The mitochondria-targeted antioxidant MitoQ modulates oxidative stress, inflammation and leukocyte-endothelium interactions in leukocytes isolated from type 2 diabetic patients.

It is not known if the mitochondria-targeted antioxidants such as mitoquinone (MitoQ) can modulate oxidative stress and leukocyte-endothelium interactions in T2D patients. We aimed to evaluate the beneficial effect of MitoQ on oxidative stress parameters and leukocyte-endothelium interactions in leukocytes of T2D patients. The study population consisted of 98 T2D patients and 71 control subjects. We assessed metabolic and anthropometric parameters, mitochondrial reactive oxygen species (ROS) production, glutathione peroxidase 1 (GPX-1), NFκB-p65, TNFα and leukocyte-endothelium interactions. Diabetic patients exhibited higher weight, BMI, waist circumference, SBP, DBP, glucose, insulin, HOMA-IR, HbA1c, triglycerides, hs-CRP and lower HDL-c with respect to controls. Mitochondrial ROS production was enhanced in T2D patients and decreased by MitoQ. The antioxidant also increased GPX-1 levels and PMN rolling velocity and decreased PMN rolling flux and PMN adhesion in T2D patients. NFκB-p65 and TNFα were augmented in T2D and were both reduced by MitoQ treatment. Our findings support that the antioxidant MitoQ has an anti-inflammatory and antioxidant action in the leukocytes of T2D patients by decreasing ROS production, leukocyte-endothelium interactions and TNFα through the action of NFκB. These data suggest that mitochondria-targeted antioxidants such as MitoQ should be investigated as a novel means of preventing cardiovascular events in T2D patients.

Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?

Mitochondrial fusion/fission alterations have been evaluated in different tissues of type 2 diabetic (T2D) patients. However, it is not known whether mitochondrial dynamics is disturbed in the leukocytes of T2D patients and whether glycemic control affects its regulation. Anthropometric and metabolic parameters in 91 T2D patients (48 with glycated hemoglobin [HbA1c] <6.5% and 43 with HbA1c >6.5%) were characteristic of the disease when compared with 78 control subjects. We observed increased reactive oxygen species production in leukocytes from diabetic patients, together with a reduced mitochondrial oxygen consumption rate, especially in poorly controlled patients. Mitochondrial fusion was reduced and fission was increased in diabetic patients, and both features were accentuated in patients with poor glycemic control. Furthermore, leukocyte rolling flux rose in parallel to HbA1c levels. The induction of leukocyte-endothelial interactions in diabetic patients was related to reduced mitochondrial fusion and higher mitochondrial fission. Our findings suggest that mitochondrial dynamics could be influenced by glycemic control in leukocytes of diabetic patients, in which there is decreased mitochondrial fusion and elevated fission related to enhanced leukocyte-endothelial interactions. These findings lead to the hypothesis that poor glycemic control during T2D may alter mitochondrial dynamics and could eventually promote leukocyte-endothelial interactions and the onset of cardiovascular diseases. Antioxid. Redox Signal. 25, 108-115.

Role of Oxidative Stress and Mitochondrial Dysfunction in Skeletal Muscle in Type 2 Diabetic Patients.

Type 2 diabetes can increase the risk of skeletal muscle dysfunction and, consequently, that of cardiovascular diseases, including coronary artery disease and stroke. It is also related to a reduced capacity for exercise, but the underlying mechanism is only partially understood. There are several factors that contribute to the development of skeletal muscle dysfunction, of which oxidative stress and mitochondrial dysfunction are among the most important. This review discusses the role of oxidative stress in the development and progression of skeletal and cardiac dysfunction associated with diabetes. It also provides an overview of the potential actions of antioxidants in general and mitochondria-targeted antioxidants in particular in the treatment of muscle dysfunction in type 2 diabetes.