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renal sitagliptin

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https://www.readbyqxmd.com/read/29163755/uncoupling-protein-2-a-key-player-and-a-potential-therapeutic-target-in-vascular-diseases
#1
REVIEW
Giorgia Pierelli, Rosita Stanzione, Maurizio Forte, Serena Migliarino, Marika Perelli, Massimo Volpe, Speranza Rubattu
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29136947/the-effect-of-the-dipeptidyl-peptidase-4-inhibitor-sitagliptin-on-gentamicin-nephrotoxicity-in-mice
#2
Yousuf M Al Suleimani, Aly M Abdelrahman, Turan Karaca, Priyadarsini Manoj, Mohammed Ashique, Abderrahim Nemmar, Badreldin H Ali
This study aimed at investigating the possible ameliorative effects of sitagliptin in mice with gentamicin (GEN) nephrotoxicity. Sitagliptin was given to the animals at an oral dose of 10mgkg(-1) per day for 10days, and in some of these mice, GEN was injected intraperitoneally at a dose of 100mgkg(-1) per day during the last seven days of the treatment. Nephrotoxicity was evaluated histopathologically by light microscopy and biochemically by measuring several indices in plasma, urine and renal cortex homogenates...
November 9, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29114002/sdf-1%C3%AE-stromal-cell-derived-factor-1%C3%AE-induces-cardiac-fibroblasts-renal-microvascular-smooth-muscle-cells-and-glomerular-mesangial-cells-to-proliferate-cause-hypertrophy-and-produce-collagen
#3
Edwin K Jackson, Yumeng Zhang, Delbert D Gillespie, Xiao Zhu, Dongmei Cheng, Travis C Jackson
BACKGROUND: Activated cardiac fibroblasts (CFs), preglomerular vascular smooth muscle cells (PGVSMCs), and glomerular mesangial cells (GMCs) proliferate, cause hypertrophy, and produce collagen; in this way, activated CFs contribute to cardiac fibrosis, and activated PGVSMCs and GMCs promote renal fibrosis. In heart and kidney diseases, SDF-1α (stromal cell-derived factor 1α; endogenous CXCR4 [C-X-C motif chemokine receptor 4] receptor agonist) levels are often elevated; therefore, it is important to know whether and how the SDF-1α/CXCR4 axis activates CFs, PGVSMCs, or GMCs...
November 7, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/29113790/the-persistent-inhibitory-properties-of-saxagliptin-on-renal-dipeptidyl-peptidase-4-studies-with-hk-2-cells-in%C3%A2-vitro-and-normal-rats-in%C3%A2-vivo
#4
Masako Uchii, Mariko Sakai, Yuhei Hotta, Satoshi Saeki, Naoya Kimoto, Akinori Hamaguchi, Tetsuya Kitayama, Shunji Kunori
Saxagliptin, a potent and selective DPP-4 inhibitor, exhibits a slow dissociation from DPP-4. We investigated the sustained effects of saxagliptin on renal DPP-4 activity in a washout study using renal tubular (HK-2) cells, and in a pharmacodynamic study using normal rats. In HK-2 cells, the inhibitory potency of saxagliptin on DPP-4 activity persisted after washout, while that of sitagliptin was clearly reduced. In normal rats, a single treatment of saxagliptin or sitagliptin inhibited the plasma DPP-4 activity to similar levels...
October 23, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29101811/ameliorative-potential-of-sitagliptin-and-or-resveratrol-on-experimentally-induced-clear-cell-renal-cell-carcinoma
#5
Ahmed M Kabel, Aliaa Atef, Remon S Estfanous
The aim of this study was to assess the effect of sitagliptin with or without resveratrol on carcinogen-induced clear cell renal cell carcinoma. Sixty male Wistar rats were divided into 6 equal groups as follows: control; clear cell renal cell carcinoma group; clear cell renal cell carcinoma+sitagliptin group; clear cell renal cell carcinoma+resveratrol group; clear cell renal cell carcinoma+carboxymethyl cellulose group and clear cell renal cell carcinoma+sitagliptin+resveratrol group. Blood urea, serum creatinine, creatinine clearance, urinary N-acetyl beta-d-glucosaminidase (NAG), gamma glutamyl transpeptidase (GGT) and urinary albumin excretion rate (UAER) were determined...
November 1, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29098166/renoprotective-effects-of-the-dipeptidyl-peptidase-4-inhibitor-sitagliptin-a-review-in-type-2-diabetes
#6
REVIEW
Cristina Mega, Edite Teixeira-de-Lemos, Rosa Fernandes, Flávio Reis
Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties...
2017: Journal of Diabetes Research
https://www.readbyqxmd.com/read/29042993/sitagliptin-ameliorates-high-glucose-induced-cell-proliferation-and-expression-of-the-extracellular-matrix-in-glomerular-mesangial-cells
#7
Guan-Ying Zhang, Dong-Dong Wang, Zheng Cao, Tong Wei, Chen-Xu Liu, Qun-Li Wei
Diabetic nephropathy (DN) is one of the most important causes that leads to end-stage renal disease and the efficacy of strategies currently available for the prevention of DN remains unsatisfactory. Sitagliptin (SIT), which is a dipeptidyl peptidase-4 inhibitor, exhibited a modest beneficial effect on glycated hemoglobin levels and is capable of ameliorating renal ischemia reperfusion injury. By determining the expression of transforming growth factor-β1 (TGF-β1), connective tissue growth factor (CTGF), collagen type IV (ColIV) and fibronectin (FN) levels in high glucose-cultured glomerular mesangial cells (MCs), the present study aimed to assess the anti-proliferative and anti-fibrotic effects of SIT on the therapeutic potential for the prevention of DN and its mechanism...
October 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29025406/impact-of-empagliflozin-on-subclinical-left-ventricular-dysfunctions-and-on-the-mechanisms-involved-in-myocardial-disease-progression-in-type-2-diabetes-rationale-and-design-of-the-empa-heart-trial
#8
Andrea Natali, Lorenzo Nesti, Iacopo Fabiani, Enrico Calogero, Vitantonio Di Bello
BACKGROUND: Asymptomatic left ventricular (LV) dysfunction is highly prevalent in type 2 diabetes patients. Unlike the other hypoglycemic drugs, SGLT2 inhibitors have shown potential benefits for reducing cardiovascular death and risk factors, aside from lowering plasma glucose levels. With this study we aim at determining whether the treatment with empagliflozin is associated with an improvement in LV functions in diabetic patients with asymptomatic LV dysfunction against Sitagliptin, which is presumably neutral on myocardial function...
October 12, 2017: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/28738449/pbpk-modeling-of-the-effect-of-reduced-kidney-function-on-the-pharmacokinetics-of-drugs-excreted-renally-by-organic-anion-transporters
#9
C-H Hsueh, V Hsu, P Zhao, L Zhang, K M Giacomini, S-M Huang
Altered pharmacokinetics (PK) in subjects with chronic kidney disease (CKD) may lead to dosing adjustment of certain drugs in subjects with CKD. It can be valuable to quantitatively predict PK in CKD for the management of drug dosing in these subjects. We developed physiologically based pharmacokinetic (PBPK) models of seven renally eliminated drugs: adefovir, avibactam, entecavir, famotidine, ganciclovir, oseltamivir carboxylate, and sitagliptin. These drugs are all substrates of renal organic anion transporters (OATs)...
July 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28652790/sitagliptin-ameliorates-oxidative-stress-in-experimental-diabetic-nephropathy-by-diminishing-the-mir-200a-keap-1-nrf2-antioxidant-pathway
#10
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/28550195/dipeptidyl-peptidase-4-inhibition-stimulates-distal-tubular-natriuresis-and-increases-in-circulating-sdf-1%C3%AE-1-67-in-patients-with-type-2-diabetes
#11
Julie A Lovshin, Harindra Rajasekeran, Yulyia Lytvyn, Leif E Lovblom, Shajiha Khan, Robel Alemu, Amy Locke, Vesta Lai, Huaibing He, Lucinda Hittle, Weixun Wang, Daniel J Drucker, David Z I Cherney
OBJECTIVE: Antihyperglycemic agents, such as empagliflozin, stimulate proximal tubular natriuresis and improve cardiovascular and renal outcomes in patients with type 2 diabetes. Because dipeptidyl peptidase 4 (DPP-4) inhibitors are used in combination with sodium-glucose cotransporter 2 (SGLT2) inhibitors, we examined whether and how sitagliptin modulates fractional sodium excretion and renal and systemic hemodynamic function. RESEARCH DESIGN AND METHODS: We studied 32 patients with type 2 diabetes in a prospective, double-blind, randomized, placebo-controlled trial...
August 2017: Diabetes Care
https://www.readbyqxmd.com/read/28432745/safety-of-sitagliptin-in-patients-with-type-2-diabetes-and-chronic-kidney-disease-outcomes-from-tecos
#12
Samuel S Engel, Shailaja Suryawanshi, Susanna R Stevens, Robert G Josse, Jan H Cornel, Neli Jakuboniene, Axel Riefflin, Tsvetalina Tankova, Julio Wainstein, Eric D Peterson, Rury R Holman
AIMS: To characterize the incidence of diabetes-associated complications and assess the safety of sitagliptin in participants with chronic kidney disease (CKD) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). MATERIALS AND METHODS: For participants with baseline eGFR measurements (n = 14 528), baseline characteristics and safety outcomes were compared for the CKD cohort (eGFR < 60 mL/min per 1.73 m(2) ) vs those without CKD...
April 22, 2017: Diabetes, Obesity & Metabolism
https://www.readbyqxmd.com/read/28423178/head-to-head-comparison-of-structurally-unrelated-dipeptidyl-peptidase-4-inhibitors-in-the-setting-of-renal-ischemia-reperfusion-injury
#13
Christoph Reichetzeder, Karoline von Websky, Oleg Tsuprykov, Azadeh Mohagheghi Samarin, Luise Gabriele Falke, Sulistyo Emantoko Dwi Putra, Ahmed Abdallah Hasan, Viktoriia Antonenko, Caterina Curato, Jörg Rippmann, Thomas Klein, Berthold Hocher
BACKGROUND AND PURPOSE: Results regarding protective effects of dipeptidyl peptidase 4 (DPP4) inhibitors in renal ischaemia-reperfusion injury (IRI) are conflicting. Here we have compared structurally unrelated DPP4 inhibitors in a model of renal IRI. EXPERIMENTAL APPROACH: IRI was induced in uninephrectomized male rats by renal artery clamping for 30 min. The sham group was uninephrectomized but not subjected to IRI. DPP4 inhibitors or vehicle were given p.o. once daily on three consecutive days prior to IRI: linagliptin (1...
July 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28382499/sitagliptin-exerts-anti-apoptotic-effect-in-nephrotoxicity-induced-by-cisplatin-in-rats
#14
Rehab S Abdelrahman
Sitagliptin is a selective inhibitor of dipeptidylpeptidase-4 enzyme used for the management of diabetes mellitus type II. The anti-inflammatory, antioxidant, and anti-apoptotic properties of sitagliptin were documented. This study was designed to explore the effect of sitagliptin (10 mg/kg, orally) on nephrotoxicity induced by cisplatin (7 mg/kg, i.p.) in Sprague-Dawley rats. Nephrotoxicity of cisplatin was manifested by elevation in renal somatic index, proteinuria, blood urea nitrogen, creatinine in serum, lactate dehydrogenase, kidney malondialdehyde, NF-κB, Bax, and annexin V...
July 2017: Naunyn-Schmiedeberg's Archives of Pharmacology
https://www.readbyqxmd.com/read/28329747/influence-of-dipeptidyl-peptidase-iv-inhibitor-sitagliptin-on-extracellular-signal-regulated-kinases-1-2-signaling-in-rats-with-diabetic-nephropathy
#15
Xiaojun Ren, Gaohong Liu, Yanhong Wang, Wan Zhang, Fuping Xue, Rongshan Li, Weimin Yu
The protective effects of sitagliptin on the kidneys of rats with diabetic nephropathy (DN) and its influence on extracellular signal-regulated kinases 1/2 (ERK1/2) signaling were investigated. Male Wistar rats (n = 40) were randomly assigned to normal control, DN, low-dose sitagliptin intervention (ST1), or high-dose sitagliptin intervention (ST2) groups. Animals were euthanized after a 16-week treatment, and blood glucose (BG), glycosylated hemoglobin (HbA1c), urinary albumin excretion rate (AER), serum creatinine (Scr), creatinine clearance rate (Ccr), active glucagon-like peptide-1 (GLP-1) levels, kidney hypertrophy index, and renal pathohistology were determined...
2017: Pharmacology
https://www.readbyqxmd.com/read/28323955/rapid-onset-of-diabetic-ketoacidosis-after-sglt2-inhibition-in-a-patient-with-unrecognized-acromegaly
#16
Marino Quarella, Daniel Walser, Michael Brändle, Jean-Yves Fournier, Stefan Bilz
Context: Diabetic ketoacidosis has been described as a rare complication of acromegaly and may be observed in 1% of affected patients. The well-described direct lipolytic effect of growth hormone results in increased availability of free fatty acids (FFAs) for hepatic ketogenesis and is an important pathogenic event. More recently, ketoacidosis has been identified as an important complication of sodium-glucose-transport-protein 2 inhibitors (SGLT2i). Increased pancreatic glucagon secretion, impaired renal ketone body clearance, and an increase in FFA concentrations secondary to decreased insulin concentrations are likely precipitating factors...
May 1, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28179965/primary-care-based-investigation-of-the-effect-of-sitagliptin-on-blood-pressure-in-hypertensive-patients-with-type-2-diabetes
#17
Shouhei Yuasa, Kazuyoshi Sato, Takamoto Furuki, Kosuke Minamizawa, Hiroyuki Sakai, Yuichi Numata, Keiichi Chin, Jisho Kojima, Masaaki Miyakawa, Ikuro Matsuba
BACKGROUND: The influence of long-term sitagliptin therapy on office blood pressure (BP) and home BP has been unclear. METHODS: In a retrospective cohort study of 454 patients with type 2 diabetes, the following variables were analyzed before and at 3, 6, 9, and 12 months after initiation of sitagliptin therapy: office systolic blood pressure (SBP), office diastolic blood pressure (DBP), office pulse rate, morning home SBP, morning home DBP, morning home pulse rate, evening home SBP, evening home DBP, evening home pulse rate, hemoglobin A1c (HbA1c), plasma glucose, lipid profile, and renal function parameters...
March 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28177527/effects-of-linagliptin-on-human-immortalized-podocytes-a-cellular-system-to-study-dipeptidyl-peptidase-4-inhibition
#18
Gianluca Miglio, Giovanna Vitarelli, Thomas Klein, Elisa Benetti
BACKGROUND AND PURPOSE: Dipeptidyl-peptidase 4 (DPP4) is expressed by resident renal cells, including glomerular cells. DPP4 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 the behaviour of immortalized human podocytes and mesangial cells were evaluated. EXPERIMENTAL APPROACH: The expression of DPP4 was measured at both the mRNA and protein levels...
May 2017: British Journal of Pharmacology
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
#19
RANDOMIZED CONTROLLED TRIAL
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)...
June 2017: Vascular Medicine
https://www.readbyqxmd.com/read/28131656/integration-of-recent-evidence-into-management-of-patients-with-atherosclerotic-cardiovascular-disease-and-type-2-diabetes
#20
REVIEW
Eberhard Standl, Oliver Schnell, Darren K McGuire, Antonio Ceriello, Lars Rydén
Cardiovascular outcome trials of antihyperglycaemic drugs and non-statin LDL-cholesterol-lowering drugs in patients with type 2 diabetes who have, or who are at high risk of, atherosclerotic cardiovascular disease have provided new evidence that has substantially affected the management of cardiovascular risk in these patients. On the basis of proven cardiovascular and renal benefit, the antihyperglycaemic drugs empagliflozin, liraglutide, and semaglutide-the latter being under review for approval by the US Food and Drug Administration and the European Medicines Agency-should be preferentially used as second-line treatments in these patient populations, typically in addition to metformin...
May 2017: Lancet Diabetes & Endocrinology
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