Chemoreactomic analysis of inositol stereoisomers: different profiles of pharmacological activity of myo-inositol and D-chiro-inositol in females with reproductive system disorders

2020 ◽  
Vol 19 (5) ◽  
pp. 57-69
Author(s):  
I.Yu.Torshin I.Yu.Torshin ◽  
◽  
L.A.Mayorova L.A.Mayorova ◽  
E.V.Uvarova E.V.Uvarova ◽  
N.I.Tapilskaya N.I.Tapilskaya ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Pharmacological Activity ◽  
Polycystic Ovary ◽  
Interleukin 1 ◽  
Biologically Active ◽  
Antitumor Effects ◽  
Key Words Insulin ◽  
Fetal Malformations ◽  
Branched Chain ◽  
String Databases

Inositol-containing drugs (stereoisomers of cyclohexane-1,2,3,4,5,6-hexol) are used to compensate insulin resistance, particularly in patients with menstrual and ovarian disorders. Inositols are effective in preventing folate-resistant fetal malformations. Objective. To analyze pharmacological differences between the four main biologically active stereoisomers of inositol: myoinositol (MI), D-chiro-inositol (DCI), neo-inositol (NI), and scylloinositol (SCI) using the comparative chemoreactomic method. Materials and methods. Chemoreactom analysis, PubChem / PHARMGKBb HMDB, STRING databases Results. DCI is more sufficient than MI for (1) processing of branched-chain amino acids, which promotes normalization of glucose metabolism, as well as (2) metabolism of folates, vitamin PP, vitamin B5, and magnesium, (3) activation of insulin-like growth factor 1 (IGF-1) receptor, whose activity is important for the prevention of sarcopenia, (4) antitumor effects (by inhibiting hyperproliferative effects, including those associated with excess glucose and an imbalance of androgens and estrogens), (5) inhibition of proinflammatory proteins (matrix metalloproteinase 15, ICAM1, and IRAK4 that mediate effects of interleukin-1). Conclusion. The profiles of pharmacological activity of DCI and SCI differ significantly from those of MI and NI. Therefore, combinations of MI and DCI are a more promising option to increase the sensitivity of cells to insulin than separate use of MI or DCI. Key words: insulin resistance, hyperandrogenism, polycystic ovary syndrome, post-genomic pharmacology, myo-inositol, D-chiro-inositol, neo-inositol, scylloinositol, Dikirogen

scholarly journals Metabolic Heterogeneity in Polycystic Ovary Syndrome Is Determined by Obesity: Plasma Metabolomic Approach Using GC-MS

2012 ◽  
Vol 58 (6) ◽  
pp. 999-1009 ◽  
Author(s):  
Héctor F Escobar-Morreale ◽  
Sara Samino ◽  
María Insenser ◽  
María Vinaixa ◽  
Manuel Luque-Ramírez ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Peripheral Tissues ◽  
Insulin Resistant ◽  
Branched Chain ◽  
Metabolic Heterogeneity ◽  
Nonobese Patients ◽  
Metabolomic Approach

Abstract BACKGROUND Abdominal adiposity and obesity influence the association of polycystic ovary syndrome (PCOS) with insulin resistance and diabetes. We aimed to characterize the intermediate metabolism phenotypes associated with PCOS and obesity. METHODS We applied a nontargeted GC-MS metabolomic approach to plasma samples from 36 patients with PCOS and 39 control women without androgen excess, matched for age, body mass index, and frequency of obesity. RESULTS Patients with PCOS were hyperinsulinemic and insulin resistant compared with the controls. The increase in plasma long-chain fatty acids, such as linoleic and oleic acid, and glycerol in the obese patients with PCOS suggests increased lipolysis, possibly secondary to impaired insulin action at adipose tissue. Conversely, nonobese patients with PCOS showed a metabolic profile consisting of suppression of lipolysis and increased glucose utilization (increased lactic acid concentrations) in peripheral tissues, and PCOS patients as a whole showed decreased 2-ketoisocaproic and alanine concentrations, suggesting utilization of branched-chain amino acids for protein synthesis and not for gluconeogenesis. These metabolic processes required effective insulin signaling; therefore, insulin resistance was not universal in all tissues of these women, and different mechanisms possibly contributed to their hyperinsulinemia. PCOS was also associated with decreased α-tocopherol and cholesterol concentrations irrespective of obesity. CONCLUSIONS Substantial metabolic heterogeneity, strongly influenced by obesity, underlies PCOS. The possibility that hyperinsulinemia may occur in the absence of universal insulin resistance in nonobese women with PCOS should be considered when designing diagnostic and therapeutic strategies for the management of this prevalent disorder.

scholarly journals Polycystic Ovary Syndrome: Dietary Approaches to Counteract Insulin Resistance

2020 ◽  
Vol 14 (1) ◽  
Author(s):  
Indrani Das
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
High Density Lipoproteins ◽  
Key Factors ◽  
Ovary Syndrome ◽  
Branched Chain Amino Acid ◽  
Amino Acid Intake ◽  
Negative Impacts ◽  
Branched Chain

Background: Polycystic ovary syndrome (PCOS) is a prevalent hormonal disorder connected to ovulatory infertility and recent research indicates that different diets alter the risk of developing PCOS. Insulin resistance (IR) is one of the key pathologies which classifies PCOS. Understanding the etiology leading to IR in PCOS patients and the disorders associated with IR can allow for a therapeutic measure to be put in place to counteract the etiology and even reduce the risk of developing the disorder. Objective: The objective of this review is to identify the key factors that lead to IR so that diet and other lifestyle aspects can be used to counteract PCOS Symptoms.Design: A total of 679 studies were taken into consideration for this review, however, I performed a literature review of 75 primary papers. Data and findings from these studies were used to gain a better understanding of the dietary etiology of IR in PCOS, and this information can be used to describe a specific diet to counteract its etiology.Results: Many symptoms and disorders in the biological pathway of PCOS is associated with IR. Clinical studies have established that an increase in carbohydrates, low-density lipoproteins, and triglycerides is associated with IR in PCOS patients. Similar studies have found that a decrease in dietary proteins (especially branched chain amino acid intake), lactate, phosphatidylcholine, high-density lipoproteins, and long-chain fatty acids are also associated with PCOS patients. The drug metformin has also been associated with ameliorating many of the negative impacts imposed by IR in PCOS patients. Addressing these factors and changing diet and lifestyle (such as increased exercise) can help reduce the IR-related effects in PCOS patients.

scholarly journals Decreased soluble leptin receptor levels in women with polycystic ovary syndrome

2006 ◽  
Vol 154 (2) ◽  
pp. 287-294 ◽  
Author(s):  
Susanne Hahn ◽  
Uwe Haselhorst ◽  
Beate Quadbeck ◽  
Susanne Tan ◽  
Rainer Kimmig ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Body Fat ◽  
Leptin Receptor ◽  
Polycystic Ovary ◽  
Biologically Active ◽  
Leptin Resistance ◽  
Ovary Syndrome ◽  
Soluble Leptin Receptor ◽  
Endocrine Parameters

Objective: Polycystic ovary syndrome (PCOS) is associated with insulin resistance and a high incidence of obesity. Leptin, the product of the ob gene, is involved in the regulation of energy balance and obesity and circulates in both free and bound forms. The soluble leptin receptor (sOB-R) is the most important leptin-binding protein, thus influencing the biologically active free leptin level. Design: We assessed the correlation of metabolic and endocrine parameters with leptin and sOB-R levels in 122 PCOS women (aged 27 ± 5.7 years) and 81 healthy controls (aged 25 ± 4.0 years). Methods: Leptin and sOB-R levels were measured using ELISA kits. In addition, anthropometric variables, body fat and endocrine parameters were evaluated and a glucose tolerance test performed to assess indices of insulin resistance and glucose metabolism. Results: In PCOS patients, no correlation was found between leptin or sOB-R and parameters of hyper-androgenism. However, as expected, body mass index (BMI), body fat, waist circumference and indices of insulin resistance were significantly correlated with leptin in PCOS subjects and controls. In a subgroup analysis of lean, overweight and obese PCOS patients, significant differences were found in leptin (29.7 ± 20.7 vs 45.4 ± 25.0 vs 67.7 ± 28.8 ng/ml, P < 0.0001) and sOB-R (8.0 ± 3.4 vs 6.4 ± 2.5 vs 5.7 ± 2.3 ng/ml, P < 0.05). Compared with BMI-matched controls, lean PCOS patients had lower sOB-R levels (8.0 ± 3.4 vs 12.7 ± 4.7 ng/ml, P < 0.0001) and higher free leptin indices (4.5 ± 3.9 vs 2.8 ± 2.2, P = 0.0285). Conclusion: Taking into account that low sOB-R levels supposedly compensate diminished leptin action, PCOS per se might cause leptin resistance.

Oxidative stress markers in women with polycystic ovary syndrome without insulin resistance

2018 ◽  
Author(s):  
Reveka Gyftaki ◽  
Sofia Gougoura ◽  
Nikolaos Kalogeris ◽  
Vasiliki Loi ◽  
George Koukoulis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Oxidative Stress Markers ◽  
Ovary Syndrome ◽  
Stress Markers

Efficiency of ceylon cinnamon on insulin resistance parameters in polycystic ovary syndrome

2020 ◽  
Author(s):  
Zeineb Jenouiz ◽  
Hajer Kandara ◽  
Nedra Bendag ◽  
Radhouan Gharbi ◽  
Manel Jemel ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary Syndrome ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Ceylon Cinnamon

Metabolic Syndrome During Menopause

2019 ◽  
Vol 17 (6) ◽  
pp. 595-603 ◽  
Author(s):  
Sezcan Mumusoglu ◽  
Bulent Okan Yildiz
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Central Obesity ◽  
Polycystic Ovary ◽  
Ovary Syndrome ◽  
Natural Menopause ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Aging Women

The metabolic syndrome (MetS) comprises individual components including central obesity, insulin resistance, dyslipidaemia and hypertension and it is associated with an increased risk of cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM). The menopause per se increases the incidence of MetS in aging women. The effect(s) of menopause on individual components of MetS include: i) increasing central obesity with changes in the fat tissue distribution, ii) potential increase in insulin resistance, iii) changes in serum lipid concentrations, which seem to be associated with increasing weight rather than menopause itself, and, iv) an association between menopause and hypertension, although available data are inconclusive. With regard to the consequences of MetS during menopause, there is no consistent data supporting a causal relationship between menopause and CVD. However, concomitant MetS during menopause appears to increase the risk of CVD. Furthermore, despite the data supporting the association between early menopause and increased risk of T2DM, the association between natural menopause itself and risk of T2DM is not evident. However, the presence and the severity of MetS appears to be associated with an increased risk of T2DM. Although the mechanism is not clear, surgical menopause is strongly linked with a higher incidence of MetS. Interestingly, women with polycystic ovary syndrome (PCOS) have an increased risk of MetS during their reproductive years; however, with menopausal transition, the risk of MetS becomes similar to that of non-PCOS women.

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