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https://www.readbyqxmd.com/read/29154902/dipeptidyl-peptidase-iv-dpp-iv-inhibition-prevents-fibrosis-in-adipose-tissue-of-obese-mice
#1
Ana Patrícia Marques, Janete Cunha-Santos, Helena Leal, Lígia Sousa-Ferreira, Luís Pereira de Almeida, Cláudia Cavadas, Joana Rosmaninho-Salgado
BACKGROUND: During the development of obesity the expansion of white adipose tissue (WAT) leads to a dysregulation and an excessive remodeling of extracellular matrix (ECM), leading to fibrosis formation. These ECM changes have high impact on WAT physiology and may change obesity progression. Blocking WAT fibrosis may have beneficial effects on the efficacy of diet regimen or therapeutical approaches in obesity. Since dipeptidyl peptidase IV (DPP-IV) inhibitors prevent fibrosis in tissues, such as heart, liver and kidney, the objective of this study was to assess whether vildagliptin, a DPP-IV inhibitor, prevents fibrosis in WAT in a mouse model of obesity, and to investigate the mechanisms underlying this effect...
November 14, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29037205/vildagliptin-ameliorates-pulmonary-fibrosis-in-lipopolysaccharide-induced-lung-injury-by-inhibiting-endothelial-to-mesenchymal-transition
#2
Toshio Suzuki, Yuji Tada, Santhi Gladson, Rintaro Nishimura, Iwao Shimomura, Satoshi Karasawa, Koichiro Tatsumi, James West
BACKGROUND: Pulmonary fibrosis is a late manifestation of acute respiratory distress syndrome (ARDS). Sepsis is a major cause of ARDS, and its pathogenesis includes endotoxin-induced vascular injury. Recently, endothelial-to-mesenchymal transition (EndMT) was shown to play an important role in pulmonary fibrosis. On the other hand, dipeptidyl peptidase (DPP)-4 was reported to improve vascular dysfunction in an experimental sepsis model, although whether DPP-4 affects EndMT and fibrosis initiation during lipopolysaccharide (LPS)-induced lung injury is unclear...
October 16, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28977602/dipeptidyl-peptidase-4-inhibition-with-saxagliptin-ameliorates-angiotensin-ii-induced-cardiac-diastolic-dysfunction-in-male-mice
#3
Scott M Brown, Cassandra E Smith, Alex I Meuth, Maloree Khan, Annayya R Aroor, Hannah M Cleeton, Gerald A Meininger, James R Sowers, Vincent G DeMarco, Bysani Chandrasekar, Ravi Nistala, Shawn B Bender
Activation of the renin-angiotensin-aldosterone system is common in hypertension and obesity and contributes to cardiac diastolic dysfunction, a condition for which no treatment currently exists. In light of recent reports that antihyperglycemia incretin enhancing dipeptidyl peptidase (DPP)-4 inhibitors exert cardioprotective effects, we examined the hypothesis that DPP-4 inhibition with saxagliptin (Saxa) attenuates angiotensin II (Ang II)-induced cardiac diastolic dysfunction. Male C57BL/6J mice were infused with either Ang II (500 ng/kg/min) or vehicle for 3 weeks receiving either Saxa (10 mg/kg/d) or placebo during the final 2 weeks...
October 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28815568/gliptin-therapy-reduces-hepatic-and-myocardial-fat-in-type-2-diabetic-patients
#4
Lana Kosi-Trebotic, Anita Thomas, Jürgen Harreiter, Marek Chmelik, Siegfried Trattnig, Alexandra Kautzky-Willer
BACKGROUND: Increased hepatic fat and cardiac fat are common in patients with type 2 diabetes mellitus (T2DM) and are associated with a greater risk of liver fibrosis and cardiovascular (CV) events. Sex-specific differences of dipeptidyl peptidase-four (DPP-4) inhibitor effects on hepatic (HCL) and myocardial fat content (MYCL) have not yet been evaluated. METHOD: Forty-one T2DM patients (20 male, 21 female) received a gliptin add-on therapy if HbA1c goals were not reached under metformin monotherapy...
August 16, 2017: European Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28652790/sitagliptin-ameliorates-oxidative-stress-in-experimental-diabetic-nephropathy-by-diminishing-the-mir-200a-keap-1-nrf2-antioxidant-pathway
#5
Esther Civantos, Enrique Bosch, Elisa Ramirez, Olha Zhenyukh, Jesús Egido, Oscar Lorenzo, Sebastián Mas
BACKGROUND: Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor used in type 2 diabetes therapy, has demonstrated protective effects in diabetic chronic kidney disease, in part due to its pleiotropic actions. However, its potential direct effects on the kidney are still not completely defined. Here, by means of proteomics and miRNA profiling, we have further unveiled the role of sitagliptin in oxidative stress, as well as the underlying mechanisms. METHODS: Renal cortex samples from 9-month-old wild-type (Wistar), type II diabetic Goto-Kakizaki (GK) and sitagliptin-treated GK rats (GK+Sita) (10 mg kg(-1) per day) were subjected to quantitative miRNA transcriptomic array, immunohistochemistry and Western blot studies...
2017: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/28635324/gliptins-suppress-inflammatory-macrophage-activation-to-mitigate-inflammation-fibrosis-oxidative-stress-and-vascular-dysfunction-in-models-of-nonalcoholic-steatohepatitis-and-liver-fibrosis
#6
Xiaoyu Wang, Michael Hausding, Shih-Yen Weng, Yong Ook Kim, Sebastian Steven, Thomas Klein, Andreas Daiber, Detlef Schuppan
AIMS: Nonalcoholic steatohepatitis (NASH) is characterized by steatosis, panlobular inflammation, liver fibrosis, and increased cardiovascular mortality. Dipeptidyl peptidase-4 inhibitors (gliptins) are indirect glucagon-like peptide 1 agonists with antidiabetic and anti-inflammatory activity, used for the treatment of type 2 diabetes. Their potential and underlying mechanisms to treat metabolic liver inflammation and fibrosis as well as the associated vascular dysfunction remain to be explored...
July 25, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28476142/dipeptidyl-peptidase-4-dpp-4-inhibition-with-linagliptin-reduces-western-diet-induced-myocardial-traf3ip2-expression-inflammation-and-fibrosis-in-female-mice
#7
Annayya R Aroor, Javad Habibi, Hemanth Kumar Kandikattu, Mona Garro-Kacher, Brady Barron, Dongqing Chen, Melvin R Hayden, Adam Whaley-Connell, Shawn B Bender, Thomas Klein, Jaume Padilla, James R Sowers, Bysani Chandrasekar, Vincent G DeMarco
BACKGROUND: Diastolic dysfunction (DD), a hallmark of obesity and primary defect in heart failure with preserved ejection fraction, is a predictor of future cardiovascular events. We previously reported that linagliptin, a dipeptidyl peptidase-4 inhibitor, improved DD in Zucker Obese rats, a genetic model of obesity and hypertension. Here we investigated the cardioprotective effects of linagliptin on development of DD in western diet (WD)-fed mice, a clinically relevant model of overnutrition and activation of the renin-angiotensin-aldosterone system...
May 5, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28462210/the-expression-of-proline-specific-enzymes-in-the-human-lung
#8
REVIEW
Gwendolyn Vliegen, Tom K Raju, Dirk Adriaensen, Anne-Marie Lambeir, Ingrid De Meester
The pathophysiology of lung diseases is very complex and proteolytic enzymes may play a role or could be used as biomarkers. In this review, the literature was searched to make an overview of what is known on the expression of the proline-specific peptidases dipeptidyl peptidase (DPP) 4, 8, 9, prolyl oligopeptidase (PREP) and fibroblast activation protein α (FAP) in the healthy and diseased lung. Search terms included asthma, chronic obstructive pulmonary disease (COPD), lung cancer, fibrosis, ischemia reperfusion injury and pneumonia...
March 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28118775/renoprotective-effects-of-a-dipeptidyl-peptidase-4-inhibitor-in-a-mouse-model-of-progressive-renal-fibrosis
#9
Takahiro Uchida, Takashi Oda, Hidehito Matsubara, Atsushi Watanabe, Hanako Takechi, Naoki Oshima, Yutaka Sakurai, Hiroo Kumagai
Although the effects of dipeptidyl peptidase 4 (DPP-4) inhibitors beyond their hypoglycemic action have been reported, whether these inhibitors have renoprotective effects in nondiabetic chronic kidney disease (CKD) is unclear. We examined the therapeutic effects of DPP-4 inhibition in mice with unilateral ureteral obstruction (UUO), a nondiabetic model of progressive renal fibrosis. After UUO surgery, mice were administered either the DPP-4 inhibitor alogliptin or a vehicle by oral gavage once a day for 10 days...
November 2017: Renal Failure
https://www.readbyqxmd.com/read/28019064/novel-antidiabetic-medications-for-non-alcoholic-fatty-liver-disease-with-type-2-diabetes-mellitus
#10
REVIEW
Yoshio Sumida, Yuya Seko, Masashi Yoneda
Liver-related diseases are the leading causes of death in patients with type 2 diabetes mellitus (T2DM) in Japan. Type 2 diabetes mellitus is closely associated with non-alcoholic fatty liver disease (NAFLD), which is the most prevalent chronic liver disease worldwide. Non-alcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma and hepatic failure. Non-alcoholic steatohepatitis can be called "diabetic hepatopathy". There are no established pharmacotherapies for NAFLD/NASH patients with T2DM...
March 2017: Hepatology Research: the Official Journal of the Japan Society of Hepatology
https://www.readbyqxmd.com/read/27918207/gemigliptin-ameliorates-western-diet-induced-metabolic-syndrome-in-mice
#11
Seung Hee Choi, Jaechan Leem, Sungmi Park, Chong-Kee Lee, Keun-Gyu Park, In-Kyu Lee
Dipeptidyl peptidase 4 (DPP-4) inhibitors are widely used antihyperglycemic agents for type 2 diabetes mellitus. Recently, increasing attention has been focused on the pleiotropic actions of DPP-4 inhibitors. The aim of the present study was to examine whether gemigliptin, a recently developed DPP-4 inhibitor, could ameliorate features of metabolic syndrome. Mice were fed a Western diet (WD) for 12 weeks and were subsequently divided into 2 groups: mice fed a WD diet alone or mice fed a WD diet supplemented with gemigliptin for an additional 4 weeks...
February 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/27820706/dipeptidyl-peptidase-4-inhibition-and-renoprotection-the-role-of-antifibrotic-effects
#12
Yuta Takagaki, Daisuke Koya, Keizo Kanasaki
PURPOSE OF REVIEW: This article analyzes the potential beneficial effects of dipeptidyl peptidase (DPP)-4 inhibitors on renal diseases. RECENT FINDINGS: The pathological significance of DPP-4, either dependent or independent on catalytic activities, on renal diseases has been reported in preclinical studies. With regard to this, we have shown that damaged endothelial cells are converted to a mesenchymal cell phenotype, which is associated with the induction of DPP-4 in endothelial cells...
January 2017: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27627981/twelve-week-liraglutide-or-sitagliptin-does-not-affect-hepatic-fat-in-type-2-diabetes-a-randomised-placebo-controlled-trial
#13
RANDOMIZED CONTROLLED TRIAL
Mark M Smits, Lennart Tonneijck, Marcel H A Muskiet, Mark H H Kramer, Petra J W Pouwels, Indra C Pieters-van den Bos, Trynke Hoekstra, Michaela Diamant, Daniël H van Raalte, Djuna L Cahen
AIMS/HYPOTHESIS: Glucagon-like peptide (GLP)-1-based therapies have been suggested to improve hepatic steatosis. We assessed the effects of the GLP-1 receptor agonist liraglutide and the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin on hepatic steatosis and fibrosis in patients with type 2 diabetes. METHODS: In this 12 week, parallel, randomised, placebo-controlled trial, performed at the VU University Medical Center between July 2013 and August 2015, 52 overweight patients with type 2 diabetes treated with metformin and/or sulphonylurea agent ([mean ± SD] age 62...
December 2016: Diabetologia
https://www.readbyqxmd.com/read/27475229/stromal-cell-derived-factor-1-is-upregulated-by%C3%A2-dipeptidyl-peptidase-4-inhibition-and-has%C3%A2-protective-roles-in-progressive-diabetic%C3%A2-nephropathy
#14
Satoru Takashima, Hiroki Fujita, Hiromi Fujishima, Tatsunori Shimizu, Takehiro Sato, Tsukasa Morii, Katsushi Tsukiyama, Takuma Narita, Takamune Takahashi, Daniel J Drucker, Yutaka Seino, Yuichiro Yamada
The role of stromal cell-derived factor-1 (SDF-1) in the pathogenesis of diabetic nephropathy and its modification by dipeptidyl peptidase-4 (DPP-4) inhibition are uncertain. Therefore, we studied this independent of glucagon-like peptide-1 receptor (GLP-1R) signaling using two Akita diabetic mouse models, the diabetic-resistant C57BL/6-Akita and diabetic-prone KK/Ta-Akita. Increased SDF-1 expression was found in glomerular podocytes and distal nephrons in the diabetic-prone mice, but not in kidneys from diabetic-resistant mice...
October 2016: Kidney International
https://www.readbyqxmd.com/read/27462372/empagliflozin-an-sglt2-inhibitor-alone-or-in-combination-with-linagliptin-a-dpp-4-inhibitor-prevents-steatohepatitis-in-a-novel-mouse-model-of-non-alcoholic-steatohepatitis-and-diabetes
#15
Teruo Jojima, Takanori Tomotsune, Toshie Iijima, Kazumi Akimoto, Kunihiro Suzuki, Yoshimasa Aso
BACKGROUND: Sodium-glucose co-transporter-2 (SGLT2) inhibitors are new oral antidiabetic drugs that reduce hyperglycemia by promoting urinary glucose excretion. Glycosuria produced by SGLT2 inhibitors is associated with weight loss, mainly due to reduced fat volume. We investigated the effects of empagliflozin (selective SGLT2 inhibitor) and linagliptin (DPP-4 inhibitor) on steatohepatitis and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH) with diabetes. METHODS: A novel NASH model was generated by administration of streptozotocin to C57BL/6J mice at 2 days old, with a high-fat diet from 4 weeks...
2016: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/27456521/novel-therapeutic-role-for-dipeptidyl-peptidase-iii-in-the-treatment-of-hypertension
#16
Xiaoling Pang, Akio Shimizu, Souichi Kurita, Dimitar P Zankov, Keisuke Takeuchi, Mako Yasuda-Yamahara, Shinji Kume, Tetsuo Ishida, Hisakazu Ogita
Dipeptidyl peptidase III (DPP III) cleaves dipeptide residues from the N terminus of polypeptides ranging from 3 to 10 amino acids in length and is implicated in pathophysiological processes through the breakdown of certain oligopeptides or their fragments. In this study, we newly identified the biochemical properties of DPP III for angiotensin II (Ang II), which consists of 8 amino acids. DPP III quickly and effectively digested Ang II with Km = 3.7×10(-6) mol/L. In the in vivo experiments, DPP III remarkably reduced blood pressure in Ang II-infused hypertensive mice without alteration of heart rate...
September 2016: Hypertension
https://www.readbyqxmd.com/read/27425816/effect-of-antifibrotic-micrornas-crosstalk-on-the-action-of-n-acetyl-seryl-aspartyl-lysyl-proline-in-diabetes-related-kidney-fibrosis
#17
Swayam Prakash Srivastava, Sen Shi, Megumi Kanasaki, Takako Nagai, Munehiro Kitada, Jianhua He, Yuka Nakamura, Yasuhito Ishigaki, Keizo Kanasaki, Daisuke Koya
N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is an endogenous antifibrotic peptide. We found that suppression of AcSDKP and induction of dipeptidyl peptidase-4 (DPP-4), which is associated with insufficient levels of antifibrotic microRNA (miR)s in kidneys, were imperative to understand the mechanisms of fibrosis in the diabetic kidneys. Analyzing streptozotocin (STZ)-induced diabetic mouse strains, diabetic CD-1 mice with fibrotic kidneys could be differentiated from less-fibrotic diabetic 129Sv mice by suppressing AcSDKP and antifibrotic miRs (miR-29s and miR-let-7s), as well as by the prominent induction of DPP-4 protein expression/activity and endothelial to mesenchymal transition...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27391040/dipeptidyl-peptidase-4-inhibition-with-linagliptin-prevents-western-diet-induced-vascular-abnormalities-in-female-mice
#18
Camila Manrique, Javad Habibi, Annayya R Aroor, James R Sowers, Guanghong Jia, Melvin R Hayden, Mona Garro, Luis A Martinez-Lemus, Francisco I Ramirez-Perez, Thomas Klein, Gerald A Meininger, Vincent G DeMarco
BACKGROUND: Vascular stiffening, a risk factor for cardiovascular disease, is accelerated, particularly in women with obesity and type 2 diabetes. Preclinical evidence suggests that dipeptidylpeptidase-4 (DPP-4) inhibitors may have cardiovascular benefits independent of glycemic lowering effects. Recent studies show that consumption of a western diet (WD) high in fat and simple sugars induces aortic stiffening in female C57BL/6J mice in advance of increasing blood pressure. The aims of this study were to determine whether administration of the DPP-4 inhibitor, linagliptin (LGT), prevents the development of aortic and endothelial stiffness induced by a WD in female mice...
July 8, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27270216/cinnamaldehyde-and-allopurinol-reduce-fructose-induced-cardiac-inflammation-and-fibrosis-by-attenuating-cd36-mediated-tlr4-6-irak4-1-signaling-to-suppress-nlrp3-inflammasome-activation
#19
Lin-Lin Kang, Dong-Mei Zhang, Chun-Hua Ma, Jian-Hua Zhang, Ke-Ke Jia, Jia-Hui Liu, Rong Wang, Ling-Dong Kong
Fructose consumption induces metabolic syndrome to increase cardiovascular disease risk. Cinnamaldehyde and allopurinol possess anti-oxidative and anti-inflammatory activity to relieve heart injury in metabolic syndrome. But the mechanisms of fructose-induced cardiac injury, and cardioprotective effects of cinnamaldehyde and allopurinol are not completely understood. In this study, fructose-fed rats displayed metabolic syndrome with elevated serum ox-LDL, cardiac oxidative stress, inflammation and fibrosis...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27151177/sitagliptin-vs-placebo-for-non-alcoholic-fatty-liver-disease-a-randomized-controlled-trial
#20
Jeffrey Cui, Len Philo, Phirum Nguyen, Heather Hofflich, Carolyn Hernandez, Ricki Bettencourt, Lisa Richards, Joanie Salotti, Archana Bhatt, Jonathan Hooker, William Haufe, Catherine Hooker, David A Brenner, Claude B Sirlin, Rohit Loomba
BACKGROUND & AIMS: Uncontrolled studies show sitagliptin, an oral DPP-4 inhibitor, may improve alanine aminotransferase and liver histology in non-alcoholic fatty liver disease (NAFLD) patients. We aimed to compare sitagliptin vs. the efficacy of a placebo in reducing liver fat measured by MRI-derived proton density-fat fraction (MRI-PDFF). METHODS: This randomized, double-blind, allocation-concealed, placebo-controlled trial included 50 NAFLD patients with prediabetes or early diabetes randomized to sitagliptin orally 100mg/day or placebo for 24weeks...
August 2016: Journal of Hepatology
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