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https://www.readbyqxmd.com/read/27898522/context-dependent-effects-of-dipeptidyl-peptidase-4-inhibitors
#1
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...
November 24, 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/27773844/a-murine-model-of-type-2-diabetes-mellitus-developed-using-a-combination-of-high-fat-diet-and-multiple-low-doses-of-streptozotocin-treatment-mimics-the-metabolic-characteristics-of-type-2-diabetes-mellitus-in-humans
#2
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...
October 20, 2016: Journal of Pharmacological and Toxicological Methods
https://www.readbyqxmd.com/read/27489282/carcinoembryonic-antigen-related-cell-adhesion-molecule-5-is-an-important-surface-attachment-factor-that-facilitates-entry-of-middle-east-respiratory-syndrome-coronavirus
#3
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
https://www.readbyqxmd.com/read/27213360/angiotensin-ii-stimulation-of-dpp4-activity-regulates-megalin-in-the-proximal-tubules
#4
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...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27000459/no-susceptibility-of-neonatal-and-adult-rats-against-the-middle-east-respiratory-syndrome-coronavirus
#5
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 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. While adult rats developed antibodies against MERS-CoV spike protein after intranasal inoculation, there was no evidence of virus replication in the lungs of adult, young, or neonatal rats after intranasal inoculation with MERS-CoV...
March 18, 2016: Japanese Journal of Infectious Diseases
https://www.readbyqxmd.com/read/26878135/da-1229-a-dipeptidyl-peptidase-iv-inhibitor-protects-against-renal-injury-by-preventing-podocyte-damage-in-an-animal-model-of-progressive-renal-injury
#6
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
https://www.readbyqxmd.com/read/26806752/-effect-of-dpp4-inhibitor-sitagliptin-on-expressions-of-early-growth-response-1-and-fibronectin-in-the-kidney-of-apoe-gene-knockout-mice
#7
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
https://www.readbyqxmd.com/read/26509887/linagliptin-limits-high-glucose-induced-conversion-of-latent-to-active-tgf%C3%A3-through-interaction-with-cim6pr-and-limits-renal-tubulointerstitial-fibronectin
#8
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
https://www.readbyqxmd.com/read/26379674/the-role-of-dipeptidyl-peptidase-4-inhibitors-in-diabetic-kidney-disease
#9
REVIEW
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
https://www.readbyqxmd.com/read/26375854/saxagliptin-reduces-renal-tubulointerstitial-inflammation-hypertrophy-and-fibrosis-in-diabetes
#10
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
https://www.readbyqxmd.com/read/26345339/the-influence-of-pharmaceutically-induced-weight-changes-on-estimates-of-renal-function-a-patient-level-pooled-analysis-of-seven-randomised-controlled-trials-of-glucose-lowering-medication
#11
COMPARATIVE STUDY
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
https://www.readbyqxmd.com/read/26021829/effects-of-a-dpp4-inhibitor-on-cisplatin-induced-acute-kidney-injury-study-protocol-for-a-randomized-controlled-trial
#12
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...
2015: Trials
https://www.readbyqxmd.com/read/25912235/a-new-combination-of-sitagliptin-and-furosemide-protects-against-remote-myocardial-injury-induced-by-renal-ischemia-reperfusion-in-rats
#13
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
https://www.readbyqxmd.com/read/25894260/-possibilities-of-therapy-glp1%C3%A2-ra-for-diabetics-with-nephropathy
#14
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
https://www.readbyqxmd.com/read/25368027/effect-of-dipeptidyl-peptidase-4-inhibition-on-arterial-blood-pressure-is-context-dependent
#15
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
https://www.readbyqxmd.com/read/25317241/treatment-of-type-2-diabetes-lifestyle-glp1-agonists-and-dpp4-inhibitors
#16
REVIEW
Gerald H Tomkin
In recent years the treatment focus for type 2 diabetes has shifted to prevention by lifestyle change and to more aggressive reduction of blood sugars during the early stage of treatment. Weight reduction is an important goal for many people with type 2 diabetes. Bariatric surgery is no longer considered a last resort treatment. Glucagon-like peptide-1 agonists given by injection are emerging as a useful treatment since they not only lower blood sugar but are associated with a modest weight reduction. The role of the oral dipeptidyl peptidase 4 inhibitors is emerging as second line treatment ahead of sulphonylureas due to a possible beneficial effect on the beta cell and weight neutrality...
October 15, 2014: World Journal of Diabetes
https://www.readbyqxmd.com/read/25249673/the-effects-of-dipeptidyl-peptidase-4-inhibition-on-microvascular-diabetes-complications
#17
REVIEW
Angelo Avogaro, Gian Paolo Fadini
We performed a review of the literature to determine whether the dipeptidyl peptidase-4 inhibitors (DPP4-I) may have the capability to directly and positively influence diabetic microvascular complications. The literature was scanned to identify experimental and clinical evidence that DPP4-I can ameliorate diabetic microangiopathy. We retrieved articles published between 1 January 1980 and 1 March 2014 in English-language peer-reviewed journals using the following terms: ("diabetes" OR "diabetic") AND ("retinopathy" OR "retinal" OR "nephropathy" OR "renal" OR "albuminuria" OR "microalbuminuria" OR "neuropathy" OR "ulcer" OR "wound" OR "bone marrow"); ("dipeptidyl peptidase-4" OR "dipeptidyl peptidase-IV" OR "DPP-4" OR "DPP-IV"); and ("inhibition" OR "inhibitor")...
October 2014: Diabetes Care
https://www.readbyqxmd.com/read/25122001/the-role-of-dipeptidyl-peptidase-4-dpp4-in-the-preservation-of-renal-function-dpp4-involvement-in-hemoglobin-expression
#18
Youichi Sato, Takanobu Kamada, Aiko Yamauchi
In a previous study, we demonstrated that dipeptidyl peptidase 4 (DPP4)-deficient rats were susceptible to reduced glomerular filtration rate as a result of streptozotocin (STZ)-induced diabetes. Therefore, we proposed that DPP4 might be responsible for the preservation of renal function. In this study, to verify the role of DPP4 in the preservation of renal function, we performed a microarray analysis of the kidneys of WT and DPP4-deficient rats after STZ treatment, and gene expression analysis using rat kidneys, human embryonic kidney 293 (HEK293) cells, and human renal cancer cells (CakI-1)...
November 2014: Journal of Endocrinology
https://www.readbyqxmd.com/read/25085841/intestinal-regulation-of-urinary-sodium-excretion-and-the-pathophysiology-of-diabetic-kidney-disease-a-focus-on-glucagon-like-peptide%C3%A2-1-and-dipeptidyl-peptidase%C3%A2-4
#19
REVIEW
Volker Vallon, Neil G Docherty
The tubular hypothesis of glomerular filtration and nephropathy in diabetes is a pathophysiological concept that assigns a critical role to the tubular system, including proximal tubular hyper-reabsorption and growth, which is relevant for early glomerular hyperfiltration and later chronic kidney disease. Here we focus on how harnessing the bioactivity of hormones released from the gut may ameliorate the early effects of diabetes on the kidney in part by attenuating proximal tubular hyper-reabsorption and growth...
September 2014: Experimental Physiology
https://www.readbyqxmd.com/read/24995775/dpp4-inhibition-attenuates-filtration-barrier-injury-and-oxidant-stress-in-the-zucker-obese-rat
#20
Ravi Nistala, Javad Habibi, Annayya Aroor, James R Sowers, Melvin R Hayden, Alex Meuth, William Knight, Tamara Hancock, Thomas Klein, Vincent G DeMarco, Adam Whaley-Connell
OBJECTIVE: Obesity-related glomerulopathy is characterized initially by glomerular hyperfiltration with hypertrophy and then development of proteinuria. Putative mechanisms include endothelial dysfunction and filtration barrier injury due to oxidant stress and immune activation. There has been recent interest in targeting dipeptidyl peptidase 4 (DPP4) enzyme due to increasing role in non-enzymatic cellular processes. METHODS: The Zucker obese (ZO) rat (aged 8 weeks) fed a normal chow or diet containing the DPP4 inhibitor linagliptin for 8 weeks (83 mg/kg rat chow) was utilized...
October 2014: Obesity
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