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Dipeptidyl peptidase

Kazuaki Negishi
We are now entering the very exciting era of treatment and management of diabetes mellitus (DM) with the emergence of new therapeutic agents, including sodium-glucose cotransporter 2 inhibitors (SGLT2i) and dipeptidyl peptidase-4 inhibitor (DPP-4i). From a cardiology and echocardiography perspective, the existence of diabetic cardiomyopathy has been proven through over four decades of discussion. DM is highly prevalent in patients with heart failure (HF). Independent associations are found after adjusting for hypertension (HTN) and coronary artery disease (CAD)...
February 2018: Cardiovascular Diagnosis and Therapy
Anita Ferraretto, Michela Bottani, Paola De Luca, Laura Cornaghi, Francesca Arnaboldi, Margherita Maggioni, Amelia Fiorilli, Elena Donetti
An intestinal 70/30 Caco2/HT-29 co-culture was set up starting from the parental populations of differentiated cells to mimic the human intestinal epithelium. Co-culture was harvested at confluence 0 (T0) and at 3, 6, 10 and 14 days of post-confluence after plating (T3, T6, T10 and T14, respectively) for morphological and functional analysis. Transmission electron microscopy revealed different features from T0 to T14: microvilli and a complete junctional apparatus from T6, mucus granules from T3, as also confirmed by PAS/Alcian Blue staining...
March 14, 2018: Bioscience Reports
Rajesh B Patil, Euzebio G Barbosa, Jaiprakash N Sangshetti, Vishal P Zambre, Sanjay D Sawant
Dipeptidyl peptidase-IV (DPP-IV) inhibitors are promising antidiabetic agents. Currently, several DPP-IV inhibitors have been approved for therapeutic use in diabetes mellitus. Receptor-dependent 4D-QSAR is comparatively a new approach which uses molecular dynamics simulations to generate conformational ensemble profiles of compounds representing a dynamic state of compounds at a target's binding site. This work describes a receptor-dependent 4D-QSAR study on triazolopiperazine derivatives. QSARINS multiple linear regression method was adopted to generate 4D-QSAR models...
March 13, 2018: Molecular Diversity
Se Hee Min, Jeong-Hwa Yoon, Sun Joon Moon, Seokyung Hahn, Young Min Cho
Sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors have complementary mode of action. For the meta-analysis comparing the efficacy and safety between SGLT2 inhibitor plus DPP4 inhibitor (SGLT2i/DPP4i) and placebo plus DPP4 inhibitor (PCB/DPP4i) in patients with type 2 diabetes mellitus (T2DM), we selected randomized controlled trials from electronic databases by predefined criteria. The primary outcome of interest was the change in glycated hemoglobin A1c (HbA1c) from baseline...
March 13, 2018: Scientific Reports
Joseph A McBride, Gregory M Gauthier, Bruce S Klein
This review article focuses on the mechanisms underlying temperature adaptation and virulence of the etiologic agents of blastomycosis, Blastomyces dermatitidis, Blastomyces gilchristii, and Blastomyces percursus. In response to temperature, Blastomyces undergoes a reversible morphologic switch between hyphae and yeast known as the phase transition. The conversion to yeast for Blastomyces and related thermally dimorphic fungi is essential for virulence. In the yeast phase, Blastomyces upregulates the essential virulence factor, BAD1, which promotes attachment to host cells, impairs activation of immune cells, and blunts cytokine release...
March 13, 2018: Virulence
Milton Packer
Three classes of anti-hyperglycaemic medications are distinguished by their urinary sodium excretion-enhancing and blood pressure-lowering actions: long-acting glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors and sodium-glucose co-transporter-2 inhibitors. Yet, these drugs exert different effects on macrovascular risk. Glucagon-like peptide-1 receptor agonists reduce atherosclerotic thromboembolic events, but have little effect on heart failure; sodium-glucose co-transporter-2 inhibitors decrease the occurrence of heart failure, but have minimal effect on myocardial infarction and stroke; and dipeptidyl peptidase-4 inhibitors do not ameliorate either atherosclerotic thromboembolic events or heart failure...
March 12, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Yeon Young Cho, Sung-Il Cho
AIMS: We explored the risks associated with metformin plus sulfonylurea (MET+SU) or MET plus a dipeptidyl peptidase-4 inhibitor (MET+DPP4i) for hypoglycemia, cardiovascular disease (CVD) events and all-cause mortality in type 2 diabetes (T2D) patients with comorbidities. METHODS: This retrospective cohort study is based on the South Korean National Health Insurance Service-National Sample Cohort, enrolling T2D patients with one or more diabetes-related comorbidities who switched from monotherapy to MET+SU or MET+DPP4i between July 1, 2008 and December 31, 2013...
March 9, 2018: Metabolism: Clinical and Experimental
Milton Packer
Although dipeptidyl peptidase (DPP)-4 inhibitors have been reported to have a neutral effect on thromboembolic vaso-occlusive events in large-scale trials, they act to potentiate several endogenous peptides that can exert deleterious cardiovascular effects. Experimentally, DPP-4 inhibitors may augment the ability of glucagon-like peptide-1 to stimulate cyclic adenosine monophosphate in cardiomyocytes, and potentiation of the effects of stromal cell-derived factor-1 by DPP-4 inhibitors may aggravate cardiac fibrosis...
March 1, 2018: JACC. Heart Failure
Silvano Fasolato, Elisabetta Trevellin, Mariagrazia Ruvoletto, Marnie Granzotto, Giacomo Zanus, Elisa Boscaro, Enrico Babetto, Liliana Terrin, Maria Alberta Battocchio, Francesco Ciscato, Cristian Turato, Santina Quarta, Umberto Cillo, Patrizia Pontisso, Roberto Vettor
AIMS: In hepatocellular carcinoma (HCC), the regulatory protease Dipeptidyl-peptidase IV (DPPIV/CD26), that possesses pro-apoptotic properties, has been found abnormally regulated. The protease inhibitor SerpinB3, exerting anti-apoptotic activity, has also been described to be upregulated, especially in HCCs with poor prognosis. The aim of this study was to investigate the possible relationship between these two molecules in HCC patients and in experimental models. MATERIALS AND METHODS: DPPIV/CD26 and SerpinB3 expression was measured in liver specimens of 67 patients with HCC...
March 7, 2018: Life Sciences
Miriam Moreno-Montoro, Paula Jauregi, Miguel Navarro-Alarcón, Manuel Olalla-Herrera, Rafael Giménez-Martínez, Lourdes Amigo, Beatriz Miralles
In this study, ultrafiltered goat milks fermented with the classical starter bacteria Lactobacillus delbrueckii subsp. bulgaricus and Streptococcus salivarus subsp. thermophilus or with the classical starter plus the Lactobacillus plantarum C4 probiotic strain were analyzed using ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and/or high performance liquid chromatography-ion trap (HPLC-IT-MS/MS). Partial overlapping of the identified sequences with regard to fermentation culture was observed...
March 10, 2018: Analytical and Bioanalytical Chemistry
Jung Gi Lee, Jae Ha Ryu, Seon-Myung Kim, Moon-Young Park, San-Ho Kim, Young G Shin, Jong-Woo Sohn, Ha Hyung Kim, Zee-Yong Park, Jae Young Seong, Jae Il Kim
Exendin-4, a 39 amino acid peptide isolated from the saliva of the Gila monster, plays an important role in regulating glucose homeostasis, and is used clinically for the treatment of type 2 diabetes. Exendin-4 shares 53% sequence identity with the incretin hormone glucagon-like peptide 1 (GLP-1) but, unlike GLP-1, is highly resistant to proteolytic enzymes such as dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase 24.11 (NEP 24.11). Herein, we focused on the structure and function of the C-terminal Trp-cage of exendin-4, and suggest that it may be structurally required for resistance to proteolysis by NEP 24...
March 6, 2018: Biochemical Pharmacology
Reema Abdelkareem Abu Khalaf, Dima Sabbah, Eveen Al-Shalabi, Iyad Al-Sheikh, Ghadeer Albadawi, Ghassan Abu Sheikha
BACKGROUND: Diabetes mellitus is a major worldwide health concern that has several serious complications including retinopathy, neuropathy, nephropathy and macrovascular diseases. OBJECTIVE: Dipeptidyl peptidase-IV (DPP-IV) inhibitors, gliptins, are a new class of antidiabetic agents that potentiates the action of incretins in decreasing the blood glucose levels. METHODS: In the present study, synthesis and characterization of a series of ten N4-sulfonamido-acrylic and phthalamic acid methyl esters (3a-e and 5a-e) were achieved...
March 8, 2018: Current Computer-aided Drug Design
Petar M Seferović, Mark C Petrie, Gerasimos S Filippatos, Stefan D Anker, Giuseppe Rosano, Johann Bauersachs, Walter J Paulus, Michel Komajda, Francesco Cosentino, Rudolf A de Boer, Dimitrios Farmakis, Wolfram Doehner, Ekaterini Lambrinou, Yuri Lopatin, Massimo F Piepoli, Michael J Theodorakis, Henrik Wiggers, John Lekakis, Alexandre Mebazaa, Mamas A Mamas, Carsten Tschöpe, Arno W Hoes, Jelena P Seferović, Jennifer Logue, Theresa McDonagh, Jillian P Riley, Ivan Milinković, Marija Polovina, Dirk J van Veldhuisen, Mitja Lainscak, Aldo P Maggioni, Frank Ruschitzka, John J V McMurray
The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice...
March 8, 2018: European Journal of Heart Failure
Jitjiroj Ittichaicharoen, Arintaya Phrommintikul, Nipon Chattipakorn, Siriporn Chattipakorn
OBJECTIVES: The present study is to investigate the salivary gland function of metabolic syndrome (MetS) patients, as indicated by salivary flow rate, amylase activity, and salivary oxidative stress, by measuring MDA level. MATERIALS AND METHODS: One hundred and eighty-one MetS patients from Maharaj Nakorn Chiang Mai Hospital were enrolled onto this study. The metabolic parameters of each patient were collected and evaluated. Unstimulated saliva was also collected for 5 min...
March 8, 2018: Clinical Oral Investigations
A H Heald, A A Fryer, S G Anderson, M Livingston, M Lunt, M Davies, Gyc Moreno, R Gadsby, R J Young, M Stedman
AIMS: Despite increasing spend on new Type 2 diabetes mellitus (T2DM) therapies, the proportion of people with T2DM achieving target glycaemia outcomes is declining. Our aim was to determine, using published General Practice level data, how differences in T2DM prescribing patterns relate to glycaemic target achievement levels. METHODS: Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of class of medication in 2015/16 and changes to 2014/15 in medication to proportions achieving target glycaemic control (TGC; glycated haemoglobin A1c (HbA1c) ≤7...
March 8, 2018: Diabetes, Obesity & Metabolism
Ganesh V Sangle, Mohan Patil, Nitin J Deshmukh, Sushant A Shengule, Shantibhushan Kamble, Kiran Kumar Vuppalavanchu, Sushil Kale, Mirza Layeeq Ahmed Baig, Geetchandra Singh, Javed Shaikh, Jitendra Tripathi, P Aravindababu
PURPOSE: Sitagliptin, a dipeptidyl peptidase (DPP)-IV inhibitor approved for the treatment of type 2 diabetes, is reported to be more efficacious in Indian patients than non-Indian patient population. The objective of the study was to evaluate pharmacokinetic and pharmacodynamic (PK/PD) parameters of single-dose sitagliptin 100 mg (Januvia) in healthy Indian male participants. METHOD: In a randomised, single-dose, open-label, three-treatment, three-period, three-sequence, crossover bioavailability study, 18 healthy male participants received single-dose of sitagliptin under fasted and fed conditions...
March 6, 2018: European Journal of Clinical Pharmacology
Jeong-Hwa Yoon, Se Hee Min, Chang Ho Ahn, Young Min Cho, Seokyung Hahn
We aimed to evaluate the comparative efficacy and safety of dipeptidyl peptidase-4 inhibitors (DPP4i), glucagon-like peptide-1 receptor agonists (GLP-1RA), sodium-glucose co-transporter 2 inhibitors (SGLT2i), or thiazolidinedione (TZD) as an adjunctive treatment in patients with poorly controlled type 2 diabetes mellitus (T2DM) on insulin therapy. We searched Medline, Embase, the Cochrane Library, and through April 2016. Bayesian network meta-analyses were performed with covariate adjustment...
March 6, 2018: Scientific Reports
Takeshi Mizushima, Shunsuke Ohnishi, Yuichi Shimizu, Yutaka Hatanaka, Kanako C Hatanaka, Yugo Kuriki, Mako Kamiya, Akihiro Homma, Keiko Yamamoto, Shouko Ono, Yasuteru Urano, Naoya Sakamoto
BACKGROUND: A fluorescent probe glutamylprolyl hydroxymethyl rhodamine green (EP-HMRG), which becomes fluorescent after cleavage by dipeptidyl peptidase-IV (DPP-IV), has been reported to be useful for the detection of esophageal cancer. Thus, we investigated whether head and neck squamous cell carcinoma (HNSCC) can be detected by spraying EP-HMRG. METHODS: Fluorescence imaging of 17 cases of HNSCCs resected using endoscopic or surgical resection was performed ex vivo after spraying EP-HMRG, and then the fluorescence intensity of the tumors and normal mucosa were measured...
March 6, 2018: Head & Neck
Yochai Birnbaum, Mandeep Bajaj, Hsiu-Chiung Yang, Yumei Ye
BACGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 inhibitors (DPP4I) are used to treat type 2 diabetes (T2DM). DPP4 inhibitors (DPP4) attenuate Nlrp3 inflammasome activation in the kidney. SGLT2 inhibition reduces inflammation and attenuates the progression of diabetic nephropathy (DN). The effects of dapagliflozin (Dapa) on the activation of the Nlrp3 inflammasome and the combined effect of SGLT2 and DPP4 on T2DM-induced inflammasome activation and progression of DN have not been previously studied...
March 5, 2018: Cardiovascular Drugs and Therapy
Qixian Wang, Min Long, Hua Qu, Rufei Shen, Rui Zhang, Jing Xu, Xin Xiong, Hui Wang, Hongting Zheng
Objective: Several clinical studies have reported the application of dipeptidyl peptidase-4 (DPP-4) inhibitors as treatments for type 1 diabetes mellitus (T1DM). This study aims to review the outcomes of these existing studies and to discuss the therapeutic effects of DPP-4 inhibitors on T1DM. Methods: We thoroughly searched the Medline, Embase, PubMed, and Cochrane Library databases and for studies concerning the use of DPP-4 inhibitors in patients with T1DM...
2018: Journal of Diabetes Research
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