Oxidative Stress in Type 1 Diabetes

Type 1 diabetes has been associated with oxidative stress. This study evaluates the rates of oxidative stress, mitochondrial function, leukocyte–endothelium interactions and adhesion molecules in type 1 diabetic patients. The study population consisted of 52 diabetic patients and 46 body-composition and age-matched controls. We assessed anthropometric and metabolic parameters, oxidative stress and mitochondrial function by evaluating reactive oxygen species (ROS) production, mitochondrial ROS production, mitochondrial membrane potential and superoxide dismutase (SOD) and catalase (CAT) expression in polymorphonuclear leukocytes from type 1 diabetic patients. In addition, we evaluated interactions between leukocytes and human umbilical vein endothelial cells (HUVEC), and serum expression of adhesion molecules (P-selectin, VCAM-1 and ICAM-1), proinflammatory cytokines (IL-6 and TNFα) and myeloperoxidase (MPO). HbA1C and glucose levels were higher in diabetic patients than in control subjects, as expected. Mitochondrial function was altered and leukocyte–endothelium interactions were enhanced in diabetic patients, which was evident in the increase in total and mitochondrial ROS production, higher mitochondrial membrane potential, enhanced leukocyte rolling and adhesion, and decreased rolling velocity. Furthermore, we observed an increase in levels of adhesion molecules P-selectin, VCAM-1, and ICAM-1 in these subjects. In addition, type 1 diabetic patients exhibited an increase in proinflammatory mediators TNFα and MPO, and a decreased expression of SOD. The enhancement of leukocyte–endothelium interactions and proinflammatory markers correlated with glucose and HbA1Clevels. Mitochondrial alteration, oxidative stress, and enhanced leukocyte–endothelium interactions are features of type 1 diabetes and may be related to cardiovascular implications.

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Relationship between bone turnover markers and oxidative stress in children with type 1 diabetes mellitus

Pediatric Research ◽

10.1038/s41390-020-01197-5 ◽

2020 ◽

Author(s):

Doaa El Amrousy ◽

Dalia El-Afify ◽

Ahmed Shabana

Keyword(s):

Oxidative Stress ◽

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Bone Turnover ◽

Type 1 Diabetes Mellitus ◽

Bone Turnover Markers ◽

Turnover Markers ◽

And Oxidative Stress

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Urinary oxidative stress markers in young patients with type 1 diabetes

Pediatrics International ◽

10.1111/j.1442-200x.2006.02156.x ◽

2006 ◽

Vol 48 (1) ◽

pp. 58-61 ◽

Cited By ~ 28

Author(s):

IKUE HATA ◽

MASAYUKI KAJI ◽

SATOKO HIRANO ◽

YOSUKE SHIGEMATSU ◽

HIROKAZU TSUKAHARA ◽

...

Keyword(s):

Oxidative Stress ◽

Type 1 Diabetes ◽

Young Patients ◽

Oxidative Stress Markers ◽

Stress Markers

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Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1

Cardiovascular Research ◽

10.1093/cvr/cvaa168 ◽

2020 ◽

Author(s):

Sofiane Ouerd ◽

Noureddine Idris-Khodja ◽

Michelle Trindade ◽

Nathanne S Ferreira ◽

Olga Berillo ◽

...

Keyword(s):

Oxidative Stress ◽

Type 1 Diabetes ◽

T Cell ◽

Aortic Arch ◽

Vascular Complications ◽

Cell Infiltration ◽

Aortic Sinus ◽

T Cell Infiltration ◽

Perivascular Fat

Abstract Aims NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe−/−) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. Methods and results Six-week-old male Apoe−/− and eET-1/Apoe−/− mice with or without Nox1 (Nox1−/y) or Nox4 knockout (Nox4−/−) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe−/− mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe−/− and eET-1/Apoe−/−/Nox4−/− mice but not eET-1/Apoe−/−/Nox1y/− mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe−/− mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe−/− mice. Conclusion Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.

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