Serum DPPIV Activity Research Articles

Consumption of a Sourdough-Leavened Croissant Enriched with a Blend of Fibers Influences Fasting Blood Glucose in a Randomized Controlled Trial in Healthy Subjects

BackgroundAn incorrect lifestyle, including diet, is responsible for the worldwide dramatic increase in obesity and type 2 diabetes. Increasing dietary fiber consumption may lead to health benefits, and reformulation of bakery products may be a strategy to globally improve the diet. ObjectivesThis study aimed to assess the impact of a 2-wk breakfast consumption with a sourdough-leavened croissant containing a blend of dietary fiber from 10 sources (4.8 g/100 g, croissant enriched with dietary fibers [FIBCRO]), compared with a control croissant (dietary fibers 1.3 g/100 g, CONCRO) on daily energy intake, appetite, metabolic variables, and the gut microbiome. MethodsThirty-two healthy participants were randomly allocated to 2 groups consuming FIBCRO or CONCRO. Participants self-recorded their diet and appetite through 7-d weighted food diaries and visual analog scales every day over the 2 wk. At baseline and after the intervention, fasting blood and urine samples, and fecal samples were collected beside blood pressure, anthropometry, and body composition. Serum glucose, lipids, C-reactive protein, and insulin according to the official methods and serum dipeptidyl peptidase-4 (DPPIV) activity by photometric method were measured. Polyphenols and urolithins in urines were analyzed by Liquid chromatography–tandem mass spectrometry (LC/MS/MS), whereas gut microbiome in feces by shotgun metagenomics. ResultsFIBCRO consumption improved fasting blood glucose compared with CONCRO (mean changes from baseline −2.0 mg/dL in FIBCRO compared with +3.1 mg/dL in CONCRO, P = 0.022), also reducing serum DPPIV activity by 1.7 IU/L (P = 0.01) and increasing urinary excretion of urolithin A-sulfate by 6.9 ng/mg creatinine (P = 0.04) compared with baseline. No further changes in any of the monitored variables or in the gut microbiome were detected. ConclusionsResults suggested that a 2-wk consumption of a sourdough croissant claimed as “source of dietary fiber” improved fasting glycemia compared with a conventional sourdough croissant in healthy subjects. The reduced serum DPPIV activity and increased bioavailability of urolithin likely contributed to determine that effect independently from gut microbiome changes.This trial was registered at clinicaltrials.gov as NCT04999280.

A sensitive fluorescence assay of serum dipeptidyl peptidase IV activity to predict the suitability of its inhibitors in patients with type 2 diabetes mellitus

DPP-IV inhibitors, which are close to the natural hypoglycemic pathway of human physiology and have few side effects, have been extensively employed in the management of type 2 diabetes mellitus (T2DM). However, there are currently no specific blood indicators that can indicate or predict a patient's suitability for DPP-IV inhibitors. In this study, based on the self-developed high-specificity fluorescent substrate glycyl-prolyl-N-butyl-4-amino-1, 8-naphthimide (GP-BAN), a detection method of human serum DPP-IV activity was established and optimized. The method demonstrates a favorable lower limit of detection (LOD) at 0.32 ng/mL and a satisfactory lower limit of quantification (LOQ) of 1.12 ng/mL, and can be used for the detection of DPP-IV activity in trace serum (2 μL). In addition, Vitalliptin and Sitagliptin showed similar IC50 values when human recombinant DPP-IV and human serum were used as enzyme sources, and the intra-day and inter-day precision obtained by the microplate analyzer were less than 15 %. These results indicate that the microplate reader based detection technique has good accuracy, repeatability and reproducibility. A total of 700 volunteers were recruited, and 646 serum samples were tested for DPP-IV activity. The results showed that serum DPP-IV activity was higher in patients with T2DM than in controls (P < 0.01). However, the statistical data of family history of diabetes, gender and age of diabetic patients showed no statistical significance, and there was no contrast difference. The DPP-IV activity of serum in T2DM patients ranged from 2.4 μmol/min/L to 78.6 μmol/min/L, with a huge difference of up to 32-fold. These results suggest that it is necessary to test DPP-IV activity in patients with T2DM when taking DPP-IV inhibitors to determine the applicability of DPP-IV inhibitors in T2DM patients. These results suggest that it is necessary to detect the activity of DPP-IV in blood before taking DPP-IV inhibitors in patients with T2DM to judge the applicability of DPP-IV inhibitors in patients with T2DM.

The Activity of Adenosine Deaminase and Dipeptidyl Peptidase IV in Children With Attention Deficit Hyperactivity Disorder

Objective: In this study, to investigate the place of T cell-mediated immunity in the etiology of ADHD, for which we do not have enough information; we aimed to investigate the activity of DPP IV and ADA, which are T cell-related enzymes, and the relationship of these enzymes with ADHD symptoms in children with ADHD. Methods: Twenty-seven children aged 6 to 12 years with a diagnosis of attention deficit hyperactivity disorder and 27 children aged 6 to 12 years without any psychiatric disease were included in the study. Results: While serum ADA and DPP-IV activity were found to be statistically significantly higher in the group with ADHD. There was no statistically significant correlation between serum ADA and DPP-IV activities and CTRS-R-L and CPRS-R-L in both groups. Conclusion: We think that T cell mediated inflammation may play a role in the etiology of ADHD due to changes in ADA and DPP-IV levels in children.

Serum IP-10 levels and increased DPPIV activity are linked to circulating CXCR3+ T cells in cholestatic HCV patients.

Background & aimsSerum interferon-gamma-inducible protein-10 (IP-10) is elevated in cholestatic liver diseases and predicts response to antiviral therapy in patients with chronic hepatitis C virus (HCV) infection. Dipeptidylpeptidase 4 (DPPIV) cleaves active IP-10 into an inactive form, which inhibits recruitment of CXCR3+ T cells to the liver. In this study the link between IP-10 levels, DPPIV activity in serum and CXCR3+ T cells is analysed in cholestatic and non-cholestatic liver patients.MethodsIn serum DPPIV activity (by enzymatic assay), IP-10 (by ELISA) and bile acids (BA) (by enzymatic assay) were analysed in 229 naive HCV genotype (GT) 1 patients and in 16 patients with cholestatic liver disease. In a prospective follow-up (FU) cohort of 27 HCV GT 1 patients peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ cells were measured by FACS.ResultsIn 229 HCV patients serum IP-10 levels correlated positively to DPPIV serum activity. Higher IP-10 levels and DPPIV activity were detected in cholestatic and in cirrhotic HCV patients. Increased IP-10 serum levels were associated with therapeutic non-response to antiviral treatment with pegylated-interferon and ribavirin. In the HCV FU cohort elevated IP-10 serum levels and increased BA were associated with higher frequencies of peripheral CD3+CXCR3+, CD4+CXCR3+ and CD8+CXCR3+ T cells. Positive correlation between serum IP-10 levels and DPPIV activity was likewise validated in patients with cholestatic liver diseases.ConclusionsA strong correlation between elevated serum levels of IP-10 and DPPIV activity was seen in different cholestatic patient groups. Furthermore, in cholestatic HCV patients a functional link to increased numbers of peripheral CXCR3+ immune cells could be observed. The source of DPPIV release in cholestatic patients remains open.

Association of CD26/dipeptidyl peptidase IV mRNA level in peripheral blood mononuclear cells with disease activity and bone erosion in rheumatoid arthritis.

Dipeptidyl peptidase IV (DPP-IV, CD26) plays many roles in the pathogenesis of several autoimmune and inflammatory diseases. The current study evaluated the association of DPP-IV enzymatic activity and its gene expression with disease activity and bone erosion in rheumatoid arthritis. Blood samples were collected from 20 rheumatoid arthritis patients and 40 healthy volunteers. Patients were divided into four subgroups using DAS28 index. CD26 gene expression levels were analyzed in peripheral blood mononuclear cells by quantitative reverse transcription-polymerase chain reaction. Additionally, the enzymatic activity of this molecule in serum was determined using Gly-Pro-p-nitroanilide as substrate. Digital radiography was applied to obtain images for bone erosion assessment. No significant difference in serum DPP-IV activity level was seen between patients and controls (p = 0.140). However, patients exhibited an increase in CD26 mRNA expression (1.68 times) when compared to controls (p = 0.001). Moreover, a strong positive correlation between CD26 gene expression and DAS28 index as well as bone erosion in the hands was observed (r = 0.71, p = 0.002 and r = 0.61, p = 0.049, respectively). This study demonstrated that CD26 mRNA expression in rheumatoid arthritis patients is associated with disease activity and bone erosion, suggesting a potential role for this molecule in the immunopathology of rheumatoid arthritis and bone erosion.

Obesity parameters, physical activity, and physical fitness are correlated with serum dipeptidyl peptidase IV activity in a healthy population

ObjectiveTo determine whether obesity, physical fitness, and physical activity parameters are associated with the enzymatic activity of serum dipeptidyl peptidase IV (sDPPIV) in a sample of healthy women and men. Design and methodsWe have correlated parameters of obesity, physical fitness, and physical activity with sDPPIV activity in 374 healthy subjects (age: 60.7 ± 6.9 years, body mass index: 26.1 ± 4.1 kg/m2). Enzymatic activity was analyzed using spectrofluorimetry, body composition was assessed by impedanciometry, physical fitness data were obtained using the Senior Fitness Test, and physical activity data were collected by accelerometer. Pearson's partial correlation analysis was applied to determine the relationship between DPPIV activity and the rest of parameters and significantly correlated variables were introduced into linear regression models to predict DPPIV. ResultsSerum DPPIV activity was negatively associated with obesity parameters such as body mass (r = −0.112), body mass index (BMI) (r = −0.147), waist circumference (r = −0.164), waist-to-hip ratio (−0.104), and percentage of fat mass (r = −0.185). Serum DPPIV activity was positively associated with cardiovascular fitness (r = 0.138), total amount of physical activity (r = 0.153), and time spent doing light exercise (r = 0.184). Regression models revealed sex differences in enzyme activity with overall activity higher in women than in men (β = 0.437, p < 0.001). Further, percent fat mass was an independent negative predictor of DPPIV activity (β = −0.184, p = 0.001). Serum DPPIV activity was positively predicted based on the amount of time spent doing light physical activity (β = 0.167, p = 0.001). ConclusionOur results demonstrate that sDPPIV activity is positively associated with healthier parameters regarding fatness, fitness and physical activity.

CD26 Expression on T Helper Populations and sCD26 Serum Levels in Patients with Rheumatoid Arthritis.

We studied dipeptidyl peptidase IV (DPP-IV, CD26) expression in different T helper cells and serum soluble DPP-IV/sCD26 levels in rheumatoid arthritis (RA) patients, correlated these with disease activity score (DAS), and examined how they were affected by different therapies, conventional or biological (anti-TNF, anti-CD20 and anti-IL6R or Ig-CTLA4). The percentage of CD4+CD45R0+CD26- cells was greatly reduced in patients (up to 50%) when compared with healthy subjects. Three other subsets of CD4 cells, including a CD26high Th1-associated population, changed variably with therapies. Data from these subsets (frequency and staining density) significantly correlated with DAS28 or DAS28 components but different in each group of patients undergoing the different therapies. Th17 and Th22 subsets were implicated in RA as independent CCR4+ and CCR4- populations each, with distinct CD26 expression, and were targeted with varying efficiency by each therapy. Serum DPP-IV activity rather than sCD26 levels was lower in RA patients compared to healthy donors. DPP-IV and sCD26 serum levels were found related to specific T cell subsets but not to disease activity. We conclude that, according to their CD26 expression, different cell subsets could serve to monitor RA course, and an uncharacterized T helper CD26- subset, not targeted by therapies, should be monitored for early diagnosis.

Serum activity of DPPIV and its expression on lymphocytes in patients with melanoma and in people with vitiligo

BackgroundDipeptidyl peptidase IV, a multifunctional serine protease, is implicated in regulation of malignant transformation, promotion and further progression of cancer, exerting tumor-suppressing or even completely opposite - tumor-promoting activities.The aim of present research was to determine the serum DPPIV activity, as well as the percentages of CD26+ lymphocytes, CD26+ overall white blood cells and the mean fluorescence intensity of CD26 expression on lymphocytes in patients with melanoma, people with vitiligo and in healthy controls.MethodsThe activity of DPPIV in serum was determined by colorimetric test. Expression of DPPIV (as CD26) on immunocompetent peripheral white blood cells was done using flow cytometry analysis.ResultsData from our study show for the first time statistically significant decrease: in the serum DPPIV activity, in the percentage of CD26+ overall white blood cells and in the percentage of lymphocytes in patients with melanoma in comparison to healthy control people. In addition, significantly lower serum DPPIV activity was found in the group of patients with melanoma in relation to people with vitiligo too.ConclusionThis study indicates the need for exploring the cause and the importance of the disturbances in the serum DPPIV activity and in the CD26 expression on immunocompetent cells in complex molecular mechanisms underlying the development and progression of melanoma.

Serum DPPIV activity and CD26 expression on lymphocytes in patients with benign or malignant breast tumors

The aim of this work was to determine serum DPPIV activity as well as the percentage of CD26+ white blood cells and of CD26+ lymphocytes and the mean fluorescence intensity (MFI) of CD26 expression on lymphocytes in groups of patients with benign or malignant breast tumors and in healthy control people. Serum DPPIV activity was determined by colorimetric test, while CD26+ cells were counted using flow cytometer. Results of this study show that there is no statistically significant difference in serum DPPIV activity between examined groups of patients and healthy controls. However, two times higher frequency of patients with breast cancers had the enhanced DPPIV enzymatic activity in comparison to controls. Significant decrease in the percentage of CD26+ total white blood cells was found in the group of breast cancer patients and in patients with benign breast tumors compared to that found for healthy people. Although there was decrease in the percentage of lymphocytes in patients with breast tumors it was not statistically significant. The MFI of CD26 expression on these cells was significantly lower for cancer patients in comparison to healthy controls.In conclusion, this work showed the enhanced frequency of breast cancer patients with higher serum DPPIV activity. Decreased percentage of CD26+ white blood cells and decreased CD26 expression on lymphocytes are also characteristics of this group of patients.Determination of the clinical outcome of analyzed patients, 1 and 2 years after the surgical resection of the tumor, would clarify potential prognostic values of examined parameters for breast cancer.

Incretin secretion and serum DPP-IV activity in Korean patients with type 2 diabetes

We evaluated incretin secretion and dipeptidyl peptidase (DPP)-IV activity in Korean type 2 diabetic patients compared with non-diabetic subjects. Type 2 diabetic patients showed intact GLP-1 and total GIP levels similar to those in non-diabetic subjects. Serum DPP-IV activity was significantly higher in type 2 diabetic patients ( p = 0.022).

Serum activity of dipeptidyl peptidase IV (DPPIV; EC 3.4.14.5) in breast-fed infants with symptoms of allergy

β-Casomorphins, opioid peptides present in mother's milk, are a good substrate for DPPIV (EC 3.4.14.5) which is a major factor limiting the half-life of biologically active peptides. Serum DPPIV activity of two groups of infants (healthy and atopic dermatitis) and contents of β-casomorphin-5 and -7 in their mothers’ milk were determined in the study. We have found correlation between those two parameters in the group of children with atopic dermatitis syndromes, while no such a correlation was found in the control group.

Similar increased serum dipeptidyl peptidase IV activity in chronic hepatitis C and other viral infections.

Dipeptidyl peptidase IV is a transmembrane enzyme widely expressed in many cell types, but also present as a soluble form in biological fluids. Its abnormal activity is sometimes associated with liver disease related pathologies. The aim of this study was to evaluate the clinical relevance of changes in serum DPPIV activity in hepatitis C and other viral infections. DPPIV activity was assessed by using a microplate-based colorimetric assay on serum from 88 subjects: 12 healthy uninfected controls, 10 patients with primary biliary cirrhosis (PBC) as a reference group, 36 HCV-infected patients, and patients suffering from viral infections of different etiologies. Levels of DPPIV activity were compared with: (1) those of other serum biochemical parameters such as alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma glutamyl transpeptidase (GGT), and bilirubin concentrations; and (2) criteria representative of liver histological status. Compared with healthy subjects, DPPIV activity was significantly increased during viral infections and in PBC (P<0.01). In HCV-infected patients, the median activity (interquartile range, IQR), 29.78 IU/l (24.66-35.95), differed significantly (P<0.05) from that of controls: 21.42 (19.76-24.93). No correlation was observed between DPPIV activity and either ALT, AST, bilirubin, or the stage of liver fibrosis and necroinflammatory activity, although GGT was moderately correlated (r=0.58, P<0.05). Although we confirmed an elevation of serum DPPIV activity in PBC, it seems to be a non-specific phenomenon common to viral infections. The absence of correlation between serum DPPIV and markers of liver disease in HCV-infected patients, suggests that this activity originates not only from the liver, but also from other sources such as peripheral blood cells involved in the control of viral infections.

Alterations in expression and in serum activity of dipeptidyl peptidase IV (DPP IV, CD26) in patients with hyporectic eating disorders.

The notion that patients with eating disorders maintain a functional immunosurveillance in spite of severe malnutrition has attracted researchers for years. Dipeptidyl peptidase IV (DPP IV), a serine protease with broad tissue distribution and known activity in serum, operates in the cascade of immune responses. Membrane-bound DPP IV expressed on lymphocytes, also known as the leucocyte antigen CD26, is considered to participate in T-cell activation. We hypothesized that the activity of DPP IV in serum and expression of CD26 in lymphocytes may be altered in patients with eating disorders. Serum DPP IV activity and the number of CD26 (DPP IV)-positive peripheral blood lymphocytes were measured in 34 patients [anorexia nervosa (AN): n = 11, bulimia (B): n = 23] in four consecutive weekly analyses. In addition, the expression of CD25 (interleukin-2 receptor alpha chain) was evaluated to estimate the degree of T-cell activation. The same analyses were carried out in healthy female volunteers (HC, n = 20). CD2-CD26-positive cells were reduced in patients compared with healthy controls [mean 40.2% (AN) and 41.1% (B) versus 47.4% (HC), P < 0.01], while the DPP IV activity in serum was elevated [mean 108.4 U/l (AN) versus 91.1 U/l (B) and 80.3 U/l (HC), P < 0.01]. The potential implications of our observations on, and beyond, immune function are discussed.

Lower serum dipeptidyl peptidase IV activity in treatment resistant major depression: relationships with immune-inflammatory markers.

Previous research in this laboratory has shown that major depression is accompanied by decreased serum activity of dipeptidyl peptidase IV (DPP IV), a serine protease that cleaves N terminal dipeptides from peptides with penultimate proline or alanine. DPP IV is involved in the metabolism of peptides, T cell activation and proliferation, including the production of cytokines, such as interleukin-1 (IL-1) and IL-2. The aim of this study was to examine (i) serum DPP IV activity in major and treatment resistant depression (TRD) in relation to other established immune and inflammatory markers of that illness, and (ii) the effects of antidepressive treatment on DPP IV activity. Serum DPP IV activity was significantly lower in major depression and TRD than in normal controls. In normal and major depressed subjects, there were significant and positive relationships between serum DPP IV activity and total serum protein, serum albumin, zinc, iron and transferrin. In the group of depressed subjects, there were significant and positive relationships between serum DPP IV activity and number of CD4+T cells and CD4+/CD8+ T cell ratio. There were no significant effects of subchronic treatment with antidepressants on serum DPP IV activity. The findings suggest that: (i) lower serum DPP activity may occur in chronic depression, TRD as well as in the acute phase of major depression; (ii) lower serum DPP IV accompanies the 'chronic' acute phase response in depression; and (iii) serum DPP IV activity is tightly coupled to increased number of CD4+ T cells in depressed subjects, but not in normal controls. Our results do not exclude the possible effects of longer-term treatment with antidepressants on serum DPP-IV activity.