title: Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance.
abstract: OBJECTIVE
  Oxidative stress and mitochondrial dysfunction are implicated in polycystic ovary syndrome (PCOS). The present study assesses the effect of metformin treatment on mitochondrial function in polymorphonuclear cells from PCOS subjects. Additionally, we evaluate endocrine parameters and levels of interleukin 6 (IL6) and tumour necrosis factor alpha (TNFα).
  
  
  METHODS
  Our study population was comprised of 35 women of reproductive age diagnosed with PCOS and treated with metformin for 12 weeks, and their corresponding controls (n=41), adjusted by age and BMI. We evaluated the alteration of endocrinological and anthropometrical parameters and androgen levels. Mitochondrial O2 consumption (using a Clark-type O2 electrode), membrane potential, mitochondrial mass, and levels of reactive oxygen species (ROS) and glutathione (GSH) (by means of fluorescence microscopy) were assessed in poymorphonuclear cells. H2O2 was evaluated with the Amplex Red(R) H2O2/Peroxidase Assay kit. IL6 and TNFα were measured using the Luminex 200 flow analyser system.
  
  
  RESULTS
  Metformin had beneficial effects on patients by increasing mitochondrial O2 consumption, membrane potential, mitochondrial mass and glutathione levels, and by decreasing levels of reactive oxygen species and H2O2. In addition, metformin reduced glucose, follicle-stimulating hormone, IL6 and TNFα levels and increased dehydroepiandrosterone sulfate levels. HOMA-IR and mitochondrial function biomarkers positively correlated with ROS production (r=0.486, P=0.025), GSH content (r=0.710, P=0.049) and H2O2 (r=0.837, P=0.010), and negatively correlated with membrane potential (r=-0.829, P=0.011) at baseline. These differences disappeared after metformin treatment.
  
  
  CONCLUSIONS
  Our results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Victor.Victor@uv.es Milagros.Rocha@uv.es hernandez_antmij@gva.es.
authors: Victor M
authors: VM
authors: Victor
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
authors: Susana
authors: S
authors: Rovira-Llopis
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
authors: Celia
authors: C
authors: Bañuls
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
authors: Noelia
authors: N
authors: Diaz-Morales
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
authors: Raquel
authors: R
authors: Castelló
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
authors: Rosa
authors: R
authors: Falcón
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain.
authors: Marcelino
authors: M
authors: Gómez
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Victor.Victor@uv.es Milagros.Rocha@uv.es hernandez_antmij@gva.es.
authors: Milagros
authors: M
authors: Rocha
authors: Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Service of EndocrinologyUniversity Hospital Doctor Peset, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Avenida Gaspar Aguilar 90, 46017 Valencia, SpainInstitute of Health Research INCLIVAUniversity of Valencia, Valencia, SpainCIBERehd - Department of Pharmacology and PhysiologyUniversity of Valencia, Valencia, SpainDepartment of MedicineUniversity of Valencia, Valencia, Spain Victor.Victor@uv.es Milagros.Rocha@uv.es hernandez_antmij@gva.es.
authors: Antonio
authors: A
authors: Hernández-Mijares
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007333:Insulin Resistance; D015850:Interleukin-6 / Q000378:metabolism; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism*; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects; D055815:Young Adult
chemical_list: D007004:Hypoglycemic Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D008687:Metformin