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Dpp4 kidney

Kiran Shah
INTRODUCTION: Teneligliptin is a recently developed Dipeptidyl Peptidase 4 (DPP4) inhibitor. Teneligliptin is suitable for glycaemic control with renal impairment including end stage renal disease. AIM: To assess the efficacy and safety of teneligliptin in Asian Indian patients of Type 2 Diabetes Mellitus (T2DM) with early Diabetic Kidney Disease (DKD). MATERIALS AND METHODS: This was a single centre, retrospective analysis of patients with early DKD, who received teneligliptin 20 mg once daily for 24 weeks...
June 2017: Journal of Clinical and Diagnostic Research: JCDR
Yen-Ta Chen, Christopher Glenn Wallace, Chih-Chao Yang, Chih-Hung Chen, Kuan-Hung Chen, Pei-Hsun Sung, Yung-Lung Chen, Han-Tan Chai, Sheng-Ying Chung, Sarah Chua, Fan-Yen Lee, Sheung-Fat Ko, Mel S Lee, Hon-Kan Yip
We analyzed the effects of acute ischemia-reperfusion (KIR) injury on the status of kidney function and architecture in dipeptidyl peptidase4-difficient (DPP4D) rats and the effect of remote small bowel ischemia-reperfusion (BIR) preconditioning. DPP4-deficient (DPP4D) and normal Fischer344 (F344) rats were divided into 6 groups: (1) sham-F344, (2) sham-DPP4D, (3) KIR-F344 (4) KIR-DPP4D, (5) DPP4D-KIR-extendin-9-39 and (6) BIR-KIR-F344. Blood creatinine and urea nitrogen levels and the urinary protein-to-creatinine ratio was higher in KIR-F344 rats than BIR-KIR-F344 or KIR-DPP4D rats 72 h after acute KIR...
July 4, 2017: Oncotarget
Clement Lo, Min Jun, Sunil V Badve, Helen Pilmore, Sarah L White, Carmel Hawley, Alan Cass, Vlado Perkovic, Sophia Zoungas
BACKGROUND: Kidney transplantation is the preferred form of kidney replacement therapy for patients with end-stage kidney disease (ESKD) and is often complicated by worsening or new-onset diabetes. Management of hyperglycaemia is important to reduce post-transplant and diabetes-related complications. The safety and efficacy of glucose-lowering agents after kidney transplantation is largely unknown. OBJECTIVES: To evaluate the efficacy and safety of pharmacological interventions for lowering glucose levels in patients who have undergone kidney transplantation and have diabetes...
February 27, 2017: Cochrane Database of Systematic Reviews
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
Ravi Nistala, Virginia Savin
The protein dipeptidyl peptidase 4 (DPP4) is a target in diabetes management and reduction of associated cardiovascular risk. Inhibition of the enzymatic function and genetic deletion of DPP4 is associated with tremendous benefits to the heart, vasculature, adipose tissue, and the kidney in rodent models of obesity, diabetes and hypertension, and associated complications. The recently concluded, "Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53" trial revealed a reduction in proteinuria in chronic kidney disease patients (stages 1-3)...
April 1, 2017: American Journal of Physiology. Renal Physiology
Edwin K Jackson
PURPOSE OF REVIEW: The antidiabetic mechanism of dipeptidyl peptidase 4 (DPP4) inhibitors is attributed to attenuation of incretin metabolism. Because DPP4 has at least 45 substrates, context-dependent off-target effects of DPP4 inhibitors are likely. Here, we consider the clinical ramifications of the context-dependent effects of DPP4 inhibitors. RECENT FINDINGS: Although incretins protect organs from diabetic injury, nonincretin DPP4 substrates also accumulate when DPP4 is inhibited...
March 2017: Current Opinion in Nephrology and Hypertension
Sayantan Nath, Sankar Kumar Ghosh, Yashmin Choudhury
INTRODUCTION: A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. METHODS: Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day...
March 2017: Journal of Pharmacological and Toxicological Methods
Che-Man Chan, Hin Chu, Yixin Wang, Bosco Ho-Yin Wong, Xiaoyu Zhao, Jie Zhou, Dong Yang, Sze Pui Leung, Jasper Fuk-Woo Chan, Man-Lung Yeung, Jinghua Yan, Guangwen Lu, George Fu Gao, Kwok-Yung Yuen
UNLABELLED: The spike proteins of coronaviruses are capable of binding to a wide range of cellular targets, which contributes to the broad species tropism of coronaviruses. Previous reports have demonstrated that Middle East respiratory syndrome coronavirus (MERS-CoV) predominantly utilizes dipeptidyl peptidase 4 (DPP4) for cell entry. However, additional cellular binding targets of the MERS-CoV spike protein that may augment MERS-CoV infection have not been further explored. In the current study, using the virus overlay protein binding assay (VOPBA), we identified carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) as a novel cell surface binding target of MERS-CoV...
October 15, 2016: Journal of Virology
Annayya Aroor, Marcin Zuberek, Cornel Duta, Alex Meuth, James R Sowers, Adam Whaley-Connell, Ravi Nistala
Proteinuria is a marker of incipient kidney injury in many disorders, including obesity. Previously, we demonstrated that megalin, a receptor endocytotic protein in the proximal tubule, is downregulated in obese mice, which was prevented by inhibition of dipeptidyl protease 4 (DPP4). Obesity is thought to be associated with upregulation of intra-renal angiotensin II (Ang II) signaling via the Ang II Type 1 receptor (AT₁R) and Ang II suppresses megalin expression in proximal tubule cells in vitro. Therefore, we tested the hypothesis that Ang II will suppress megalin protein via activation of DPP4...
May 20, 2016: International Journal of Molecular Sciences
Naoko Iwata-Yoshikawa, Shuetsu Fukushi, Aiko Fukuma, Tadaki Suzuki, Makoto Takeda, Masato Tashiro, Hideki Hasegawa, Noriyo Nagata
The present study examined the susceptibility of rats to the Middle East respiratory syndrome coronavirus (MERS-CoV) and determined whether this animal is a suitable model for MERS-CoV infection. Immunohistochemical analysis identified dipeptidyl peptidase 4 (DPP4), a known receptor for MERS-CoV on type I pneumocytes from infected rats. Whereas adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of viral replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV...
November 22, 2016: Japanese Journal of Infectious Diseases
Jee Eun Lee, Jung Eun Kim, Mi Hwa Lee, Hye Kyoung Song, Jung Yeon Ghee, Young Sun Kang, Hye Sook Min, Hyun Wook Kim, Jin Joo Cha, Jee Young Han, Sang Youb Han, Dae Ryong Cha
Although dipeptidyl peptidase IV (DPPIV) inhibitors are known to have renoprotective effects, the mechanism underlying these effects has remained elusive. Here we investigated the effects of DA-1229, a novel DPPIV inhibitor, in two animal models of renal injury including db/db mice and the adriamycin nephropathy rodent model of chronic renal disease characterized by podocyte injury. For both models, DA-1229 was administered at 300 mg/kg/day. DPPIV activity in the kidney was significantly higher in diabetic mice compared with their nondiabetic controls...
May 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
Wenqi Li, Meiping Guan, Zongji Zheng, Yaoming Xue
OBJECTIVE: To investigate the effects of the DPP4 inhibitor sitagliptin on the expressions of early growth response-1 (Egr-1) and fibronectin in the kidney of ApoE gene knockout mice. METHODS: Eight-week-old male ApoE gene knockout mice were randomly divided into sitagliptin + apoE(-/-) group and apoE(-/-) group (n=6), with 6 C57BL mice as the normal control group. After feeding with high-fat diet and drug treatment for 16 weeks, the mice underwent intraperitoneal glucose tolerance test (IPGTT) and were measured for 24-h urinary albumin using ELISA...
January 2016: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Muralikrishna Gangadharan Komala, Simon Gross, Amgad Zaky, Carol Pollock, Usha Panchapakesan
BACKGROUND: In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic. We have previously shown that cation independent mannose-6-phosphate receptor (CIM6PR) facilitates the conversion of latent to active transforming growth factor β1 (GFß1) in renal proximal tubular cells (PTCs) and linagliptin (a DPP4 inhibitor) reduced this conversion with downstream reduction in fibronectin transcription...
2015: PloS One
Usha Panchapakesan, Carol Pollock
Despite major advances in the understanding of the molecular mechanisms that underpin the development of diabetic kidney disease, current best practice still leaves a significant proportion of patients with end-stage kidney disease requiring renal replacement therapy. This is on a background of an increasing diabetes epidemic worldwide. Although kidney failure is a major cause of morbidity the main cause of death remains cardiovascular in nature. Hence, diabetic therapies which are both "cardio-renal" protective seem the logical way forward...
2015: Frontiers in Immunology
Muralikrishna Gangadharan Komala, Simon Gross, Amgad Zaky, Carol Pollock, Usha Panchapakesan
AIM: In addition to lowering blood glucose in patients with type 2 diabetes mellitus, dipeptidyl peptidase 4 (DPP4) inhibitors have been shown to be antifibrotic and anti-inflammatory. We have previously shown that DPP4 inhibition in human kidney proximal tubular cells exposed to high glucose reduced fibrotic and inflammatory markers. Hence, we wanted to demonstrate renoprotection in an in vivo model. METHODS: We used a type 1 diabetic animal model to explore the renoprotective potential of saxagliptin independent of glucose lowering...
May 2016: Nephrology
Bernt Johan von Scholten, David Dynnes Ørsted, Anne Louise Svendsen, Frederik Persson, Peter Rossing
BACKGROUND: Estimation of kidney function (eGFR) is essential in monitoring of patients with kidney disease. Estimates of kidney function based on serum creatinine are derived from cross-sectional studies. If body weight (BW) changes, this might affect creatinine and eGFR. The Cockcroft-Gault (CG) equation includes creatinine and BW, whereas the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations only include creatinine...
November 2015: Journal of Diabetes and its Complications
Seon Ha Baek, Se Hyun Kim, Jin Won Kim, Yu Jung Kim, Keun-Wook Lee, Ki Young Na
BACKGROUND: Cisplatin is a potent chemotherapeutic agent, but its nephrotoxicity, which results in acute kidney injury (AKI), often limits its clinical application. Although many studies have attempted to target the mechanism responsible for its nephrotoxicity, no such method has been demonstrated to be effective in clinical trials. Recently, a dipeptidyl peptidase-4 (DPP4) inhibitor has been reported to have a renoprotective effect in a mouse model of cisplatin-induced AKI. Therefore, we will evaluate whether a DPP4 inhibitor protects the kidney from cisplatin-induced injury in humans...
May 29, 2015: Trials
Mahmoud I Youssef, Amr A A Mahmoud, Rasha H Abdelghany
Acute kidney injury (AKI) is associated with high mortality resulting from extra-renal organ damage, particularly the heart. The present study aimed to investigate the protective effect of sitagliptin, a dipeptidyl peptidase-4 (DPP4) inhibitor, against renal and remote cardiac damage induced by ischemia/reperfusion (IR), a leading cause of AKI. In this attempt, we compared the effects of sitagliptin to furosemide, a loop diuretic. Furosemide is commonly used clinically in AKI however, there is a lack of evidence regarding its beneficial effects in AKI...
July 1, 2015: Biochemical Pharmacology
Alena Adamíková
The incretin hormone GLP1 (glucagon-like peptide 1) has also systemic effects besides its effects on the pancreas. The renal expression for the receptors GLP1 and DPP4 has been described in a whole line of experimental stu-dies. Activation of the receptors for GLP1 in the kidneys has diuretic and natriuretic effects apparently through the renal tubular cells and sodium transporters. Pre-clinical incretin therapy decreased albuminuria, affected glomerulosclerosis, oxidative stress and fibrosis in the kidneys...
April 2015: Vnitr̆ní Lékar̆ství
Edwin K Jackson, Zaichuan Mi, Stevan P Tofovic, Delbert G Gillespie
UNLABELLED: Because the effects of dipeptidyl peptidase 4 (DPP4) inhibitors on blood pressure are controversial, we examined the long-term effects of sitagliptin (80 mg/kg per day) on blood pressure (radiotelemetry) in spontaneously hypertensive rats (SHR), Wistar-Kyoto rats, and Zucker Diabetic-Sprague Dawley rats (metabolic syndrome model). In SHR, chronic (3 weeks) sitagliptin significantly increased systolic, mean, and diastolic blood pressures by 10.3, 9.2, and 7.9 mm Hg, respectively, a response abolished by coadministration of BIBP3226 (2 mg/kg per day; selective Y1-receptor antagonist)...
January 2015: Hypertension
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