Greater circulating DPP4 activity is associated with impaired flow-mediated dilatation in adults with type 2 diabetes mellitus

被引：18

作者：

Barchetta, Ilaria ^{[1
]}

Ciccarelli, Gea ^{[1
]}

Barone, Eugenio ^{[2
]}

Cimini, Flavia A. ^{[1
]}

Ceccarelli, Valentina ^{[1
]}

Bertoccini, Laura ^{[1
]}

Sentinelli, Federica ^{[1
]}

Tramutola, Antonella ^{[2
]}

Del Ben, Maria ^{[3
]}

Angelico, Francesco ^{[3
]}

Baroni, Marco G. ^{[1
]}

Lenzi, Andrea ^{[1
]}

Cavallo, Maria G. ^{[1
]}

机构：

[1] Sapienza Univ Rome, Dept Expt Med, Rome, Italy

[2] Sapienza Univ Rome, Dept Biochem Sci, Rome, Italy

[3] Sapienza Univ Rome, Dept Internal Med & Med Specialties, Rome, Italy

来源：

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES | 2019年 / 29卷 / 10期

关键词：

Dipeptidyl peptidase 4; Endothelial function; Cardiovascular disease; Type 2 diabetes mellitus; DIPEPTIDYL PEPTIDASE 4; FATTY LIVER-DISEASE; IV ACTIVITY; ENDOTHELIAL FUNCTION; INSULIN-RESISTANCE; PROGENITOR CELLS; ATHEROSCLEROSIS; CHINESE; OBESITY; INHIBITOR;

D O I：

10.1016/j.numecd.2019.07.010

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background and aim: Dipeptidyl peptidase 4 (DPP4) is a key enzyme involved in the regulation of the incretin system exerted by cleaving the glucagon-like peptide 1 (GLP-1); the blockage of DPP4, exerted by the antidiabetic agents DPP4-inhibitors (DPP4-I), results in greater GLP-1 concentration and improved glycaemic control. DPP4 acts also as a pro-inflammatory molecule and mediates vascular damage in experimental models. The relationship between DPP4 activity and endothelial function in diabetes has not been explored yet. Aim of this study was to investigate systemic plasma DPP4 activity in relation to endothelial function in patients with type 2 diabetes mellitus (T2DM). Methods and results: Sixty-two T2DM individuals were recruited in our Diabetes outpatient clinics, Sapienza University, Rome, Italy. All participants underwent complete clinical work-up; endothelial function was evaluated by flow-mediated dilatation (FMD) test; plasma DPP4 activity was assessed by measuring the 7-amino-4-methylcoumarin (AMC) cleavage rate from the synthetic substrate H-glycyl-prolyl-AMC and compared with DPP4 activity measured in sixty-two age-, sex-, BMI-matched non-diabetic subjects. Patients with T2DM had significantly higher DPP4 activity than non-diabetic individuals (211,466 +/- 87657 vs 158,087 +/- 60267 nmol/min/ml, p < 0.001); in T2DM patients, greater DPP4 activity significantly correlated with lower FMD whereas was not associated with BMI and metabolic control. Greater systemic DPP4 activity was an independent predictor of reduced FMD after adjusting for age, gender and other confounders. Conclusions: Circulating DPP4 activity is increased in individuals with T2DM and associated with signs of endothelial dysfunction such as impaired FMD. DPP4 may negatively affect endothelial function through mechanisms beyond glucose homeostasis and metabolic control. (C) 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

引用

页码：1087 / 1094

页数：8

共 52 条

[1] The chemokine SDF-1 is a chemoattractant for human CD34(+) hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34(+) progenitors to peripheral blood [J].