Humanin alleviates insulin resistance in polycystic ovary syndrome: a human and rat model-based study

Endocrinology ◽  
2021 ◽  
Author(s):  
Yingying Wang ◽  
Zhengyan Zeng ◽  
Shuhua Zhao ◽  
Li Tang ◽  
Jin Yan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Follicular Fluid ◽  
Polycystic Ovary ◽  
Glucose Consumption ◽  
Cell Types ◽  
Reproductive Age ◽  
Therapeutic Drug ◽  
Ovary Syndrome

Abstract Polycystic ovary syndrome (PCOS), the most common endocrine disorder in women of reproductive age, is characterized by hyperandrogenism and insulin resistance (IR); however, the pathogenesis of local ovarian IR in PCOS remains largely unclear. Humanin, a mitochondria-derived peptide, has been reported to be associated with IR. Our previous study confirmed that humanin is expressed in multiple cell types and is present in follicular fluid. However, it remains unknown whether humanin participates in the pathogenesis of local ovarian IR or whether humanin supplementation can improve IR in PCOS patients. In this study, we compared humanin concentrations in follicular fluid from PCOS patients with and without IR. We further investigated the effect of humanin analogue (HNG) supplementation on IR in a rat model of dehydroepiandrosterone-induced PCOS. Humanin concentrations in the follicular fluid were found to be significantly lower in PCOS patients with IR than in those without IR. HNG supplementation attenuated both the increases in the levels of fasting plasma glucose and fasting insulin in rats with PCOS and the decreases in phosphorylation of IRS1, PI3K, AKT, and GLUT4 proteins in the granulosa cells of these rats. Combined supplementation with HNG and insulin significantly improved glucose consumption in normal and humanin-siRNA-transfected COV434 cells. In conclusion, downregulated humanin in the ovaries may be involved in the pathogenesis of IR in PCOS, and exogenous supplementation with HNG improved local ovarian IR through modulation of the IRS1/PI3K/Akt signaling pathway in a rat model. This finding supports the potential future use of HNG as a therapeutic drug for PCOS.

Polycystic ovary syndrome and probiotics: a natural approach to an inflammatory disease

2020 ◽  
Vol 16 ◽  
Author(s):  
Antonio Schiattarella ◽  
Gaetano Riemma ◽  
Marco La Verde ◽  
Gianluigi Franci ◽  
Annalisa Chianese ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Critical Role ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Natural Approach ◽  
New Treatment ◽  
Gut Microbial Community ◽  
New Evidence

: Polycystic ovary syndrome (PCOS) is a condition that affects about 15% of women of reproductive age and is correlated with infertility, insulin resistance, and obesity. The etiology of PCOS is multifactorial and genetic, endocrine, and metabolic causes were involved. New evidence suggests a link between microorganisms residing in the digestive tracts of humans and the development of PCOS. Moreover, an imbalance in the gut microbial community could be a possible factor for the onset of insulin resistance and obesity. Hyperandrogenism, a key feature of PCOS, could also play a critical role in shaping the microbiome community. Probiotics could modify the gut microbiota and serve as a potential treatment for PCOS. Here we disclose the association between PCOS and intestinal microbiota and the possible role of probiotics as a new treatment approach.

scholarly journals Hyperandrogenism and Insulin Resistance, Not Changes in Body Weight, Mediate the Development of Endothelial Dysfunction in a Female Rat Model of Polycystic Ovary Syndrome (PCOS)

Endocrinology ◽  
2015 ◽  
Vol 156 (11) ◽  
pp. 4071-4080 ◽  
Author(s):  
Amanda Hurliman ◽  
Jennifer Keller Brown ◽  
Nicole Maille ◽  
Maurizio Mandala ◽  
Peter Casson ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Endothelial Dysfunction ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Phase 1 ◽  
Ovary Syndrome

This study was designed to differentiate the contributions of hyperandrogenism, insulin resistance (IR), and body weight to the development of endothelial dysfunction in polycystic ovary syndrome and determine the effectiveness of insulin sensitization and antiandrogenic therapy after the establishment of vascular and metabolic dysfunction using a rat model of polycystic ovary syndrome. We hypothesized that the observed endothelial dysfunction was a direct steroidal effect, as opposed to changes in insulin sensitivity or body weight. Prepubertal female rats were randomized to the implantation of a pellet containing DHT or sham procedure. In phase 1, DHT-exposed animals were randomized to pair feeding to prevent weight gain or metformin, an insulin-sensitizing agent, from 5 to 14 weeks. In phase 2, DHT-exposed animals were randomized to treatment with metformin or flutamide, a nonsteroidal androgen receptor blocker from 12 to 16 weeks. Endothelial function was assessed by the vasodilatory response of preconstricted arteries to acetylcholine. Serum steroid levels were analyzed in phase 1 animals. Fasting blood glucose and plasma insulin were analyzed and homeostasis model assessment index calculated in all animals. Our data confirm the presence of endothelial dysfunction as well as increased body weight, hypertension, hyperinsulinemia, and greater IR among DHT-treated animals. Even when normal weight was maintained through pair feeding, endothelial dysfunction, hyperinsulinemia, and IR still developed. Furthermore, despite weight gain, treatment with metformin and flutamide improved insulin sensitivity and blood pressure and restored normal endothelial function. Therefore, the observed endothelial dysfunction is most likely a direct result of hyperandrogenism-induced reductions in insulin sensitivity, as opposed to weight gain.

Polycystic ovary syndrome: reproductive aspects

2011 ◽  
pp. 1229-1234
Author(s):  
Sophie Catteau-Jonard ◽  
Cécile Gallo ◽  
Didier Didier
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Therapeutic Approaches ◽  
Women Of Reproductive Age ◽  
Ovary Syndrome ◽  
Common Cause ◽  
The Metabolic Syndrome

The polycystic ovary syndrome (PCOS) is the most common cause of anovulation and hyperandrogenism in women, affecting between 5 and 10% of women of reproductive age worldwide (1). Although this difficult topic in endocrine gynaecology is under extensive research, controversies still remain about the pathophysiology, diagnosis, and therapy of PCOS. The PCOS phenotype can be structured in three components: manifestations of anovulation, hyperandrogenism, and the metabolic syndrome (of which hyperinsulinaemia secondary to insulin resistance is the central abnormality). The latter two are addressed in other chapters. Our knowledge about the mechanism of disturbed folliculogenesis in PCOS that is responsible for its reproductive aspects has much increased these last years, thus opening new avenues for the diagnostic and therapeutic approaches.

scholarly journals A review of therapeutic options for managing the metabolic aspects of polycystic ovary syndrome

2020 ◽  
Vol 11 ◽  
pp. 204201882093830 ◽  
Author(s):  
Mohammed Altigani Abdalla ◽  
Harshal Deshmukh ◽  
Stephen Atkin ◽  
Thozhukat Sathyapalan
Keyword(s):  
Insulin Resistance ◽  
Weight Loss ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Therapeutic Options ◽  
Reproductive Age ◽  
Obese Women ◽  
Cardiovascular Risk Reduction ◽  
Ovary Syndrome ◽  
Incretin Mimetics

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Metabolic sequelae associated with PCOS range from insulin resistance to type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Insulin resistance plays a significant role in the pathophysiology of PCOS and it is a reliable marker for cardiometabolic risk. Although insulin sensitising agents such as metformin have been traditionally used for managing metabolic aspects of PCOS, their efficacy is low in terms of weight reduction and cardiovascular risk reduction compared with newer agents such as incretin mimetics and SGLT2 inhibitors. With current pharmaceutical advances, potential therapeutic options have increased, giving patients and clinicians more choices. Incretin mimetics are a promising therapy with a unique metabolic target that could be used widely in the management of PCOS. Likewise, bariatric procedures have become less invasive and result in effective weight loss and the reversal of metabolic morbidities in some patients. Therefore, surgical treatment targeting weight loss becomes increasingly common in the management of obese women with PCOS. Newer emerging therapies, including twincretins, triple GLP-1 agonists, glucagon receptor antagonists and imeglemin, are promising therapeutic options for treating T2DM. Given the similarity of metabolic and pathological features between PCOS and T2DM and the variety of therapeutic options, there is the potential to widen our strategy for treating metabolic disorders in PCOS in parallel with current therapeutic advances. The review was conducted in line with the recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome 2018.

scholarly journals Role of Lipotoxicity and Contribution of the Renin-Angiotensin System in the Development of Polycystic Ovary Syndrome

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Alexandre Connolly ◽  
Samuel Leblanc ◽  
Jean-Patrice Baillargeon
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Renin Angiotensin System ◽  
Ovary Syndrome ◽  
Nonesterified Fatty Acids ◽  
Insulin Resistant ◽  
Cellular Dysfunction

Polycystic ovary syndrome (PCOS) is a common and significant condition associated with hyperandrogenism, infertility, low quality of life, and metabolic comorbidities. One possible explanation of PCOS development is cellular dysfunction induced by nonesterified fatty acids (NEFAs), that is, lipotoxicity, which could explain both the hyperandrogenemia and insulin resistance that characterize women with PCOS. The literature suggests that androgen biosynthesis may be induced by overexposure of androgen-secreting tissues to NEFA and/or defective NEFA metabolism, leading to lipotoxic effects. Indeed, lipotoxicity could trigger androgenic hyperresponsiveness to insulin, LH, and ACTH. In most PCOS women, lipotoxicity also causes insulin resistance, inducing compensatory hyperinsulinemia, and may thus further increase hyperandrogenemia. Many approaches aimed at insulin sensitization also reduce lipotoxicity and have been shown to treat PCOS hyperandrogenemia. Furthermore, our group and others found that angiotensin II type 2 receptor (AT2R) activation is able to improve lipotoxicity. We provided evidence, using C21/M24, that AT2R activation improves adipocytes’ size and insulin sensitivity in an insulin-resistant rat model, as well as androgen levels in a PCOS obese rat model. Taken together, these findings point toward the important role of lipotoxicity in PCOS development and of the RAS system as a new target for the treatment of PCOS.

scholarly journals Promotion of reproductive and metabolic health - current trends in the treatment and prevention of polycystic ovary syndrome in different periods of life

2021 ◽  
Vol 47 (3) ◽  
pp. 130-149
Author(s):  
Joanna Smyczyńska
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Diagnostic Criteria ◽  
Polycystic Ovary ◽  
Hormonal Contraception ◽  
Reproductive Age ◽  
Metabolic Effects ◽  
Adult Women ◽  
Ovary Syndrome ◽  
Treatment And Prevention

Polycystic ovary syndrome (PCOS) is one of the most common hormonal disorders and causes of infertility in women in reproductive age. Diagnostic criteria of PCOS in adult women include: ovulation disorders, hyperandrogenism and  polycystic ovaries. According to most recommendations, 2 out of these 3 criteria are confirm the diagnosis of PCOS. In girls during puberty and in the first years after menarche, different diagnostic criteria of menstrual disorders should be taken into account (variable length of menstrual cycles, monophasic cycles) and the limited usefulness of ultrasound examination for PCOS diagnosis within 8 years after menarche. Fairly extensive differential diagnosis is also necessary, especially – exclusion of adrenal hyperandrogenism. Moreover, the diagnostic criteria of PCOS do not take into account the metabolic disorders found in most patients (obesity, insulin resistance, type 2 diabetes), which should be diagnosed as early as possible and treated appropriately. This is especially true for teenagers, in whom the unequivocal diagnosis of PCOS or its exclusion may be very difficult. Current recommendations regard hormonal contraception as the first-line therapy in PCOS, in both adult women and adolescents. Together with its beneficial effect on the reduction of hyperandrogenism and obtaining regular bleeding (which in fact are not menstruations), the unfavorable metabolic effects of hormonal contraception are emphasized, as well as the inadequacy of its use if it is expected to achieve or restore ovulation and fertility. The latest reports indicate the legitimacy of treatment aimed at correcting disorders of carbohydrate metabolism and its greater effectiveness compared to the use of oral contraceptives in both adult women and girls with PCOS. In the pharmacotherapy of insulin resistance, metformin is of fundamental importance, the use of pioglitazone, GLP-1 receptor agonists or inositols is also proposed. Adequate lifestyle and dietary modification are of major importance in the treatment and prevention of PCOS. The mechanisms of "inheritance" of PCOS and insulin resistance with the participation of epigenetic modifications are still better understood, taking into account the effects of exposure to androgen excess in utero, intrauterine growth retardation, and maternal obesity and hyperalimentation. This creates new possibilities for PCOS prophylaxis.

scholarly journals Troxerutin protects against DHT-induced polycystic ovary syndrome in rats

2020 ◽  
Author(s):  
Zixuan Gao ◽  
Xiaochen Ma ◽  
Yuhang Ge ◽  
Lei Wang ◽  
Ping Fu ◽  
...  
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Protective Effect ◽  
Rat Model ◽  
Polycystic Ovary ◽  
Body Weight Gain ◽  
Neuroprotective Effect ◽  
The Body ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Gonadotrophin Releasing Hormone

Abstract The exact pathogenesis of polycystic ovary syndrome (PCOS), the most common neuroendocrine disorder in women of reproductive age, has not been fully elucidated. Recent studies suggested that chronic inflammation and neurotransmitter disorder involved in the progress of PCOS. Troxerutin, a natural flavonoid, was reported to possess neuroprotective effect in several disease models by inhibiting inflammation or enhancing neurotrophic factor. In this study, we investigated the possible protective effect and mechanism of troxerutin in a dihydrotestosterone (DHT)-induced rat model of PCOS. The PCOS rat models were treated with troxerutin at a dose of 150mg/kg or 300mg/kg for up to 4 weeks. Results showed that 300mg/kg troxerutin significantly decreased the body weight gain and improved the pathological changes of ovary induced by DHT. Meanwhile, the elevated gonadotrophin-releasing hormone (GnRH), gonadotrophin and testosterone in the serum of PCOS rats were reduced with the treatment of troxerutin. The expression of kisspeptin and NKB in arcuate nucleus and their receptors kiss1r and NK3r in GnRH positive neurons of median eminence were markedly decreased in troxerutin-treated rats. Of note, the GnRH inhibitory regulator GABA and stimulatory regulator glutamate were also restored to the normal level by troxerutin. The present study indicated that troxerutin may exhibit a protective effect in PCOS rat model via regulating neurotransmitter release.

scholarly journals A study of metabolic syndrome in women with polycystic ovary syndrome at tertiary care center

2021 ◽  
Vol 10 (6) ◽  
pp. 2427
Author(s):  
Chelsae Kuntal ◽  
Jyotsna Vyas ◽  
Asha Chaudhary ◽  
Sunita Hemani ◽  
Lata Rajoria
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Polycystic Ovary Syndrome ◽  
Urban Areas ◽  
Polycystic Ovary ◽  
Tertiary Care ◽  
Reproductive Age ◽  
Ovary Syndrome ◽  
Hormonal Profile ◽  
Increased Risk

Background: Polycystic ovary syndrome is a common endocrinopathy in women of reproductive age with prevalence of 6-10% which is characterized by hyper androgenic features and chronic oligo – anovulation and polycystic ovary morphology. Most women with polycystic ovary syndrome are also characterized by metabolic abnormalities like insulin resistance, hyperinsulinemia, dyslipidemia and abdominal obesity, these forming risk factors for metabolic syndrome. The objective of the study was to compare the clinical, biochemical and hormonal profile of polycystic ovary syndrome patients with and without metabolic syndrome.Methods: A comparative cross- sectional study was undertaken on 79 PCOS women diagnosed with PCOS according to Rotterdam criteria, in which the clinical data and hormonal profile of two groups of polycystic ovary syndrome women with and without metabolic syndrome was compared.Results: The mean age of 79 patients in this study group with and without metabolic syndrome was 26.17±3.18 and 25.57±3.41 years respectively. There were more patients from urban areas as compared to rural areas and maximum patients. Significantly higher number of PCOS women with metabolic syndrome had hirsutism and acanthosis nigricans than those without metabolic syndrome. Mean value of Waist circumference, systolic BP pressure, diastolic BP, S. Triglyceride and fasting glucose were higher and HDL levels were lower in women with metabolic syndrome than those without metabolic syndrome. Fasting insulin and HOMA-IR values were significantly higher in PCOS women with metabolic syndrome in comparison to those without metabolic syndrome.Conclusion: PCOS is not only is the most frequent cause of anovulation, but it is also associated with characteristic metabolic disturbances that may have important implications for the long term health. Metabolic syndrome is a cluster of endocrine disturbances, including insulin resistance, dyslipidemia, obesity, and hypertension. It is associated with a two-fold increased risk of cardiovascular disease and a five-fold increased risk of type 2 diabetes. This illustrates the importance of early detection of insulin resistance and metabolic syndrome with subsequent application of preventive measures in women with polycystic ovary syndrome.

scholarly journals Total flavonoids extracted from Nervilia Fordii function in polycystic ovary syndrome through IL-6 mediated JAK2/STAT3 signaling pathway

2019 ◽  
Vol 39 (1) ◽  
Author(s):  
Yanyuan Zhou ◽  
Liang Lv ◽  
Qinghua Liu ◽  
Jiale Song
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Rat Model ◽  
Molecular Mechanisms ◽  
Polycystic Ovary ◽  
Serum Levels ◽  
Cytokine Signaling ◽  
Therapeutic Drug ◽  
Total Flavonoids ◽  
Ovary Syndrome

Abstract Large doses of flavonoids could cure many diseases with no serious side effects. However, the role of flavonoids in the treatment of polycystic ovary syndrome (PCOS) has not been reported. Therefore, total flavonoids extracted from Nervilia Fordii were selected to explore its therapeutic efficiency in PCOS. PCOS rat model was constructed to explore the role of total flavonoids in the treatment of PCOS. ELISA was used to assess the changes of ovulation function under the treatment of total flavonoids with or without exogenous interleukin-6 (IL-6). Western blot, real-time PCR and immunohistochemistry were carried out to assess the related molecular mechanisms. We explored that total flavonoids obviously increased the serum levels of follicle-stimulating hormone (FSH), and sharply decreased the serum levels of luteinizing hormone (LH), testosterone (T) and insulin (INS) in the PCOS-IR rats via partly inhibiting the activation of JAK2/STAT3 pathway, partially up-regulating the IL-6 expression and partially down-regulating the suppressor of cytokine signaling 3 (SOCS3) expression in ovaries of PCOS rats. The effect of total flavonoids on estrous cycles, serum levels of FSH, LH, T and INS were partially attenuated by IL-6 in PCOS rat model. Moreover, IL-6 significantly reversed the effect of total flavonoids on the phosphorylation of JAK2/STAT3, the expression of IL-6 and SOCS3 in ovaries of PCOS rats. Total flavonoids extracted from Nervilia Fordii might induce the expression of IL-6 in ovary and act as a potential therapeutic drug for the treatment of PCOS.

Adiposity and metabolic dysfunction in polycystic ovary syndrome

2015 ◽  
Vol 21 (2) ◽  
Author(s):  
Susan Sam
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Polycystic Ovary Syndrome ◽  
Metabolic Disorders ◽  
Polycystic Ovary ◽  
Reproductive Age ◽  
Metabolic Dysfunction ◽  
Obese Women ◽  
Ovary Syndrome ◽  
Insulin Resistant

AbstractPolycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-age women and is associated with a high risk for metabolic disorders. Adiposity and insulin resistance are two prevalent conditions in PCOS and the likely culprits for the heightened metabolic risk. Up to 60% of women with PCOS are considered to be overweight or obese, and even among non-obese women with PCOS there is an increased accumulation of adipose tissue in abdominal depots. Insulin resistance in PCOS is unique and independent of obesity, as even non-obese women with this condition are frequently insulin resistant. However, obesity substantially aggravates the insulin resistance and the metabolic and reproductive abnormalities in women with PCOS. Recently, it has been shown that many aspects of adipose tissue function in PCOS are abnormal, and these abnormalities likely predispose to development of insulin resistance even in the absence of obesity. This review provides an overview of these abnormalities and their impact on development of metabolic disorders. At the end, an overview of the therapeutic options for management of adiposity and its complications in PCOS are discussed.

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