Dataset Information

Circulating Zinc-?2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

ABSTRACT: The aim of study was to assess the relationship between zinc-?2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring between midnight and early morning. Circulating ZAG and M-value were much lower in PCOS women than in the controls. In all population, overweight/obese subjects had significantly lower circulating ZAG levels than lean individuals. Multiple linear regression analysis revealed that only M-value and the area under the curve for glucose were independently related factors to circulating ZAG in PCOS women. Multivariate logistic regression analysis showed that circulating ZAG was significantly associated with PCOS even after controlling for anthropometric variables, blood pressure, lipid profile and hormone levels. The PCOS women with high ZAG had fewer MetS, IGT and polycystic ovaries as compared with the low ZAG PCOS women. Taken together, circulating ZAG levels are reduced in women with PCOS and ZAG may be a cytokine associated with insulin resistance in PCOS women.

SUBMITTER: Lai Y

PROVIDER: S-EPMC4867572 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

Lai Yerui Y Chen Jinhua J Li Ling L Yin Jingxia J He Junying J Yang Mengliu M Jia Yanjun Y Liu Dongfang D Liu Hua H Liao Yong Y Yang Gangyi G

Scientific reports 20160516

The aim of study was to assess the relationship between zinc-α2-glycoprotein (ZAG) and androgen excess with insulin resistance in polycystic ovary syndrome (PCOS) women. 99 PCOS women and 100 healthy controls were recruited. Euglycemic-hyperinsulinemic clamp (EHC) was preformed to assess their insulin sensitivity. Circulating ZAG was determined with an ELISA kit. In healthy subjects, circulating ZAG levels exhibited a characteristic diurnal rhythm in humans, with a major nocturnal rise occurring ...[more]

PMID: 27180914

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Project description:BACKGROUND:Women with Polycystic Ovary Syndrome (PCOS) present a heterogeneous reproductive and metabolic profile with an increased lifetime risk of Type 2 Diabetes (T2D). Early biomarkers of these metabolic disturbances in PCOS women have not been identified. The abundance of circulating insulin gene promotor cell-free DNA (INS cfDNA) was shown to be valuable as a predictive biomarker of ?-cell death in individuals with Type 1 diabetes (T1D) as well as with gestational diabetes. Since ?-cell death is common to the development of T1D as well as in T2D, we aimed to investigate if insulin-coding DNA is more abundant in circulation of PCOS women (vs Controls) and if their levels change after 6?yr. follow-up as a potential measure to predict future T2D. METHODS:A cohort of 40 women diagnosed with PCOS according to Rotterdam 2003 criteria and eight healthy controls were examined at baseline and 6?years follow-up. Clinical measurements for evaluation of glucose homeostasis as well as blood/serum samples were obtained at each visit. Methylated and unmethylated INS cfDNA were quantified using droplet digital PCR. Differences between groups were assessed using Kruskall-Wallis test and Wilcoxon Signed rank test. RESULTS:At baseline, there was no detectable difference in copy number (copies/?L) of methylated (p =?0.74) or unmethylated INS cfDNA (p =?0.34) between PCOS and Control groups. At follow up, neither methylated (p =?0.50) nor unmethylated INScfDNA levels (p =?0.48) differed significantly between these groups. Likewise, when pooling the groups, there was no difference between baseline and follow up, in terms of copies of methylated or unmethylated INS cfDNA (p =?0.38 and p =?0.52, respectively). There were no significant correlations between counts of unmethylated or methylated cfDNA and the clinical measurements of ?-cell function and pre-diabetes. CONCLUSION:The circulating level of unmethylated and methylated INScfDNA is similar between PCOS and Controls and cannot be used to predict islet ?-cell loss and progression to Type 2 diabetes in a 6-year follow-up. TRIAL REGISTRATION:The Danish Data Protection Agency (REG-31-2016. Approval: 01-12-2015) and by the Danish Scientific Ethical committee of Region Zealand (Journal no. SJ-525. Approval: 13-06-2016), Clinicaltrials.gov, ( NCT03142633 , registered 1. March, 2017, Retrospectively registered).

Project description:Polycystic ovary syndrome (PCOS) is a common metabolic and reproductive disorder with an increasing risk for type 2 diabetes. Insulin resistance is a common feature of women with PCOS, but the underlying molecular mechanism remains unclear. This study aimed to screen critical long non-coding RNAs (lncRNAs) that might play pivotal roles in insulin resistance, which could provide candidate biomarkers and potential therapeutic targets for PCOS. Gene expression profiles of the skeletal muscle in patients with PCOS accompanied by insulin resistance and healthy patients were obtained from the publicly available Gene Expression Omnibus (GEO) database. A global triple network including RNA-binding protein, mRNA, and lncRNAs was constructed based on the data from starBase. Then, we extracted an insulin resistance-associated lncRNA-mRNA network (IRLMN) by integrating the data from starBase and GEO. We also performed a weighted gene co-expression network analysis (WGCNA) on the differentially expressed genes between the women with and without PCOS, to identify hub lncRNAs. Additionally, the findings of key lncRNAs were examined in an independent GEO dataset. The expression level of lncRNA RP11-151A6.4 in ovarian granulosa cells was increased in patients with PCOS compared with that in control women. Levels were also increased in PCOS patients with higher BMI, hyperinsulinemia, and higher HOMA-IR values. As a result, RP11-151A6.4 was identified as a hub lncRNA based on IRLMN and WGCNA and was highly expressed in ovarian granulosa cells, skeletal muscle, and subcutaneous and omental adipose tissues of patients with insulin resistance. This study showed the differences between lncRNA and mRNA profiles from healthy women and women with PCOS and insulin resistance. Here, we demonstrated that RP11-151A6.4 might play a vital role in insulin resistance, androgen excess, and adipose dysfunction in patients with PCOS. Further study concerning RP11-151A6.4 could elucidate the underlying mechanisms of insulin resistance.

Dataset Information

Circulating Zinc-?2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

Publications

Circulating Zinc-α2-glycoprotein levels and Insulin Resistance in Polycystic Ovary Syndrome.

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