Increased plasma DPP4 activities predict new-onset hyperglycemia in Chinese over a four-year period: Possible associations with inflammation

Zheng, Tianyuan; Baskota, Attit; Gao, Yun; Chen, Tao; Tian, Haoming; Yang, Fan

doi:10.1016/j.metabol.2014.12.004

Cited by 22 publications

(19 citation statements)

References 24 publications

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“…In contrast, our finding that body composition variables, such as body weight, BMI and fat mass, were not associated with the glucose‐lowering effect of alogliptin is inconsistent with previous reports. Our finding was unexpected, because DPP‐4 activity is positively associated with BMI and waist‐to‐hip ratio, and because DPP‐IV inhibitors have been shown to significantly lower blood glucose in participants with a low baseline BMI. C‐peptide immunoreactivity was not associated with a reduction in FPG and HbA1c in both the metformin and alogliptin groups in the present study.…”

Section: Discussioncontrasting

confidence: 99%

Effects of metformin and alogliptin on body composition in people with type 2 diabetes

Takeshita

Kita

Kato

et al. 2018

J of Diabetes Invest

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Section: Discussioncontrasting

confidence: 99%

Effects of metformin and alogliptin on body composition in people with type 2 diabetes

Takeshita

Kita

Kato

et al. 2018

J of Diabetes Invest

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“…Although plasma DPP4a levels have been directly associated with higher age in healthy volunteers and diabetic patients 12, 13 , inverse associations were found between DPP4a and age in this study. This may be caused by sialylation (a type of glycosylation) of soluble DPP4, which is strongly enhanced in the elderly.…”

Section: Discussioncontrasting

confidence: 72%

Plasma dipeptidyl-peptidase-4 activity is associated with left ventricular systolic function in patients with ST-segment elevation myocardial infarction

Chen

Liu

et al. 2017

Sci Rep

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Plasma dipeptidyl-peptidase-4 activity (DPP4a) is inversely associated with left ventricular function in patients with heart failure (HF) or diabetes. However, the association between DPP4a and left ventricular function in ST-segment elevation myocardial infarction (STEMI) patients has not been reported. We studied this association in 584 consecutive STEMI patients at a tertiary referral center from July 2014 to October 2015. DPP4a and plasma N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels were quantified by enzymatic assays. The median serum NT-proBNP levels were highest in patients of the lowest tertile (T1) of DPP4a compared with that of the highest tertile (T3) (p = 0.028). The STEMI patients in T1 exhibited lower left ventricular systolic function (T1 vs. T3: left ventricular ejection fraction (LVEF): 50.13 ± 9.12 vs. 52.85 ± 6.82%, p = 0.001). Multivariate logisticregression analyses (adjusted for confounding variables) showed that a 1 U/L increase in DPP4a was associated with a decreased incidence of left ventricular systolic dysfunction (LVSD) (adjusted odds ratio: 0.90; 95% CI: 0.87-0.94; p < 0.01). In conclusion, low DPP4a is independently associated with LVSD in STEMI patients, which suggests that DPP4 may be involved in the mechanisms of LVSD in STEMI patients.Left ventricular systolic dysfunction (LVSD), whose representative indicator is left ventricular ejection fraction (LVEF), is an important marker of poorer prognosis in patients after an acute myocardial infarction (AMI), for both in-hospital and long-term follow-up 1, 2 . Plasma biomarkers may provide insight into the pathogenesis of LVSD while also providing prognostic information in MI patients.Dipeptidyl-peptidase-4 (DPP4) is a widely expressed enzyme, cleaving off proteins containing a position 2 alanine or proline, and thus inactivating peptides 3 . DPP4 plays an important role in glucose metabolism and is responsible for the degradation of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide. DPP4 regulates immune responses via cleavage of many cytokines and chemokines, such as stromal-cell-derived factor-1 (SDF-1) 4 . Inhibition of DPP4 enhances endothelial regeneration and reduces atherosclerotic progression via the SDF1/chemokine receptor (CXCR)-4 axis 5 . Soluble DPP4 circulating in the plasma exerts catalytic activity cleaving oxyntomodulin 6 and SDF-1 7 , as does membrane-type DPP4. Soluble DPP4 plays a role in the development of insulin resistance, smooth muscle cell (SMC) proliferation, inflammation, and vasorelaxation 8 . Increased soluble DPP4 levels are associated with coronary artery disease 9 and heart failure (HF) 10 . We found that plasma DPP4 activity (DPP4a) is decreased in patients with MI compared with those with only chest pain or unstable angina pectoris. Also, we found that elevated DPP4a is associated with no-reflow phenomenon and a decreased rate of major bleeding events in ST-segment elevation myocardial infarction (STEMI) patients treated with percutaneous coronary ...

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“…Circulating levels of interleukin-6 (IL-6), C-reactive protein (CRP), 8-iso-PGF2a, nitrotyrosine, fasting active GLP-1, and DPP4 activity were measured as previously described (Zheng T. et al, 2014; Zheng et al, 2015a,b, 2016). …”

Section: Methodsmentioning

confidence: 99%

“…Dipeptidyl peptidase-4 (DPP4) is a widely expressed multifunctional exopeptidase that exists as a membrane-anchored cell surface protein or in a soluble form in the plasma (Matteucci and Giampietro, 2009). It has been identified as a novel adipokine playing crucial roles in GLP-1 degradation and in the development of inflammation and oxidative stress (Drucker and Nauck, 2006; Lamers et al, 2011; Zheng et al, 2015a,b). More interestingly, animal studies have proved that DPP4 activity inhibitors ameliorated cognitive impairment through suppressing inflammatory reaction, oxidative stress, or GLP-1 degradation (Gault et al, 2015; Ma et al, 2015; Tsai et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance

Chen

Zheng

Qin

et al. 2017

Front. Aging Neurosci.

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Objective: Inflammation, oxidative stress, and decreased glucagon-like peptide-1 (GLP-1) are risk factors for cognitive impairment. Dipeptidyl peptidase-4 (DPP4) was identified as a novel adipokine capable of enhancing these risk factors. Hence, we investigated the relationship between plasma DPP4 activity and impaired cognitive function in elderly Chinese population with normal glucose tolerance (NGT).Methods: We performed a cross-sectional study using data from 1229 elderly participants (60 years or older) in Guilin. Plasma DPP4 activity, oxidative stress parameters, fasting active GLP-1, and inflammatory markers were measured in all participants. Impaired cognitive function was diagnosed according to the National Institute on Aging-Alzheimer’s Association workgroups criteria.Results: Participants in the upper quartile of plasma DPP4 activity had higher C-reactive protein (CRP), interleukin-6 (IL-6), 8-iso-PGF2a, nitrotyrosine, and lower GLP-1 and Montreal Cognitive Assessment (MoCA) scores compared with those in the lowest quartile (P < 0.001). The odds ratios (ORs) for increased CRP, IL-6, 8-iso-PGF2a, nitrotyrosine, and decreased active GLP-1 were higher with increasing DPP4 quartiles after adjustment for confounders (all P < 0.001). In the highest DPP4 quartile, impaired cognitive function risk was higher (OR, 2.26; 95% confidence interval, 1.36–3.76) than in the lowest quartile after adjustment for potential confounders. The risk for impaired cognitive function increased more with higher levels of DPP4 activity, nitrotyrosine and 8-iso-PGF2a (P < 0.05), but not with higher IL-6, CRP or lower GLP-1.Conclusion: Plasma DPP4 activity is significantly and independently associated with impaired cognitive function, mainly executive, in elderly Chinese population with NGT. The underlying mechanisms for this association may be partly attributed to the effect of DPP4 on oxidative stress. Plasma DPP4 activity might serve as a risk biomarker or therapeutic target for the prevention and treatment of impaired cognitive function.

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Increased plasma DPP4 activities predict new-onset hyperglycemia in Chinese over a four-year period: Possible associations with inflammation

Cited by 22 publications

References 24 publications

Effects of metformin and alogliptin on body composition in people with type 2 diabetes

Effects of metformin and alogliptin on body composition in people with type 2 diabetes

Plasma dipeptidyl-peptidase-4 activity is associated with left ventricular systolic function in patients with ST-segment elevation myocardial infarction

Strong Association between Plasma Dipeptidyl Peptidase-4 Activity and Impaired Cognitive Function in Elderly Population with Normal Glucose Tolerance

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