Glucose-Stimulated Oxidative Stress in Mononuclear Cells Is Related to Pancreatic β-Cell Dysfunction in Polycystic Ovary Syndrome

Abstract Introduction Insulin resistance (IR) is associated with polycystic ovary syndrome (PCOS). Oxidative stress (OS) is, in turn, related to IR. Studies in PCOS evidenced an increase in OS markers, but they are mainly performed in obese patients, while the complex picture of normal weight PCOS is still poorly investigated. Matherials and Methods To investigate OS in PCOS and relationship with hormonal and metabolic picture, we performed a case-control study in 2 PCOS groups: normal weight (N-PCOS, n=21, age 18–25 ys, mean±SEM BMI 20.7±0.2 kg/m2) and obese (OB-PCOS, n=15, 20–30 ys, BMI 32.8±1.1), compared with control groups matched for BMI: normal (N-C, n=10, 20–30 ys, BMI 21.6±0.9) and obese (OB-C, n=20, 21–31ys, BMI 36.8±1.0). Malondialdehyde (MDA) in blood plasma and peripheral mononuclear cells, obtained by density-gradient centrifugation, was assayed spectrophotometrically by TBARS assay. CoenzymeQ10 (CoQ10) in plasma and cells was assayed by HPLC. Plasma Total Antioxidant Capacity (TAC) was also measured by spectrophotometric method. Results PCOS patients exhibited higher Testosterone levels than controls, but OB-PCOS had highest HOMA (Homeostasis Model Assessment) index, suggesting marked insulin resistance. Despite plasma MDA levels were not significantly different (N-PCOS 3380±346.94 vs. N-C 7 120±541.66; OB-PCOS 5 517.5±853.9 vs. OB. 3 939.66±311.2 pmol/ml), intracellular MDA levels were significantly higher in N-PCOS than controls (mean 3 259±821.5 vs. 458±43.2 pmol/106/cells) and higher than OB-PCOS, although not significantly (1363.1±412.8 pmol/106/cells). Intracellular CoenzymeQ10 was higher in N-PCOS than in N-C, but the highest levels were found in OB-C. Conclusions Our data, while confirming the presence of OS in obese PCOS patients in agreement with literature, suggest that OS could be present also in normal weight PCOS, but it can be revealed in tissue rather than in plasma. The relationship with metabolic status remains to be established, but could be a physiopathological basis for antioxidant treatment in such patients.

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Heritability of Insulin Secretion and Insulin Action in Women with Polycystic Ovary Syndrome and Their First Degree Relatives1

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jcem.86.5.7518 ◽

2001 ◽

Vol 86 (5) ◽

pp. 2027-2031

Author(s):

Susan Colilla ◽

Nancy J. Cox ◽

David A. Ehrmann

Keyword(s):

Insulin Secretion ◽

Polycystic Ovary Syndrome ◽

Insulin Action ◽

Polycystic Ovary ◽

Reproductive Age ◽

Endocrine Disorders ◽

Β Cell ◽

Ovary Syndrome ◽

Cell Dysfunction ◽

Increased Risk

Polycystic ovary syndrome (PCOS), one of the most common endocrine disorders of reproductive age women, is associated with an increased risk of type 2 diabetes mellitus. Defects in both insulin action and insulin secretion contribute to this predisposition to diabetes, but the extent to which these defects are heritable among PCOS families has not been examined. In the present study we used the frequently sampled iv glucose tolerance test to quantitate insulin secretion (AIRg), insulin action (Si), and their product (AIRg × Si) among women with PCOS (n= 33) and their nondiabetic first degree relatives (n = 48). We then quantitated the heritability of these measures from familial correlations estimated within a genetic model. Familial (spousal, ρMF; parent-offspring, ρPO; and sibling, ρSS) correlations were derived for log-transformed body mass index (BMI) as well as for AIRg, Si, and AIRg × Si, the latter three of which were adjusted for BMI. There was no evidence of significant heritability for either lnBMI or lnSi in these families. In contrast, the sibling correlation (ρSS = 0.74) for lnAIRg was highly significant (χ2 = 7.65; 1 df; P= 0.006). In addition, the parameter quantitating insulin secretion in relation to insulin sensitivity [i.e. ln(AIRg × Si)] was significant among siblings (ρSS = 0.74;χ 2 = 4.32; 1 df; P = 0.04). In summary, the results of the present study indicate that there is an heritable component to β-cell dysfunction in families of women with PCOS. We conclude that heritability of β-cell dysfunction is likely to be a significant factor in the predisposition to diabetes in PCOS.

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