Read by QxMD icon Read

Fibrosis AND linagliptin

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-)
Umakant Ashok Bahirat, Rekha Raghuveer Shenoy, Rashmi Talwar, Rajan Naresh Goel, Kumar V S Nemmani
Non-Alcoholic SteatoHepatitis (NASH) is the more severe form of Non-Alcoholic Fatty Liver Disease (NAFLD) and is characterized by the presence of hepatic steatosis, oxidative stress, inflammation, hepatocyte injury with or without fibrosis. Recently, GPR119 receptor has emerged as a novel therapeutic target for the treatment of dyslipidemia and non-alcoholic steatohepatitis. In the present study, we investigated the effect of APD668, a GPR119 agonist alone or in combination with linagliptin, a DPPIV inhibitor on the progression of steatohepatitis in mice fed on a high trans-fat diet...
January 8, 2018: Biochemical and Biophysical Research Communications
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
Per-Henrik Groop, Mark E Cooper, Vlado Perkovic, Berthold Hocher, Keizo Kanasaki, Masakazu Haneda, Guntram Schernthaner, Kumar Sharma, Robert C Stanton, Robert Toto, Jessica Cescutti, Maud Gordat, Thomas Meinicke, Audrey Koitka-Weber, Sandra Thiemann, Maximilian von Eynatten
AIMS: The MARLINA-T2D study (, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. METHODS: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/mol), estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 and urinary albumin-to-creatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks...
November 2017: Diabetes, Obesity & Metabolism
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
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
Ahmed M Kabel, Maaly A Abd Elmaaboud, Aliaa Atef, Mohammed H Baali
Pulmonary fibrosis is a serious medical problem that may significantly compromise respiratory functions. The aim of this work was to study the effect of linagliptin and/or calcipotriol on bleomycin-induced pulmonary fibrosis and to explore the possible mechanisms underlying this effect. One hundred and twenty male C57BL/6 mice were divided into 6 equal groups as follows: control group; bleomycin group; bleomycin+carboxymethylcellulose group; bleomycin+linagliptin group; bleomycin+calcipotriol group and bleomycin+linagliptin+calcipotriol group...
March 2017: Environmental Toxicology and Pharmacology
Takuo Nagai, Shigehiro Doi, Ayumu Nakashima, Taisuke Irifuku, Kensuke Sasaki, Toshinori Ueno, Takao Masaki
Recent studies have reported increases of methylglyoxal (MGO) in peritoneal dialysis patients, and that MGO-mediated inflammation plays an important role in the development of peritoneal fibrosis through production of transforming growth factor-β1 (TGF-β1). Linagliptin, a dipeptidyl peptidase-4 inhibitor, exerts anti-inflammatory effects independent of blood glucose levels. In this study, we examined whether linagliptin suppresses MGO-induced peritoneal fibrosis in mice. Male C57/BL6 mice were divided into three groups: control, MGO injection plus saline, and MGO injection plus linagliptin (n = 6 per group)...
2016: PloS One
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
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
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
Oleg Tsuprykov, Ryotaro Ando, Christoph Reichetzeder, Karoline von Websky, Viktoriia Antonenko, Yuliya Sharkovska, Lyubov Chaykovska, Jan Rahnenführer, Ahmed A Hasan, Harald Tammen, Markus Alter, Thomas Klein, Seiji Ueda, Sho-Ichi Yamagishi, Seiya Okuda, Berthold Hocher
Dipeptidyl peptidase (DPP)-4 inhibitors delay chronic kidney disease (CKD) progression in experimental diabetic nephropathy in a glucose-independent manner. Here we compared the effects of the DPP-4 inhibitor linagliptin versus telmisartan in preventing CKD progression in non-diabetic rats with 5/6 nephrectomy. Animals were allocated to 1 of 4 groups: sham operated plus placebo; 5/6 nephrectomy plus placebo; 5/6 nephrectomy plus linagliptin; and 5/6 nephrectomy plus telmisartan. Interstitial fibrosis was significantly decreased by 48% with linagliptin but a non-significant 24% with telmisartan versus placebo...
May 2016: Kidney International
Sen Shi, Keizo Kanasaki, Daisuke Koya
Dipeptidyl peptidase (DPP)-4 plays an important role in endothelial cell biology. We have shown that the DPP-4 inhibitor Linagliptin can inhibit the endothelial-mesenchymal transition (EndMT) and ameliorate diabetic kidney fibrosis associated with the suppression of DPP-4 protein levels via the induction of miR-29. The current study demonstrated that such effects of Linagliptin on endothelial cell profibrotic programs were drug-specific but not class effects. In the cell-free system, both Linagliptin and Sitagliptin inhibited recombinant DPP-4 activity in a concentration-dependent manner...
February 26, 2016: Biochemical and Biophysical Research Communications
Yuki Tanaka, Shinji Kume, Masami Chin-Kanasaki, Hisazumi Araki, Shin-Ichi Araki, Satoshi Ugi, Takeshi Sugaya, Takashi Uzu, Hiroshi Maegawa
Dipeptidyl peptidase (DPP)-4 inhibitors, a new class of antidiabetic agent, have recently been suggested to exert pleiotropic effects beyond glucose lowering. Renal prognosis in patients with diabetic nephropathy depends on the severity of tubulointerstitial injury induced by massive proteinuria. We thus examined the renoprotective effect of DPP-4 inhibitors on inflammation in cultured mouse proximal tubular cells stimulated with free fatty acid (FFA)-bound albumin. Linagliptin and higher concentrations of sitagliptin, vildagliptin, and alogliptin all inhibited FFA-bound albumin-induced increases in mRNA expression of MCP-1 in cultured mouse proximal tubular cells...
February 12, 2016: Biochemical and Biophysical Research Communications
Michael Zeisberg, Elisabeth M Zeisberg
Among gliptins, linagliptin is unique, because decreased glomerular filtration rate does not require dose reduction. Linagliptin was originally developed to lower blood glucose by inhibiting dipeptidyl peptidase-4 (DPP-4). However, DPP-4 has numerous additional substrates, and thus gliptins possess a vast range of additional off-target effects. Shi et al. report that linagliptin directly targets interaction of DPP-4 with integrin β1, preventing endothelial-mesenchymal transition and ultimately renal fibrosis, providing additional rationale for use of linagliptin in diabetic nephropathy...
September 2015: Kidney International
Li-Hui Zhang, Xue-Fen Pang, Feng Bai, Ning-Ping Wang, Ahmed Ijaz Shah, Robert J McKallip, Xue-Wen Li, Xiong Wang, Zhi-Qing Zhao
PURPOSE: The glucagon-like peptide-1 (GLP-1) has been shown to exert cardioprotective effects in animals and patients. This study tests the hypothesis that preservation of GLP-1 by the GLP-1 receptor agonist liraglutide or the dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin is associated with a reduction of angiotensin (Ang) II-induced cardiac fibrosis. METHODS AND RESULTS: Sprague-Dawley rats were subjected to Ang II (500 ng/kg/min) infusion using osmotic minipumps for 4 weeks...
June 2015: Cardiovascular Drugs and Therapy
Sen Shi, Swayam Prakash Srivastava, Megumi Kanasaki, Jianhua He, Munehiro Kitada, Takako Nagai, Kyoko Nitta, Susumu Takagi, Keizo Kanasaki, Daisuke Koya
Integrin β1 and dipeptidyl peptidase (DPP)-4 play roles in endothelial cell biology. Vascular endothelial growth factor (VEGF)-A inhibits endothelial-to-mesenchymal transition (EndMT) through VEGF-R2, but through VEGF-R1 promotes EndMT by reducing the bioavailability of VEGF-A. Here we tested whether DPP-4-integrin β1 interactions have a role in EndMT in the renal fibrosis of diabetic nephropathy. In streptozotocin-induced fibrotic kidneys in diabetic CD-1 mice, levels of endothelial DPP-4, integrin β1, and phospho-integrin β1 were all higher and associated with plasma cystatin C elevation...
September 2015: Kidney International
Hiroyuki Hirakawa, Hirofumi Zempo, Masahito Ogawa, Ryo Watanabe, Jun-Ichi Suzuki, Hiroshi Akazawa, Issei Komuro, Mitsuaki Isobe
Myocarditis is a critical inflammatory disorder which causes life-threatening conditions. No specific or effective treatment has been established. DPP-4 inhibitors have salutary effects not only on type 2 diabetes but also on certain cardiovascular diseases. However, the role of a DPP-4 inhibitor on myocarditis has not been investigated. To clarify the effects of a DPP-4 inhibitor on myocarditis, we used an experimental autoimmune myocarditis (EAM) model in Balb/c mice. EAM mice were assigned to the following groups: EAM mice group treated with a DPP-4 inhibitor (linagliptin) (n = 19) and those untreated (n = 22)...
2015: PloS One
Nobutaka Koibuchi, Yu Hasegawa, Tetsuji Katayama, Kensuke Toyama, Ken Uekawa, Daisuke Sueta, Hiroaki Kusaka, MingJie Ma, Takashi Nakagawa, Bowen Lin, Shokei Kim-Mitsuyama
BACKGROUND: It remains to be elucidated whether dipeptidylpeptidase-4 (DPP-4) inhibitor can ameliorate cardiovascular injury in salt-sensitive hypertension. The present study was undertaken to test our hypothesis that linagliptin, a DPP-4 inhibitor, administration initiated after onset of hypertension and cardiac hypertrophy can ameliorate cardiovascular injury in Dahl salt-sensitive hypertensive rats (DS rats). METHODS: High-salt loaded DS rats with established hypertension and cardiac hypertrophy were divided into two groups, and were orally given (1) vehicle or (2) linagliptin (3 mg/kg/day) once a day for 4 weeks, and cardiovascular protective effects of linagliptin in DS rats were evaluated...
2014: Cardiovascular Diabetology
Chiung-Huei Peng, Yi-Sun Yang, Kuei-Chuan Chan, Chau-Jong Wang, Mu-Lin Chen, Chien-Ning Huang
The epithelial to mesenchymal transition (EMT) is important in renal fibrosis. Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1 (S307)) is a hallmark of insulin resistance. We report that polyphenol extracts of Hibiscus sabdariffa (HPE) ameliorate diabetic nephropathy and EMT. Recently it has been observed that type 4 dipeptidyl peptidase (DPP-4) inhibitor linagliptin is effective for treating type 2 diabetes and albuminuria. We investigated if DPP-4 and insulin resistance are involved in renal EMT and explored the role of HPE...
October 8, 2014: Journal of Agricultural and Food Chemistry
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"