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https://www.readbyqxmd.com/read/29806214/mechanisms-and-pathways-of-anti-inflammatory-activity-of-dpp-4-inhibitors-in-cardiovascular-and-renal-protection
#1
REVIEW
Katarina Tomovic, Jelena Lazarevic, Gordana Kocic, Marina Deljanin-Ilic, Marko Anderluh, Andrija Smelcerovic
Dipeptidyl peptidase-4 (DPP-4) cleaves N-terminal dipeptides, with Pro, Ala or Ser at the penultimate position, and, in that way, modulates biological activity of certain polypeptides. Due to its ubiquitous distribution, many pathological processes are associated with altered DPP-4 expression and activity. Besides the regulation of glucose metabolism, DPP-4 also exhibits many other systemic effects, and the inhibition of its activity might lead to cardiovascular and renal protection. Mechanisms underlying these protective effects of DPP-4 inhibition are ascribed to elevated bioavailability of its substrates, to impacts on mediators and signaling pathways that ameliorate cardiovascular and renal function through the suppression of oxidative stress, inflammation, fibrosis and apoptosis, improved endothelial function and tissue reparation...
May 28, 2018: Medicinal Research Reviews
https://www.readbyqxmd.com/read/29740221/effect-of-sitagliptin-on-hepatic-histological-activity-and-fibrosis-of-nonalcoholic-steatohepatitis-patients-a-1-year-randomized-control-trial
#2
Shahinul Alam, Jhumur Ghosh, Golam Mustafa, Mohammad Kamal, Nooruddin Ahmad
Background/purpose: Dipeptidyl peptidase 4 (DPP-4) expression is directly associated with hepatic lipogenesis and liver injury in nonalcoholic steatohepatitis (NASH). This study has been designed to elucidate the histological improvement of NASH with the DPP-4 inhibitor sitagliptin. Materials and methods: In this open-label randomized control trial, paired liver biopsy was taken from 40 NASH patients. Sitagliptin 100 mg was given once daily to the SL group and no sitagliptin was given to the L group for 1 year...
2018: Hepatic Medicine: Evidence and Research
https://www.readbyqxmd.com/read/29721673/linagliptin-prevents-atrial-electrical-and-structural-remodeling-in-a-canine-model-of-atrial-fibrillation
#3
Tazuru Igarashi, Shinichi Niwano, Hiroe Niwano, Tomoharu Yoshizawa, Hironori Nakamura, Hidehira Fukaya, Tamami Fujiishi, Naruya Ishizue, Akira Satoh, Jun Kishihara, Masami Murakami, Junya Ako
Dipeptidyl peptidase 4 (DPP-4) inhibitors have recently been reported to exhibit additional cardioprotective effects; however, their effect in atrial remodeling, such as in atrial fibrillation (AF), remains unclear. In this study, the effect of linagliptin on atrial electrical and structural remodeling was evaluated in a canine AF model. Sixteen beagle dogs with 3-week atrial rapid stimulation were divided into the linagliptin group (9 mg/kg/day, n = 8) and pacing control group (n = 8). Three additional dogs without rapid pacing were assigned into non-pacing group, which was used as sham in this study...
May 2, 2018: Heart and Vessels
https://www.readbyqxmd.com/read/29607314/glucagon-like-peptide-1-mediates-the-protective-effect-of-the-dipeptidyl-peptidase-iv-inhibitor-on-renal-fibrosis-via-reducing-the-phenotypic-conversion-of-renal-microvascular-cells-in-monocrotaline-treated-rats
#4
Jian Xu, Jingjing Wang, Yusheng Cheng, Xiang Li, Mengyu He, Jiali Zhu, Honghao Han, Guihong Wei, Hui Kong, Weiping Xie, Hong Wang, Xiangrong Zuo
Chronic kidney diseases are characterized by renal fibrosis with excessive matrix deposition, leading to a progressive loss of functional renal parenchyma and, eventually, renal failure. Renal microcirculation lesions, including the phenotypic conversion of vascular cells, contribute to renal fibrosis. Here, renal microcirculation lesions were established with monocrotaline (MCT, 60 mg/kg). Sitagliptin (40 mg/kg/d), a classical dipeptidyl peptidase-4 (DPP-4) inhibitor, attenuated the renal microcirculation lesions by inhibiting glomerular tuft hypertrophy, glomerular mesangial expansion, and microvascular thrombosis...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29600430/targeting-incretin-hormones-and-the-ask-1-pathway-as-therapeutic-options-in-the-treatment-of-non-alcoholic-steatohepatitis
#5
REVIEW
Alexander J Kovalic, Sanjaya K Satapathy, Naga Chalasani
Non-alcoholic fatty liver disease (NAFLD) is currently one of the leading forms of chronic liver disease, and its rising frequency worldwide has reached epidemic proportions. NAFLD, particularly its progressive variant NASH (non-alcoholic steatohepatitis), can lead to advanced fibrosis, cirrhosis, and HCC. The pathophysiologic mechanisms that contribute to the development and progression of NAFLD and NASH are complex, and as such myriad therapies are under investigation targeting different pathophysiological mechanisms...
March 2018: Hepatology International
https://www.readbyqxmd.com/read/29525332/worsening-heart-failure-during-the-use-of-dpp-4-inhibitors-pathophysiological-mechanisms-clinical-risks-and-potential-influence-of-concomitant-antidiabetic-medications
#6
REVIEW
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...
June 2018: JACC. Heart Failure
https://www.readbyqxmd.com/read/29491123/the-role-of-renal-dipeptidyl-peptidase-4-in-kidney-disease-renal-effects-of-dipeptidyl-peptidase-4-inhibitors-with-a-focus-on-linagliptin
#7
REVIEW
Keizo Kanasaki
Emerging evidence suggests that dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes may have nephroprotective effects beyond the reduced renal risk conferred by glycemic control. DPP-4 is a ubiquitous protein with exopeptidase activity that exists in cell membrane-bound and soluble forms. The kidneys contain the highest levels of DPP-4, which is increased in diabetic nephropathy. DPP-4 inhibitors are a chemically heterogeneous class of drugs with important pharmacological differences. Of the globally marketed DPP-4 inhibitors, linagliptin is of particular interest for diabetic nephropathy as it is the only compound that is not predominantly excreted in the urine...
February 28, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/29310647/have-dipeptidyl-peptidase-4-inhibitors-ameliorated-the-vascular-complications-of-type-2-diabetes-in-large-scale-trials-the-potential-confounding-effect-of-stem-cell-chemokines
#8
REVIEW
Milton Packer
Drugs that inhibit dipeptidyl peptidase-4 (DPP-4) are conventionally regarded as incretin-based agents that signal through the glucagon-like peptide-1 (GLP-1) receptor. However, inhibition of DPP-4 also potentiates the stem cell chemokine, stromal cell-derived factor-1 (SDF-1), which can promote inflammation, proliferative responses and neovascularization. In large-scale cardiovascular outcome trials, enhanced GLP-1 signaling has reduced the risk of atherosclerotic ischemic events, potentially because GLP-1 retards the growth and increases the stability of atherosclerotic plaques...
January 8, 2018: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/29249634/the-effects-of-dipeptidyl-peptidase-4-on-cardiac-fibrosis-in-pressure-overload-induced-heart-failure
#9
Masanori Hirose, Hiroyuki Takano, Hiroshi Hasegawa, Hiroyuki Tadokoro, Naoko Hashimoto, Genzo Takemura, Yoshio Kobayashi
Dipeptidyl peptidase-4 (DPP-4) inhibitors are hypoglycemic agents. DPP-4 inhibitor has cardioprotective effects after transverse aortic constriction (TAC), but role of DPP-4 on cardiac fibrosis after TAC is not well known. Our aim was to determine the effects of DPP-4 on cardiac fibrosis in murine TAC model. Wild-type mice and DPP-4 knockout mice were subjected to TAC. Wild-type mice were then treated with vehicle or DPP-4 inhibitor. DPP-4 activities in serum and heart tissue were significantly increased at 2 weeks after TAC, but they were significantly decreased by DPP-4 inhibitor treatment...
December 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29154902/dipeptidyl-peptidase-iv-dpp-iv-inhibition-prevents-fibrosis-in-adipose-tissue-of-obese-mice
#10
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...
March 2018: 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
#11
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
#12
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
#13
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
#14
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
#15
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...
January 10, 2018: 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
#16
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
#17
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
#18
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
#19
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
#20
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
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