Mitochondrial complex I impairment in leukocytes from type 2 diabetic patients.
Diabetes is associated with oxidative stress. This study evaluated the rates of oxidative stress and mitochondrial impairment in type 2 diabetes patients. The study population consisted of 182 diabetic patients and 50 body-composition- and age-matched controls. We assessed anthropometric and metabolic parameters and mitochondrial function by evaluating mitochondrial oxygen (O2) consumption, reactive oxygen species (ROS) production, glutathione (GSH) levels, GSH/GSSG ratio, mitochondrial membrane potential, and mitochondrial complex I activity in polymorphonuclear cells from diabetes type 2 patients. We found an increase in waist circumference and augmented serum levels of triglycerides, proinflammatory cytokines (IL-6 and TNF-α), homocysteine, glycated hemoglobin, ultrasensitive C-reactive protein, glucose, insulin, and homeostasis model assessment of insulin resistance score in diabetic patients versus controls. There was an impairment of mitochondrial function in diabetic patients, evidenced by a decrease in mitochondrial O2 consumption, an increase in ROS production, decreased GSH/GSSG ratio, a drop in GSH levels, and an undermining of the mitochondrial membrane potential. Furthermore, an impairment of mitochondrial complex I was detected. This study supports the hypothesis of an association of type 2 diabetes and the rate of impaired mitochondrial function. We also propose that one of the targets of oxidative stress responsible for diabetes is mitochondrial complex I.
Endocrinology Service, University Hospital Dr. Peset, and Department of Medicine, University of Valencia, Valencia, Spain.
Antonio
A
Hernandez-Mijares
Milagros
M
Rocha
Nadezda
N
Apostolova
Consuelo
C
Borras
Ana
A
Jover
Celia
C
Bañuls
Eva
E
Sola
Victor M
VM
Victor
D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000378:metabolism* / Q000473:pathology; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012402:Rotenone / Q000494:pharmacology
D017382:Reactive Oxygen Species; D012402:Rotenone; D042967:Electron Transport Complex I; D010100:Oxygen