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https://www.readbyqxmd.com/read/28213130/dipeptidyl-peptidase-4-impairs-insulin-signalling-and-promotes-lipid-accumulation-in-hepatocytes
#1
Kerstin Rufinatscha, Bernhard Radlinger, Jochen Dobner, Sabrina Folie, Claudia Bon, Elisabeth Profanter, Claudia Ress, Karin Salzmann, Gabriele Staudacher, Herbert Tilg, Susanne Kaser
Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signalling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively...
February 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28207986/novel-multiplex-assay-platforms-to-detect-influenza-a-hemagglutinin-subtype-specific-antibody-responses-for-high-throughput-and-in-field-applications
#2
Zhu-Nan Li, Jessica F Trost, Kimberly M Weber, Elizabeth H LeMasters, Sharifa Nasreen, Javan Esfandiari, Angelo H Gunasekera, Megan McCausland, Katharine Sturm-Ramirez, Jens Wrammert, Sean Gregory, Vic Veguilla, James Stevens, Joseph D Miller, Jacqueline M Katz, Min Z Levine
BACKGROUND: Detections of influenza A subtype specific antibody responses are often complicated by the presence of cross-reactive antibodies. We developed two novel multiplex platforms for antibody detection. The multiplexed magnetic fluorescence microsphere immunoassay (MAGPIX) is a high throughput laboratory-based assay. Chembio Dual Path Platform (DPP) is a portable and rapid test that could be used in the field. METHODS: Twelve recombinant globular head domain hemagglutinin (GH HA1) antigens from A(H1N1)pdm09 (pH1N1), A(H2N2), A(H3N2), A(H5N1), A(H7N9), A(H9N2), A(H13N9), B/Victoria lineage, B/Yamagata lineage viruses, and protein A control were used...
February 16, 2017: Influenza and Other Respiratory Viruses
https://www.readbyqxmd.com/read/28207538/comparison-of-baseline-characteristics-and-clinical-course-in-japanese-patients-with-type-2-diabetes-among-whom-different-types-of-oral-hypoglycemic-agents-were-chosen-by-diabetes-specialists-as-initial-monotherapy-jddm-42
#3
Kazuya Fujihara, Risa Igarashi, Satoshi Matsunaga, Yasuhiro Matsubayashi, Takaho Yamada, Hiroki Yokoyama, Shiro Tanaka, Hitoshi Shimano, Hiroshi Maegawa, Katsuya Yamazaki, Koichi Kawai, Hirohito Sone
Little is known about the relationships between patient factors and the antihyperglycemic agents that have been prescribed as initial therapy by diabetes specialists for patients with type 2 diabetes. Moreover, there has been little clarification of the subsequent usage patterns and related factors that influenced the continuation or discontinuation of the drug or the addition of another drug. To provide information on these issues, we evaluated the clinical characteristics of Japanese patients with type 2 diabetes for whom different types of oral hypoglycemic agents (i...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28207252/metal-metal-bridging-using-the-dppp-dye-system-electronic-configurations-within-multiple-redox-series
#4
Arijit Singha Hazari, Abhishek Mandal, Katharina Beyer, Alexa Paretzki, Wolfgang Kaim, Goutam Kumar Lahiri
Redox series [LnRu(μ-DPPP)RuLn](k), H2DPPP = 2,5-dihydro-3,6-di-2-pyridylpyrrolo(3,4-c)pyrrole-1,4-dione and L = 2,4-pentanedionato (acac(-)), 2,2'-bipyridine (bpy), and 2-phenylazopyridine (pap), have been studied by voltammetry (CV, DPV), EPR, and UV-vis-NIR spectroelectrochemistry, supported by TD-DFT calculations. Crystal structure analysis and (1)H NMR revealed oxidation states [(acac)2Ru(III)(μ-DPPP(2-))Ru(III)(acac)2] and [(bpy)2Ru(II)(μ-DPPP(2-))Ru(II)(bpy)2](2+) for the corresponding precursors, isolated as rac diastereomers...
February 16, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28203015/-effect-of-thermal-conductivity-on-apical-sealing-ability-of-4-dental-gutta-percha-cones
#5
C Fan, C Y Yuan, J C Zhang, X Y Wang
OBJECTIVE: To investigate the effect of thermal conductivity on the apical sealing ability of different dental gutta-percha cones during the warm vertical condensation obturation. METHODS: Four kinds of dental gutta-percha cones were used in this study: Bio-GP points (BP, B&L, Korea), large-tapered gutta-percha (DP, DENTSPLY, America), PROTAPER Universal gutta-percha points (DPP, DENTSPLY, America) and mtwo gutta-percha points (VP, VDW, Germany). Volume differences method was used to determine the main components and the thermal conductivity determinator was used to measure the thermal conductivity of these dental gutta-percha cones...
February 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28197917/sumo-in-drosophila-development
#6
Joseph Cao, Albert J Courey
The ubiquitin -like protein SUMO is conjugated covalently to hundreds of target proteins in organisms throughout the eukaryotic domain. Genetic and biochemical studies using the model organism Drosophila melanogaster are beginning to reveal many essential functions for SUMO in cell biology and development. For example, SUMO regulates multiple signaling pathways such as the Ras/MAPK, Dpp, and JNK pathways. In addition, SUMO regulates transcription through conjugation to many transcriptional regulatory proteins, including Bicoid, Spalt , Scm, and Groucho...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28195389/no-increased-risk-of-cardiovascular-events-in-older-adults-initiating-dipeptidyl-peptidase-4-inhibitors-versus-therapeutic-alternatives
#7
Mugdha Gokhale, John B Buse, Michele Jonsson Funk, Jennifer Lund, Virginia Pate, Ross J Simpson, Til Stürmer
OBJECTIVE: Randomized placebo-controlled trials have examined the cardiovascular (CV) effects of dipeptidyl peptidase-4 inhibitors (DPP-4i), but data on incidence relative to therapeutic alternatives are limited in the older US Medicare population. We compared the CV risk with DPP-4i relative to sulfonylureas (SU) and thiazolidinediones (TZD). METHODS: During 2007-2013, using Medicare beneficiaries >65 years we identified two new-user cohorts without the use of drugs being compared in the 6 months before initiation: DPP-4i versus SU and DPP-4i versus TZD...
February 14, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28192030/medical-care-expenditures-for-individuals-with-prediabetes-the-potential-cost-savings-in-reducing-the-risk-of-developing-diabetes
#8
Tamkeen Khan, Stavros Tsipas, Gregory Wozniak
The United States has 86 million adults with prediabetes. Individuals with prediabetes can prevent or delay the development of type 2 diabetes through lifestyle modifications such as participation in the National Diabetes Prevention Program (DPP), thereby mitigating the medical and economic burdens associated with diabetes. A cohort analysis of a commercially insured population was conducted using individual-level claims data from Truven Health MarketScan(®) Lab Database to identify adults with prediabetes, track whether they develop diabetes, and compare medical expenditures for those who are newly diagnosed with diabetes to those who are not...
February 13, 2017: Population Health Management
https://www.readbyqxmd.com/read/28188318/purls-need-an-add-on-to-metformin-consider-this
#9
REVIEW
David Wyncott, Corey Lyon, Anne Mounsey
Sulfonylureas have been the preferred add-on therapy to metformin for T2DM, but a study finds that DPP-4s have lower risks of death, CV events, and hypoglycemia.
January 2017: Journal of Family Practice
https://www.readbyqxmd.com/read/28188173/maresin-1-improves-insulin-sensitivity-and-attenuates-adipose-tissue-inflammation-in-ob-ob-and-diet-induced-obese-mice
#10
Leyre Martínez-Fernández, Pedro González-Muniesa, Laura M Laiglesia, Neira Sáinz, Pedro L Prieto-Hontoria, Xavier Escoté, Leticia Odriozola, Fernando J Corrales, Jose M Arbones-Mainar, José A Martínez, María J Moreno-Aliaga
The beneficial actions of n-3 fatty acids on obesity-induced insulin resistance and inflammation have been related to the synthesis of specialized proresolving lipid mediators (SPMs) like resolvins. The aim of this study was to evaluate the ability of one of these SPMs, maresin 1 (MaR1), to reverse adipose tissue inflammation and/or insulin resistance in two models of obesity: diet-induced obese (DIO) mice and genetic (ob/ob) obese mice. In DIO mice, MaR1 (2 μg/kg; 10 d) reduced F4/80-positive cells and expression of the proinflammatory M1 macrophage phenotype marker Cd11c in white adipose tissue (WAT)...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28183314/dpp-4-inhibition-has-no-acute-effect-on-bnp-and-its-n-terminal-pro-hormone-measured-by-commercial-immune-assays-a-randomized-cross-over-trial-in-patients-with-type-2-diabetes
#11
Gian Paolo Fadini, Benedetta Maria Bonora, Mattia Albiero, Martina Zaninotto, Mario Plebani, Angelo Avogaro
BACKGROUND: Use of dipeptidyl peptidase-4 inhibitors (DPP4-i) for the treatment of type 2 diabetes (T2D) has been associated with a possible increase in the risk for heart failure (HF). B-type natriuretic peptide (BNP), which is both a biomarker of HF and a hemodynamically active hormone, is a substrate of DPP-4. We herein tested the acute effects of the DPP-4i linagliptin on BNP and NT-proBNP in a cross-over placebo-controlled trial in patients with T2D with and without chronic kidney disease (CKD)...
February 10, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28182722/hemoglobin-glycation-index-as-a-useful-predictor-of-therapeutic-responses-to-dipeptidyl-peptidase-4-inhibitors-in-patients-with-type-2-diabetes
#12
Yu-Wei Chen, Jun-Sing Wang, Wayne H-H Sheu, Shih-Yi Lin, I-Te Lee, Yuh-Min Song, Chia-Po Fu, Chia-Lin Lee
INTRODUCTION: A high hemoglobin glycation index (HGI) and glycated hemoglobin (HbA1c) level are associated with greater inflammatory status, and dipeptidyl peptidase-4 (DPP-4) inhibitors can suppress inflammation. We aimed to evaluate the relationship between HGI and the therapeutic effect of DPP-4 inhibitors. METHODS: This retrospective cohort study followed 468 patients with type 2 diabetes receiving DPP-4 inhibitor treatment for 1 year. Estimated HbA1c was calculated using a linear regression equation derived from another 2969 randomly extracted patients with type 2 diabetes based on fasting plasma glucose (FPG) level...
2017: PloS One
https://www.readbyqxmd.com/read/28180064/dipeptidyl-peptidase-4-inhibitor-treatment-induces-a-greater-increase-in-plasma-levels-of-bioactive-gip-than-glp-1-in-non-diabetic-subjects
#13
Tsuyoshi Yanagimachi, Yukihiro Fujita, Yasutaka Takeda, Jun Honjo, Hidemitsu Sakagami, Hiroya Kitsunai, Yumi Takiyama, Atsuko Abiko, Yuichi Makino, Timothy J Kieffer, Masakazu Haneda
OBJECTIVE: Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) possess multiple bioactive isoforms that are rendered non-insulinotropic by the enzyme dipeptidyl peptidase-4 (DPP-4). Recently, some ELISA kits have been developed to specifically measure "active" GIP and GLP-1, but it is unclear if these kits can accurately quantify all bioactive forms. Therefore, it remains uncertain to what extent treatment with a DPP-4 inhibitor boosts levels of biologically active GIP and GLP-1...
February 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28179397/dipeptidyl-peptidase-4-induces-aortic-valve-calcification-by-inhibiting-insulin-like-growth-factor-1-signaling-in-valvular-interstitial-cells
#14
Bongkun Choi, Sahmin Lee, Sang-Min Kim, Eun-Jin Lee, Sun Ro Lee, Dae-Hee Kim, Jeong Yoon Jang, Sang-Wook Kang, Ki-Up Lee, Eun-Ju Chang, Jae-Kwan Song
Background -Calcification of the aortic valve leads to increased leaflet stiffness, and consequently to the development of calcific aortic valve disease (CAVD); however, the underlying molecular and cellular mechanisms of calcification remain unclear. Here, we identified that dipeptidyl peptidase-4 (DPP-4, also known as CD26) increases valvular calcification and promotes CAVD progression. Methods -We obtained the aortic valve tissues from humans and murine models (wild type and eNOS(-/-) mice), and cultured the valvular interstitial cells (VICs) and valvular endothelial cells (VECs) from the cusps...
February 8, 2017: Circulation
https://www.readbyqxmd.com/read/28178698/dipeptidyl-peptidase-4-inhibitors-in-chronic-kidney-disease-a-systematic-review-of-randomized-clinical-trials
#15
Simon R Walker, Paul Komenda, Suhail Khojah, Wafa Al-Tuwaijri, Kerry MacDonald, Brett Hiebert, Neil Tangri, Stewart W D Nadurak, Thomas W Ferguson, Claudio Rigatto, Navdeep Tangri
BACKGROUND: Chronic kidney disease (CKD) is common in patients with type 2 diabetes mellitus (T2DM) and limits therapeutic options. Dipeptidyl peptidase-4 (DPP-4) inhibitors represent a novel class of oral glucose-lowering agents and are known to be safe and effective in the general population. METHODS: We searched Cochrane, EMBASE, and PubMed from the time of their inception until March 2015. We included randomized controlled trials analyzing the efficacy (change in hemoglobin A1C [HbA1C]) and safety of DPP-4 agents in individuals with reduced kidney function (estimated glomerular filtration rate <60 mL/min/1...
February 9, 2017: Nephron
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#16
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase (DPP)4 is expressed by resident renal cells, including glomerular cells. Dipeptidyl-peptidase 4 inhibitors (gliptins) exert albuminuria lowering effects, but the role of renal DPP4 as a pharmacological target has not been elucidated. To better understand the actions of gliptins, the effects of linagliptin on behaviour of immortalized human podocytes and mesangial cells have been evaluated. EXPERIMENTAL APPROACH: Expression of DPP4 was measured at both the mRNA and protein levels...
February 8, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28177187/efficacy-and-safety-of-canagliflozin-as-add-on-therapy-to-teneligliptin-in-japanese-patients-with-type-2-diabetes-mellitus-results-of-a-24-week-randomised-double-blind-placebo-controlled-trial
#17
Takashi Kadowaki, Nobuya Inagaki, Kazuoki Kondo, Kenichi Nishimura, Genki Kaneko, Nobuko Maruyama, Nobuhiro Nakanishi, Hiroaki Iijima, Yumi Watanabe, Maki Gouda
AIMS: To investigate efficacy and safety of the sodium glucose co-transporter 2 (SGLT2) inhibitor canagliflozin administered as add-on therapy to the dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin in patients with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: We conducted a multicentre, randomised, double-blind, placebo-controlled, phase 3 clinical trial in Japanese patients with T2DM who had inadequate glycaemic control with teneligliptin. Patients were randomised to receive teneligliptin 20 mg plus either canagliflozin 100 mg (T + C, n = 70) or placebo (T + P, n = 68) once daily...
February 8, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28176959/a-systematic-literature-review-on-the-efficacy-effectiveness-gap-comparison-of-randomized-controlled-trials-and-observational-studies-of-glucose-lowering-drugs
#18
REVIEW
Mikkel Z Ankarfeldt, Erpur Adalsteinsson, Rolf Hh Groenwold, M Sanni Ali, Olaf H Klungel
AIM: To identify a potential efficacy-effectiveness gap and possible explanations (drivers of effectiveness) for differences between results of randomized controlled trials (RCTs) and observational studies investigating glucose-lowering drugs. METHODS: A systematic literature review was conducted in English language articles published between 1 January, 2000 and 31 January, 2015 describing either RCTs or observational studies comparing glucagon-like peptide-1 analogs (GLP-1) with insulin or comparing dipeptidyl peptidase-4 inhibitors (DPP-4i) with sulfonylurea, all with change in glycated hemoglobin (HbA1c) as outcome...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176886/assessment-of-channeling-bias-among-initiators-of-glucose-lowering-drugs-a-uk-cohort-study
#19
Mikkel Z Ankarfeldt, Brian L Thorsted, Rolf Hh Groenwold, Erpur Adalsteinsson, M Sanni Ali, Olaf H Klungel
BACKGROUND: Channeling bias may occur when a newly marketed drug and an established drug, despite similar indications, are prescribed to patients with different prognostic characteristics (ie, confounding). AIM: To investigate channeling bias and its impact on relative effectiveness of glucagon-like peptide-1 (GLP-1) analogs versus basal insulin and dipeptidyl peptidase-4 inhibitors (DPP-4i) versus sulfonylurea. METHODS: In the UK Clinical Practice Research Datalink, patients with type 2 diabetes initiating treatment between 2006 and 2015 were included...
2017: Clinical Epidemiology
https://www.readbyqxmd.com/read/28176222/saxagliptin-dapagliflozin-a-review-in-type-2-diabetes-mellitus
#20
Karly P Garnock-Jones
Saxagliptin/dapagliflozin fixed-dose combination tablets (Qtern(®)) are indicated in the EU for the improvement of glycaemic control in adults with type 2 diabetes mellitus (T2DM), either when treatment with metformin and/or a sulfonylurea plus a monocomponent of saxagliptin/dapagliflozin provides inadequate glycaemic control, or when the patient is already being treated with the free combination of saxagliptin + dapagliflozin. This narrative review summarizes pharmacological, efficacy and tolerability data relevant to the use of saxagliptin/dapagliflozin in this indication...
February 7, 2017: Drugs
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