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Polycystic ovary syndrome (PCOS) is associated with infertility, increased androgen levels, and insulin resistance. In adipose tissue, zinc facilitates insulin signaling. Circulating zinc levels are altered in obesity, diabetes, and PCOS; and zinc supplementation can ameliorate metabolic disturbances in PCOS. In adipose tissue, expression of zinc influx transporter ZIP14 varies with body mass index (BMI), clinical markers of metabolic syndrome, and peroxisome proliferator-activated receptor gamma ( PPARG ). In this study, we investigated expression levels of ZIP14 and PPARG in subcutaneous adipose tissue of 36 PCOS women (17 lean and 19 obese women) compared with 23 healthy controls (7 lean and 16 obese women). Further, expression levels of zinc transporter ZIP9 , a recently identified androgen receptor, and zinc efflux transporter ZNT1 were investigated, alongside lipid profile and markers of glucose metabolism [insulin degrading enzyme, retinol-binding protein 4 ( RBP4 ), and glucose transporter 4 ( GLUT4 )]. We find that ZIP14 expression is reduced in obesity and positively correlates with PPARG expression, which is downregulated with increasing BMI. ZNT1 is upregulated in obesity, and both ZIP14 and ZNT1 expression significantly correlates with clinical markers of altered glucose metabolism. In addition, RBP4 and GLUT4 associate with obesity, but an association with PCOS as such was present only for PPARG and RBP4 . ZIP14 and ZNT1 does not relate to clinical androgen status and ZIP9 is unaffected by all parameters investigated. In conclusion, our findings support the existence of a zinc dyshomeostasis in adipose tissue in metabolic disturbances including PCOS-related obesity.

Objective: To investigate the individual parameters included in the diagnosis of polycystic ovary syndrome (PCOS), and their impact on insulin sensitivity., Design: Cross-sectional study., Setting: Department of Obstetrics and Gynaecology, Copenhagen University Hospital, Hvidovre, Denmark., Patient(s): Sixty-one women; 36 women with PCOS and 25 age- and weight-matched control women were investigated., Intervention(s): Peripheral insulin sensitivity was evaluated by the hyperinsulinemic euglycemic clamp, glucose tolerance by an oral glucose tolerance test (OGTT), and ovarian morphology by transvaginal ultrasonography (TVS)., Main Outcome Measure(s): The Rotterdam criteria were used for diagnosing PCOS, and hirsutism was evaluated by the Ferriman Gallwey score. Insulin sensitivity was calculated as the insulin sensitivity index, and whole body insulin sensitivity was assessed by the homeostatic model assessment insulin resistance (IR) index., Result(s): Multiple regression analysis showed that body mass index (BMI) and hirsutism were independent predictors of IR evaluated by insulin sensitivity index, whereas BMI, total T, and hirsutism were independent predictors of IR evaluated by the homeostatic model assessment IR index. We found no significant association between ovarian morphology and insulin sensitivity or between menstrual frequency and insulin sensitivity., Conclusion(s): The PCOS is associated with IR. Body mass index, hyperandrogenemia, and hyperandrogenism are independent predictors of low insulin sensitivity., (Copyright (c) 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Background: We determined the impact of polycystic ovary syndrome (PCOS) and obesity on glucose and lipid metabolism and beta-cell function in women with PCOS., Methods: In 35 women with PCOS (17 lean, lean PCOS and 18 obese, obese PCOS) and 25 control women (9 lean, lean controls and 16 obese, obese controls), beta-cell function was evaluated by the first-phase insulin response after intravenous glucose, acute insulin response to glucose (AIRg); insulin sensitivity, determined as insulin sensitivity index (ISI), was evaluated by the euglycemic hyperinsulinemic clamp. Indirect calorimetry was used for the assessment of glucose and lipid oxidation. Body composition was estimated by dual X-ray absorptiometry scan., Results: When adjusted for obesity, PCOS was associated with higher 2-h glucose levels (P < 0.05), higher trunk/periphery fat ratio (P < 0.001), lower ISI (P < 0.001), lower insulin-stimulated glucose oxidation (GOX 2) (P < 0.05) and lower non-oxidative glucose metabolism (P < 0.05), but a normal AIRg compared with control women. Lean women with PCOS had lower ISI (P < 0.001), GOX-2 (P < 0.05) and higher trunk/periphery fat ratio (P < 0.05) than lean control women. In obese women with PCOS, ISI was reduced with 25% compared with obese control women, whereas trunk/peripheral fat ratio did not differ. AIRg was increased in obese groups compared with lean groups (P < 0.05), but was, in all groups, appropriate for the ambient action of insulin., Conclusions: PCOS is associated with a low ISI, which in lean women with PCOS may partly be explained by higher trunk/peripheral fat ratio. AIRg was amplified by obesity, but was, in all groups, appropriate for prevailing insulin sensitivity, suggesting a normal beta-cell adaptation.