Effects of metformin on mitochondrial function of leukocytes from polycystic ovary syndrome patients with insulin resistance

ObjectiveOxidative 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).Design and methodsOur 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 RedR H2O2/Peroxidase Assay kit. IL6 and TNFα were measured using the Luminex 200 flow analyser system.ResultsMetformin 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.ConclusionsOur results demonstrate the beneficial effects of metformin treatment on mitochondrial function in leukocytes of PCOS patients.

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Hyperandrogenism and insulin resistance‐induced fetal loss: evidence for placental mitochondrial abnormalities and elevated reactive oxygen species production in pregnant rats that mimic the clinical features of polycystic ovary syndrome

The Journal of Physiology ◽

10.1113/jp277879 ◽

2019 ◽

Vol 597 (15) ◽

pp. 3927-3950 ◽

Cited By ~ 10

Author(s):

Yuehui Zhang ◽

Wei Zhao ◽

Hongfei Xu ◽

Min Hu ◽

Xiaozhu Guo ◽

...

Keyword(s):

Insulin Resistance ◽

Reactive Oxygen Species ◽

Polycystic Ovary Syndrome ◽

Reactive Oxygen Species Production ◽

Polycystic Ovary ◽

Fetal Loss ◽

Oxygen Species ◽

Ovary Syndrome ◽

Pregnant Rats ◽

Species Production

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Reactive Oxygen Species-Induced Oxidative Stress in the Development of Insulin Resistance and Hyperandrogenism in Polycystic Ovary Syndrome

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2005-1696 ◽

2006 ◽

Vol 91 (1) ◽

pp. 336-340 ◽

Cited By ~ 214

Author(s):

Frank González ◽

Neal S. Rote ◽

Judi Minium ◽

John P. Kirwan

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Reactive Oxygen Species ◽

Polycystic Ovary Syndrome ◽

Polycystic Ovary ◽

Reactive Oxygen ◽

Ros Generation ◽

Oxygen Species ◽

Ovary Syndrome ◽

Percent Change

Abstract Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on reactive oxygen species (ROS) generation from mononuclear cells (MNCs) in PCOS. Design: This was a prospective controlled study. Setting: The study was conducted at an academic medical center. Patients: The study population consisted of 16 women with PCOS (eight lean, eight obese) and 15 age- and body composition-matched controls (eight lean, seven obese). Main Outcome Measures: Insulin sensitivity was derived from a 2-h, 75-g oral glucose tolerance test (ISOGTT). ROS generation and p47phox protein expression were quantitated from MNCs obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS, compared with controls (3.1 ± 0.3 vs. 6.3 ± 0.9, P < 0.003). The percent change in ROS generation from MNCs was higher in lean and obese PCOS, compared with lean controls (138.8 ± 21.3 and 154.2 ± 49.1 vs. 0.6 ± 12.7, P < 0.003). The percent change in ROS generation from MNCs correlated positively with glucose area under the curve (r = 0.38, P < 0.05), and plasma levels of testosterone (r = 0.59, P < 0.002) and androstenedione (r = 0.50, P < 0.009). The percent change in p47phox from MNCs was also higher in lean and obese PCOS, compared with lean controls (36.2 ± 18.2 and 39.1 ± 8.0 vs. −13.7 ± 8.7, P < 0.02), and correlated negatively with ISOGTT (r = −0.39, P < 0.05). Conclusion: ROS generation from MNCs in response to hyperglycemia is increased in PCOS independent of obesity. The resultant oxidative stress may contribute to a proinflammatory state that induces insulin resistance and hyperandrogenism in women with this disorder.

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