluated the effect of orally administered LX2761 on glycemic control in preclinical models. In healthy mice and rats treated with LX2761, blood glucose excursions were lower and plasma total glucagon-like peptide-1 (GLP-1) levels higher after an oral glucose challenge; these decreased glucose excursions persisted even when the glucose challenge occurred 15 hours after LX2761 dosing in ad-lib-fed mice...
April 25, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28440488/dipeptidyl-peptidase%C3%A2-4-inhibitor-sitagliptin-prevents-high-glucose%C3%A2-induced-apoptosis-via-activation-of-amp%C3%A2-activated-protein-kinase-in-endothelial-cells
#2
Chao Wu, Shunying Hu, Nanping Wang, Jianwei Tian
Diabetes mellitus (DM), which is a chronic metabolic disorder, is the primary risk factor of life‑threatening vascular complications. Endothelial apoptosis is important in the development of the initial vascular lesion preceding the diabetic disease. Sitagliptin is a dipeptidyl peptidase‑4 (DPP‑4) inhibitor and extensively used in the clinical treatment of DM. DPP‑4 inhibitors have been demonstrated to be beneficial in the improvement of endothelial homeostasis, however the molecular mechanism by which they exhibit these effects remains to be elucidated...
April 21, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28440199/anti-hyperglycemic-agents-for-the-treatment-of-type-2-diabetes-mellitus-role-in-cardioprotection-during-the-last-decade
#3
Duygu Kocyigit, Kadri Murat Gurses, Muhammed Ulvi Yalcin, Lale Tokgozoglu
Type 2 diabetic patients are known to have a tendency to develop cardiovascular (CV) disease (CVD), and related unfavourable outcomes such as heart failure, myocardial infarction (MI), cerebrovascular events (eg. stroke), and related mortality. Long- term clinical trials have revealed contradictory findings regarding the relationship between glycemic control and CV benefits due to variations in the key characteristics of the study population. During the last decade, number of pharmacological agents used for glucose- lowering in the treatment of type 2 diabetes mellitus (T2DM) has increased owing to the introduction of dipeptidyl peptidase- IV (DPP- IV) inhibitors, glucagon- like peptide- 1 (GLP- 1) receptor agonists, and sodium-glucose co-transporter 2 (SGLT- 2) inhibitors...
April 23, 2017: Endocrine, Metabolic & Immune Disorders Drug Targets
https://www.readbyqxmd.com/read/28435305/glucagon-like-peptide-1-receptor-agonists-a-systematic-review-of-comparative-effectiveness-research
#4
REVIEW
Philip A Levin, Hiep Nguyen, Eric T Wittbrodt, Seoyoung C Kim
BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1RAs) act by increasing insulin secretion, decreasing glucagon secretion, slowing gastric emptying, and increasing satiety. OBJECTIVE: Published evidence directly comparing GLP-1RAs with other approved treatments for type 2 diabetes (T2D) was systematically reviewed. METHODS: A literature search was performed using MEDLINE and Embase databases to identify papers comparing GLP-1RAs with other classes of glucose-lowering therapy in patients with T2D...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28432752/incretin-based-glucose-lowering-medications-and-the-risk-for-acute-pancreatitis-and-or-pancreatic-cancer-risk-reassuring-data-from-cardio-vascular-outcome-trials
#5
Michael A Nauck, Juris J Meier, Wolfgang E Schmidt
Incretin-based medications (glucagon-like peptide-1 [GLP-1] receptor agonists and inhibitors of dipeptidyl peptidase-4 [DPP-4] are glucose-lowering drugs approved and introduced after 2006 (1). Although both classes of drugs appeared to be relatively safe based on results from clinical trials and standard animal toxicology studies, epidemiological data (2, 3) and histological findings (4) in genetically modified rodents exposed to such agents have raised concern that pancreatitis and pancreatic cancer may be long-term risks associated with this therapy...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28431666/glp-1-receptor-agonists-and-heart-failure-in-diabetes
#6
André J Scheen
The prevalence of heart failure (HF) is increasing in patients with type 2 diabetes (T2D), and glucose-lowering agents have distinctive effects on the risk of developing HF that requires hospitalization. Such an increased risk has been consistently reported with thiazolidinediones (glitazones) and perhaps also with the dipeptidyl peptidase (DPP)-4 inhibitor saxagliptin (at least in SAVOR - TIMI 53), whereas a markedly decreased risk was highlighted with the sodium - glucose cotransporter type 2 (SGLT2) inhibitor empagliflozin in EMPA-REG OUTCOME...
April 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28420715/role-of-soluble-and-membrane-bound-dipeptidylpeptidase-4-in-diabetic-nephropathy
#7
Ahmed A Hasan, Berthold Hocher
Diabetic nephropathy is one of the most frequent, devastating, and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might have in addition reno-protective properties. DPP-4 exists in two forms: a plasma membrane-bound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians...
April 18, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28420699/erratum-alogliptin-a-dipeptidyl-peptidase-4-inhibitor-prevents-the-progression-of-carotid-atherosclerosis-in-patients-with-type-2-diabetes-the-study-of-preventive-effects-of-alogliptin-on-diabetic-atherosclerosis-spead-a-diabetes-care-2016-39-139-148
#8
Tomoya Mita, Naoto Katakami, Hidenori Yoshii, Tomio Onuma, Hideaki Kaneto, Takeshi Osonoi, Toshihiko Shiraiwa, Keisuke Kosugi, Yutaka Umayahara, Tsunehiko Yamamoto, Hiroki Yokoyama, Nobuichi Kuribayashi, Hideaki Jinnouchi, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
No abstract text is available yet for this article.
April 18, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28420649/a-sandwich-elisa-for-measurement-of-the-primary-glucagon-like-peptide-1-metabolite
#9
Nicolai J Wewer Albrechtsen, Ali Asmar, Frederik Jensen, Signe Törang, Lene Simonsen, Rune E Kuhre, Meena Asmar, Simon Veedfald, Astrid Plamboeck, Filip K Knop, Tina Vilsboll, Sten Madsbad, Michael A Nauck, Carolyn F Deacon, Jens Bulow, Jens J Holst, Bolette Hartmann
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted from the gastrointestinal tract. It is best known for its glucose-dependent insulinotropic effects GLP-1 is secreted in its intact (active) form (7-36NH2) but is rapidly degraded by the dipeptidyl peptidase 4 (DPP-4) enzyme, converting >90% to the primary metabolite (9-36NH2) before reaching the targets via the circulation. Although originally thought to be inactive or antagonistic, GLP-1 9-36NH2 may have independent actions, and it is therefore relevant to be able to measure it...
April 18, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28418203/effectiveness-of-vildagliptin-as-add-on-to-metformin-monotherapy-among-uncontrolled-type-2-diabetes-mellitus-patients-in-a-real-world-setting
#10
Cheli Melzer Cohen, Carla Davis, Varda Shalev, Gabriel Chodick
BACKGROUND: Vildagliptin is a dipeptidyl peptidase-4 inhibitor (DPP4-i) commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized clinical trials but little evidence exists from observational studies. The aims of the present study were to evaluate the effectiveness of vildagliptin as an add-on therapy to metformin in reducing HbA1c as well as its influences on body weight and blood lipids in a real-life setting...
April 18, 2017: Journal of Diabetes
https://www.readbyqxmd.com/read/28411801/optimization-of-gold-nanoparticle-based-real-time-colorimetric-assay-of-dipeptidyl-peptidase-iv-activity
#11
Hasan Saad Aldewachi, Nicola Woodroofe, Simon Turega, Philip H E Gardiner
Dipeptidyl peptidase IV (DPP-IV also referred to as CD-26) is a serine protease enzyme with remarkable diagnostic and prognostic value in a variety of health and disease conditions. Herein, we describe a simple and real-time colorimetric assay for DPP-IV/CD-26 activity based on the aggregation of gold nanoparticles (AuNPs) functionalized with the peptide substrates: Gly-Pro-Asp-Cys (GPDC) or Val-Pro-ethylene diamine-Asp-Cys (VP-ED-DC). Cleavage of the substrates by DPP-IV resulted in aggregation of the AuNPs with accompanying color change in the solution from red to blue that was monitored using either a UV-visible spectrophotometer or by the naked eye...
July 1, 2017: Talanta
https://www.readbyqxmd.com/read/28408925/combination-therapy-with-a-sodium-glucose-cotransporter-2-inhibitor-and-a-dipeptidyl-peptidase-4-inhibitor-additively-suppresses-macrophage-foam-cell-formation-and-atherosclerosis-in-diabetic-mice
#12
Michishige Terasaki, Munenori Hiromura, Yusaku Mori, Kyoko Kohashi, Hideki Kushima, Makoto Ohara, Takuya Watanabe, Olov Andersson, Tsutomu Hirano
Dipeptidyl peptidase-4 inhibitors (DPP-4is), in addition to their antihyperglycemic roles, have antiatherosclerotic effects. We reported that sodium-glucose cotransporter 2 inhibitors (SGLT2is) suppress atherosclerosis in a glucose-dependent manner in diabetic mice. Here, we investigated the effects of combination therapy with SGLT2i and DPP-4i on atherosclerosis in diabetic mice. SGLT2i (ipragliflozin, 1.0 mg/kg/day) and DPP-4i (alogliptin, 8.0 mg/kg/day), either alone or in combination, were administered to db/db mice or streptozotocin-induced diabetic apolipoprotein E-null (Apoe(-/-) ) mice...
2017: International Journal of Endocrinology
https://www.readbyqxmd.com/read/28408838/dpp-4-inhibitor-treatment-%C3%AE-cell-response-but-not-hba1c-reduction-is-dependent-on-the-duration-of-diabetes
#13
Plamen Kozlovski, Vaishali Bhosekar, James E Foley
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by enhancing insulin and suppressing glucagon secretion. Since T2DM is associated with progressive loss of β-cell function, we hypothesized that the DPP-4 inhibitor action to improve β-cell function would be attenuated with longer duration of T2DM. METHODS: Data from six randomized, placebo-controlled trials of 24 weeks duration, where β-cell response to vildagliptin 50 mg twice daily was assessed, were pooled...
2017: Vascular Health and Risk Management
https://www.readbyqxmd.com/read/28406239/cmd-05-a-novel-promising-clinical-anti-diabetic-drug-candidate-in-vivo-and-vitro-studies
#14
Jie Ma, Huan Li, Xiangnan Hu, Lu Yang, Qi Chen, Congli Hu, Zhihao Chen, Xiaoyan Tian, Yang Yang, Ying Luo, Run Gan, Junqing Yang
Dipeptidyl peptidase IV (DPP-IV) inhibitor has been expected to be a new class of anti-diabetic agent. The present study was designed to characterize the pharmacological profiles of CMD-05, a novel DPP-IV inhibitor discovered in our laboratory, in vitro and in vivo. The IC50 of CMD-05 on DPP-IV inhibitory activity was approximately 12 nM while vildagliptin was 3.5 nM in vitro. In diabetes rat model established by high fat diet/low dose streptozotocin, CMD-05 inhibited DPP-IV activity, significantly improved glucose tolerance, increased GLP-1 and insulin levels in plasma...
April 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28403877/a-comparison-of-effects-of-dpp-4-inhibitor-and-sglt2-inhibitor-on-lipid-profile-in-patients-with-type-2-diabetes
#15
Seon-Ah Cha, Yong-Moon Park, Jae-Seung Yun, Tae-Seok Lim, Ki-Ho Song, Ki-Dong Yoo, Yu-Bae Ahn, Seung-Hyun Ko
BACKGROUND: Previous studies suggest that dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium glucose cotransporter 2 (SGLT2) inhibitors have different effects on the lipid profile in patients with type 2 diabetes. We investigated the effects of DPP-4 inhibitors and SGLT2 inhibitors on the lipid profile in patients with type 2 diabetes. METHODS: From January 2013 to December 2015, a total of 228 patients with type 2 diabetes who were receiving a DPP-4 inhibitor or SGLT2 inhibitor as add-on therapy to metformin and/or a sulfonylurea were consecutively enrolled...
April 13, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28403729/cost-effectiveness-of-vildagliptin-for-people-with-type-2-diabetes-mellitus-in-brazil-findings-and-implications
#16
REVIEW
Gustavo Laine Araujo De Oliveira, Augusto Afonso Guerra Júnior, Brian Godman, Francisco de Assis Acurcio
Vildagliptin is an inhibitor of the enzyme dipeptidyl peptidase 4, indicated for the treatment of type 2 diabetes mellitus, combined or not with metformin. This study aims to evaluate the cost-effectiveness of vildagliptin in the Brazilian context. Areas covered: Using MEDLINE, Cochrane Library, Lilacs and CRD, six studies were selected for the economic models. This study utilised cost data in the Brazilian health system to provide the context. Expert commentary: Type 2 diabetes mellitus is an epidemic disease and represents a challenge for all health care systems...
April 2017: Expert Review of Pharmacoeconomics & Outcomes Research
https://www.readbyqxmd.com/read/28402902/cardiovascular-outcome-studies-with-incretin-based-therapies-comparison-between-dpp-4-inhibitors-and-glp-1-receptor-agonists
#17
REVIEW
André J Scheen
Dipeptidyl peptidase-4 inhibitors (DPP-4is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent two distinct classes of incretin-based therapies used for the treatment of type 2 diabetes. Non-inferiority versus placebo was shown in large prospective cardiovascular outcome trials in patients with high cardiovascular risk: SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), and TECOS (sitagliptin); ELIXA (lixisenatide), LEADER (liraglutide) and SUSTAIN 6 (semaglutide). The promises raised by meta-analyses of phase 2-3 trials with DPP-4is were non confirmed as no cardiovascular protection could be evidenced...
March 25, 2017: Diabetes Research and Clinical Practice
https://www.readbyqxmd.com/read/28402172/rational-design-and-synthesis-of-affinity-matrices-based-on-proteases-immobilized-onto-cellulose-membranes
#18
Alberto Del Monte-Martínez, Jorge González-Bacerio, Bessy Cutiño-Avila, Jorge Rojas, Mae Chappé, Emir Salas-Sarduy, Isel Pascual, José M Guisán
Discovery of new protease inhibitors may result in potential therapeutic agents or useful biotechnological tools. Obtainment of these molecules from natural sources requires simple, economic and highly efficient purification protocols. The aim of this work was the obtainment of affinity matrices by the covalent immobilization of dipeptidyl peptidase IV (DPP-IV) and papain onto cellulose membranes, previously activated with formyl (FCM) or glyoxyl groups (GCM). GCM showed the highest activation grade (10.2 µmol aldehyde/cm(2))...
April 12, 2017: Preparative Biochemistry & Biotechnology
https://www.readbyqxmd.com/read/28397367/continuous-glucose-monitoring-reveals-hypoglycemia-risk-in-elderly-patients-with-type-2-diabetes-mellitus
#19
Takahiro Ishikawa, Masaya Koshizaka, Yoshiro Maezawa, Minoru Takemoto, Yoshiharu Tokuyama, Toshihiro Saito, Koutaro Yokote
INTRODUCTION: The incidence of type 2 diabetes is higher in elderly patients, in whom this disease is associated with dementia, falling, stroke, and death. We utilized a continuous glucose monitoring (CGM) device to analyze the relationship between hypoglycemia and diabetes treatments to identify risk factors for hypoglycemia (defined as a blood glucose level <70 mg/dL). MATERIALS AND METHODS: We classified 170 patients aged ≥65 years with type 2 diabetes who were receiving steady-state medication (29 of whom were inpatients) into hypoglycemic and non-hypoglycemic groups, and compared their HbA1c levels, treatment types, continuous glucose monitoring data, and other parameters...
April 11, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28393419/synthesis-and-evaluation-of-novel-1-2-4-triazolo-5-1-c-1-2-4-triazines-and-pyrazolo-5-1-c-1-2-4-triazines-as-potential-antidiabetic-agents
#20
Vladimir L Rusinov, Irina M Sapozhnikova, Anastasiya M Bliznik, Oleg N Chupakhin, Valery N Charushin, Alexander A Spasov, Pavel M Vassiliev, Valentina A Kuznetsova, Andrey I Rashchenko, Denis A Babkov
Inhibition of the dipeptidyl peptidase-4 (DPP4) enzyme activity and prevention of advanced glycation end (AGE) products formation represents a reliable approach to achieve control over hyperglycemia and the associated pathogenesis of diabetic vascular complications. In the frames of this research study, several triazolo- and pyrazolotriazines were synthesized and evaluated as inhibitors of AGE products formation, DPP4, glycogen phosphorylase and α-glucosidase activities, as well as AGE cross-link breakers...
April 10, 2017: Archiv der Pharmazie
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