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

Abstract

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.

Circulating dipeptidyl peptidase-4 activity is associated with insulin resistance in type 1 diabetic patients

“…Serum DPP4 activity is also higher in T2DM individuals with IR compared to those without [16]. DPP4 is highly expressed on kidney cell surface and data are available to suggest that DPP4 levels may associated with of renal function [17]. Moreover, insulin sensitivity, assessed by hyperinsulinemic-euglycemic clamp, is continuously associated with a greater risk of increasing albuminuria [18].…”

“…Furthermore, we also demonstrated that systolic and diastolic blood pressure are lowest in the first tertile and that systolic blood pressure correlates positively with enzymatic activity. With respect to this and the recent data on high expression of this enzyme in the kidney [17] there is a possibility that kidney function may play a role in DPP4 serum activity. Following the data interpretation in the light of indexes of kidney function, DPP4 serum activity remained independently associated with lower insulin sensitivity.…”

Microvesicles and diabetic complications — novel mediators, potential biomarkers and therapeutic targets

“…Moreover, urinary excretion of MV-associated DPP-IV is increased in T2DM patients, and the levels of MV-associated DPP-IV in urine are positively correlated with the urinary albumin/ creatinine ratio [127] . Therefore, MV-associated DPP-IV in urine may be an early marker of renal damage before the onset of albuminuria [127] .…”

“…Elevated levels of endothelial-derived MVs and monocytederived MVs may serve as biomarkers for nephropathy progression in T2DM [14,55,74] . A recent study showed that MVassociated dipeptidyl peptidase-IV (DPP-IV) is the major form of DPP-IV in urine, which is secreted from tubular epithelial cells and is related to early tubular impairment [127] . Moreover, urinary excretion of MV-associated DPP-IV is increased in T2DM patients, and the levels of MV-associated DPP-IV in urine are positively correlated with the urinary albumin/ creatinine ratio [127] .…”

“…A recent study showed that MVassociated dipeptidyl peptidase-IV (DPP-IV) is the major form of DPP-IV in urine, which is secreted from tubular epithelial cells and is related to early tubular impairment [127] . Moreover, urinary excretion of MV-associated DPP-IV is increased in T2DM patients, and the levels of MV-associated DPP-IV in urine are positively correlated with the urinary albumin/ creatinine ratio [127] . Therefore, MV-associated DPP-IV in urine may be an early marker of renal damage before the onset of albuminuria [127] .…”