scholarly journals SLC6A4 5HTTLPR Polymorphism Affects Insulin Secretion in Patients with Polycystic Ovary Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Barbara Šenk ◽  
Katja Goričar ◽  
Nika Aleksandra Kravos ◽  
Mojca Jensterle Sever ◽  
Andrej Janež ◽  
...  

Purpose. To investigate in a pilot study of genetic polymorphisms in serotonin system influencing basal- and glucose-stimulated insulin secretion in women with polycystic ovary syndrome (PCOS). Methods. A cross-sectional study included 65 female patients with PCOS followed up at the endocrine outpatient clinic of the University Medical Center Ljubljana and a control group of 94 young healthy female blood donors. Oral glucose tolerance test was performed only in PCOS patients and basal- and glucose-stimulated blood glucose and insulin levels were measured. All the subjects were genotyped for 5HTR1A rs6295, 5HTR1B rs13212041, and SLC6A4 5HTTLPR polymorphisms in the serotonin system. Results. Genotype distributions were in accordance with the Hardy-Weinberg equilibrium (HWE), except for 5HTR1A rs6295 in healthy controls and 5HTR1B rs13212041 in PCOS patients that were not consistent with HWE. SLC6A4 5HTTLPR polymorphism was significantly associated with insulin secretion (p=0.030) and with the area under the curve of insulin blood levels during OGTT (p=0.021). None of the investigated polymorphisms was significantly associated with basal- or glucose-stimulated blood glucose levels at any point in time during OGTT or with the basal insulin concentration. Conclusions. Serotonin system may play a role in glucose-stimulated insulin secretion in patients with insulin resistance (IR) and decreased insulin sensitivity. Further studies are needed to conclude whether the observed effect is characteristic for PCOS-related metabolic disturbances or for the identified mutation in different high metabolic risk populations.

2005 ◽  
Vol 153 (6) ◽  
pp. 831-835 ◽  
Author(s):  
Erika Lystedt ◽  
Hanna Westergren ◽  
Jan Brynhildsen ◽  
Lotta Lindh-Åstrand ◽  
Johanna Gustavsson ◽  
...  

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.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sarantis Livadas ◽  
Christina Bothou ◽  
Justyna Kuliczkowska-Płaksej ◽  
Ioannis Androulakis ◽  
Ralitsa Robeva ◽  
...  

Abstract Background: Insulin secretory defects and insulin resistance exists in women with polycystic ovary syndrome (PCOS) and are prerequisites for the development of type 2 diabetes (T2D). Objective: To determine the prevalence of T2D, impaired glucose tolerance (IGT) and impaired fasting glucose (IFG), as well as the factors associated with these dysglycemic conditions. Participants: 1614 women with PCOS of Caucasian origin (Rotterdam criteria) with a mean age 25.14±5.56 years and BMI 27.34±7.09 kg/m2 comprised the study group, whereas 359 normally ovulating, not hyperandrogenic women of comparable age and BMI, served as controls. Design: Observational study. Setting: Outpatient clinics of tertiary hospitals. Main Outcome and Measures: Clinical, biochemical, hormonal and ovarian ultrasound as well oral glucose tolerance test were performed in all subjects participating in the study. Diabetes and intermediate hypeglycemia was categorised according to WHO criteria and PCOS subgroups was based on the Rotterdam criteria. Results: In the PCOS group 2.2%, 9.5% and 12,4% of subjects had T2D, IGT and IFG, respectively. In control group 1,11%, 7.5% and 8.9% had T2D, IGT and IFG, respectively. When the existence of T2D was stratified according to age and BMI, no difference was found among age and BMI subgroups or PCOS subgroups. Namely in patients aged 17-22 years, T2D was detected in 3 lean and 2 obese subjects. The corresponding distribution for patients aged 22-30 years was 4 lean, one overweight and 2 obese, whereas in those older than 31 years, 2 overweight and 5 obese suffered from T2D. Free Androgen Index (FAI), waist to hip ratio (WHR) and LDL levels were significantly higher in T2D subjects in comparison to PCOS women with normal glucose metabolism. Diagnosis of T2D was significantly associated with Free Androgen Index (r: 0.469, p&lt;0.05), while subjects with either IFG and IGT had positive association with BMI, WHR, FAI and HOMA-IR. In controls, T2D, IGT and IFG were positively associated with BMI and androgen concentrations. Conclusions: The prevalence of T2D and IGT is significantly higher in our large cohort of PCOS women in comparison to controls. The existence of T2D is irrespective of age and BMI, and seems to be inherent for PCOS women. Hence, the evaluation of glycemic status in women with PCOS using OGTT is supported.


2016 ◽  
Vol 4 (4) ◽  
pp. 607-612
Author(s):  
Sasha Jovanovska-Mishevska ◽  
Aleksandra Atanasova-Boshku ◽  
Iskra Bitoska ◽  
Irfan Ahmeti ◽  
Biljana Todorova ◽  
...  

BACKGROUND: Polycystic ovary syndrome (PCOS) is complex hormonal, metabolic and reproductive disorder and is a leading cause of female infertility. Hyperinsulinemia secondary to insulin resistance plays important role in the pathogenesis of PCOS.AIM: To assess the sensitivity of different indices of insulin resistance and their relevance in a clinical setting.MATERIAL AND METHODS: A cross-sectional study of 43 patients with PCOS and 29 noromo ovulatory women as a control group was conducted. Standard clinical, anthropometrical and hormonal testing for hyperandrogenism was conducted, as well as oral glucose tolerance test with determination of basal and stimulated glucose and insulin values.RESULTS: The dynamic I/G index showed the highest sensitivity and specificity, but the static indexes HOMA-IR and QUICKI, although based on only basal glycemic and insulinemic values, showed good sensitivity, 90.38% and 94.01% respectively. HOMA-IR showed significant positive correlation with the stimulated insulin values.CONCLUSIONS: Our results support the use of static indexes in the evaluation of insulin resistance in women with PCOS in a clinical setting, offering a simple assessment of insulin resistance in PCOS, which holds great prognostic and treatment implications.


1998 ◽  
Vol 83 (5) ◽  
pp. 1742-1745 ◽  
Author(s):  
Maurizio Guido ◽  
Virginia Pavone ◽  
Mario Ciampelli ◽  
Francesca Murgia ◽  
Anna Maria Fulghesu ◽  
...  

To evaluate the possible involvement of ovarian steroids on the opioid-mediated disorders of insulin in patients affected by polycystic ovary syndrome (PCOS), we studied 40 PCOS women. All patients underwent an oral glucose tolerance test (OGTT; 75 g) and basal hormone assay; based on the insulin response to OGTT, 26 women were classified as hyperinsulinemic and continued the study protocol. Patients were randomly divided into three groups characterized by different treatments: group A (nine patients) was treated with GnRH analog (one ampule every 28 days for 2 months), group B (eight patients) was treated with naltrexone (an oral opioid antagonist, 50 mg/day, orally) for 8 weeks, and group C (nine patients) was treated with GnRH analog plus naltrexone for 2 months. After continuation of treatment, all patients repeated the basal study in a second hospitalization. Naltrexone treatment significantly reduced the insulin response to OGTT, whereas GnRH analogue administration did not significantly change the insulin secretion after the glucose load. The GnRH analog/naltrexone cotreatment was not able to influence the insulin secretory pattern; in fact, the insulin area under the curve was superimposable before and after therapy. These data could lead to the hypothesis that the opioidergic regulation of insulin secretion requires a normal steroidogenic pattern, thus suggesting that ovarian steroids modulate opioid activity also at peripheric districts.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Mohammed Azeemuddin ◽  
Suryakanth D. Anturlikar ◽  
Mallappa Onkaramurthy ◽  
Mirza R. Baig ◽  
Basti K. Ashok ◽  
...  

The objective of the present study was to evaluate “DXB-2030,” a polyherbal combination of Trigonella foenum-graecum, Aloe vera, Sphaeranthus indicus, Nardostachys jatamansi, and Symplocos racemosa extracts in an experimental model of testosterone propionate (TP), induced polycystic ovary syndrome (PCOS) in female rats. Thirty animals were divided into 3 groups of 10 each; group 1 served as normal control; group 2 was administered with TP and served as positive control; along with TP, group 3 was treated with “DXB-2030” at a dose of 100 mg/kg p.o., for 60 days. At the end of the study period, the animals were subjected for the estimation of serum testosterone levels, oral glucose tolerance test (OGTT), weight of the ovaries, estrous cycle, and histopathological evaluation. An in vitro assay on GLUT4 expression was carried out to understand the effect of “DXB-2030” on insulin resistance. Results showed that treatment with “DXB-2030” reversed the TP-induced changes by increasing the GLUT4 expression and decreasing the body weight, testosterone levels, AUC of glucose in OGTT, and the cystic follicles of the ovaries, thus indicating its beneficial effect in PCOS by ameliorating the metabolic dysfunction and reproductive impairment, which are the pathophysiological conditions associated with PCOS. From the results obtained, it can be concluded that “DXB-2030” was effective in the management of experimental PCOS and hence may be recommended in the treatment of PCOS.


2017 ◽  
pp. 7-13 ◽  
Author(s):  
Minh Tam Le ◽  
Viet Hung Le ◽  
Thi Phuong Le Nguyen ◽  
Dinh Duong Le ◽  
Viet Nguyen Sa Le ◽  
...  

Introduction: Polycystic ovary syndrome (STD) is a common endocrine and metabolic disorder that affects significantly the general health of 6-18% of women. Data on metabolic disorders in PCOS is so far still limited and lack of uniformity in terms of race, geographic location, human-origin, age, sample size or lifestyle. Methodology: A cross-sectional description of 759 cases of reproductive-age women who were diagnosed with PCOS by Rotterdam criteria (391) and non-PCOS (368) visited 3 ART centers in central Vietnam including Hue University Hospital, Hue Central Hospital and Danang Hospital for Women and Children, from June 2016 to June 2017. Inclusion criteria to the control group consisted of infertile women without PCOS, regular menstrual cycle, no ovarian disease (ovary cyst/tumor or endometriosis), without history of ovarian surgery or determined ovarian failure. Clinical characteristics and basic hormonal profile, AMH, lipidemia variables, fasting blood glucose and glucose tolerance testing were performed to evaluate endocrine and metabolic status. Input and process data using SPSS 19.0 software. Results: The PCOS group had a 1.2-fold increase in overweight BMI (RR=1.20 with 95%CI: 1.02-1.42). The mean of waist circumference and waist / hip ratio was higher than that of control group. Lipidemia dysfunction was observed in 176 cases of PCOS (45%), of which total cholesterol abnormalities accounted for 21.0%, triglycerides 21.5%, LDL-C 25.6% and decreased HDL in 7.9%. Glycemia disturbances occurred in 119 cases (accounting for 30.4%) with abnormal blood glucose 16.4% and abnormal glucose tolerance test after 2 hours was 25.0%. Considering the metabolic factors, 68.8% of PCOS cases have at least one disorder. There is a correlation between metabolic disorders and clinical and endocrine factors: increased WHR with age, body mass index, AMH and prolactin; Total cholesterol associated with BMI and prolactin; Triglycerides related to age; HDL-C decrease is associated with BMI, LH and FSH; Hyperglycemia is associated with BMI. Conclusions: Endocrine disorders and especially metabolic syndrome are common in the infertile patients with PCOS in Central Vietnam. Appropriate screening strategy, early detection and timely intervention are needed to prevent systemic complications related to metabolic disorders. Key words: polycystic ovary syndrome, endocrine disorders, metabolic disorders


Author(s):  
Zora Lazúrová ◽  
Jana Figurová ◽  
Beáta Hubková ◽  
Jana Mašlanková ◽  
Ivica Lazúrová

Abstract Objectives There is a growing evidence indicating an impact of endocrine distrupting chemicals such as bisphenol A (BPA) on human reproduction. Its higher levels in serum or urine have been documented in women with polycystic ovary syndrome (PCOS), however the relationship to ovarian steroidogenesis remains unclear. Aim of the study was to compare urinary BPA (U-BPA) concentrations among PCOS women and control group. Second aim was to assess the relationship of U-BPA to ovarian steroidogenesis in the group with PCOS. Methods Eighty six Caucasian women (age 28.5 ± 5.1 years) diagnosed with PCOS and 32 controls of age 24.9 ± 4.4 years were included in the study. Fasting blood samples were analyzed for biochemical parameters and steroid hormones. U-BPA was measured in the morning urine sample using high pressure liquid chromatography. Results PCOS women had significantly higher U-BPA as compared with control group (p=0.0001). Those with high levels of U-BPA (U-BPA ≥2.14 ug/g creatinine) demonstrated higher serum insulin (p=0.029) and HOMA IR (p=0.037), lower serum estrone (p=0.05), estradiol (p=0.0126), FSH (p=0.0056), and FAI (p=0.0088), as compared with low-BPA group (U- BPA <2.14 ug/g creatinine). In PCOS women, U-BPA positively correlated with age (p=0.0026; R2=0.17), negatively with estradiol (p=0.0001, R2=0.5), testosterone (p=0.0078, R2=0.15), free-testosterone (p=0.0094, R2=0.12) and FAI (p=0.0003, R2=0.32), respectively. Conclusions PCOS women have significantly higher U-BPA concentrations than healthy controls. U-BPA positively correlates with age and negatively with ovarian steroid hormones suggesting a possible suppressive effect of bisphenol A on ovarian steroidogenesis.


Sign in / Sign up

Export Citation Format

Share Document