scholarly journals Cysteine–Cysteine Motif Chemokine Receptor 5 Expression in Letrozole-Induced Polycystic Ovary Syndrome Mice

2021 ◽  
Vol 23 (1) ◽  
pp. 134
Author(s):  
Kok-Min Seow ◽  
Pin-Shiou Liu ◽  
Kuo-Hu Chen ◽  
Chien-Wei Chen ◽  
Luen-Kui Chen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Chemokine Receptor ◽  
Polycystic Ovary ◽  
Serine Phosphorylation ◽  
Plasma Testosterone ◽  
Control Group ◽  
Ovary Syndrome ◽  
Cysteine Motif ◽  
Chemokine Receptor 5

Polycystic ovary syndrome (PCOS), which affects 5–10% of women of reproductive age, is associated with reproductive and metabolic disorders, such as chronic anovulation, infertility, insulin resistance, and type 2 diabetes. However, the mechanism of PCOS is still unknown. Therefore, this study used a letrozole-exposed mouse model in which mice were orally fed letrozole for 20 weeks to investigate the effects of letrozole on the severity of reproductive and metabolic consequences and the expression of cysteine–cysteine motif chemokine receptor 5 (CCR5) in letrozole-induced PCOS mice. The letrozole-treated mice showed a disrupted estrous cycle and were arrested in the diestrus phase. Letrozole treatment also increased plasma testosterone levels, decreased estradiol levels, and caused multicystic follicle formation. Furthermore, histological analysis of the perigonadal white adipose tissue (pgWAT) showed no significant difference in the size and number of adipocytes between the letrozole-treated mice and the control group. Further, the letrozole-treated mice demonstrated glucose intolerance and insulin resistance during oral glucose and insulin tolerance testing. Additionally, the expression of CCR5 and cysteine-cysteine motif ligand 5 (CCL5) were significantly higher in the pgWAT of the letrozole-treated mice compared with the control group. CCR5 and CCL5 were also significantly correlated with the homeostasis model assessment of insulin resistance (HOMA-IR). Finally, the mechanisms of insulin resistance in PCOS may be caused by an increase in serine phosphorylation and a decrease in Akt phosphorylation.

scholarly journals Increased Activation of Nuclear Factor κB Triggers Inflammation and Insulin Resistance in Polycystic Ovary Syndrome

2006 ◽  
Vol 91 (4) ◽  
pp. 1508-1512 ◽  
Author(s):  
Frank González ◽  
Neal S. Rote ◽  
Judi Minium ◽  
John P. Kirwan
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Nuclear Factor Κb ◽  
Controlled Study ◽  
Plasma Testosterone ◽  
Nuclear Factor ◽  
Ovary Syndrome ◽  
Percent Change ◽  
Glucose Ingestion

Context: Insulin resistance and chronic low level inflammation are often present in women with polycystic ovary syndrome (PCOS). Objective: The purpose of this study was to determine the effects of hyperglycemia on nuclear factor κB (NFκB) activation and inhibitory κB (IκB) from mononuclear cells (MNC) in PCOS. Design and Setting: This was a prospective controlled study conducted at an academic medical center. Patients: The study population consisted of 16 reproductive-age women with PCOS (eight lean, eight obese) and 16 age- and body composition-matched controls (eight lean, eight obese). Main Outcome Measures: Insulin sensitivity (IS) was derived from a 2-h 75-g oral glucose tolerance test (ISOGTT). Intranuclear NFκB and IκB protein expression were quantitated from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Results: ISOGTT was lower in PCOS compared with controls (3.3 ± 0.3 vs. 6.4 ± 0.9, P < 0.004). The percent change in intranuclear NFκB was higher in lean and obese PCOS compared with lean controls (42.5 ± 19.1 and 54.5 ± 12.5 vs. −14.1 ± 10.9, P < 0.006). The percent change in intranuclear NFκB correlated positively with 2-h post-glucose ingestion levels (r = 0.37; P < 0.04) and plasma testosterone (r = 0.49; P < 0.006) and correlated negatively with ISOGTT (r = 0.39; P < 0.04). The percent change in IκB was lower in lean and obese PCOS compared with lean controls (−22.3 ± 3.2 and −17.0 ± 5.0 vs. 8.4 ± 11.8, P < 0.02). Conclusion: In response to hyperglycemia, intranuclear NFκB increases and IκB decreases in MNC of women with PCOS independent of obesity. This may represent a cardinal inflammatory signal that contributes to the induction of insulin resistance and hyperandrogenism in PCOS.

scholarly journals Subcutaneous adipocytes from obese hyperinsulinemic women with polycystic ovary syndrome exhibit normal insulin sensitivity but reduced maximal insulin responsiveness

2005 ◽  
Vol 153 (6) ◽  
pp. 831-835 ◽  
Author(s):  
Erika Lystedt ◽  
Hanna Westergren ◽  
Jan Brynhildsen ◽  
Lotta Lindh-Åstrand ◽  
Johanna Gustavsson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Subcutaneous Fat ◽  
Diabetic Control ◽  
Control Group ◽  
Blood Levels ◽  
Ovary Syndrome ◽  
Insulin Effect

Background: Polycystic ovary syndrome (PCOS) has a high prevalence in women and is often associated with insulin resistance and hence with aspects of the so-called metabolic syndrome. Methods: Ten women diagnosed with PCOS were consecutively included (aged 21–39 years, average 30.2 ± 1.9 years; body mass index 28.4–42.5 kg/m2, average 37.5 ± 1.7 kg/m2 (mean ± s.e.)). Adipocytes were isolated from the subcutaneous fat and, after overnight incubation to recover from insulin resistance due to the surgical cell isolation procedures, they were analyzed for insulin sensitivity. Results: The patients with PCOS exhibited marked clinical hyperinsulinemia with 3.6-fold higher blood levels of C-peptide than a healthy lean control group (1.7 ± 0.2 and 0.5 ± 0.02 nmol/l respectively, P < 0.0001). The patients with PCOS also exhibited 2.4-fold higher concentrations of serum triacylglycerol (2.1 ± 0.3 and 0.9 ± 0.06 mmol/l respectively, P < 0.0001), but only slightly elevated blood pressure (118 ± 12/76 ± 6 and 113 ± 7/72 ± 6 mmHg respectively, P = 0.055/0.046). However, insulin sensitivity for stimulation of glucose transport in the isolated adipocytes was indistinguishable from a non-PCOS, non-diabetic control group, while the maximal insulin effect on glucose uptake was significantly lower (2.2 ± 0.2- and 3.8 ± 0.8-fold respectively, P = 0.02). Conclusions: Subcutaneous adipocytes from patients with PCOS do not display reduced insulin sensitivity. The findings show that the insulin resistance of PCOS is qualitatively different from that of type 2 diabetes.

scholarly journals Adipokine levels and carbohydrate metabolism in patients diagnosed de novo with polycystic ovary syndrome

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Ewelina Kolan′ska-Dams ◽  
Joanna Boinska ◽  
Maciej W. Socha
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Carbohydrate Metabolism ◽  
De Novo ◽  
Polycystic Ovary ◽  
Control Group ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Positive Correlation ◽  
Pcos Group

Introduction: Central obesity appears to play a major role in the pathogenesis of metabolic disorders in polycystic ovary syndrome. Insulin resistance and carbohydrate disorders are associated with dysfunctional secretion of various adipokines by the adipose tissue. Objectives: This study aimed to evaluate leptin, apelin, and visfatin against a background of carbohydrate metabolism parameters in patients diagnosed de novo with polycystic ovary syndrome (PCOS). Material and methods: The study group consisted of 40 patients with PCOS (mean age, 29 years) diagnosed in accordance with the American Society for Reproductive Medicine criteria from 2003. The control group consisted of 37 clinically healthy women (mean age, 26 years). All controls had regular menses and no clinical or biochemical signs of hyperandrogenism. Concentrations of leptin, apelin, visfatin, and insulin were measured by immunoenzymatic methods. Glucose concentrations were determined using spectrophotometry. Results: Significantly higher concentrations of leptin, insulin, homeostatic model assessment for insulin resistance (HOMA-IR) index, and the immunoreactive insulin (IRI)/glucose index were found in the PCOS group than in the control group. Notably, the concentration of apelin was over five times lower in the PCOS group than in the control group. In patients with PCOS, a positive correlation was found between the concentrations of insulin and leptin and concentrations of leptin and IRI/glucose. Patients of the PCOS group with body mass index (BMI) ≥  25 had significantly higher values of leptin, insulin, HOMA-IR index, and IRI/glucose index than patients of the PCOS group with normal BMI. In the PCOS group, a positive correlation was found between BMI and leptin concentration (r = 0.7176; p < 0.0001) and carbohydrate metabolism, such as insulin (r = 0.5524; p = 0.0003), glucose (r = 0.3843; p = 0.0157), HOMA-IR (r = 0.5895; p < 0.0001), and IRI/glucose (r = 0.3872; p = 0.0163). These findings were not observed in the control group. Conclusions: (1) Increased leptin concentration observed in women diagnosed de novo with PCOS as well as positive correlations between leptin and HOMA-IR, and IRI/glucose and BMI may indicate a potential role of leptin in the reduction of tissue sensitivity to insulin. (2) Significantly lower apelin concentration in the PCOS group (>5 fold) than in the control group, associated with a concomitant increase in leptin, may also contribute to carbohydrate metabolism disorders occurring in the course of PCOS.

scholarly journals Body Composition, Serum Concentrations of Androgens and Insulin Resistance in Different Polycystic Ovary Syndrome Phenotypes

2020 ◽  
Vol 9 (3) ◽  
pp. 732 ◽  
Author(s):  
Aleksandra Maria Polak ◽  
Agnieszka Adamska ◽  
Anna Krentowska ◽  
Agnieszka Łebkowska ◽  
Justyna Hryniewicka ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Control Group ◽  
Model Assessment ◽  
Serum Concentrations ◽  
Metabolic Disturbances ◽  
Ovary Syndrome ◽  
G Ratio

Insulin resistance and hyperandrogenemia observed in polycystic ovary syndrome (PCOS) are associated with metabolic disturbances and could be connected with body composition pattern. To date, several studies defining the parameters of body composition using dual energy X-ray absorptiometry (DXA) method in the group of PCOS patients have been published, however, without the analysis in different phenotypes. The aim of the present study was to investigate the relationships between serum androgens concentration, insulin resistance and distribution of fat mass using DXA method in various PCOS phenotypes according to the Rotterdam criteria. We examined 146 women: 34 (38%) had PCOS phenotype A, 20 (23%) phenotype B, 20 (23%) phenotype C and 15 (16%) phenotype D (with mean age of each phenotype 25 years), and 57 control subjects (mean age of 25.5 years). Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Serum concentrations of testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEA-S) were assessed and free androgen index (FAI) was calculated. In phenotypes A, B and C, we observed higher FAI in comparison to the control group (all p < 0.01). Serum concentrations of androstenedione and DHEA-S were higher in phenotypes A and C in comparison to the control group (all p < 0.01). However, only in phenotype A we found higher visceral adipose tissue (VAT) mass and android/gynoid ratio (A/G ratio) in comparison to the control group (all p < 0.01). In phenotype A, we observed connection of VAT with FAI (r = 0.58, p < 0.01). Accordingly, A/G ratio was related with FAI in all phenotypes (all p < 0.05). Additionally, in phenotype C, A/G ratio was related to serum concentrations of DHEA-S and androstenedione (r = 0.46, p = 0.03; r = 0.53, p = 0.01, respectively). We also found connections of HOMA-IR with VAT and A/G ratio in all phenotypes (all p < 0.05). Women with phenotype A had higher amount of VAT and A/G ratio in comparison to the control group. Serum concentration of androgens and insulin resistance are connected with VAT and A/G ratio in normoandrogenic and hyperandrogenic PCOS phenotypes.

scholarly journals Auricular points acupressure for insulin resistance in overweight/obese women with polycystic ovary syndrome: protocol for a randomised controlled pilot trial

BMJ Open ◽  
2019 ◽  
Vol 9 (5) ◽  
pp. e027498 ◽  
Author(s):  
Yan Li ◽  
Lihui Hou ◽  
Yingji Wang ◽  
Liangzhen Xie ◽  
Meiwei Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Chinese Medicine ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Pilot Trial ◽  
Intervention Group ◽  
Well Being ◽  
Control Group ◽  
Model Assessment ◽  
Ovary Syndrome

IntroductionApproximately 5%–20% of reproductive women suffer from polycystic ovary syndrome (PCOS). Auricular points acupressure (AA) may serve as alternative management for PCOS for its benefits in both physical and psychological well-being. However, the effects of AA for insulin resistance (IR) in overweight/obese PCOS women have not been confirmed.Methods and analysisThe present study is designed as a randomised, placebo-controlled pilot trial to evaluate the effectiveness and safety of AA in treating IR in women with PCOS. A total of 60 eligible PCOS subjects will be randomised into an intervention group (AA group) and a control group (sham AA group) in a ratio of 1:1. Magnetic beads will be taped to the auricular points by the same senior acupuncture specialist from the First Affiliated Hospital, Heilongjiang University of Chinese Medicine. The treatment will last for 12 weeks. Primary outcome measure will be changes in homeostasis model assessment of IR between baseline and after 3 months of AA/sham AA treatment. Secondary outcomes include hormonal profile, weight, waist/hip circumference, body mass index, blood pressure, Ferriman-Gallwey score, acne and the assessment of health-related quality of life. Outcome measures are collected at baseline and the end of treatment visit.Ethics and disseminationThe protocol has been approved by the ethics committee of the First Affiliated Hospital of Heilongjiang University of Chinese Medicine (HZYLLKY201800301). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications.Trial registration numberNCT03546595; Pre-results.

Is the association between insulin resistance and diabetogenic haematopoietically expressed homeobox (HHEX) polymorphism (rs1111875) affected by polycystic ovary syndrome status?

2017 ◽  
Vol 29 (4) ◽  
pp. 670 ◽  
Author(s):  
F. Ramezani Tehrani ◽  
M. Zarkesh ◽  
M. Tohidi ◽  
F. Azizi ◽  
A. Zadeh-Vakili
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Control Group ◽  
Model Assessment ◽  
Nucleotide Polymorphisms ◽  
Ovary Syndrome ◽  
Single Nucleotide ◽  
Polymerase Chain ◽  
Study Participants

Polycystic ovary syndrome (PCOS) is frequently accompanied by insulin resistance (IR). The aim of the present study was to investigate whether the genetic association between insulin resistance and two single nucleotide polymorphisms (SNPs), namely rs7903146 (C/T) in transcription factor 7-like 2 (TCF7L2) and rs1111875 (A/G) in haematopoietically expressed homeobox (HHEX), is affected by PCOS status in Iranian women. The study participants consisted of 582 women with PCOS (cases) referred to the Reproductive Endocrinology Research Center and 504 subjects without PCOS (controls), randomly selected from the Tehran Lipid and Glucose Study. Cases and controls were further subdivided to two groups according to IR status: those with and without IR. IR was identified on the basis of homeostasis model assessment of insulin resistance (HOMA-IR) ≥2.63. The SNPs in TCF7L2 and HHEX were genotyped by polymerase chain reaction–restriction fragment length polymorphism. There were no significant differences in the distribution of genotypes and alleles between cases and controls (P < 0.05). Among cases, the prevalence of the CC, CT and TT genotypes was 37.8%, 46.3% and 15.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 13.5%, 46.1% and 40.4%, respectively. In the control group, the prevalence of the CC, CT and TT genotypes was 32.2%, 53.9% and 13.9%, respectively, whereas the prevalence of the AA, AG and GG genotypes was 11.3%, 48.6% and 40.0%, respectively. After adjustment for age and body mass index, the probability of IR was decreased by 49% among carriers of the A allele in the control group (95% confidence interval 0.33–0.78; P = 0.002). The findings of the present study suggest that the association between IR and diabetogenic polymorphisms may be affected by PCOS status.

scholarly journals THE EFFECT OF Moringa oleifera LEAF EXTRACT ON THECA CELL IN POLYCYSTIC OVARY SYNDROME MODEL WITH INSULIN RESISTANCE

2020 ◽  
Vol 14 (3) ◽  
Author(s):  
Lisa Purbawaning Wulandari ◽  
Anindya Hapsari
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Leaf Extract ◽  
Moringa Oleifera ◽  
Polycystic Ovary ◽  
Wistar Rat ◽  
Control Group ◽  
Female Rat ◽  
Ovary Syndrome ◽  
Anti Oxidant

The use of Moringa oleifera as an anti-oxidant should be investigated as an alternative treatment of follicular refinement in Polycystic ovary syndrome (PCOS) with insulin resistance. We aimed to prove the effect of Moringa oleifera leaf extract in various dosages to decrease the thecacell thickness of PCOS female rat with insulin resistance. This study was a laboratory experimental research. Three month old Rattus norvegicusstrain Wistar rat weighing 100-130 g were divided into 5 groups (n= 8). PCOS model obtained by giving injection of testosterone propionate for28 days, followed by metformin therapy and Moringa oleifera leaf extract at 250 and 500 mg/kg BW for 14 days. The examination of ovariumhistology showed that leaf extract Moringa oleifera 500 mg/kg BW (0.931±0.457) significantly decreased the thickness of theca cells (P0.05)compared to the PCOS control group. The conclusion was Moringa oleifera leaf extract as an anti-oxidant proven to decrease the thickness oftheca cell of the female rat model of PCOS.

Evaluation of serum lipid profile and sex hormones in women with polycystic ovary syndrome - A comparative study

2021 ◽  
Vol 16 (11) ◽  
pp. 13-18
Author(s):  
Pravesh Hegde ◽  
Lakshmi Manjeera ◽  
Prasanna Shetty Kumar ◽  
Shilpa S. Shetty ◽  
Suchetha N. Kumari
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Lipid Profile ◽  
Sex Hormones ◽  
Polycystic Ovary ◽  
Clinical Manifestations ◽  
Sex Hormone ◽  
Control Group ◽  
Ovary Syndrome ◽  
The Mean

Polycystic ovary syndrome (PCOS), an endocrinological disorder with lipid disturbances leads to a wide spectrum of clinical manifestations including menstrual irregularities, infertility, obesity and hyperandrogenism. This study aimed to determine the levels of lipid profile and sex hormones and its effect on PCOS from a State in southern India. This comparative hospital-based study was conducted in the State of Karnataka, India from June 2019 to January 2020. 57 age-matched PCOS and 67 healthy controls were enrolled for the study. Fasting glucose, insulin, lipid profile and sex hormone levels were analyzed after taking informed consent from all participants. The mean age of patients with PCOS was 25.05 ± 6.04 years and the mean age of subjects in the control group was 27.36 ± 7.08 years. Lipid profile showed statistically significant increased levels of triglyceride 147.3±86.6 (p<0.05) and decreased levels of HDL 52.2±8.7 (p<0.05) whereas hormones LH and testosterone were significantly higher in women with PCOS when compared to controls. The altered lipid profile, sex hormone and insulin levels exhibit a key role in the pathophysiology of PCOS that affects health. Insulin resistance is found to be linked with dyslipidemia in PCOS. Our findings suggest that the differences found may play a key role in the pathophysiology of PCOS which in turn affects the health and therefore it is advisable to emphasize the necessity for screening insulin resistance and perform early and periodic examination of lipid profile and sex hormones in women with PCOS to reduce complications.

scholarly journals Continuous Administration of a P450 Aromatase Inhibitor Induces Polycystic Ovary Syndrome with a Metabolic and Endocrine Phenotype in Female Rats at Adult Age

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 434-445 ◽  
Author(s):  
Manuel Maliqueo ◽  
Miao Sun ◽  
Julia Johansson ◽  
Anna Benrick ◽  
Fernand Labrie ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Female Rats ◽  
Control Group ◽  
Ovary Syndrome ◽  
Continuous Administration ◽  
P450 Aromatase ◽  
Fat Depots ◽  
Estrogen Synthesis

Studying the mechanisms for the complex pathogenesis of polycystic ovary syndrome (PCOS) requires animal models with endocrine, reproductive, and metabolic features of the syndrome. Hyperandrogenism seems to be a central factor in PCOS, leading to anovulation and insulin resistance. In female rats, continuous administration of letrozole, a nonsteroidal inhibitor of P450 aromatase, at 400 μg/d starting before puberty induces hyperandrogenemia and reproductive abnormalities similar to those in women with PCOS. However, despite high circulating testosterone levels, these rats do not develop metabolic abnormalities, perhaps because of their supraphysiological testosterone concentrations or because estrogen synthesis is completely blocked in insulin-sensitive tissues. To test the hypothesis that continuous administration of lower doses of letrozole starting before puberty would result in both metabolic and reproductive phenotypes of PCOS, we performed a 12-wk dose-response study. At 21 d of age, 46 female Wistar rats were divided into two letrozole groups (100 or 200 μg/d) and a control group (placebo). Both letrozole doses resulted in increased body weight, inguinal fat accumulation, anovulation, larger ovaries with follicular atresia and multiples cysts, endogenous hyperandrogemia, and lower estrogen levels. Moreover, rats that received 200 μg/d had insulin resistance and enlarged adipocytes in inguinal and mesenteric fat depots, increased circulating levels of LH, decreased levels of FSH, and increased ovarian expression of Cyp17a1 mRNA. Thus, continuous administration of letrozole, 200 μg/d, to female rats for 90 d starting before puberty results in a PCOS model with reproductive and metabolic features of the syndrome.

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