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Dipeptidyl peptidase

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https://www.readbyqxmd.com/read/28109184/comparative-cardiovascular-risks-of-dipeptidyl-peptidase-4-inhibitors-with-other-2-nd-and-3-rd-line-antidiabetic-drugs-in-patients-with-type-2-diabetes
#1
Huang-Tz Ou, Kai-Cheng Chang, Chung-Yi Li, Jin-Shang Wu
AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4i) are suggested as 2(nd) and 3(rd) add-on antidiabetic treatment for type 2 diabetes. Previous studies only assessed cardiovascular effects of DPP4i as 2(nd) line treatment, included sulfonylurea as only one comparator, and yielded inconclusive results on the risk of heart failure. This study therefore evaluated comparative cardiovascular risks of DPP4i with other 2(nd) and 3(rd) line antidiabetic drugs. METHODS: Based on a large nation-wide diabetic cohort, 113,051 patients with type 2 diabetes newly on metformin-based dual or triple therapy were identified in 2009-2011 and followed until death or 2013...
January 21, 2017: British Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28106217/flavanol-concentrations-do-not-predict-dipeptidyl-peptidase-iv-inhibitory-activities-of-four-cocoas-with-different-processing-histories
#2
Caroline M Ryan, Weslie Khoo, Amanda C Stewart, Sean F O'Keefe, Joshua D Lambert, Andrew P Neilson
Cocoa and its constituent bioactives (particularly flavanols) have reported anti-diabetic and anti-obesity activities. One potential mechanism of action is inhibition of dipeptidyl peptidase-IV (DPP4), the enzyme that inactivates incretin hormones such as glucagon-like peptide-1 and gastric inhibitory peptide. The objective of this study was to determine the DPP4 inhibitory activities of cocoas with different processing histories, and identify processing factors and bioactive compounds that predict DPP4 inhibition...
January 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28102710/development-and-validation-of-a-uplc-ms-ms-method-for-simultaneous-determination-of-fotagliptin-and-its-two-major-metabolites-in-human-plasma-and-urine
#3
Zhenlei Wang, Ji Jiang, Pei Hu, Qian Zhao
AIM: Fotagliptin is a novel dipeptidyl peptidase IV inhibitor under clinical development for the treatment of Type II diabetes mellitus. The objective of this study was to develop and validate a specific and sensitive ultra-performance liquid chromatography (UPLC)-MS/MS method for simultaneous determination of fotagliptin and its two major metabolites in human plasma and urine. Methodology & results: After being pretreated using an automatized procedure, the plasma and urine samples were separated and detected using a UPLC-ESI-MS/MS method, which was validated following the international guidelines...
January 19, 2017: Bioanalysis
https://www.readbyqxmd.com/read/28098291/investigation-into-the-bioavailability-of-milk-protein-derived-peptides-with-dipeptidyl-peptidase-iv-inhibitory-activity-using-caco-2-cell-monolayers
#4
Isabelle M E Lacroix, Xiu-Min Chen, David D Kitts, Eunice C Y Li-Chan
In recent years, peptides derived from a variety of dietary proteins have been reported to exhibit inhibitory activity against the dipeptidyl-peptidase IV (DPP-IV) enzyme, a target in the management of type 2 diabetes. While much attention has been given to the production and identification of peptides with DPP-IV inhibitory activity from food proteins, particularly dairy proteins, little is known on the bioavailability of these molecules. In this study, the stability and transport of five previously identified milk-derived peptides (LKPTPEGDL, LPYPY, IPIQY, IPI and WR) and a whey protein isolate (WPI) digest with DPP-IV-inhibitory activity were investigated using Caco-2 cell monolayers as a model system for human intestinal absorption...
January 18, 2017: Food & Function
https://www.readbyqxmd.com/read/28094469/immunohistochemical-assessment-of-glucagon-like-peptide-1-receptor-glp-1r-expression-in-the-pancreas-of-patients-with-type-2-diabetes
#5
Rikke Kaae Kirk, Charles Pyke, Matthias G von Herrath, Jane Preuss Hasselby, Lars Pedersen, Pia Gottrup Mortensen, Lotte Bjerre Knudsen, Ken Coppieters
Glucagon-like peptide-1 (GLP-1) is an incretin hormone which stimulates insulin release and inhibits glucagon secretion from the pancreas in a glucose-dependent manner. Incretin-based therapies, consisting of GLP-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are used for the treatment of T2D. Immunohistochemical studies for GLP-1R expression have previously been hampered by the use of unspecific polyclonal antibodies. This study used a new monoclonal antibody to assess GLP-1R expression in pancreatic tissue from 23 patients with T2D, including 7 with a DPP-4 inhibitor and 1 with a GLP-1R agonist treatment history...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28093996/challenges-related-to-glycemic-control-in-type-2-diabetes-mellitus-patients
#6
Masoumeh Kheirandish, Hamidreza Mahboobi, Maryam Yazdanparast, Mohammad Amjad Kamal
Diabetes mellitus (DM) is a chronic disease with long-term complications. Glycemic control is an important part in management of DM. The first line in treatment of type 2 DM (T2DM) is diet and life style change. Metformin is the first choice of medication in T2DM patients. Sulfonylureas have high risk of hypoglycemia. Glinides are associated with lower risk of hypoglycemia in comparison to sulfonylureas. Also α-glucosidase inhibitors decrease the polysacarides digestion in small intestine and less effective in comparison to metformin and sulfonylureas in lowering hemoglobin A1c (HbA1c)...
January 15, 2017: Current Drug Metabolism
https://www.readbyqxmd.com/read/28093853/randomized-clinical-trial-comparing-the-efficacy-and-safety-of-treatment-with-the-once-weekly-dipeptidyl-peptidase-4-dpp-4-inhibitor-omarigliptin-or-the-once-daily-dpp-4-inhibitor-sitagliptin-in-patients-with-type-2-diabetes-inadequately-controlled-on-metformin
#7
Ronald Goldenberg, Ira Gantz, Paula J Andryuk, Edward A O'Neill, Keith D Kaufman, Eseng Lai, Yin Na Wang, Shailaja Suryawanshi, Samuel S Engel
AIM: To compare the efficacy and safety of the once-weekly oral dipeptidyl peptidase-4 (DPP-4) inhibitor omarigliptin or once-daily DPP-4 inhibitor sitagliptin in patients with type 2 diabetes (T2DM) and inadequate glycaemic control on metformin. MATERIALS AND METHODS: Patients with T2DM with a glycated haemoglobin (HbA1c) concentration ≥6.5% to ≤9.0% while on a stable dose of metformin (≥1500 mg/d) were randomized in a double-blind manner to receive omarigliptin 25 mg once weekly (n = 322) or sitagliptin 100 mg once daily (n = 320)...
January 17, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28093794/design-synthesis-and-biological-evaluation-of-novel-quinazoline-clubbed-thiazoline-derivatives
#8
Zulphikar Ali, Md J Akhtar, Anees A Siddiqui, Ahsan A Khan, Md R Haider, Mohammad S Yar
A novel series of quinazoline clubbed thiazoline derivatives was rationally designed and synthesized. The newly synthesized compounds were evaluated for in vitro dipeptidyl peptidase IV (DPP-4) inhibitory activity. Compounds that showed good to moderate activity were compared using linagliptin as standard. Compound 4x (IC50  = 1.12 nM) exhibited the most promising results. The special chemical feature of compound 4x also imparts good inhibition selectivity for DPP-4 over DPP-8/9. Moreover, docking of compound 4x into the active site of DPP-4 illustrates its possible binding interactions...
January 17, 2017: Archiv der Pharmazie
https://www.readbyqxmd.com/read/28091829/inhibition-of-dpp-4-activity-and-neuronal-atrophy-with-genistein-attenuates-neurological-deficits-induced-by-transient-global-cerebral-ischemia-and-reperfusion-in-streptozotocin-induced-diabetic-mice
#9
Mithun Singh Rajput, Purnima Dey Sarkar, Nilesh Prakash Nirmal
Genistein, an isoflavonoid phytoestrogen, has been known for its potential pharmacological properties especially for neuroprotection and treating diabetes. The present study aims to determine the neuroprotective efficacy of genistein against global cerebral ischemia-reperfusion-induced neuronal injury in streptozotocin-induced diabetic mice and explore the underlying mechanisms. Streptozotocin-induced diabetic mice were subjected to transient cerebral ischemia by occluding both common carotid arteries for 30 min followed by 24 h reperfusion to induce neuronal injury...
January 16, 2017: Inflammation
https://www.readbyqxmd.com/read/28088007/impairment-of-host-liver-repopulation-by-transplanted-hepatocytes-in-aged-rats-and-the-release-by-short-term-growth-hormone-treatment
#10
Peggy Stock, Maximilian Bielohuby, Martin S Staege, Mei-Ju Hsu, Martin Bidlingmaier, Bruno Christ
Hepatocyte transplantation is an alternative to whole liver transplantation. Yet, efficient liver repopulation by transplanted hepatocytes is low in livers of old animals. This restraint might be because of the poor proliferative capacity of aged donor hepatocytes or the regenerative impairment of the recipient livers. The age-dependent liver repopulation by transplanted wild-type hepatocytes was investigated in juvenile and senescent rats deficient in dipeptidyl-peptidase IV. Repopulation was quantified by flow cytometry and histochemical estimation of dipeptidyl-peptidase IV enzyme activity of donor cells in the negative host liver...
January 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28087908/-berberine-regulates-glycemia-via-local-inhibition-of-intestinal-dipeptidyl-peptidase-%C3%A2
#11
Jiesheng Wang, Guanhai Dai, Weijia Li
Objective: To investigate the effect of berberine on glycemia regulation in rats with diabetes and the related mechanisms. Methods: Diabetic-like rat model was successfully induced by intraperitoneal injection of streptozotocin in 50 out of 60 male SD rats, which were then randomly divided into 5 groups with 10 rats in each:control group (received vehicle only), positive drug control group (sitagliptin 10 mg·kg(-1)·d(-1)), low-dose berberine group (30 mg·kg(-1)·d(-1)), moderate-dose berberine group (60 mg·kg(-1)·d(-1)), and high-dose berberine group (120 mg·kg(-1)·d(-1))...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28086872/dapagliflozin-decreases-small-dense-low-density-lipoprotein-cholesterol-and-increases-high-density-lipoprotein-2-cholesterol-in-patients-with-type-2-diabetes-comparison-with-sitagliptin
#12
Toshiyuki Hayashi, Tomoyasu Fukui, Noriko Nakanishi, Saki Yamamoto, Masako Tomoyasu, Anna Osamura, Makoto Ohara, Takeshi Yamamoto, Yasuki Ito, Tsutomu Hirano
BACKGROUND: The sodium-glucose co-transporter-2 (SGLT-2) inhibitors have been reported to increase both low-density lipoprotein (LDL) and high-density lipoprotein (HDL)-cholesterol (C). This study aimed to determine how SGLT-2 inhibitors affect LDL and HDL-C subspecies. METHODS: This single center, open-label, randomized, prospective study included 80 patients with type 2 diabetes taking prescribed oral hypoglycemic agents. Patients were allocated to receive dapagliflozin (n = 40) or sitagliptin (n = 40) as add-on treatment...
January 13, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28078647/sitagliptin-a-review-in-type-2-diabetes
#13
Lesley J Scott
The dipeptidyl peptidase-4 inhibitor sitagliptin (Januvia(®); Glactiv(®); Tesavel(®); Xelevia™) is approved in more than 130 countries worldwide as monotherapy and in combination with other antihyperglycaemic drugs for the treatment of adult patients with type 2 diabetes (T2D). Extensive clinical experience has firmly established the glycaemic efficacy of oral sitagliptin (±other antihyperglycaemic drugs) in a broad spectrum of patients with T2D, including obese, elderly and renally impaired patients and those with established cardiovascular (CV) disease (CVD)...
January 11, 2017: Drugs
https://www.readbyqxmd.com/read/28077733/identification-of-potential-plasma-biomarkers-for-nonalcoholic-fatty-liver-disease-by-integrating-transcriptomics-and-proteomics-in-laying-hens
#14
Meng-Tsz Tsai, Yu-Jen Chen, Ching-Yi Chen, Mong-Hsun Tsai, Chia-Li Han, Yu-Ju Chen, Harry J Mersmann, Shih-Torng Ding
BACKGROUND: Prevalent worldwide obesity is associated with increased incidence of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. The identification of noninvasive biomarkers for NAFLD is of recent interest. Because primary de novo lipogenesis occurs in chicken liver as in human liver, adult chickens with age-associated steatosis resembling human NAFLD is an appealing animal model. OBJECTIVE: The objective of this study was to screen potential biomarkers in the chicken model for NAFLD by transcriptomic and proteomic analysis...
January 11, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28073873/recurrent-angioedema-associated-with-pharmacological-inhibition-of-dipeptidyl-peptidase-iv
#15
Thorbjørn Hermanrud, Anette Bygum, Eva Rye Rasmussen
Angioedema (AE) of the upper airways is a severe and potentially life-threatening condition. The incidence has been increasing in the past two decades, primarily due to increased use of medications inhibiting the degradation of vasoactive peptides. Acquired angioedema related to angiotensin-converting enzyme inhibitors (ACEI-AAE) is well known, but other pharmaceutical agents also affect the degradation of bradykinin and substance P. We present a middle-aged man with recurrent episodes of severe AE of the oral cavity, hypopharynx and larynx due to pharmacological inhibition of dipeptidyl peptidase IV...
January 10, 2017: BMJ Case Reports
https://www.readbyqxmd.com/read/28065853/sitagliptin-inhibit-human-lymphocytes-proliferation-and-th1-th17-differentiation-in-vitro
#16
Marcelo Maia Pinheiro, Caroline Lais Stoppa, Claudete Justina Valduga, Cristina Eunice Okuyama, Renata Gorjão, Regina Mara Silva Pereira, Susana Nogueira Diniz
Dipeptidyl peptidase-4 (DPP-4) inhibitors are a new class of anti-diabetic agents that are widely used in clinical practice to improve glycemic control in patients with type 2 diabetes. DPP-4 is also known as lymphocyte cell surface protein, CD26, and plays an important role in T-cell immunity. Recent studies suggest that DPP-4 inhibitors improve beta-cell function and attenuate autoimmunity in type 1 diabetic mouse models. To investigate the direct effect of DPP4 in immune response, human peripheral blood mononuclear cells (PBMC) from healthy volunteers were obtained by Ficoll gradient and cultivated in the absence (control) or presence of phytohemagglutinin (PHA), or stimulated with PHA and treated with sitagliptin...
January 5, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28062644/ligand-induced-conformational-changes-in-prolyl-oligopeptidase-a-kinetic-approach
#17
R Van Elzen, E Schoenmakers, I Brandt, P Van Der Veken, A M Lambeir
Most kinetic studies of prolyl oligopeptidase (PREP) were performed with the porcine enzyme using modified peptide substrates. Yet recent biophysical studies used the human homolog. Therefore, the aim of this study was to compare the kinetic behavior of human and porcine PREP, as well as to find a suitable method to study enzyme kinetics with an unmodified biological substrate. It was found that human PREP behaves identically to the porcine homolog, displaying a double bell-shaped pH profile and a pH-dependent solvent kinetic isotope effect of the kcat/Km, features that set it apart from the related exopeptidase dipeptidyl peptidase IV (DPP IV)...
January 5, 2017: Protein Engineering, Design & Selection: PEDS
https://www.readbyqxmd.com/read/28060721/dppiv-promotes-endometrial-carcinoma-cell-proliferation-invasion-and-tumorigenesis
#18
Xiaoqing Yang, Xinhua Zhang, Rongrong Wu, Qicheng Huang, Yao Jiang, Jianbing Qin, Feng Yao, Guohua Jin, Yuquan Zhang
Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo...
January 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058753/effect-of-gemigliptin-on-glycemic-variability-in-patients-with-type-2-diabetes
#19
Se E Park, Byung W Lee, Jae H Kim, Woo J Lee, Jae H Cho, Chang H Jung, Seung H Lee, Sunghwan Suh, Gwong C Hur, Sung H Kim, Young H Jang, Cheol Y Park
The aim of this study was to evaluate the effect of gemigliptin vs sitagliptin or glimepiride as initial combination therapy with metformin on glycemic variability and to assess the correlation between glycemic variability reduction and the dipeptidyl peptidase-4 (DPP-4) inhibition in patients with type 2 diabetes. This multicenter, randomized, active-controlled, open-label exploratory study included 69 patients with HbA1c >7.5%. Subjects were randomized to receive gemigliptin 50 mg (n = 24), sitagliptin 100 mg (n = 23), or glimepiride 2 mg (n = 22) for 12 weeks...
January 6, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28058750/efficacy-and-safety-of-adding-evogliptin-versus-sitagliptin-in-metformin-treated-patients-with-type-2-diabetes-a-24-week-randomised-controlled-trial-with-open-label-extension
#20
Sang-Mo Hong, Cheol-Young Park, Dong-Min Hwang, Kyung Ah Han, Chang Beom Lee, Choon Hee Chung, Kun-Ho Yoon, Ji-Oh Mok, Kyong Soo Park, Sung-Woo Park
AIMS: This trial consisted of a 24-week multicenter, randomised, double-blind, double-dummy, active-controlled study and a 52-week open label extension study to assess the efficacy and safety of evogliptin, a novel dipeptidyl peptidase-4 inhibitor, compared to sitagliptin in patients with type 2 diabetes who have inadequate glycaemic control with metformin alone. MATERIALS AND METHODS: Adult type 2 diabetes mellitus patients (N = 222) with HbA1c 6.5-11% on stable metformin doses (≥1000 mg/day) were randomised 1:1 to add-on 5 mg evogliptin (N = 112) or 100 mg sitagliptin (N = 110) once daily for 24 weeks...
January 6, 2017: Diabetes, Obesity & Metabolism
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