Diagnostic Value of the Aminopeptidase N, N-Acetyl-β-D-Glucosaminidase and Dipeptidylpeptidase IV in Evaluating Tubular Dysfunction in Patients with Glomerulopathies

Mitić, Branka; Lazarević, Gordana; Vlahović, Predrag; Rajić, Milena; Stefanović, Vladisav

doi:10.1080/08860220802359048

Cited by 39 publications

(26 citation statements)

References 23 publications

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“…Interestingly, Wang and coworkers (Wang et al 2014) found that rat kidney extracts showed the highest DPP-4 activity; however, plasma DPP-4 activity did not decrease after kidney transplantation from a DPP-4-deficient rat into a wild-type one indicating that the kidney is not the main source of soluble DPP-4 under normal healthy conditions. In addition, it was reported that urinary DPP-4 activity was significantly higher in type 2 diabetic patients with microalbuminuria, an early sign of diabetic nephropathy, compared to healthy individuals (Mitic et al 2008). These observations highlight a potential role of DPP-4 in the development of diabetic nephropathy (von Websky et al 2014).…”

Section: Discovery Molecular Biology and Renal Expression Of Dpp-4mentioning

confidence: 73%

Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

Hasan

Hocher

2017

Journal of Molecular Endocrinology

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Diabetic nephropathy is one of the most frequent, devastating and costly complications of diabetes. The available therapeutic approaches are limited. Dipeptidyl peptidase type 4 (DPP-4) inhibitors represent a new class of glucose-lowering drugs that might also have reno-protective properties. DPP-4 exists in two forms: a plasma membranebound form and a soluble form, and can exert many biological actions mainly through its peptidase activity and interaction with extracellular matrix components. The kidneys have the highest DPP-4 expression level in mammalians. DPP-4 expression and urinary activity are up-regulated in diabetic nephropathy, highlighting its role as a potential target to manage diabetic nephropathy. Preclinical animal studies and some clinical data suggest that DPP-4 inhibitors decrease the progression of diabetic nephropathy in a blood pressure-and glucose-independent manner. Many studies reported that these reno-protective effects could be due to increased half-life of DPP-4 substrates such as glucagon-like peptide-1 (GLP-1) and stromal derived factor-1 alpha (SDF-1a). However, the underlying mechanisms are far from being completely understood and clearly need further investigations.

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Section: Discovery Molecular Biology and Renal Expression Of Dpp-4mentioning

confidence: 73%

Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

Hasan

Hocher

2017

Journal of Molecular Endocrinology

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“…DPP IV activity increases in the urine of patients with diabetes, especially those with microalbuminuria (Golubović et al, 1996;Mitic et al, 2008). These findings indicate that the change of DPP IV in urine is probably associated with diabetic nephropathy.…”

Section: Introductionmentioning

confidence: 83%

“…Increased DPP IV activity in the kidney or urine is a well recognized hallmark of diabetic patients and animals with renal dysfunction, which is probably an important sign or booster of the progression of diabetic nephropathy (Golubović et al, 1996;Yang et al, 2007;Mitic et al, 2008). In addition, patients with diabetes mellitus show dramatic loss of GLP-1 potency (Hojbjerg et al, 2007;Holst et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl Peptidase IV Inhibitor Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats

Liu¹,

Xie²,

Liu³

et al. 2011

J Pharmacol Exp Ther

198

164

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Dipeptidyl peptidase (DPP) IV inhibitors are probably beneficial for preventing diabetic complication and modulating glucagonlike peptide-1 receptor (GLP-1R) expression. The aim of this study was to determine whether the DPP IV inhibitor LAF237 (vildagliptin) has renoprotective qualities in streptozotocin-induced diabetic rats. Diabetic and nondiabetic rats were treated with an oral dose of 4 or 8 mg/kg/day LAF237 or placebo for 24 weeks, and renal injury was observed by light and electron microscopy. We also assessed DPP IV activity, active GLP-1 level, cAMP and 8-hydroxy-deoxyguanosine excretion, and GLP-1R, cleaved caspase 3, and transforming growth factor-␤1 (TGF-␤1) expression. LAF237 significantly decreased proteinuria, albuminuria, and urinary albumin/creatinine ratio, improved creatinine clearance, and dose-dependently inhibited interstitial expansion, glomerulosclerosis, and the thickening of the glomerular basement membrane in diabetic rats. It is noteworthy that LAF237 markedly down-regulated DPP IV activity and increased active GLP-1 levels, which probably prevented oxidative DNA damage and renal cell apoptosis by activating the GLP-1R and modulating cAMP. Renoprotection was also associated with a reduction in TGF-␤1 overexpression. Our study suggests that DPP IV inhibitors may ameliorate diabetic nephropathy as well as reduce the overproduction of TGF-␤1. The observed renoprotection is probably attributable to inhibition of DPP IV activity, mimicking of incretin action, and activation of the GLP-1R.

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“…[18][19][20] In addition to its role in T-cell biology, DPP IV also plays an important role in the pathogenesis of kidney diseases such as IgA nephropathy. 21 We here studied the excretion of DPP IV in urinary microvesicles in a small cohort of patients with T2DM by categorising them into three groups according to the severity of kidney damage. In this study, we first assessed the feasibility of using urine as a microvesicle source in the context of a clinical trial, and then investigated the changes in urinary microvesicle-DPP IV levels during different stages of DKD.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

Sun

Deng

Guan

et al. 2012

Diabetes and Vascular Disease Research

114

113

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The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group (n = 50); macroalbuminuria group (n = 34) and normoalbuminuria group (n = 43), and 34 age-and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.

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Diagnostic Value of the Aminopeptidase N, N-Acetyl-β-D-Glucosaminidase and Dipeptidylpeptidase IV in Evaluating Tubular Dysfunction in Patients with Glomerulopathies

Cited by 39 publications

References 23 publications

Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

Role of soluble and membrane-bound dipeptidyl peptidase-4 in diabetic nephropathy

Dipeptidyl Peptidase IV Inhibitor Attenuates Kidney Injury in Streptozotocin-Induced Diabetic Rats

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

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