Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance
Por:
Victor, V, Rovira-Llopis, S, Banuls, C, Diaz-Morales, N, Castello, R, Falcon, R, Gomez, M, Rocha, M and Hernandez-Mijares, A
Publicada:
1 nov 2015
Resumen:
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 (TNF alpha).
Design and 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 O-2 consumption (using a Clark-type O-2 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 TNF alpha were measured using the Luminex 200 flow analyser system.
Results: Metformin had beneficial effects on patients by increasing mitochondrial O-2 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 TNF alpha 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.
Filiaciones:
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain
Univ Valencia, CIBERehd Dept Pharmacol & Physiol, Valencia, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain
Univ Valencia, CIBERehd Dept Pharmacol & Physiol, Valencia, Spain
:
Univ Hosp Doctor Peset, Fdn Promot Hlth & Biomed Res Valencian Reg FISABI, Serv Endocrinol, Valencia 46017, Spain
Univ Valencia, Inst Hlth Res INCLIVA, Valencia, Spain
Univ Valencia, Dept Med, Valencia, Spain
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