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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/28938487/regulation-of-endogenous-male-rodent-glp-1-secretion-and-human-islet-insulin-secretion-by-antagonism-of-somatostatin-receptor-5
#1
Thomas B Farb, Marta Adeva, Thomas J Beauchamp, Over Cabrera, David A Coates, Tamika DeShea Meredith, Brian A Droz, Alexander Efanov, James V Ficorilli, Susan L Gackenheimer, Maria A Martinez-Grau, Victoriano Molero, Gema Ruano, Michael A Statnick, Todd M Suter, Samreen K Syed, Miguel A Toledo, Francis S Willard, Xin Zhou, Krister B Bokvist, David G Barrett
Incretin and insulin responses to nutrient loads are suppressed in persons with diabetes, resulting in decreased glycemic control. Whereas agents including sulfonylureas and Dipeptidyl peptidase-4 inhibitors (DPP4i) partially reverse these effects and provide therapeutic benefit, their modes of action limit efficacy. Because somatostatin (SST) has been shown to suppress both insulin and GLP-1 secretion through the Gi-coupled SST receptor 5 (SSTR5) isoform in vitro, antagonism of SSTR5 may improve glycemic control via intervention in both pathways...
September 11, 2017: Endocrinology
https://www.readbyqxmd.com/read/28934557/a-safety-evaluation-of-empagliflozin-plus-linagliptin-for-treating-type-2-diabetes
#2
Baptist Gallwitz
Dipeptidyl-peptidase-IV inhibitors (DPP-4i) and sodium-glucose-transporter-2 inhibitors (SGLT-2i) are oral antidiabetic drugs that improve glycemic parameters and possess a very low intrinsic hypoglycemia risk and favorable cardiovascular data. Areas covered: An overview on the clinical studies investigating the combination therapy with the DPP-4i linagliptin and the SGLT-2i empagliflozin is given. The clinical evidence for the efficacy and safety of free combinations as well as for their fixed dose combinations is presented...
September 21, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28933039/dose-dependent-effect-of-sitagliptin-on-carotid-atherosclerosis-in-patients-with-type-2-diabetes-mellitus-receiving-insulin-treatment-a-post-hoc-analysis
#3
Tomoya Mita, Naoto Katakami, Toshihiko Shiraiwa, Hidenori Yoshii, Masahiko Gosho, Iichiro Shimomura, Hirotaka Watada
INTRODUCTION: Dipeptidyl peptidase-4 (DPP-4) inhibitors reduce blood glucose in a dose-dependent manner, but the dose-dependent effect relationship between DPP-4 inhibitors and atherosclerosis has not been investigated. METHODS: Patients with type 2 diabetes mellitus (T2DM) treated with insulin were randomized to the sitagliptin (n = 137) or conventional treatment group (n = 137). In the sitagliptin group, each investigator was allowed to adjust the sitagliptin dose to avoid hypoglycemia...
September 20, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28932239/computational-analysis-of-gynura-bicolor-bioactive-compounds-as-dipeptidyl-peptidase-iv-inhibitor
#4
Lina Rozano, Muhammad Redha Abdullah Zawawi, Muhamad Aizuddin Ahmad, Indu Bala Jaganath
The inhibition of dipeptidyl peptidase-IV (DPPIV) is a popular route for the treatment of type-2 diabetes. Commercially available gliptin-based drugs such as sitagliptin, anagliptin, linagliptin, saxagliptin, and alogliptin were specifically developed as DPPIV inhibitors for diabetic patients. The use of Gynura bicolor in treating diabetes had been reported in various in vitro experiments. However, an understanding of the inhibitory actions of G. bicolor bioactive compounds on DPPIV is still lacking and this may provide crucial information for the development of more potent and natural sources of DPPIV inhibitors...
2017: Advances in Bioinformatics
https://www.readbyqxmd.com/read/28931178/the-oral-dipeptidyl-peptidase-4-inhibitor-sitagliptin-increases-circulating-levels-of-stromal-derived-factor-1-alpha
#5
Athanasia K Papazafiropoulou, Nikolaos Papanas, Aikaterini Trikkalinou, Evaggelos Fousteris, Andreas Melidonis
Recent studies have demonstrated that stromal derived factor-1α (SDF-1α) is a substrate of dipeptidyl-peptidase-4 (DPP-4) inhibitors. It has also been shown that SDF-1α shares anti-apoptotic as well as nephroprotective properties and exerts a beneficial effect in the cardiovascular system. Therefore, the aim of this study was to estimate the effect of treatment with the DDP-4 inhibitor sitagliptin on SDF-1α levels in subjects with type 2 diabetes mellitus (T2D). Overall, 32 patients (16 males) with T2D, mean age (±SD) 67...
September 20, 2017: Experimental and Clinical Endocrinology & Diabetes
https://www.readbyqxmd.com/read/28929327/possible-long-term-efficacy-of-sitagliptin-a-dipeptidyl-peptidase-4-inhibitor-for-slowly-progressive-type-1-diabetes-spiddm-in-the-stage-of-non-insulin-dependency-an-open-label-randomized-controlled-pilot-trial-span-s
#6
Takuya Awata, Akira Shimada, Taro Maruyama, Yoichi Oikawa, Nobuyuki Yasukawa, Susumu Kurihara, Yumi Miyashita, Masako Hatano, Yuichi Ikegami, Masafumi Matsuda, Masataka Niwa, Youichiro Kazama, Shoichiro Tanaka, Tetsuro Kobayashi
INTRODUCTION: We tested the hypothesis that dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in preserving the β-cell function for long-term periods in patients with slowly progressive type 1 diabetes (SPIDDM) or latent autoimmune diabetes in adults (LADA). METHODS: In the present open-label, randomized, controlled trial, 14 non-insulin-requiring diabetic patients with glutamic acid decarboxylase autoantibodies (GADAb) were randomly assigned to receive either sitagliptin (S group) or pioglitazone (P group)...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28929319/a-practical-approach-to-hypertension-management-in-diabetes
#7
REVIEW
Altamash Shaikh
Hypertension is one of the most important comorbidities of diabetes, contributing significantly to death and disability and leads to macrovascular and microvascular complications. When assessing the medical priorities for patients with diabetes, treating hypertension should be a primary consideration. Practical approaches to hypertension in diabetes, including individualized targets are discussed, as per stage and complication of diabetes, according to current studies and guidelines. Angiotensin converting enzyme inhibitors (ACEI)/angiotensin receptor blockers (ARBs) are the most effective drugs for treating hypertension in diabetes, in the absence of contraindications...
September 19, 2017: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
https://www.readbyqxmd.com/read/28923942/identification-of-sialic-acid-binding-function-for-the-middle-east-respiratory-syndrome-coronavirus-spike-glycoprotein
#8
Wentao Li, Ruben J G Hulswit, Ivy Widjaja, V Stalin Raj, Ryan McBride, Wenjie Peng, W Widagdo, M Alejandra Tortorici, Brenda van Dieren, Yifei Lang, Jan W M van Lent, James C Paulson, Cornelis A M de Haan, Raoul J de Groot, Frank J M van Kuppeveld, Bart L Haagmans, Berend-Jan Bosch
Middle East respiratory syndrome coronavirus (MERS-CoV) targets the epithelial cells of the respiratory tract both in humans and in its natural host, the dromedary camel. Virion attachment to host cells is mediated by 20-nm-long homotrimers of spike envelope protein S. The N-terminal subunit of each S protomer, called S1, folds into four distinct domains designated S1(A) through S1(D) Binding of MERS-CoV to the cell surface entry receptor dipeptidyl peptidase 4 (DPP4) occurs via S1(B) We now demonstrate that in addition to DPP4, MERS-CoV binds to sialic acid (Sia)...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923291/use-of-prohibited-medication-a-potentially-overlooked-confounder-in-clinical-trials-omarigliptin-once-weekly-dpp-4-inhibitor-monotherapy-trial-in-18-to-45-year-olds
#9
Ira Gantz, Liubov Sokolova, Lokesh Jain, Carol Iredale, Edward A O'Neill, Ziwen Wei, Raymond Lam, Shailaja Suryawanshi, Keith D Kaufman, Samuel S Engel, Eseng Lai
PURPOSE: The objective of this clinical trial was to assess the efficacy and safety of omarigliptin monotherapy in young adult patients with type 2 diabetes mellitus (T2DM). Unexpected efficacy results in this trial led to a series of investigations that identified the use of prohibited medication by a substantial number of trial patients. METHODS: Patients with T2DM who were ≥18 to <45 years of age and either drug-naive or not on an antihyperglycemic agent for ≥12 weeks with inadequate glycemic control were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 102) or placebo once weekly (n = 101) for 24 weeks...
September 15, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28923269/dpp-4-inhibition-protects-human-umbilical-vein-endothelial-cells-from-hypoxia-induced-vascular-barrier-impairment
#10
Naoko Hashimoto, Kento Ikuma, Yui Konno, Masanori Hirose, Hiroyuki Tadokoro, Hiroshi Hasegawa, Yoshio Kobayashi, Hiroyuki Takano
Dipeptidyl peptidase-4 (DPP-4) inhibitors are relatively new class of anti-diabetic drugs. Some protective effects of DPP-4 on cardiovascular disease have been described independently from glucose-lowering effect. However, the detailed mechanisms by which DPP-4 inhibitors exert on endothelial cells remain elusive. The purpose of this research was to determine the effects of DPP-4 inhibitor on endothelial barrier function. Human umbilical vein endothelial cells (HUVECs) were cultured and exposed to hypoxia in the presence or absence of Diprotin A, a DPP-4 inhibitor...
August 26, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/28921919/oral-glucose-lowering-with-linagliptin-and-metformin-compared-with-linagliptin-alone-as-initial-treatment-in-asian-patients-with-newly-diagnosed-type-2-diabetes-and-marked-hyperglycemia-subgroup-analysis-of-a-randomized-clinical-trial
#11
Ronald Cw Ma, Stefano Del Prato, Baptist Gallwitz, Vyankatesh K Shivane, Diane Lewis-D'Agostino, Zelie Bailes, Sanjay Patel, Jisoo Lee, Maximilian von Eynatten, Maximiliano Di Domenico, Stuart A Ross
AIMS/INTRODUCTION: Type 2 diabetes mellitus (T2DM) is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enrol predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed T2DM patients in Asia with marked hyperglycemia. MATERIALS AND METHODS: This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed T2DM patients with glycated hemoglobin A1c (HbA1c) 8...
September 16, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28916574/systematic-review-of-the-gastrointestinal-effects-of-a1-compared-with-a2-%C3%AE-casein
#12
REVIEW
Simon Brooke-Taylor, Karen Dwyer, Keith Woodford, Natalya Kost
This is the first systematic review, to our knowledge, of published studies investigating the gastrointestinal effects of A1-type bovine β-casein (A1) compared with A2-type bovine β-casein (A2). The review is relevant to nutrition practice given the increasing availability and promotion in a range of countries of dairy products free of A1 for both infant and adult nutrition. In vitro and in vivo studies (all species) were included. In vivo studies were limited to oral consumption. Inclusion criteria encompassed all English-language primary research studies, but not reviews, involving milk, fresh-milk products, β-casein, and β-casomorphins published through 12 April 2017...
September 2017: Advances in Nutrition
https://www.readbyqxmd.com/read/28915418/purification-identification-and-molecular-mechanism-of-two-dipeptidyl-peptidase-iv-dpp-iv-inhibitory-peptides-from-antarctic-krill-euphausia-superba-protein-hydrolysate
#13
Wei Ji, Chaohua Zhang, Hongwu Ji
Dipeptidyl peptidase IV (DPP-IV) played an important role in blood glucose regulation. Inhibition of DPP-IV may improve glycemic control in diabetics by preventing the rapid breakdown of incretin hormones and prolonging their physiological action. In this study, Antarctic krill (Euphausia superba) protein was hydrolyzed using animal proteolytic enzymes. The hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and reversed phase high-performance liquid chromatography (RP-HPLC)...
September 5, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28912645/anti-inflammatory-effect-of-glucagon-like-peptide-1-receptor-agonist-exendin-4-through-modulation-of-ib1-jip1-expression-and-jnk-signaling-in-stroke
#14
Soojin Kim, Jaewon Jeong, Hye-Seon Jung, Bokyung Kim, Ye-Eun Kim, Da-Sol Lim, So-Dam Kim, Yun Seon Song
Glucagon like peptide-1 (GLP-1) stimulates glucose-dependent insulin secretion. Dipeptidyl peptidase-4 (DPP-4) inhibitors, which block inactivation of GLP-1, are currently in clinical use for type 2 diabetes mellitus. Recently, GLP-1 has also been reported to have neuroprotective effects in cases of cerebral ischemia. We therefore investigated the neuroprotective effects of GLP-1 receptor (GLP-1R) agonist, exendin-4 (ex-4), after cerebral ischemia-reperfusion injury. Transient middle cerebral artery occlusion (tMCAO) was induced in rats by intracerebroventricular (i...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28899989/dipeptidyl-peptidase-4-inhibitors-and-risk-of-heart-failure-in-patients-with-type-2-diabetes-mellitus-a-population-based-cohort-study
#15
Young-Gun Kim, Dukyong Yoon, Sooyoung Park, Seung Jin Han, Dae Jung Kim, Kwan-Woo Lee, Rae Woong Park, Hae Jin Kim
BACKGROUND: The association between dipeptidyl-peptidase IV inhibitors (DPP-4i) and heart failure (HF) remains unclear. In 1 randomized controlled trial and some observational studies, DPP-4i reportedly increased the risk of HF, but 2 other randomized controlled trials and observational studies have shown no such risk. Here, we evaluated the risk of HF and cardiovascular outcomes of DPP-4i compared with sulfonylureas. METHODS AND RESULTS: A population-based retrospective cohort study was conducted using the Korean Health Insurance Review and Assessment Service database from January 1, 2009, to December 31, 2015...
September 2017: Circulation. Heart Failure
https://www.readbyqxmd.com/read/28895067/a-gc-ms-untargeted-metabolomics-analysis-in-the-plasma-and-liver-of-rats-lacking-dipeptidyl-peptidase-type-iv-enzyme-activity
#16
Antonio Murgia, Pierluigi Caboni, Erika Cadoni, Monica Serra, Fabio Marongiu, Ezio Laconi
This study was achieved with the aim to find metabolic changes between Fischer rats with different dipeptidyl peptidase-type 4 (DPPIV) expression. The DPPIV is an enzyme expressed in several tissues and is critically involved in the regulation of meal-related insulin secretion in healthy individuals. The metabolic consequences of chronic DPPIV inhibition were analyzed in a surrogate animal model of genetic enzyme deficiency. Hyphenated gas chromatography-mass spectrometry (GC-MS) and multivariate data analysis techniques were used to study the metabolic aqueous fraction profile of 18 plasma and liver samples in two syngeneic rat strains differing in DPPIV activity (DPPIV(+) vs...
September 11, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28895030/type-2-diabetes-and-cardiovascular-prevention-the-dogmas-disputed
#17
Dario Giugliano, Maria Ida Maiorino, Giuseppe Bellastella, Katherine Esposito
In randomized controlled trials (RCTs), more intensive glucose control in patients with type 2 diabetes leads to a modest (9%) reduction in major cardiovascular events (MACE), associated with a 20% reduction of kidney events and 13% reduction of eye events. The FDA issued guidance in 2008 led to the conduct of numerous cardiovascular outcomes (CVOT) trials to assess cardiovascular safety of new antihyperglycemic therapies in patients with type 2 diabetes. The results of these trials show that insulin glargine, three different dipeptidyl peptidase-4 (DPP-4) inhibitors (saxagliptin, alogliptin, and sitagliptin) and lixisenatide (a glucagon like peptide-1 receptor agonist) produce no significant difference in CVOT when compared with usual care or placebo...
September 11, 2017: Endocrine
https://www.readbyqxmd.com/read/28894748/new-antihyperglycemic-drugs-and-heart-failure-synopsis-of-basic-and-clinical-data
#18
REVIEW
Dirk von Lewinski, Ewald Kolesnik, Markus Wallner, Michael Resl, Harald Sourij
The assessment of the cardiovascular safety profile of any newly developed antihyperglycemic drug is mandatory before registration, as a meta-analysis raised alarm describing a significant increase in myocardial infarction with the thiazolidinedione rosiglitazone. The first results from completed cardiovascular outcome trials are already available: TECOS, SAVOR-TIMI, and EXAMINE investigated dipeptidyl peptidase 4 (DPP-4) inhibitors, ELIXA, LEADER, and SUSTAIN-6 investigated glucagon-like peptide 1 (GLP-1) receptor agonists, and EMPA-REG OUTCOME and CANVAS investigated sodium-dependent glucose transporter 2 (SGLT-2) inhibitors...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28894474/a-novel-dynamic-model-describing-the-spread-of-the-mers-cov-and-the-expression-of-dipeptidyl-peptidase-4
#19
Siming Tang, Wanbiao Ma, Peifan Bai
The Middle East respiratory syndrome (MERS) coronavirus, a newly identified pathogen, causes severe pneumonia in humans. MERS is caused by a coronavirus known as MERS-CoV, which attacks the respiratory system. The recently defined receptor for MERS-CoV, dipeptidyl peptidase 4 (DPP4), is generally expressed in endothelial and epithelial cells and has been shown to be present on cultured human nonciliated bronchiolar epithelium cells. In this paper, a class of novel four-dimensional dynamic model describing the infection of MERS-CoV is given, and then global stability of the equilibria of the model is discussed...
2017: Computational and Mathematical Methods in Medicine
https://www.readbyqxmd.com/read/28891142/network-meta-analysis-of-lorcaserin-and-oral-hypoglycaemics-for-patients-with-type-2-diabetes-mellitus-and-obesity
#20
L M Neff, M S Broder, D Beenhouwer, E Chang, E Papoyan, Z W Wang
In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments...
September 10, 2017: Clinical Obesity
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