Pathophysiological correlation of arginase-1 in development of type 2 diabetes from obesity in adolescents

被引:1
|
作者
Mazrouei, Safoura [1 ]
Petry, Sebastian Friedrich [2 ]
Sharifpanah, Fatemeh [3 ]
Javanmard, Shaghayegh Haghjooy [4 ]
Kelishadi, Roya [5 ]
Schulze, P. Christian [1 ]
Franz, Marcus [1 ]
Jung, Christian [6 ]
机构
[1] Univ Hosp Jena, Dept Internal Med 1, Jena, Germany
[2] Justus Liebig Univ, Ctr Internal Med, Med Clin & Polyclin 3, Clin Res Unit, Giessen, Germany
[3] Philipps Univ Marburg, Fac Med, Dent Dept, Marburg, Germany
[4] Isfahan Univ Med Sci, Cardiovasc Res Inst, Appl Physiol Res Ctr, Esfahan, Iran
[5] Isfahan Univ Med Sci, Res Inst Primordial Prevent Noncommunicable Dis, Child Growth & Dev Res Ctr, Esfahan, Iran
[6] Univ Hosp Dusseldorf, Dept Cardiol Pulmonol & Vasc Med, Dusseldorf, Germany
来源
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2023年 / 1867卷 / 02期
关键词
Arginase; NOS III; Adipocytokines; Insulin resistance; Obesity; Diabetes mellitus; ENDOTHELIAL-CELLS; INSULIN-RESISTANCE; OXIDATIVE STRESS; UP-REGULATION; TNF-ALPHA; INFLAMMATION; DYSFUNCTION; DISEASE; ADIPOCYTOKINES; COMPLICATIONS;
D O I
10.1016/j.bbagen.2022.130263
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Background: There is great interest to understand causal pathophysiological correlation between obesity and diabetes mellitus (DM). Vascular endothelial dysfunction is crucially involved in pathogenesis of vascular complications in DM. Recently, increased arginase expression and activity have been described as underlying mechanisms of endothelial dysfunction in DM and vascular inflammation in obesity. By limiting L-arginine bioavailability to endothelial nitric oxide synthase (NOS III), nitric oxide production is potentially impaired.Methods: We investigated the impact of plasma from diabetic and obese adolescents on arginase and NOS III expression in cultured human endothelial cells (ECs). A total of 148 male adolescents participated in this study including 18 obese, 28 type 1-, 28 type 2-DM patients, and 74 age-matched healthy volunteers.Results: A concurrent increase in arginase-1 (1.97-fold) and decrease in NOS III expression (1.45-fold) was observed in ECs exposed to type 2 diabetic plasma compared to control subjects. ECs incubated with type 1 DM plasma had a diminished NOS III level without impact on arginase-1 expression. Urea-assay featured an increased arginase activity in treated ECs with type 1-or 2-DM plasma. Despite increased pro-inflammatory cytokines and chemokines in obese plasma, arginase-1 expression/activity did not change in treated ECs. However, NOS III expression was significantly reduced. Pearson analysis revealed positive correlation between arginase-1, but not NOS III, expression with FBS in ECs treated with type 2-DM plasma.Conclusions: Our data demonstrate that increased arginase-1 expression/activity in ECs, as critical pathogenic factor is correlated with development of obesity-related type 2-DM and linked vascular disease.
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页数:13
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