scholarly journals Developmental Programming: Insulin Sensitizer Treatment Improves Reproductive Function in Prenatal Testosterone-Treated Female Sheep

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 4007-4017 ◽  
Author(s):  
Almudena Veiga-Lopez ◽  
James S. Lee ◽  
Vasantha Padmanabhan
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Breeding Season ◽  
Polycystic Ovary ◽  
Sensitivity Index ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Prenatal Testosterone ◽  
Glucose Ratio ◽  
Pregnant Sheep

Prenatal testosterone (T) excess causes reproductive and metabolic disruptions including insulin resistance, attributes of women with polycystic ovary syndrome. This study tested the hypothesis that insulin resistance contributes toward severity of reproductive disruptions in prenatally T-treated females. Pregnant sheep were injected im with 100 mg of T-propionate semiweekly from d 30–90 of gestation. Immediately after the first breeding season, a subset of controls and prenatal T-treated (TR) sheep were administered an insulin sensitizer (rosiglitazone; 8 mg/d) orally for 8 months. Untreated control and prenatal T-treated females (T group) were studied in parallel. Biochemical analyses revealed rosiglitazone to be safe for use in sheep. Glucose tolerance tests performed before and after the insulin sensitizer treatment found that insulin sensitizer decreased cumulative insulin, cumulative insulin/glucose ratio, and insulin area under the curve by about 50% and increased the insulin sensitivity index by about 70% in the TR compared with the T group. Twenty percent of TR females showed a reduced number of cycles in the second relative to first breeding season as opposed to 80% of T group females showing such deterioration. Insulin sensitizer treatment also decreased the number of aberrant cycles (≥18 d) during the second breeding season in the TR group relative to the first as opposed to the T group females showing an increase in the second breeding season relative to the first. These findings provide evidence that insulin sensitizer treatment prevents further deterioration of the reproductive axis in prenatal T-treated sheep, a finding of translational relevance to women with polycystic ovary syndrome.

Polycystic ovary syndrome: a contemporary clinical approach

2021 ◽  
Vol 27 ◽  
Author(s):  
Jelica Bjekić-Macut ◽  
Tamara Vukašin ◽  
Zelija Velija-Ašimi ◽  
Azra Bureković ◽  
Marija Zdravković ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Cardiovascular Complications ◽  
Reproductive Period ◽  
Clinical Approach ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Central Type ◽  
Increased Risk

: Polycystic ovary syndrome (PCOS) is a frequent endocrine disease in women during reproductive period. It is considered a complex metabolic disorder with long-term metabolic, as well as reproductive consequences. Main pathophysiological pathways are related to the increased androgen levels and insulin resistance. Nowadays, genetic origins of PCOS are acknowledged, with numerous genes involved in the pathogenesis of hyperandrogenemia, insulin resistance, inflammation and disturbed folliculogenesis. Rotterdam diagnostic criteria are most widely accepted and four PCOS phenotypes have been recognized. Metabolic abnormalities are more common in phenotypes 1 and 2. Women with classic PCOS are more obese and typically have central type of obesity, more prevalently displaying dyslipidemia, insulin resistance and metabolic syndrome that could be associated with an increased risk of cardiovascular complications during life. Heterogeneity of phenotypes demands an individualized approach in the treatment of women with PCOS. Metabolic therapies involve a lifestyle intervention followed by the introduction of insulin sensitizers including metformin and inositols, glucagon-like peptide 1 receptor agonists (GLP-1 RA), as recently sodium glucose contransporter-2 (SGLT2) inhibitors. Addition of an insulin sensitizer to the standard infertility therapy such as CC improves ovulation and pregnancy rates. Our current review analyzes the contemporary knowledge of PCOS etiology and etiopathogenesis, its cardiometabolic risks and their outcomes, as well as therapeutic advances for women with PCOS.

scholarly journals Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Bingjie Zhang ◽  
Jing Wang ◽  
Shanmei Shen ◽  
Jiayi Liu ◽  
Jie Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Polycystic Ovary Syndrome ◽  
Glucose Intolerance ◽  
Cell Function ◽  
Polycystic Ovary ◽  
Sensitivity Index ◽  
Androgen Excess ◽  
Ovary Syndrome ◽  
Family History Of Diabetes

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISIM); β-cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p<0.001). Furthermore, there was a direct association between FAI levels and frequency of glucose intolerance (OR = 2.480, 95% CI 1.387–4.434), even after adjusting for age, BMI, waist circumference, hypertension, fasting insulin, testosterone, SHBG, and family history of diabetes. In addition, with FAI increase, glycosylated hemoglobin (HbA1c), plasma glucose concentrations, and serum insulin levels increased, while insulin sensitivity and β-cell function decreased. Our results suggested that androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β-cell dysfunction in women with PCOS.

Polycystic Ovary Syndrome is Associated with Elevated Periostin Levels

2018 ◽  
Vol 127 (09) ◽  
pp. 571-577
Author(s):  
Xinwei Chen ◽  
Lijing Huo ◽  
Luping Ren ◽  
Yali Li ◽  
Yanmei Sun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Matrix Protein ◽  
Polycystic Ovary ◽  
Fasting Blood Glucose ◽  
Extracellular Matrix Protein ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Ovary Syndrome ◽  
Serum Periostin

Abstract Purpose Periostin is a secreted extracellular matrix protein that is strongly associated with triglyceride metabolism, chronic inflammation, and insulin resistance. Growing evidence suggests that there is a link between periostin and ovarian function. Our aim was to ascertain whether circulating periostin levels are altered in women with polycystic ovary syndrome (PCOS) and to further explore the relationship between periostin and glucose metabolism disorder in PCOS patients. Methods In total, 50 women with PCOS and 30 age-matched controls without PCOS were recruited for this cross-sectional study. Periostin levels were measured using ELISA as well. Results Circulating periostin levels were significantly elevated in PCOS women compared with controls [4206.75(222.00, 4815.25) vs. 430.75(142. 13, 730.86) ng/ml, P=0. 005]. Spearman’s correlation analysis showed that serum periostin levels had a positive correlation with body mass index (BMI), uric acid, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitive C reactive protein (hs-CRP), and a negative correlation with insulin sensitivity index (ISI). Logistic regression models revealed that PCOS was correlated with waist to hip ratio (WHR), fasting blood glucose (FBG), and periostin levels. In addition, multivariate linear regression analyses showed that FBG, HOMA-IR, and the lipid accumulation index (LAP) were independent factors influencing serum periostin levels. Conclusion PCOS is associated with elevated levels of periostin.

Astragalus hamosus Acts as an Insulin Sensitizer Through the Treatment of Polycystic Ovary Syndrome Rat Models by Affecting IRS1 Expression

2021 ◽  
Vol 21 ◽  
Author(s):  
Amir Nejati ◽  
Maryam Parvini Kohneh Shahri ◽  
Tarlan Farahvash
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Rat Models ◽  
Qrt Pcr ◽  
Pcos Group ◽  
The Impact

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality among women of reproductive age. Insulin resistance is known as the hallmark of PCOS that leads to hyperinsulinemia and type 2 diabetes in PCOS patients. Objective: This study aimed to evaluate the expression pattern of IRS1 as a candidate gene in insulin resistance development in the PCOS Rat models. Methods: In this study, estradiol valerate was used for PCOS induction. Then, all of the rats were divided into five experimental groups and treated with Astragalus hamosus extract. Ethanol was used for extraction by Soxhlet, and extracts were analyzed by GC-MS. Ovarian morphology was analyzed using histological experiments. Finally, the expression of IRS1 and hormonal titration of testosterone and insulin were evaluated using qRT-PCR and ELISA assays, respectively. Results: Induction of PCOS led to an increase in body weight, which decreased after treatment with the extract. Histological assessment declared an increased number of corpus luteums in treated groups and reduced cystic follicles compared with the PCOS group. Astragalus hamosus extract-treated groups exhibited decreased levels of insulin and testosterone compared to the PCOS group. qRT-PCR results showed an increase in the expression levels of IRS1 in the treated groups compared to the PCOS group. Conclusions: This study indicated the impact of Astragalus hamosus extract on PCOS by clarifying the increased levels of IRS1 expression in the treated groups compared to the PCOS group.

scholarly journals Serum zonulin is elevated in women with polycystic ovary syndrome and correlates with insulin resistance and severity of anovulation

2015 ◽  
Vol 172 (1) ◽  
pp. 29-36 ◽  
Author(s):  
Dongmei Zhang ◽  
Li Zhang ◽  
Fangzhi Yue ◽  
Yingying Zheng ◽  
Ryan Russell
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Inverse Correlation ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Gut Permeability ◽  
Menstrual Disorders ◽  
Ovary Syndrome ◽  
Therapeutic Outcomes

ObjectiveEvidence suggests that increased gut permeability may be associated with polycystic ovary syndrome (PCOS). Human zonulin is currently the only physiological mediator known to reversibly regulate gut permeability by disassembling intestinal tight junctions. So far, no data on serum zonulin levels in patients with PCOS are available. This study aimed to determine circulating serum zonulin levels in women with PCOS and discuss the relationship between zonulin, insulin resistance, and menstrual disorders in this group.DesignA case–control study.MethodsThe study includes 78 women recently diagnosed with PCOS and 63 age-matched healthy controls recruited. Serum zonulin levels were determined by ELISA. Insulin resistance was assessed by homeostasis model assessment of insulin resistance (HOMA-IR) and Matsuda and DeFronzo's insulin sensitivity index (ISI).ResultsPCOS women had higher serum zonulin levels (P=0.022). After adjustment for age and BMI, zonulin levels significantly correlated with HOMA-IR and ISI. Furthermore, PCOS women with more severe menstrual disorders had significantly higher zonulin levels and displayed an inverse correlation between zonulin and the number of menstrual cycles per year (r=−0.398, P<0.001).ConclusionsSerum zonulin, a biomarker for gut permeability, is increased in PCOS women and correlates with insulin resistance and severity of menstrual disorders. It suggests that alterations in gut permeability may play a role in the pathophysiology of PCOS, and serum zonulin might be used as a biomarker for both risk stratification and therapeutic outcomes in PCOS women.

scholarly journals Study of carbohydrate metabolism indices and adipocytokine profile and their relationship with androgens in polycystic ovary syndrome after menopause

2013 ◽  
Vol 168 (1) ◽  
pp. 83-90 ◽  
Author(s):  
Marios C Markopoulos ◽  
George Valsamakis ◽  
Evangelia Kouskouni ◽  
Anastassios Boutsiadis ◽  
Ioannis Papassotiriou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Insulin Secretion ◽  
Insulin Sensitivity ◽  
Waist Circumference ◽  
Polycystic Ovary Syndrome ◽  
Carbohydrate Metabolism ◽  
Polycystic Ovary ◽  
Sensitivity Index ◽  
Ovary Syndrome ◽  
Hs Crp

ObjectiveHyperandrogenism, insulin resistance, and altered adipocytokine levels characterize polycystic ovary syndrome (PCOS) women of reproductive age. Hyperandrogenism persists in postmenopausal PCOS women. In the latter, this study aimed at investigating carbohydrate metabolism, adipocytokines, androgens, and their relationships.Subjects and methodsBlood sampling from overweight postmenopausal women (25 PCOS and 24 age- and BMI-matched controls) at baseline and during oral glucose tolerance test for measurement of insulin and glucose levels, baseline leptin, adiponectin, visfatin, retinol-binding protein 4, lipocalin-2, androgen, and high-sensitivity C-reactive protein (hs-CRP) levels and for calculation of insulin sensitivity (glucose-to-insulin ratio (G/I), quantitative insulin sensitivity check index, and insulin sensitivity index (ISI)), resistance (homeostasis mathematical model assessment-insulin resistance (HOMA-IR)), secretion (Δ of the area under the curve of insulin (ΔAUCI), first-phase insulin secretion (1st PHIS), and second-phase insulin secretion (2nd PHIS)), and free androgen indices (FAI).ResultsPCOS women had higher insulin secretion indices, hs-CRP, androgen, and FAI levels than controls without differing in baseline glucose, insulin and adipocytokines levels, insulin sensitivity, and resistance indices. In PCOS women, FAI levels correlated positively with baseline insulin, ΔAUCI, HOMA-IR, and ΔAUCG and negatively with G/I; hs-CRP levels correlated positively with ΔAUCI and negatively with ISI. PCOS status, waist circumference, and 17-hydroxyprogesterone (17-OHP) levels were positive predictors for ΔAUCI. In all women, waist circumference was a negative predictor for ISI; 17-OHP and FAI levels were positive predictors respectively for baseline insulin levels and for 1st PHIS and 2nd PHIS.ConclusionsEarly postmenopausal PCOS women are characterized by hyperinsulinemia but attenuated insulin resistance. PCOS status and waist circumference are predictors of hyperinsulinemia while insulin sensitivity correlates negatively with FAI. The differences reported in adipocytokine levels between PCOS and non-PCOS women in reproductive years seem to disappear after menopause.

scholarly journals Targeting Metabolic Consequences of Insulin Resistance in Polycystic Ovary Syndrome by D-chiro-inositol and Emerging Nutraceuticals: A Focused Review

2020 ◽  
Vol 9 (4) ◽  
pp. 987 ◽  
Author(s):  
Sergio Davinelli ◽  
Daria Nicolosi ◽  
Cinzia Di Cesare ◽  
Giovanni Scapagnini ◽  
Roberto Di Marco
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Insulin Sensitizer ◽  
Complex Disorder ◽  
Naturally Occurring ◽  
Initial Support

Polycystic ovary syndrome (PCOS) is a complex disorder associated with ovarian dysfunction, infertility, menstrual irregularity, and hormonal impairments. Over the last decade, several studies have shown that some PCOS women have insulin resistance (InsR) and hyperinsulinemia, apart from being overweight or obese. Therefore, a crucial clinical aspect is that PCOS patients might develop glucose intolerance and type 2 diabetes. Insulin-sensitizing drugs have been used as first-line treatment to improve hyperinsulinemia in women with PCOS. Although reducing PCOS symptoms and signs, several used insulin-sensitizer drugs may induce side effects, which reduces compliance. D-chiro-inositol (DCI), which is a naturally occurring stereoisomer of inositol, has been classified as an insulin-sensitizer and seems to mitigate multiple InsR-related metabolic alterations in PCOS with a safe profile. However, according to a multi-targeted design, the supplementation with DCI can be synergistically integrated by combining other potential insulin-sensitizing drugs and/or nutraceuticals. The literature provides the initial support for using several unexplored nutraceutical interventions that may target relevant metabolic abnormalities associated with InsR in PCOS. With a need to promote interest in clinical research, this review aims to discuss the efficacy of DCI and the role of emerging nutraceuticals for managing InsR in PCOS.

Effects of the Insulin Sensitizer Pioglitazone on Menstrual Irregularity, Insulin Resistance and Hyperandrogenism in Young Women with Polycystic Ovary Syndrome

2014 ◽  
Vol 27 (3) ◽  
pp. 177-182 ◽  
Author(s):  
Gaspare Stabile ◽  
Irene Borrielli ◽  
Alfredo Carducci Artenisio ◽  
Lucia Maria Bruno ◽  
Salvatore Benvenga ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Young Women ◽  
Polycystic Ovary ◽  
Menstrual Irregularity ◽  
Ovary Syndrome ◽  
Insulin Sensitizer
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