title: Are Mitochondrial Fusion and Fission Impaired in Leukocytes of Type 2 Diabetic Patients?
abstract: 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.
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Noelia
authors.initials: N
authors.lastname: Diaz-Morales
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .
authors.forename: Susana
authors.initials: S
authors.lastname: Rovira-Llopis
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .
authors.forename: Celia
authors.initials: C
authors.lastname: Bañuls
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Irene
authors.initials: I
authors.lastname: Escribano-Lopez
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Arantxa Martinez
authors.initials: AM
authors.lastname: de Marañon
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Sandra
authors.initials: S
authors.lastname: Lopez-Domenech
authors.affiliation: 3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .
authors.forename: Samuel
authors.initials: S
authors.lastname: Orden
authors.affiliation: 4 Service of Cardiology, University Hospital Doctor Peset , Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Valencia, Spain .
authors.forename: Ildefonso
authors.initials: I
authors.lastname: Roldan-Torres
authors.affiliation: 3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .
authors.forename: Angeles
authors.initials: A
authors.lastname: Alvarez
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Silvia
authors.initials: S
authors.lastname: Veses
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .
authors.forename: Ana
authors.initials: A
authors.lastname: Jover
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .
authors.forename: Milagros
authors.initials: M
authors.lastname: Rocha
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .|5 Department of Medicine, University of Valencia , Valencia, Spain .
authors.forename: Antonio
authors.initials: A
authors.lastname: Hernandez-Mijares
authors.affiliation: 1 Service of Endocrinology, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), University Hospital Doctor Peset , Valencia, Spain .|2 Institute of Health Research INCLIVA, University of Valencia , Valencia, Spain .|3 CIBERehd-Department of Pharmacology and Physiology, University of Valencia , Valencia, Spain .|6 Department of Physiology, University of Valencia, Valencia, Spain .
authors.forename: Victor M
authors.initials: VM
authors.lastname: Victor
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D016022:Case-Control Studies; D002450:Cell Communication; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D063154:Mitochondrial Dynamics / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015415:Biomarkers; D033681:Mitochondrial Membrane Transport Proteins; D017382:Reactive Oxygen Species