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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/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
#2
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/28188173/maresin-1-improves-insulin-sensitivity-and-attenuates-adipose-tissue-inflammation-in-ob-ob-and-diet-induced-obese-mice
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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/28176222/saxagliptin-dapagliflozin-a-review-in-type-2-diabetes-mellitus
#11
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
https://www.readbyqxmd.com/read/28169086/basal-insulin-treatment-intensification-in-patients-with-type-2-diabetes-mellitus-a-comprehensive-systematic-review-of-current-options
#12
REVIEW
D Raccah
AIM: As type 2 diabetes mellitus progresses, most patients require treatment with basal insulin in combination with another agent to achieve recommended glycaemic targets. The purpose of this systematic review was to examine the evidence supporting the use of the available add-on treatments [rapid-acting insulin (RAI), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), dipeptidyl peptidase (DPP)-4 inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors] to basal insulin...
February 3, 2017: Diabetes & Metabolism
https://www.readbyqxmd.com/read/28166651/dipeptidyl-peptidase-4-inhibitor-associated-risk-of-bleeding
#13
Md Motiur Rahman, Michael J Scalese, Richard A Hansen
BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control, and sitagliptin has been associated with a reduction in cardiovascular events. In vivo data suggest reduced platelet activation, and aggregation may play a role, and therefore, increased bleeding risk is possible. OBJECTIVE: Comparatively assess bleeding risks associated with DPP-4 inhibitors against standard treatment. METHODS: Exploratory analyses of adverse event reports (AERs) from the US Food and Drug Administration Adverse Event Reporting System (FAERS) database (2004-2012 periods) were conducted...
February 1, 2017: Annals of Pharmacotherapy
https://www.readbyqxmd.com/read/28160554/pharmacogenetics-of-dipeptidyl-peptidase-4-inhibitors-in-a-taiwanese-population-with-type-2-diabetes
#14
Wen-Ling Liao, Wen-Jane Lee, Ching-Chu Chen, Chieh Hsiang Lu, Chien-Hsiun Chen, Yi-Chun Chou, I-Te Lee, Wayne H-H Sheu, Jer-Yuarn Wu, Chi-Fan Yang, Chung-Hsing Wang, Fuu-Jen Tsai
Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral anti-hyperglycemic drugs enabling effective glycemic control in type 2 diabetes (T2D). Despite DPP-4 inhibitors' advantages, the patients' therapeutic response varies. In this retrospective cohort study, 171 Taiwanese patients with T2D were classified as sensitive or resistant to treatment based on the mean change in HbA1c levels. Using an assumption-free genome-wide association study, 45 single nucleotide polymorphisms (SNPs) involved in the therapeutic response to DPP-4 inhibitors (P < 1 × 10-4) were identified at or near PRKD1, CNTN3, ASK, and LOC10537792...
February 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28158894/is-the-inhibition-of-dipeptidyl-peptidase-4-ddp-4-enzyme-route-dependent-and-or-driven-by-high-peak-concentration-seeking-answers-with-zydpla1-a-novel-long-acting-dpp-4-inhibitor-in-a-rodent-model
#15
Harilal Patel, Amit A Joharapurkar, Rajesh Bahekar, Prakash Patel, Samadhan G Kshirsagar, Nirav Modi, Ashok Ghoghari, Vishal J Patel, Mukul R Jain, Nuggehally R Srinivas, Pankaj R Patel, Ranjit C Desai
ZYDPLA1 is a long acting enzyme dipeptidyl peptidase-4 (DPP-4) inhibitor. The comparative effect of DPP-4 inhibition after intravenous (IV) and oral administration of ZYDPLA1 in a rat model was evaluated to answer the question of route dependency and/or the need of high plasma levels of ZYDPLA1. The study was conducted using parallel design in male Wistar rats for IV/oral route (n=9 and 6, for IV and oral respectively). A single 30 mg/kg dose of ZYDPLA1 was administered. Plasma samples were analysed for ZYDPLA1 concentration and DPP-4 inhibition...
February 3, 2017: Drug Research
https://www.readbyqxmd.com/read/28150034/association-of-dpp-4-activity-with-bmd-body-composition-and-incident-hip-fracture-the-cardiovascular-health-study
#16
L D Carbone, P Bůžková, H A Fink, J A Robbins, M Bethel, C M Isales, W D Hill
: There was no association of plasma DPP-4 activity levels with bone mineral density (BMD), body composition, or incident hip fractures in a cohort of elderly community-dwelling adults. INTRODUCTION: Dipeptidyl peptidase IV (DPP-4) inactivates several key hormones including those that stimulate postprandial insulin secretion, and DPP-4 inhibitors (gliptins) are approved to treat diabetes. While DPP-4 is known to modulate osteogenesis, the relationship between DPP-4 activity and skeletal health is uncertain...
February 2, 2017: Osteoporosis International
https://www.readbyqxmd.com/read/28145158/impact-of-dpp-4-inhibition-on-acute-and-chronic-endothelial-function-in-humans-with-type-2-diabetes-on-background-metformin-therapy
#17
Michael E Widlansky, Venkata K Puppala, Tisha M Suboc, Mobin Malik, Amberly Branum, Kara Signorelli, Jingli Wang, Rong Ying, Michael J Tanner, Sudhi Tyagi
: Cell culture and animal work indicate that dipeptidyl peptidase-4 (DPP-4) inhibition may exert cardiovascular benefits through favorable effects on the vascular endothelium. Prior human studies evaluating DPP-4 inhibition have shown conflicting results that may in part be related to heterogeneity of background anti-diabetes therapies. No study has evaluated the acute response of the vasculature to DPP-4 inhibition in humans. We recruited 38 patients with type 2 diabetes on stable background metformin therapy for a randomized, double-blind, placebo-controlled crossover trial of DPP-4 inhibition with sitagliptin (100 mg/day)...
January 1, 2017: Vascular Medicine
https://www.readbyqxmd.com/read/28130883/evaluation-of-large-scale-clinical-trials-on-cardiovascular-disease-risk-in-patients-with-type-2-diabetes-mellitus-treated-with-dpp-4-inhibitors-and-new-class-of-drugs
#18
EDITORIAL
Takeshi Kurose, Yoshiyuki Hamamoto, Yutaka Seino
Recent major progress in clinical management of type 2 diabetes mellitus has been accomplished with the introduction of several new classes of drugs, some of which may also improve cardiovascular outcomes. Most of these studies are supported by pharmaceutical companies and claim CV (cardiovascular) benefits. However whether or not these benefits hold in clinical settings is dubious. This article is protected by copyright. All rights reserved.
January 28, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28128944/design-and-elaboration-of-a-tractable-tricyclic-scaffold-to-synthesize-drug-like-inhibitors-of-dipeptidyl-peptidase-4-dpp-4-antagonists-of-the-c-c-chemokine-receptor-type-5-ccr5-and-highly-potent-and-selective-phosphoinositol-3-kinase-%C3%AE-pi3k%C3%AE-inhibitors
#19
Carolin Schwehm, Barrie Kellam, Aimie Elizabeth Garces, Prof Stephen J Hill, Nicholas D Kindon, Tracey D Bradshaw, Jin Li, Simon J F Macdonald, James E Rowedder, Leigh A Stoddart, Michael John Stocks
A novel molecular scaffold has been synthesized and its incorporation into new analogues of biologically active molecules across multiple target classes will be discussed. In these studies we have shown use of the tricyclic scaffold to synthesize potent inhibitors of the serine peptidase DPP-4, antagonists of the CCR5 receptor, and highly potent and selective PI3K δ isoform inhibitors. We also describe the predict-ed physicochemical properties of the resulting inhibitors and conclude that the tractable molecular scaffold could have potential application in future drug discovery programs...
January 27, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28127851/impact-of-insulin-sensitivity-beta-cell-function-and-glycemic-control-on-initiation-of-second-line-glucose-lowering-treatment-in-newly-diagnosed-type-2-diabetes
#20
Wolfgang Rathmann, Klaus Strassburger, Brenda Bongaerts, Pavel Bobrov, Oliver Kuss, Karsten Müssig, Daniel F Markgraf, Julia Szendroedi, Christian Herder, Michael Roden
AIMS: The aim was to investigate whether insulin sensitivity, beta-cell function or glycemic control at diagnosis predict initiation of second-line treatment in newly diagnosed type 2 diabetes. MATERIAL AND METHODS: Type 2 diabetes patients (n = 138) on initial metformin monotherapy (age [mean ± SD]: 52 ± 10 years; 67% males; BMI: 32 ± 6 kg/m(2) ) from the prospective German Diabetes Study cohort (n = 398) were included. Patients remained under treatment of their general practitioners, yet underwent detailed metabolic characterization after diabetes diagnosis for study purposes (hyperinsulinemic-euglycemic clamp: M value; i...
January 27, 2017: Diabetes, Obesity & Metabolism
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