scholarly journals Ectonucleotide Pyrophosphatase Phosphodiesterase 1 Is Correlated With Insulin Resistance and Lipid Metabolism Disorders in the Rat Model of Polycystic Ovary Syndrome

Author(s):  
Jing Xia ◽  
Yiqing Yang ◽  
Zhe Yang ◽  
Gengxiang Wu ◽  
Jing Yang

Abstract Previous studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovary syndrome (PCOS). This study was aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS. Eighteen 23-day-old Sprague-Dawley rats were divided into PCOS and control groups (n= 9/group). Samples were collected after 20 days. Pathological examination and immunofluorescence were performed. Western blotting results of ENPP1 in the ovaries were analysed. Serum levels of ENPP1, hormones, fasting blood glucose (FBG), serum lipids were measured. Levels of ENPP1, testosterone (T), FBG, fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), free fatty acids (FFAs), leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in PCOS group, while adiponectin (ADP) and high-density lipoprotein cholesterol (HDL-C) were significantly lower. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, HOMA-IR, FFAs, leptin, serum lipids and ADP. MRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. Our results revealed that ENPP1 is highly associated with IR and lipid metabolism-related molecules, which may have play important roles in PCOS pathophysiological changes.

2021 ◽  
Author(s):  
Jing Xia ◽  
Yiqing Yang ◽  
Zhe Yang ◽  
Gengxiang Wu ◽  
Jing Yang

Abstract Purpose Previous studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovary syndrome (PCOS). This study was aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS. Methods Eighteen 23-day-old Sprague-Dawley rats were divided into PCOS and control groups (n= 9/group). Samples were collected after 20 days. Pathological examination and immunofluorescence were performed. Western blotting results of ENPP1 in the ovaries were analysed. Serum levels of ENPP1, hormones, fasting blood glucose (FBG), serum lipids were measured. Results Levels of ENPP1, testosterone (T), FBG, fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR), free fatty acids (FFAs), leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in PCOS group, while adiponectin (ADP) and high-density lipoprotein cholesterol (HDL-C) were significantly lower. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, HOMA-IR, FFAs, leptin, serum lipids and ADP. MRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. Conclusions Our results revealed that ENPP1 is highly associated with IR and lipid metabolism-related molecules, which may have play important roles in PCOS pathophysiological changes.


2021 ◽  
Author(s):  
Jing Xia ◽  
Yiqing Yang ◽  
Zhe Yang ◽  
Gengxiang Wu ◽  
Jing Yang

Abstract BackgroundPrevious studies have shown that ectonucleotide pyrophosphatase phosphodiesterase 1 (ENPP1) may be an inhibitor of the insulin signalling pathway, and insulin resistance (IR) is believed to be the core mechanism in the pathophysiology of polycystic ovarian syndrome (PCOS). This study aimed to investigate the expression of ENPP1 in different tissues of PCOS rats and to analyse its potential role in the pathophysiology of PCOS.MethodsEighteen 23-day-old Sprague-Dawley rats were divided into the PCOS and control groups (n= 9/group). Serum, ovaries, skeletal muscle, and subcutaneous and visceral fat were collected after 20 days. Pathological examination, immunofluorescence and western blotting analyses were performed. Serum indicator levels were measured, including ENPP1, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T), monocyte chemoattractant protein-1 (MCP-1), fasting blood glucose (FBG), fasting insulin (FINS), free fatty acids (FFAs), adiponectin (ADP), leptin, and serum lipids. ResultsThe levels of ENPP1, T, MCP-1, FBG, FINS, homeostasis model assessment of IR (HOMA-IR), FFAs, leptin, cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) were significantly higher in the PCOS group, while ADP and high-density lipoprotein cholesterol (HDL-C) were significantly lower than in the control group. Spearman’s rank correlation analysis showed that ENPP1 was correlated with T, MCP-1, HOMA-IR, FFAs, leptin, serum lipids and ADP. The mRNA levels of ENPP1, BAX, and IRS1 were higher in the ovaries, skeletal muscle, subcutaneous fat, and visceral fat of PCOS rats, and the protein expression of ENPP1 was significantly higher in the ovaries. ConclusionENPP1 is highly associated with IR and lipid metabolism-related molecules, which may promote pathophysiological changes in PCOS.


Author(s):  
Sreenivasulu Karli ◽  
Kiranmayi V. S. ◽  
Rajendra Prasad Namburi ◽  
Aparna Rajeshwar Rao Bitla ◽  
Alok Sachan

Background: Insulin resistance (IR) is frequently observed in women with polycystic ovary syndrome (PCOS). Recent studies advocated that triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) can be used as a simple clinical indicator of IR. Hence, the present study was performed to investigate the use of TG/HDL-C and its association with IR in PCOS.Methods: Forty-one patients with PCOS and 40 healthy age matched women were randomly enrolled. Demographic and clinical characteristics were obtained. Insulin resistance was defined by the homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI).Results: In PCOS group, the insulin, HOMA-IR and TG/HDL-C ratio were significantly higher (p=0.001) than controls while, QUICKI was lower (p=0.001). Insulin, HOMA-IR were positively correlated with TG/HDL-C (ρ=0.303, p=0.006 and ρ=0.312, p=0.005 respectively) while, QUICKI was negatively correlated (ρ=-0.698, p=0.001). In receiver operating characteristic (ROC) analysis, area under the curve (AUC) for model based on QUICKI levels was better 0.898 (95% CI: 0.811-0.955, p=0.001) than HOMA-IR 0.636 (95% CI: 0.522-0.740, p=0.03). A cut-off value 3.23 for TG/HDL-C is proposed from the model based on QUICKI with best combination of sensitivity 83.3% and specificity 86.7%.Conclusions: Results of present study support that TG/HDL-C ratio may be a simple indicator of IR in PCOS patients which helps clinicians to identify IR in small centers, where the assays for insulin measurement are not available.


2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Tommy Kyaw Tun ◽  
Anne McGowan ◽  
Niamh Phelan ◽  
Neuman Correia ◽  
Gerard Boran ◽  
...  

Postprandial dyslipidaemia may be a plausible mechanism by which polycystic ovary syndrome (PCOS) increases cardiovascular risk. We sought to investigate whether the postprandial glucose and insulin and lipid and lipoprotein responses, including that of apolipoprotein B-48 (apoB-48) containing chylomicrons, to a mixed meal are different in obese PCOS women when compared to obese control subjects and whether differences, if any, are related to obesity, insulin resistance (IR), hyperandrogenaemia, or PCOS status. 26 women with PCOS (age30.4±1.2years (mean ± SEM), body mass index (BMI)36.8±1.5 kg/m2) and 26 non-PCOS subjects (age34.1±0.9years, BMI31.5±1.0 kg/m2) were studied before and up to 8 hours following a standard mixed meal. AUC-triglyceride (AUC-TG) was higher and AUC-high-density lipoprotein (AUC-HDL) lower in PCOS women. These differences were not apparent when BMI was accounted for. Insulin sensitivity (SI), AUC-apoB-48, and AUC-apolipoprotein B (AUC-apoB) were found to be independent predictors of AUC-TG, accounting for 55% of the variance. Only AUC-insulin remained significantly elevated following adjustment for BMI. Obesity related IR explains postprandial hypertriglyceridaemia and hyperinsulinaemic responses. Management of obesity in premenopausal women with PCOS is likely to reduce their cardiovascular risk burden.


2021 ◽  
Vol 12 ◽  
pp. 204201882110496
Author(s):  
Gurhan Guney ◽  
Mine Islimye Taskin ◽  
Ozgur Baykan ◽  
Ertan Adali ◽  
Selin Gul Tezcan ◽  
...  

Background: Polycystic ovary syndrome is known to be the most common hormonal disorder in women of reproductive age. Current evidence shows that regulatory proteins secreted from the adipose tissue called adipokines may have a role in polycystic ovary syndrome. We planned to investigate the role of endotrophin that has never been researched in polycystic ovary syndrome before and its correlation with other metabolic parameters and adipokines such as adiponectin and ghrelin in patients with polycystic ovary syndrome. Methods: Forty-three women ( n: 43) with polycystic ovary syndrome and 43 ( n: 43) women as a control group were enrolled in this cross-sectional study. Serum levels of endotrophin, adiponectin, and ghrelin levels were measured with the enzyme-linked immunosorbent assay method. High-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol levels, luteinizing hormone/follicle-stimulating hormone ratio, total testosterone, and triglyceride levels were measured. Homeostasis model assessment for insulin resistance index, body mass index, Ferriman Gallwey Score, and waist-to-hip ratio were also evaluated. Results: Total testosterone, homeostasis model assessment for insulin resistance, C-reactive protein, luteinizing hormone/follicle-stimulating hormone ratio, and triglyceride levels were higher in patients with polycystic ovary syndrome ( p < 0.01). No difference was detected between the groups in terms of body mass index, Ferriman Gallwey Score, waist-to-hip ratio, total cholesterol, low-density lipoprotein, and high-density lipoprotein levels ( p > 0.05). We did not observe any significant difference in adiponectin and ghrelin levels between the groups ( p > 0.05). Patients with polycystic ovary syndrome had significantly higher endotrophin levels ( p < 0.01). According to our regression analyses [area under the curve: 0.973 (0.935–1.000), 95% confidence interval, 95.2% sensitivity, and 100% specificity], it was shown that endotrophin greater than 92 ng/ml and homeostasis model assessment for insulin resistance greater than 2.5 might be good predictors for polycystic ovary syndrome diagnosis. Conclusion: We demonstrated that endotrophin level is higher in patients with polycystic ovary syndrome and may have predicted polycystic ovary syndrome with increased homeostasis model assessment for insulin resistance index. There was no significant difference in adiponectin and ghrelin levels in the polycystic ovary syndrome group. Endotrophin may have a role in polycystic ovary syndrome etiology rather than other adipokines.


2020 ◽  
Vol 23 (2) ◽  
pp. 25-34
Author(s):  
Sipel Younis Mustafa ◽  
Shereen. A. Ibrahim

Background and Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting 10–15 % of women in reproductive age. The objective was to evaluate the effect of irisin in the etiology of obese patient with PCOS. Study Design and Methods: The study design its a case control study. This study involved fifty obese ladies (50) with confirmed diagnosis of PCOS. The second group served as control group and included forty apparently normal (non-polycystic ovary) obese ladies (40). The following main parameters were measured: Fasting serum levels of total Cholesterol, triglyceride, high density lipoprotein-cholesterol, low density lipoprotein– cholesterol, glycohaemoglobin (HbA1c%), Insulin , Testosterone, FSH, serum LH and Irisin. Results: The median serum Irisin was significantly higher among PCOS cases (119.1 ng/ml) compared to healthy controls (74.7 ng/ml). The median serum FSH was significantly higher among PCOS cases (6.52 ng/ml ) compared to controls (4.72 ng/ml). Serum LH was obviously higher among PCOS cases (6.88 ng/ml) compared to controls (6.08 ng/ml). The mean pulse rate, blood WBC count and serum VLDL were significantly higher (71.6/min, 8.3 mg/dl and 22.5 mg/dl respectively) in cases with PCOS compared to controls (67.5/min, 7.2 mg/dl and 18.5 mg/dl respectively). Conversely, the serum HDL was significantly lower among PCOS cases (43.8 mg/dl) compared to controls (48.4 mg/dl), serum testosterone showed statistically non-significant differences. Conclusion: Data of the present study showed that serum Irisin was significantly higher among PCOS cases. These findings suggest important role of irisin as a biomarker for PCOS and an important factor in the development of PCOS.


2012 ◽  
Vol 166 (1) ◽  
pp. 99-105 ◽  
Author(s):  
Wei Wei ◽  
Hongmin Zhao ◽  
Aili Wang ◽  
Ming Sui ◽  
Kun Liang ◽  
...  

ObjectivePolycystic ovary syndrome (PCOS) is a frequent reproductive and metabolic disorder associated with insulin resistance (IR). Berberine (BBR) is an isoquinoline derivative alkaloid extracted from Chinese medicinal herbs that has been used as an insulin sensitizer. BBR may have a potential therapeutic value for PCOS. The aim of this study was to evaluate the effects of BBR in comparison to metformin (MET) on the metabolic features of women with PCOS.Design and methodsEighty-nine subjects with PCOS and IR subjects were randomized into one of three treatment groups: BBR+compound cyproterone acetate (CPA; n=31), MET+CPA (n=30), and placebo+CPA (n=28) for 3 months. Clinical characteristics of the women and metabolic and hormonal parameters were assessed before and after the period of treatment.ResultsTreatment with BBR in comparison to MET showed decrease in waist circumference and waist-to-hip ratio (WHR; P<0.01), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDLC; P<0.05) as well as increase in high-density lipoprotein cholesterol (HDLC) and sex hormone-binding globulin (SHBG; P<0.05). Similarly, treatment with BBR in comparison to placebo showed decrease in WHR, fasting plasma glucose, fasting insulin, homeostasis model assessment for IR, area under the curve of insulin, TC, LDLC, and TG (P<0.05) as well as increase in HDLC and SHBG (P<0.01).ConclusionsIntake of BBR improved some of the metabolic and hormonal derangements in a group of treated Chinese women with PCOS. Main effects could be related to the changes in body composition in obesity and dyslipidemia. Further controlled studies are needed for the assessment of the potential favorable metabolic effects of BBR in women with PCOS.


2021 ◽  
Vol 53 (08) ◽  
pp. 504-511
Author(s):  
Xiang-Juan Li ◽  
Hui Wang ◽  
Dan-Yang Lu ◽  
Tian-Tian Yu ◽  
Kamran Ullah ◽  
...  

AbstractInsulin resistance (IR) is one of the most common features of polycystic ovary syndrome (PCOS), which is related to obesity. Whether increased anti-Müllerian hormone (AMH) levels in PCOS are involved in the pathogenesis of insulin resistance remains unclear. We investigated serum levels of leptin and AMH along with basic clinical and metabolic parameters in 114 PCOS patients and 181 non-PCOS women. PCOS patients presented higher fasting blood glucose, insulin concentrations and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) in addition to body mass index (BMI), lipids profiles and hormone levels. HOMA-IR showed a positive correlation with BMI, AMH, leptin, and low-density lipoprotein-cholesterol (LDL-c) levels. Interestingly, AMH is strongly positively correlated with HOMA-IR and insulin concentrations for 1st and 2nd hours of glucose treatment after fasting. Among PCOS women with BMI≥25 kg/m2, high AMH level group showed an increased HOMA-IR when compared to normal AMH level. However, among PCOS women with normal BMI, women with high AMH presented an elevated fasting insulin levels but not HOMA-IR when compared to normal AMH group. In vitro treatment of isolated islet cells with high concentration of leptin (200 ng/ml) or high leptin plus high concentration of AMH (1 ng/ml) significantly enhanced insulin secretion. Importantly, co-treatment of AMH plus leptin upregulates the expression of pro-apoptotic proteins, such as Bax, caspase-3, and caspase-8 after incubating with a high level of glucose. These results suggest that AMH may involve in the pathological process of pancreatic β-cells in obese PCOS women.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Hong Gao ◽  
YanTao Li ◽  
WenNan Yan ◽  
Fei Gao

Purpose. Studies have found that vitamin D supplementation may improve blood lipids in patients with polycystic ovary syndrome, but the results are controversial, so this study will further analyze the effect of vitamin D supplementation on blood lipids in patients with polycystic ovary syndrome. Methods. PubMed, Embase, Cochrane Library, CNKI, and Wanfang databases were searched up to May 2020, to identify randomized controlled trials of the effect of vitamin D supplementation on blood lipids in patients with polycystic ovary syndrome. The Cochrane risk of bias tool was applied to assess the risk of bias, and RevMan5.3 software was used for statistical analysis. Results. Ten studies were included in this study, including 543 subjects. The results of the meta-analysis showed that, compared with placebo, vitamin D supplementation can significantly reduce total cholesterol level (WMD = –11.32, 95% CI = [–14.51, –8.41], P < 0.00001 ), low-density lipoprotein cholesterol level (WMD = –4.83, 95% CI = [–7.52, –2.14], P = 0.0004 ), and triglyceride level (WMD = –8.23, 95% CI = [–13.08, –3.38], P = 0.0009 , but the effect on high-density lipoprotein cholesterol level is not statistically significant (WMD = –0.32, 95%CI = [–1.24, 0.60], P = 0.50 ). Conclusion. Vitamin D supplementation can significantly reduce total cholesterol, low-density lipoprotein cholesterol, and triglycerides in patients with polycystic ovary syndrome. However, it has no significant effect on high-density lipoprotein cholesterol.


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