scholarly journals The role of serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome

PLoS ONE ◽  
2020 ◽  
Vol 15 (8) ◽  
pp. e0235404 ◽  
Author(s):  
Hongying Kuang ◽  
Yuwei Duan ◽  
Dan Li ◽  
Yanwen Xu ◽  
Wenxia Ai ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Insulin Signaling ◽  
Polycystic Ovary ◽  
Insulin Signaling Pathway ◽  
Ovary Syndrome

scholarly journals Local Cortisol Elevation Contributes to Endometrial Insulin Resistance in Polycystic Ovary Syndrome

2018 ◽  
Vol 103 (7) ◽  
pp. 2457-2467 ◽  
Author(s):  
Jia Qi ◽  
Wangsheng Wang ◽  
Qinling Zhu ◽  
Yaqiong He ◽  
Yao Lu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Glucose Uptake ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Glucose Transporter ◽  
Polycystic Ovary ◽  
Implantation Rate ◽  
Insulin Signaling Pathway ◽  
Ovary Syndrome

Abstract Context Endometrial insulin resistance (IR) may account for the endometrial dysfunction in polycystic ovary syndrome (PCOS). The underlying mechanism remains to be elucidated. Objective To investigate whether the abundance of 11β-hydroxysteroid dehydrogenases (11β-HSDs) 1 and 2 and cortisol as well as the insulin signaling pathway are altered in PCOS endometrium and to clarify the relationship between endometrial IR and local cortisol. Design We measured cortisol and cortisone concentrations, 11β-HSD1 and 11β-HSD2, and core insulin signaling molecules in endometrial biopsies collected from non-PCOS and PCOS with or without IR patients on the seventh day after human chorionic gonadotropin injection. We also studied the effects of cortisol on glucose uptake and the insulin signaling pathway in primary cultured endometrial epithelial cells (EECs). Results The cortisol concentration was elevated, whereas 11β-HSD2 expression was diminished in endometrial biopsies obtained from PCOS with IR patients compared with those from non-PCOS and PCOS without IR patients. The implantation rate was relatively impaired and the endometrial insulin signaling pathway was defective in PCOS with IR patients. In addition, cortisol attenuated insulin-stimulated glucose uptake in EECs, which was mediated by inhibition of Akt phosphorylation and glucose transporter type 4 translocation via induction of phosphatase and tensin homolog deleted on chromosome ten (PTEN). Conclusions Decreased oxidation of cortisol and defects of insulin signaling in endometrium were observed in PCOS with IR patients. The excessive cortisol level, derived from the reduction of 11β-HSD2, might contribute to the development of endometrial IR by inhibiting the insulin signaling pathway via induction of PTEN expression in EECs.

scholarly journals Changes in the Expression of Insulin Signaling Pathway Molecules in Endometria from Polycystic Ovary Syndrome Women with or without Hyperinsulinemia

2009 ◽  
Vol 16 (3-4) ◽  
pp. 129-136 ◽  
Author(s):  
Romina Fornes ◽  
Paulina Ormazabal ◽  
Carlos Rosas ◽  
Fernando Gabler ◽  
David Vantman ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Insulin Signaling ◽  
Polycystic Ovary ◽  
Insulin Signaling Pathway ◽  
Ovary Syndrome

scholarly journals Shaoyao-Gancao Decoction Ameliorates the Inflammation State in Polycystic Ovary Syndrome Rats via Remodeling Gut Microbiota and Suppressing the TLR4/NF-κB Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhuang-peng Chang ◽  
Gui-feng Deng ◽  
Yun-yun Shao ◽  
Ding Xu ◽  
Yi-nan Zhao ◽  
...  
Keyword(s):  
Body Weight ◽  
Polycystic Ovary Syndrome ◽  
Gut Microbiota ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Polycystic Ovary ◽  
Therapeutic Effects ◽  
Ovary Syndrome ◽  
Protein Expressions ◽  
Pro Inflammatory Cytokines

Background: Emerging evidence suggests that gut microbiota plays a vital role in the occurrence of multiple endocrine disorders including polycystic ovary syndrome (PCOS). Shaoyao-Gancao Decoction (SGD), a classical Chinese prescription, has been widely used in the treatment of PCOS for decades. In previous studies, we found that SGD treatment could effectively reduce ovarian inflammation in PCOS rats. However, whether the anti-inflammation effect of SGD involves the regulation of the gut microbiota remains elusive.Methods: Letrozole-induced PCOS rat models were established, and the therapeutic effects of SGD were evaluated. Specifically, body weight, serum hormone concentrations, estrus phase and ovary histopathology were assessed. Then the structure of gut microbiota was determined by 16s rRNA sequencing. Additionally, the serum levels of pro-inflammatory cytokines and LPS were measured by ELISA kits. The key gene and protein expressions of TLR4/NF-κB signaling pathway were detected by quantitative real-time PCR and western blot.Results: SGD could effectively reduce body weight, regulate estrous cycles and ameliorate hyperandrogenism in PCOS rats. In addition, SGD treatment decreased releases of pro-inflammatory cytokines, enhanced the expressions of tight junction (occludin and claudin1), and then prevented a translocation of LPS into bloodstream. SGD could significantly reduce the ratio of Firmicutes to Bacteroidetes, decrease the abundance of LPS-producing pathogens Proteobateria and enrich the abundance of Butyricicoccus, Coprococcus, Akkermansia Blautia and Bacteroides in PCOS rats. Furthermore, SGD blunted the key gene and protein expressions of TLR4/NF-κB signaling pathway both in vivo and in LPS-induced RAW264.7 cells.Conclusion: SGD administration could ameliorate the inflammatory response in PCOS rats by remodeling gut microbiome structure, protecting gut barrier, and suppressing TLR4/NF-κB signaling pathway.

scholarly journals Effects of Nesfatin-1 and Wnt /β-Catenin Pathway on OGCs in PCOS

2020 ◽  
Author(s):  
Peihui Ding ◽  
Ding-Ding Ai ◽  
Kai-Xue Lao ◽  
Ying Huang ◽  
Yan Zhang ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Complex Disease ◽  
Polycystic Ovary ◽  
Hormone Production ◽  
Ovary Syndrome ◽  
Ovarian Granulosa Cells

Abstract Background Polycystic ovary syndrome is a complex disease related to the endocrine and metabolism. Its specific cause and pathogenesis have not been clear. Nesfatin-1 could not only regulate energy balance and glucose metabolism, but also affect the reproductive system. The Wnt/β-catenin signaling pathway affects follicle development, ovulation, corpus luteum formation, and steroid hormone production. Results Here, we studied the roles of nesfatin-1 and Wnt/β-catenin signaling pathway in the pathogenesis of polycystic ovary syndrome. Firstly, the human primary ovarian granulosa cells in vitro was cultured. The results showed that the apoptosis rate of ovarian granulosa cells in polycystic ovary syndrome patients was significantly higher than that of granular cells in normal people. Moreover, nesfatin-1 and Wnt/β-catenin pathway inhibitor IWR-1could inhibit the expressions of ovarian granulosa cells apoptosis genes and promote their proliferation, as well as nesfatin-1 affected the expressions of foxo3a and its downstream factors. Then, an in vitro culture system for ovarian granulosa cells (OGCs) was established by employing a rat model. The results are the same with those mentioned above. Conclusion This strongly proves that the nesfatin-1 participates in regulating the apoptosis and proliferation of granulosa cells by the Wnt/β-catenin pathway. According to the role of nesfatin-1 and IWR in polycystic ovary syndrome, nesfatin-1 and Wnt/β-catenin pathway can provide a guideline for the diagnosis and treatment of Polycystic ovary syndrome (PCOS).

scholarly journals MON-002 The Effect of GNRHR Autoantibody on Reproduction Function and Insulin Signaling Intermediates in a New Animal Model of Polycystic Ovary Syndrome

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Hongliang Li ◽  
Yankai Guo ◽  
Gege Zhang ◽  
Jielin Deng ◽  
Hayley Fischer ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Inflammatory Cytokines ◽  
Insulin Signaling ◽  
Solid Phase ◽  
Polycystic Ovary ◽  
Ovarian Tissue ◽  
Peptide Sequence ◽  
Control Group ◽  
Ovary Syndrome ◽  
Reproductive Dysfunction

Abstract Background: Polycystic ovary syndrome (PCOS), a metabolic and reproductive associated disease, defined as hyperandrogenism with reproductive dysfunction including menstrual disorder, anovulation, infertility, polycystic ovary and so on. We previously showed reported a high percentage of activating autoantibodies (AAb) directed toward the second extracellular loop (ECL2) of gonadotropin-releasing hormone receptor (GnRHR) in PCOS patients, and further demonstrated elevated GnRHR-autoantibody (GnRHR-AAb) could induced insulin resistance in energy storage and peripheral tissue in immunized animals. In the present study, we have now induced specific GnRHR-ECL2 AAb in rats and explored the underlying mechanisms of their resultant reproductive dysfunction. Methods: Sixteen SD rats were randomly divided into 2 groups: a GnRHR group (n=8) and a control group (n=8). Rats in the GnRHR group were immunized with GnRHR ECL2 peptide while the controls were not. Epitope mapping of GnRHR-ECL2-directed AAb was performed using octapeptide multipin solid-phase peptides. Rat estrus cycle was measured through pudendum appearance and vaginal smears. Ovarian and pituitary tissues were collected to observe ovarian morphological changes, to examine the expressions of proteins and genes of insulin signaling pathway by Quantitative real-time PCR respectively. The concentration of inflammatory cytokines in the ovary was detected by Bio-plex Pro™ magnetic bead-based assays on the Bio-plex®. Results: The GnRHR-AAb titers and activity in the GnRHR group were significantly higher than the control group, and the GnRHR-AAb from the immunized rats reacted predominantly with the peptide sequence FSQCVTHC of the GnRHR-ECL2. Numbers of LH pulses and concentration of testosterone in GnRHR group were significantly higher than control group. The GnRHR group exhibited lower frequency of in the appearance of proestrus and estrous phases while the control group represented had a higher frequency in the appearance of metestrus and diestrus stages on estrus cyclicity. The GnRHR-immunized group showed demonstrated increased atretic follicles, decreased corpora lutea, loosely packed granulosa cells, and thecal cell hyperplasia in ovarian tissue compared with controls group. There was GnRHR group represented increased expressions of IRS-1, PI3K and GLUT-1 in ovarian and pituitary tissues compared with control group. However, no obvious changes of inflammatory cytokines are observed in ovarian tissues between two groups. Conclusion: Chronic elevated GnRHR-AAb exerts induced reproductive dysfunction through increased ovarian LH secretion and androgen production, thus likely leading to compensatory hyperinsulinemia which ultimately enhanced insulin signaling in reproductive tissues to exert more and androgen production to, which may provide a novel etiological mechanism for PCOS.

scholarly journals A Potential Pathological Role of Wingless Type1 Inducible Signaling Pathway Protein-1 and Betatrophin in Obese Women with Polyststic Ovary Syndrome

2020 ◽  
pp. 1-11
Author(s):  
Abrar Gomaa Abd-Elfatah Hassan ◽  
Mohammed Ali Mohammed Mohammed ◽  
Doaa Mohammed Mohammed Abd-Elatif ◽  
Ashraf Taha Abd-Elmouttaleb Mohammed
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Polycystic Ovary ◽  
Pancreatic Beta Cell ◽  
Normal Weight ◽  
Control Group ◽  
Beta Cell Proliferation ◽  
Ovary Syndrome

Background: Polycystic Ovary Syndrome is a common female endocrinopathy. It is associated with adipokines dysfunctional secretion pattern and insulin resistance, which is considered as the main reason for its clinical feature. Wingless type1 inducible signaling pathway protein-1 is a novel adipokine that displays insulin resistance and adipose tissue inflammation where it strongly related to adipocyte accumulation and regeneration. Betatrophin has a potential role in pancreatic beta-cell proliferation and obesity and several studies showed inconsistent betatrophin levels in patients with diabetes and obesity but, its relation to polycystic ovary syndrome is unclear. Aim: Investigation of the role of serum wingless type1 inducible signaling pathway protein-1 and betatrophin in normal weight and obese patients with polycystic ovary syndrome. Studying their association with other markers, then determine whether obesity and insulin resistance is associated with them. Methods: Wingless type1 inducible signaling pathway protein-1 and betatrophin serum levels were measured in 44 patients with polycystic ovary syndrome (22 obese and 22 non-obese) and 44 matched control (22 obese and 22 non-obese) females using specific ELISA kits.  Results: Betatrophin and wingless type1 inducible signaling pathway protein-1 levels were elevated in the polycystic ovary syndrome group (49.4 pg/ml, 187.6 pg/ml) than in the control group (32.08 pg/ml, 108.4 pg/ml) respectively. Moreover, their levels were higher in the obese subgroup than in normal weight subgroup. There were positive correlations between wingless type1 inducible signaling pathway protein-1 and betatrophin in non-obese (r=0.89, p=0.0001***) and in obese (r=0.78, p=0.0001***) polycystic ovary syndrome groups. Conclusion: Betatrophin and wingless type1 inducible signaling pathway protein-1 are associated with adiposity and insulin resistance in polycystic ovary syndrome. Hence wingless type1 inducible signaling pathway protein-1 and betatrophin may play a role in the incidence of polycystic ovary syndrome. They may be valuable in diagnosis and prediction of polycystic ovary syndrome patients.

scholarly journals Mangiferin ameliorates insulin resistance in a rat model of polycystic ovary syndrome via inhibition of inflammation

2020 ◽  
Vol 19 (1) ◽  
pp. 89-94
Author(s):  
Qiaohong Qian ◽  
Minjie Tang ◽  
Xinrong Li ◽  
Qi Cao ◽  
Zhiling Zhu
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Inflammatory Cytokines ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Serum Glucose ◽  
Enzyme Linked Immunosorbent Assay ◽  
Ovary Syndrome ◽  
Ovarian Weight

Purpose: To examine the effect of mangiferin on insulin resistance (IR) in a rat polycystic ovary syndrome (PCOS) model.Methods: The rat PCOS model was established via subcutaneous injection of 6 mg/kg of dehydroepiandrosterone (DHEA), and mangiferin was orally administered. Body and ovarian weights were recorded. Serum levels of glucose, insulin, and related inflammatory cytokines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and enzyme-linked immunosorbent assay, while the expression levels of key proteins were analyzed by western blotting.Results: DHEA significantly increased ovarian weight and the ratio of ovarian weight/body weight (p <0.001), while mangiferin treatment decreased them (p < 0.001). Mangiferin also lowered DHEA-induced enhancements in serum glucose and insulin levels (p < 0.001). The mRNA and, expression and concentrations of inflammatory cytokines (interleukin-6(IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)) were also significantly reduced by mangiferin treatment (p < 0.001). Furthermore, mangiferin suppressed phosphorylation of nuclear factor-kappa B (NF-κB) but increased the phosphorylation of protein kinase B (AKT, p < 0.001).Conclusion: These results reveal that mangiferin not only decreases inflammatory cytokine levels by regulating NF-κB signaling pathway but also ameliorates IR in a rat PCOS model via regulating AKT signaling pathway. Thus, mangiferin is a potential therapeutic strategy for the management of PCOS. Keywords: Polycystic ovary syndrome, Mangiferin, Inflammation, Insulin resistance, NF-κB, AKT

Role of the PI3K-Akt Signaling Pathway in the Pathogenesis of Polycystic Ovary Syndrome

2016 ◽  
Vol 24 (5) ◽  
pp. 646-655 ◽  
Author(s):  
Tiantian Li ◽  
Hui Mo ◽  
Wenfeng Chen ◽  
Li Li ◽  
Yao Xiao ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Signaling Pathway ◽  
Polycystic Ovary ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Ovary Syndrome
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