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 Polycystic Ovary Syndrome in Insulin-Resistant Adolescents with Obesity: The Role of Nutrition Therapy and Food Supplements as a Strategy to Protect Fertility

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1848
Author(s):  
Valeria Calcaterra ◽  
Elvira Verduci ◽  
Hellas Cena ◽  
Vittoria Carlotta Magenes ◽  
Carolina Federica Todisco ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Dietary Intervention ◽  
Polycystic Ovary ◽  
Nutrition Therapy ◽  
Lifestyle Changes ◽  
Food Supplements ◽  
Ovary Syndrome ◽  
Insulin Resistant

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in young reproductive-aged women. PCOS is often associated with obesity and impairs reproductive health. Even though several theories have been proposed to explain the pathogenic mechanism of PCOS, the role of insulin resistance (IR) as a key etiological component, independently of (but amplified by) obesity, is well recognized. The consequent hyperinsulinemia activates excessive ovarian androgen production, leading to PCOS. Additionally, the state of chronic inflammation related to obesity impacts ovarian physiology due to insulin sensitivity impairment. The first-line treatment for adolescents with obesity and PCOS includes lifestyle changes; personalized dietary interventions; and, when needed, weight loss. Medical nutrition therapy (MNT) and the use of specific food supplements in these patients aim at improving symptoms and signs, including insulin resistance and metabolic and reproductive functions. The purpose of this narrative review is to present and discuss PCOS in adolescents with obesity, its relationship with IR and the role of MNT and food supplements in treatment. Appropriate early dietary intervention for the management of adolescents with obesity and PCOS should be considered as the recommended approach to restore ovulation and to protect fertility.

Insulin Therapy in Pregnancy Hypertensive Diseases and its Effect on the Offspring and Mother Later in Life

2019 ◽  
Vol 17 (5) ◽  
pp. 455-464 ◽  
Author(s):  
Alfonso Mate ◽  
Antonio J. Blanca ◽  
Rocío Salsoso ◽  
Fernando Toledo ◽  
Pablo Stiefel ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Insulin Therapy ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Insulin Resistant ◽  
Hypertensive Disorders ◽  
The Impact ◽  
In Pregnancy

Pregnancy hypertensive disorders such as Preeclampsia (PE) are strongly correlated with insulin resistance, a condition in which the metabolic handling of D-glucose is deficient. In addition, the impact of preeclampsia is enhanced by other insulin-resistant disorders, including polycystic ovary syndrome and obesity. For this reason, there is a clear association between maternal insulin resistance, polycystic ovary syndrome, obesity and the development of PE. However, whether PE is a consequence or the cause of these disorders is still unclear. Insulin therapy is usually recommended to pregnant women with diabetes mellitus when dietary and lifestyle measures have failed. The advantage of insulin therapy for Gestational Diabetes Mellitus (GDM) patients with hypertension is still controversial; surprisingly, there are no studies in which insulin therapy has been used in patients with hypertension in pregnancy without or with an established GDM. This review is focused on the use of insulin therapy in hypertensive disorders in the pregnancy and its effect on offspring and mother later in life. PubMed and relevant medical databases have been screened for literature covering research in the field especially in the last 5-10 years.

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.

scholarly journals Limitations of insulin resistance assessment in polycystic ovary syndrome

2018 ◽  
Vol 7 (3) ◽  
pp. 403-412 ◽  
Author(s):  
Krzysztof C Lewandowski ◽  
Justyna Płusajska ◽  
Wojciech Horzelski ◽  
Ewa Bieniek ◽  
Andrzej Lewiński
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Fasting Glucose ◽  
Polycystic Ovary ◽  
Detailed Comparison ◽  
Ovary Syndrome ◽  
Extreme Caution ◽  
Insulin Resistant ◽  
Method Of Assessment ◽  
Surrogate Method

Background Though insulin resistance (IR) is common in polycystic ovary syndrome (PCOS), there is no agreement as to what surrogate method of assessment of IR is most reliable. Subjects and methods In 478 women with PCOS, we compared methods based on fasting insulin and either fasting glucose (HOMA-IR and QUICKI) or triglycerides (McAuley Index) with IR indices derived from glucose and insulin during OGTT (Belfiore, Matsuda and Stumvoll indices). Results There was a strong correlation between IR indices derived from fasting values HOMA-IR/QUICKI, r = −0.999, HOMA-IR/McAuley index, r = −0.849 and between all OGTT-derived IR indices (e.g. r = −0.876, for IRI/Matsuda, r = −0.808, for IRI/Stumvoll, and r = 0.947, for Matsuda/Stumvoll index, P < 0.001 for all), contrasting with a significant (P < 0.001), but highly variable correlation between IR indices derived from fasting vs OGTT-derived variables, ranging from r = −0.881 (HOMA-IR/Matsuda), through r = 0.58, or r = −0.58 (IRI/HOMA-IR, IRI/QUICKI, respectively) to r = 0.41 (QUICKI/Stumvoll), and r = 0.386 for QUICKI/Matsuda indices. Detailed comparison between HOMA-IR and IRI revealed that concordance between HOMA and IRI was poor for HOMA-IR/IRI values above 75th and 90th percentile. For instance, only 53% (70/132) women with HOMA-IR >75th percentile had IRI value also above 75th percentile. There was a significant, but weak correlation of all IR indices with testosterone concentrations. Conclusions Significant number of women with PCOS can be classified as being either insulin sensitive or insulin resistant depending on the method applied, as correlation between various IR indices is highly variable. Clinical application of surrogate indices for assessment of IR in PCOS must be therefore viewed with an extreme caution.

Polycystic Ovary Syndrome Is Associated With Obstructive Sleep Apnea and Daytime Sleepiness: Role of Insulin Resistance

2001 ◽  
Vol 56 (7) ◽  
pp. 418-419 ◽  
Author(s):  
Alexandros N. Vgontzas ◽  
Richard S. Legro ◽  
Edward O. Bixler ◽  
Allison Grayev ◽  
Anthony Kales ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Obstructive Sleep Apnea ◽  
Sleep Apnea ◽  
Polycystic Ovary Syndrome ◽  
Daytime Sleepiness ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Obstructive Sleep
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