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Систематический анализ биологических ролей и фармакологических свойств D-хироинозитола
Систематический анализ биологических ролей и фармакологических свойств D-хироинозитола
Громова О.А., Торшин И.Ю., Уварова Е.В. и др. Систематический анализ биологических ролей и фармакологических свойств D-хироинозитола. Гинекология. 2020; 22 (3): 21–28. DOI: 10.26442/20795696.2020.3.200210
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Аннотация
D-хироинозитол (ДХИ) – один из 9 изомеров инозитола, который входит в состав инозитоловых фосфогликанов, являющихся медиаторами действия инсулина. Обмен ДХИ и мио-инозитола (МИ) нарушается на фоне инсулинорезистентности, в том числе у пациенток с синдромом поликистозных яичников (СПКЯ).
Цель. Выделить наиболее характерные фармакологические свойства ДХИ.
Материалы и методы. Систематический компьютерный анализ 45 600 публикаций по биологическим ролям инозитолов методами топологической теории распознавания и системно-биологического анализа белков протеома человека.
Результаты. Описан комплекс взаимодействий между нарушениями обмена ДХИ, СПКЯ, нарушениями овуляции, ожирением, ассоциированными с многочисленными нарушениями гормональной активности. Дотации ДХИ и МИ способствуют повышению чувствительности клеток к инсулину и нормализации метаболизма андрогенов. Важным отличием ДХИ от МИ является наличие ДХИ в составе инозитоловых фосфогликанов, опосредующих действие инсулина на клетки, а также его участие в реализации терапевтических эффектов метформина. Использование комбинации МИ+ДХИ позволяет достичь положительной динамики в снижении избыточной массы тела, нормализации уровней липидов, глюкозы и инсулина в крови, восстановления овуляторного менструального цикла, повышения качества ооцитов, способствует профилактике гестационного диабета у беременных и макросомии у плода. ДХИ более эффективен, чем МИ, в снижении риска фолат-резистентных дефектов нервной трубки.
Заключение. Очевиден терапевтический потенциал ДХИ в комбинации с МИ для лечения женщин с СПКЯ и гиперандрогенией. В зависимости от терапевтической целесообразности в препаратах для терапии СПКЯ и нарушений углеводного и липидного обмена могут использоваться различные соотношения МИ:ДХИ.
Ключевые слова: восстановление чувствительности к инсулину, инозитолы, овуляция, гиперандрогения, метаболизм андрогенов, Дикироген
Aim. Highlight the most characteristic pharmacological properties of DCI.
Materials and methods. Systematic computer analysis of 45 600 publications on the biological roles of inositol by methods of the topological theory of pattern recognition and systems biology analysis of human proteome.
Results. A complex of interactions between metabolic disorders of DCI, PCOS, ovulation disorders, obesity associated with numerous hormonal disorders is described. Supplements with DCI and MI increase the sensitivity of cells to insulin and normalize the metabolism of androgens. An important difference between DCI and MI is the presence of DCI in the composition of inositol phosphoglycans that mediate the action of insulin on cells, as well as its participation in the realization of the therapeutic effects of metformin. The use of the MI+DCI combination allows achieving positive dynamics in reducing excess body weight, normalizing blood lipids, glucose and insulin levels, restoring the ovulatory menstrual cycle, improving oocyte quality, and helps prevent gestational diabetes in pregnant women and macrosomia of the fetus. DCI is more effective than MI in reducing the risk of folate-resistant neural tube defects.
Conclusion. The therapeutic potential of DCI in combination with MI for treating PCOS and hyperandrogenism is evident. Depending on the therapeutic expediency, various ratios of MI:DCI can be used for the treatment of PCOS and disorders of carbohydrate and lipid metabolism.
Key words: restoration of insulin sensitivity, inositol, ovulation, hyperandrogenism, androgen metabolism, Dikirogen.
Цель. Выделить наиболее характерные фармакологические свойства ДХИ.
Материалы и методы. Систематический компьютерный анализ 45 600 публикаций по биологическим ролям инозитолов методами топологической теории распознавания и системно-биологического анализа белков протеома человека.
Результаты. Описан комплекс взаимодействий между нарушениями обмена ДХИ, СПКЯ, нарушениями овуляции, ожирением, ассоциированными с многочисленными нарушениями гормональной активности. Дотации ДХИ и МИ способствуют повышению чувствительности клеток к инсулину и нормализации метаболизма андрогенов. Важным отличием ДХИ от МИ является наличие ДХИ в составе инозитоловых фосфогликанов, опосредующих действие инсулина на клетки, а также его участие в реализации терапевтических эффектов метформина. Использование комбинации МИ+ДХИ позволяет достичь положительной динамики в снижении избыточной массы тела, нормализации уровней липидов, глюкозы и инсулина в крови, восстановления овуляторного менструального цикла, повышения качества ооцитов, способствует профилактике гестационного диабета у беременных и макросомии у плода. ДХИ более эффективен, чем МИ, в снижении риска фолат-резистентных дефектов нервной трубки.
Заключение. Очевиден терапевтический потенциал ДХИ в комбинации с МИ для лечения женщин с СПКЯ и гиперандрогенией. В зависимости от терапевтической целесообразности в препаратах для терапии СПКЯ и нарушений углеводного и липидного обмена могут использоваться различные соотношения МИ:ДХИ.
Ключевые слова: восстановление чувствительности к инсулину, инозитолы, овуляция, гиперандрогения, метаболизм андрогенов, Дикироген
________________________________________________
Aim. Highlight the most characteristic pharmacological properties of DCI.
Materials and methods. Systematic computer analysis of 45 600 publications on the biological roles of inositol by methods of the topological theory of pattern recognition and systems biology analysis of human proteome.
Results. A complex of interactions between metabolic disorders of DCI, PCOS, ovulation disorders, obesity associated with numerous hormonal disorders is described. Supplements with DCI and MI increase the sensitivity of cells to insulin and normalize the metabolism of androgens. An important difference between DCI and MI is the presence of DCI in the composition of inositol phosphoglycans that mediate the action of insulin on cells, as well as its participation in the realization of the therapeutic effects of metformin. The use of the MI+DCI combination allows achieving positive dynamics in reducing excess body weight, normalizing blood lipids, glucose and insulin levels, restoring the ovulatory menstrual cycle, improving oocyte quality, and helps prevent gestational diabetes in pregnant women and macrosomia of the fetus. DCI is more effective than MI in reducing the risk of folate-resistant neural tube defects.
Conclusion. The therapeutic potential of DCI in combination with MI for treating PCOS and hyperandrogenism is evident. Depending on the therapeutic expediency, various ratios of MI:DCI can be used for the treatment of PCOS and disorders of carbohydrate and lipid metabolism.
Key words: restoration of insulin sensitivity, inositol, ovulation, hyperandrogenism, androgen metabolism, Dikirogen.
Полный текст
Список литературы
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2. Gromova O.A., Torshin I.Yu., Grishina T.R. et al. Systematic analysis of the molecular physiological effects of myoinositol: data from molecular biology, experimental and clinical medicine. Effective pharmacotherapy. 2013; 28: 32–41 (in Russian).
3. Gromova O.A., Torshin I.Yu., Kalacheva A.G. et al. The role of myo-inositol in maintaining the reproductive health of women. Improving the effectiveness of in vitro fertilization technologies. Breast cancer. Mother and Child 2018; 1 (1): 88–95. DOI: 10.32364/2618-8430-2018-1-1-88-95 (in Russian).
4. Thomas MP, Mills SJ, Potter BV. The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry). Angew Chem Int Ed Engl 2016; 55 (5): 1614–50. DOI: 10.1002/anie.201502227
5. Vitagliano A, Saccone G, Cosmi E et al. Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 2019; 299 (1): 55–68. DOI: 10.1007/s00404-018-5005-0
6. Giménez-Bastida JA, Zieliński H. Buckwheat as a Functional Food and Its Effects on Health. J Agric Food Chem 2015; 63 (36): 7896–913. DOI: 10.1021/acs.jafc.5b02498
7. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of recognition and classification problems. Part 1: properties of compactness. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2016; 26 (2): 274.
8. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of problems of recognition and classification. Part 2: density properties. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2016; 26 (3): 483–96.
9. Torshin I.Yu. Optimal Dictionaries output information based on the criterion of Solvability and their applications in Bioinformatics. Pattern Recognition and Image Analysis 2013; 23 (2): 319–27.
10. Torshin I.Yu., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: metric approach within the framework of the theory of classification of feature values. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2017; 27 (2): 184–99.
11. Jeon Y, Aja S, Ronnett GV, Kim EK. D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway. Biochem Biophys Res Commun 2016; 470 (4): 818–23. DOI: 10.1016/j.bbrc.2016.01.115
12. Hada B, Yoo MR, Seong KM et al. D-chiro-inositol and pinitol extend the life span of Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 2013; 68 (3): 226–34. DOI: 10.1093/gerona/gls156
13. Laganà AS, Unfer V. D-Chiro-Inositol's action as aromatase inhibitor: rationale and potential clinical targets. Eur Rev Med Pharmacol Sci 2019; 23 (24): 10575–6. DOI: 10.26355/eurrev_201912_19752
14. Larner J. D-chiro-inositol in insulin action and insulin resistance-old-fashioned biochemistry still at work. IUBMB Life 2001; 51 (3): 139–48. DOI: 10.1080/152165401753544205
15. Rendle PM, Kassibawi F, Johnston KA et al. Synthesis and biological activities of d-chiro-inositol analogues with insulin-like actions. Eur J Med Chem 2016; 122: 442–51. DOI: 10.1016/j.ejmech.2016.06.047
16. Larner J. D-chiro-inositol – its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 2002; 3 (1): 47–60. DOI: 10.1080/15604280212528
17. Baillargeon JP, Iuorno MJ, Apridonidze T, Nestler JE. Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome. Metab Syndr Relat Dis 2010; 8 (2): 127–36. DOI: 10.1089/met.2009.0052
18. Ostlund RE Jr, Seemayer R, Gupta S et al. A stereospecific myo-inositol/D-chiro-inositol transporter in HepG2 liver cells. Identification with D-chiro-[3-3H]inositol. J Biol Chem 1996; 271 (17): 10073–8. DOI: 10.1074/jbc.271.17.10073
19. Lazarenko R, Geisler J, Bayliss D et al. D-chiro-inositol glycan stimulates insulin secretion in pancreatic b cells. Mol Cell Endocrinol 2014; 387 (1–2): 1–7. DOI: 10.1016/j.mce.2014.02.004
20. Hu Y, Zhao Y, Ren D et al. Hypoglycemic and hepatoprotective effects of D-chiro-inositol-enriched tartary buckwheat extract in high fructose-fed mice. Food Funct 2015; 6 (12): 3760–9. DOI: 10.1039/c5fo00612k
21. Fan C, Liang W, Wei M et al. Effects of D-Chiro-Inositol on Glucose Metabolism in db/db Mice and the Associated Underlying Mechanisms. Front Pharmacol 2020; 11: 354. DOI: 10.3389/fphar.2020.00354
22. Ostlund RE Jr, McGill JB, Herskowitz I et al. D-chiro-inositol metabolism in diabetes mellitus. Proc Natl Acad Sci USA 1993; 90 (21): 9988–92. DOI: 10.1073/pnas.90.21.9988
23. Murphy A, Shamshirsaz A, Markovic D et al. Urinary Excretion of Myo-Inositol and D-Chiro-Inositol in Early Pregnancy Is Enhanced in Gravidas With Gestational Diabetes Mellitus. Reprod Sci 2016; 23 (3): 365–71. DOI: 10.1177/1933719115602767
24. La Marca A, Grisendi V, Dondi G et al. The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study. Gynecol Endocrinol 2015; 31 (1): 52–6. DOI: 10.3109/09513590.2014.964201
25. Iuorno MJ, Jakubowicz DJ, Baillargeon JP et al. Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 2002; 8 (6): 417–23. DOI: 10.4158/EP.8.6.417
26. Nestler JE, Jakubowicz DJ, Reamer P et al. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999; 340 (17): 1314–20. DOI: 10.1056/NEJM199904293401703
27. Baillargeon JP, Iuorno MJ, Jakubowicz DJ et al. Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89 (1): 242–9. DOI: 10.1210/jc.2003-030437
28. Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol 2011; 27 (4): 256–62. DOI: 10.3109/09513590.2010.538099
29. Fonteles MC, Almeida MQ, Larner J. Antihyperglycemic effects of 3-O-methyl-D-chiro-inositol and D-chiro-inositol associated with manganese in streptozotocin diabetic rats. Horm Metab Res 2000; 32 (4): 129–32. DOI: 10.1055/s-2007-978606
30. Gluck G, Anguelova T, Heimark D, Larner J. Synergistic Effects of d-Chiro-Inositol and Manganese on Blood Glucose and Body Weight of Streptozotocin-Induced Diabetic Rats. Curr Bioactive Compounds 2010; 6: 90. DOI: 10.2174/157340710791184831
31. Dell'Edera D, Sarlo F, Allegretti A et al. The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance. Biomed Rep 2017; 7 (2): 169–72. DOI: 10.3892/br.2017.939
32. Maurizi AR, Menduni M, Del Toro R et al. A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes. Acta Diabetol 2017; 54 (4): 361–5. DOI: 10.1007/s00592-016-0954-x
33. Malvasi A, Casciaro F, Minervini MM et al. Myo-inositol, D-chiro-inositol, folic acid and manganese in second trimester of pregnancy: a preliminary investigation. Eur Rev Med Pharmacol Sci 2014; 18 (2): 270–4. PMID: 24488919.
34. Cheng F, Han L, Xiao Y et al. D-chiro-Inositol Ameliorates High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance via PKCe-PI3K/AKT Pathway. J Agric Food Chem 2019; 67 (21): 5957–67. DOI: 10.1021/acs.jafc.9b01253
35. Zhao SS, Li NR, Zhao WL et al. D-chiro-inositol effectively attenuates cholestasis in bile duct ligated rats by improving bile acid secretion and attenuating oxidative stress. Acta Pharmacol Sin 2018; 39 (2): 213–21. DOI: 10.1038/aps.2017.98
36. Carlomagno G, Unfer V, Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril 2011; 95 (8): 2515–6. DOI: 10.1016/j.fertnstert.2011.05.027
37. Laganà AS, Garzon S, Casarin J et al. Inositol in Polycystic Ovary Syndrome: Restoring Fertility through a Pathophysiology-Based Approach. Trends Endocrinol Metab 2018; 29 (11): 768–80. DOI: 10.1016/j.tem.2018.09.001
38. Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE Jr et al. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 2006; 29 (2): 300–5. DOI: 10.2337/diacare.29.02.06.dc05-1070
39. Ravanos K, Monastra G, Pavlidou T et al. Can high levels of D-chiro-inositol in follicular fluid exert detrimental effects on blastocyst quality? Eur Rev Med Pharmacol Sci 2017; 21 (23): 5491–8. DOI: 10.26355/eurrev_201712_13940
40. Cogram P, Tesh S, Tesh J et al. D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects. Hum Reprod 2002; 17 (9): 2451–8. DOI: 10.1093/humrep/17.9.2451
41. Nordio M, Basciani S, Camajani E. The 40: 1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios. Eur Rev Med Pharmacol Sci 2019; 23 (12): 5512–21. DOI: 10.26355/eurrev_201906_18223
42. Le Donne M, Metro D, Alibrandi A et al. Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 2019; 23 (5): 2293–301. DOI: 10.26355/eurrev_201903_17278
43. Nordio M, Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci 2012; 16 (5): 575–81. PMID: 22774396.
44. Januszewski M, Issat T, Jakimiuk AA et al. Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS). Ginekol Pol 2019; 90 (1): 7–10. DOI: 10.5603/GP.2019.0002
45. Mendoza N, Diaz-Ropero MP, Aragon M et al. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol 2019; 35 (8): 695–700. DOI: 10.1080/09513590.2019.1576620
46. Mendoza N, Galan MI, Molina C et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol 2020; 36 (5): 398–401. DOI: 10.1080/09513590.2019.1681959
47. Pizzo A, Laganà AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol 2014; 30 (3): 205–8. DOI: 10.3109/09513590.2013.860120
48. Gromova O.A., Torshin I.Yu., Andreeva E.N. et al. System-biological analysis of the roles of manganese in obstetrics and gynecology: reproductive health of women, regulation of the menstrual cycle and prevention of fetal malformations. Questions of Gynecology, Obstetrics and Perinatology. 2020; 19 (1): 103–13. DOI: 10.20953/1726-1678-2020-1-103-113 (in Russian).
2. Громова О.А., Торшин И.Ю., Гришина Т.Р. и др. Систематический анализ молекулярно-физиологических эффектов миоинозитола: данные молекулярной биологии, экспериментальной и клинической медицины. Эффективная фармакотерапия. 2013; 28: 32–41.
[Gromova O.A., Torshin I.Yu., Grishina T.R. et al. Systematic analysis of the molecular physiological effects of myoinositol: data from molecular biology, experimental and clinical medicine. Effective pharmacotherapy. 2013; 28: 32–41 (in Russian).]
3. Громова О.А., Торшин И.Ю., Калачева А.Г., Тетруашвили Н.К. Роли мио-инозитола в поддержании репродуктивного здоровья женщины. Повышение эффективности технологий экстракорпорального оплодотворения. РМЖ. Мать и дитя. 2018; 1 (1): 88–95. DOI: 10.32364/2618-8430-2018-1-1-88-95
[Gromova O.A., Torshin I.Yu., Kalacheva A.G. et al. The role of myo-inositol in maintaining the reproductive health of women. Improving the effectiveness of in vitro fertilization technologies. Breast cancer. Mother and Child 2018; 1 (1): 88–95. DOI: 10.32364/2618-8430-2018-1-1-88-95 (in Russian).]
4. Thomas MP, Mills SJ, Potter BV. The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry). Angew Chem Int Ed Engl 2016; 55 (5): 1614–50. DOI: 10.1002/anie.201502227
5. Vitagliano A, Saccone G, Cosmi E et al. Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 2019; 299 (1): 55–68. DOI: 10.1007/s00404-018-5005-0
6. Giménez-Bastida JA, Zieliński H. Buckwheat as a Functional Food and Its Effects on Health. J Agric Food Chem 2015; 63 (36): 7896–913. DOI: 10.1021/acs.jafc.5b02498
7. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of recognition and classification problems. Part 1: properties of compactness. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2016; 26 (2): 274.
8. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of problems of recognition and classification. Part 2: density properties. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2016; 26 (3): 483–96.
9. Torshin I.Yu. Optimal Dictionaries output information based on the criterion of Solvability and their applications in Bioinformatics. Pattern Recognition and Image Analysis 2013; 23 (2): 319–27.
10. Torshin I.Yu., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: metric approach within the framework of the theory of classification of feature values. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2017; 27 (2): 184–99.
11. Jeon Y, Aja S, Ronnett GV, Kim EK. D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway. Biochem Biophys Res Commun 2016; 470 (4): 818–23. DOI: 10.1016/j.bbrc.2016.01.115
12. Hada B, Yoo MR, Seong KM et al. D-chiro-inositol and pinitol extend the life span of Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 2013; 68 (3): 226–34. DOI: 10.1093/gerona/gls156
13. Laganà AS, Unfer V. D-Chiro-Inositol's action as aromatase inhibitor: rationale and potential clinical targets. Eur Rev Med Pharmacol Sci 2019; 23 (24): 10575–6. DOI: 10.26355/eurrev_201912_19752
14. Larner J. D-chiro-inositol in insulin action and insulin resistance-old-fashioned biochemistry still at work. IUBMB Life 2001; 51 (3): 139–48. DOI: 10.1080/152165401753544205
15. Rendle PM, Kassibawi F, Johnston KA et al. Synthesis and biological activities of d-chiro-inositol analogues with insulin-like actions. Eur J Med Chem 2016; 122: 442–51. DOI: 10.1016/j.ejmech.2016.06.047
16. Larner J. D-chiro-inositol – its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 2002; 3 (1): 47–60. DOI: 10.1080/15604280212528
17. Baillargeon JP, Iuorno MJ, Apridonidze T, Nestler JE. Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome. Metab Syndr Relat Dis 2010; 8 (2): 127–36. DOI: 10.1089/met.2009.0052
18. Ostlund RE Jr, Seemayer R, Gupta S et al. A stereospecific myo-inositol/D-chiro-inositol transporter in HepG2 liver cells. Identification with D-chiro-[3-3H]inositol. J Biol Chem 1996; 271 (17): 10073–8. DOI: 10.1074/jbc.271.17.10073
19. Lazarenko R, Geisler J, Bayliss D et al. D-chiro-inositol glycan stimulates insulin secretion in pancreatic b cells. Mol Cell Endocrinol 2014; 387 (1–2): 1–7. DOI: 10.1016/j.mce.2014.02.004
20. Hu Y, Zhao Y, Ren D et al. Hypoglycemic and hepatoprotective effects of D-chiro-inositol-enriched tartary buckwheat extract in high fructose-fed mice. Food Funct 2015; 6 (12): 3760–9. DOI: 10.1039/c5fo00612k
21. Fan C, Liang W, Wei M et al. Effects of D-Chiro-Inositol on Glucose Metabolism in db/db Mice and the Associated Underlying Mechanisms. Front Pharmacol 2020; 11: 354. DOI: 10.3389/fphar.2020.00354
22. Ostlund RE Jr, McGill JB, Herskowitz I et al. D-chiro-inositol metabolism in diabetes mellitus. Proc Natl Acad Sci USA 1993; 90 (21): 9988–92. DOI: 10.1073/pnas.90.21.9988
23. Murphy A, Shamshirsaz A, Markovic D et al. Urinary Excretion of Myo-Inositol and D-Chiro-Inositol in Early Pregnancy Is Enhanced in Gravidas With Gestational Diabetes Mellitus. Reprod Sci 2016; 23 (3): 365–71. DOI: 10.1177/1933719115602767
24. La Marca A, Grisendi V, Dondi G et al. The menstrual cycle regularization following D-chiro-inositol treatment in PCOS women: a retrospective study. Gynecol Endocrinol 2015; 31 (1): 52–6. DOI: 10.3109/09513590.2014.964201
25. Iuorno MJ, Jakubowicz DJ, Baillargeon JP et al. Effects of d-chiro-inositol in lean women with the polycystic ovary syndrome. Endocr Pract 2002; 8 (6): 417–23. DOI: 10.4158/EP.8.6.417
26. Nestler JE, Jakubowicz DJ, Reamer P et al. Ovulatory and metabolic effects of D-chiro-inositol in the polycystic ovary syndrome. N Engl J Med 1999; 340 (17): 1314–20. DOI: 10.1056/NEJM199904293401703
27. Baillargeon JP, Iuorno MJ, Jakubowicz DJ et al. Metformin therapy increases insulin-stimulated release of D-chiro-inositol-containing inositolphosphoglycan mediator in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2004; 89 (1): 242–9. DOI: 10.1210/jc.2003-030437
28. Galazis N, Galazi M, Atiomo W. D-Chiro-inositol and its significance in polycystic ovary syndrome: a systematic review. Gynecol Endocrinol 2011; 27 (4): 256–62. DOI: 10.3109/09513590.2010.538099
29. Fonteles MC, Almeida MQ, Larner J. Antihyperglycemic effects of 3-O-methyl-D-chiro-inositol and D-chiro-inositol associated with manganese in streptozotocin diabetic rats. Horm Metab Res 2000; 32 (4): 129–32. DOI: 10.1055/s-2007-978606
30. Gluck G, Anguelova T, Heimark D, Larner J. Synergistic Effects of d-Chiro-Inositol and Manganese on Blood Glucose and Body Weight of Streptozotocin-Induced Diabetic Rats. Curr Bioactive Compounds 2010; 6: 90. DOI: 10.2174/157340710791184831
31. Dell'Edera D, Sarlo F, Allegretti A et al. The influence of D-chiro-inositol and D-myo-inositol in pregnant women with glucose intolerance. Biomed Rep 2017; 7 (2): 169–72. DOI: 10.3892/br.2017.939
32. Maurizi AR, Menduni M, Del Toro R et al. A pilot study of D-chiro-inositol plus folic acid in overweight patients with type 1 diabetes. Acta Diabetol 2017; 54 (4): 361–5. DOI: 10.1007/s00592-016-0954-x
33. Malvasi A, Casciaro F, Minervini MM et al. Myo-inositol, D-chiro-inositol, folic acid and manganese in second trimester of pregnancy: a preliminary investigation. Eur Rev Med Pharmacol Sci 2014; 18 (2): 270–4. PMID: 24488919.
34. Cheng F, Han L, Xiao Y et al. D-chiro-Inositol Ameliorates High Fat Diet-Induced Hepatic Steatosis and Insulin Resistance via PKCe-PI3K/AKT Pathway. J Agric Food Chem 2019; 67 (21): 5957–67. DOI: 10.1021/acs.jafc.9b01253
35. Zhao SS, Li NR, Zhao WL et al. D-chiro-inositol effectively attenuates cholestasis in bile duct ligated rats by improving bile acid secretion and attenuating oxidative stress. Acta Pharmacol Sin 2018; 39 (2): 213–21. DOI: 10.1038/aps.2017.98
36. Carlomagno G, Unfer V, Roseff S. The D-chiro-inositol paradox in the ovary. Fertil Steril 2011; 95 (8): 2515–6. DOI: 10.1016/j.fertnstert.2011.05.027
37. Laganà AS, Garzon S, Casarin J et al. Inositol in Polycystic Ovary Syndrome: Restoring Fertility through a Pathophysiology-Based Approach. Trends Endocrinol Metab 2018; 29 (11): 768–80. DOI: 10.1016/j.tem.2018.09.001
38. Baillargeon JP, Diamanti-Kandarakis E, Ostlund RE Jr et al. Altered D-chiro-inositol urinary clearance in women with polycystic ovary syndrome. Diabetes Care 2006; 29 (2): 300–5. DOI: 10.2337/diacare.29.02.06.dc05-1070
39. Ravanos K, Monastra G, Pavlidou T et al. Can high levels of D-chiro-inositol in follicular fluid exert detrimental effects on blastocyst quality? Eur Rev Med Pharmacol Sci 2017; 21 (23): 5491–8. DOI: 10.26355/eurrev_201712_13940
40. Cogram P, Tesh S, Tesh J et al. D-chiro-inositol is more effective than myo-inositol in preventing folate-resistant mouse neural tube defects. Hum Reprod 2002; 17 (9): 2451–8. DOI: 10.1093/humrep/17.9.2451
41. Nordio M, Basciani S, Camajani E. The 40: 1 myo-inositol/D-chiro-inositol plasma ratio is able to restore ovulation in PCOS patients: comparison with other ratios. Eur Rev Med Pharmacol Sci 2019; 23 (12): 5512–21. DOI: 10.26355/eurrev_201906_18223
42. Le Donne M, Metro D, Alibrandi A et al. Effects of three treatment modalities (diet, myoinositol or myoinositol associated with D-chiro-inositol) on clinical and body composition outcomes in women with polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 2019; 23 (5): 2293–301. DOI: 10.26355/eurrev_201903_17278
43. Nordio M, Proietti E. The combined therapy with myo-inositol and D-chiro-inositol reduces the risk of metabolic disease in PCOS overweight patients compared to myo-inositol supplementation alone. Eur Rev Med Pharmacol Sci 2012; 16 (5): 575–81. PMID: 22774396.
44. Januszewski M, Issat T, Jakimiuk AA et al. Metabolic and hormonal effects of a combined Myo-inositol and d-chiro-inositol therapy on patients with polycystic ovary syndrome (PCOS). Ginekol Pol 2019; 90 (1): 7–10. DOI: 10.5603/GP.2019.0002
45. Mendoza N, Diaz-Ropero MP, Aragon M et al. Comparison of the effect of two combinations of myo-inositol and D-chiro-inositol in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol 2019; 35 (8): 695–700. DOI: 10.1080/09513590.2019.1576620
46. Mendoza N, Galan MI, Molina C et al. High dose of d-chiro-inositol improves oocyte quality in women with polycystic ovary syndrome undergoing ICSI: a randomized controlled trial. Gynecol Endocrinol 2020; 36 (5): 398–401. DOI: 10.1080/09513590.2019.1681959
47. Pizzo A, Laganà AS, Barbaro L. Comparison between effects of myo-inositol and D-chiro-inositol on ovarian function and metabolic factors in women with PCOS. Gynecol Endocrinol 2014; 30 (3): 205–8. DOI: 10.3109/09513590.2013.860120
48. Громова О.А., Торшин И.Ю., Андреева Е.Н. и др. Системно-биологический анализ ролей марганца в акушерстве и гинекологии: репродуктивное здоровье женщины, регуляция менструального цикла и профилактика пороков развития плода. Вопр. гинекологии, акушерства и перинатологии. 2020; 19 (1): 103–13. DOI: 10.20953/1726-1678-2020-1-103-113
[Gromova O.A., Torshin I.Yu., Andreeva E.N. et al. System-biological analysis of the roles of manganese in obstetrics and gynecology: reproductive health of women, regulation of the menstrual cycle and prevention of fetal malformations. Questions of Gynecology, Obstetrics and Perinatology. 2020; 19 (1): 103–13. DOI: 10.20953/1726-1678-2020-1-103-113 (in Russian).]
________________________________________________
2. Gromova O.A., Torshin I.Yu., Grishina T.R. et al. Systematic analysis of the molecular physiological effects of myoinositol: data from molecular biology, experimental and clinical medicine. Effective pharmacotherapy. 2013; 28: 32–41 (in Russian).
3. Gromova O.A., Torshin I.Yu., Kalacheva A.G. et al. The role of myo-inositol in maintaining the reproductive health of women. Improving the effectiveness of in vitro fertilization technologies. Breast cancer. Mother and Child 2018; 1 (1): 88–95. DOI: 10.32364/2618-8430-2018-1-1-88-95 (in Russian).
4. Thomas MP, Mills SJ, Potter BV. The "Other" Inositols and Their Phosphates: Synthesis, Biology, and Medicine (with Recent Advances in myo-Inositol Chemistry). Angew Chem Int Ed Engl 2016; 55 (5): 1614–50. DOI: 10.1002/anie.201502227
5. Vitagliano A, Saccone G, Cosmi E et al. Inositol for the prevention of gestational diabetes: a systematic review and meta-analysis of randomized controlled trials. Arch Gynecol Obstet 2019; 299 (1): 55–68. DOI: 10.1007/s00404-018-5005-0
6. Giménez-Bastida JA, Zieliński H. Buckwheat as a Functional Food and Its Effects on Health. J Agric Food Chem 2015; 63 (36): 7896–913. DOI: 10.1021/acs.jafc.5b02498
7. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of recognition and classification problems. Part 1: properties of compactness. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2016; 26 (2): 274.
8. Torshin I.Yu., Rudakov K.V. On metric spaces arising during formalization of problems of recognition and classification. Part 2: density properties. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2016; 26 (3): 483–96.
9. Torshin I.Yu. Optimal Dictionaries output information based on the criterion of Solvability and their applications in Bioinformatics. Pattern Recognition and Image Analysis 2013; 23 (2): 319–27.
10. Torshin I.Yu., Rudakov K.V. Combinatorial analysis of the solvability properties of the problems of recognition and completeness of algorithmic models. Part 2: metric approach within the framework of the theory of classification of feature values. Pattern Recognition and Image Analysis (Advances in Mathematical Theory and Applications). 2017; 27 (2): 184–99.
11. Jeon Y, Aja S, Ronnett GV, Kim EK. D-chiro-inositol glycan reduces food intake by regulating hypothalamic neuropeptide expression via AKT-FoxO1 pathway. Biochem Biophys Res Commun 2016; 470 (4): 818–23. DOI: 10.1016/j.bbrc.2016.01.115
12. Hada B, Yoo MR, Seong KM et al. D-chiro-inositol and pinitol extend the life span of Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 2013; 68 (3): 226–34. DOI: 10.1093/gerona/gls156
13. Laganà AS, Unfer V. D-Chiro-Inositol's action as aromatase inhibitor: rationale and potential clinical targets. Eur Rev Med Pharmacol Sci 2019; 23 (24): 10575–6. DOI: 10.26355/eurrev_201912_19752
14. Larner J. D-chiro-inositol in insulin action and insulin resistance-old-fashioned biochemistry still at work. IUBMB Life 2001; 51 (3): 139–48. DOI: 10.1080/152165401753544205
15. Rendle PM, Kassibawi F, Johnston KA et al. Synthesis and biological activities of d-chiro-inositol analogues with insulin-like actions. Eur J Med Chem 2016; 122: 442–51. DOI: 10.1016/j.ejmech.2016.06.047
16. Larner J. D-chiro-inositol – its functional role in insulin action and its deficit in insulin resistance. Int J Exp Diabetes Res 2002; 3 (1): 47–60. DOI: 10.1080/15604280212528
17. Baillargeon JP, Iuorno MJ, Apridonidze T, Nestler JE. Uncoupling between insulin and release of a D-chiro-inositol-containing inositolphosphoglycan mediator of insulin action in obese women With polycystic ovary syndrome. Metab Syndr Relat Dis 2010; 8 (2): 127–36. DOI: 10.1089/met.2009.0052
18. Ostlund RE Jr, Seemayer R, Gupta S et al. A stereospecific myo-inositol/D-chiro-inositol transporter in HepG2 liver cells. Identification with D-chiro-[3-3H]inositol. J Biol Chem 1996; 271 (17): 10073–8. DOI: 10.1074/jbc.271.17.10073
19. Lazarenko R, Geisler J, Bayliss D et al. D-chiro-inositol glycan stimulates insulin secretion in pancreatic b cells. Mol Cell Endocrinol 2014; 387 (1–2): 1–7. DOI: 10.1016/j.mce.2014.02.004
20. Hu Y, Zhao Y, Ren D et al. Hypoglycemic and hepatoprotective effects of D-chiro-inositol-enriched tartary buckwheat extract in high fructose-fed mice. Food Funct 2015; 6 (12): 3760–9. DOI: 10.1039/c5fo00612k
21. Fan C, Liang W, Wei M et al. Effects of D-Chiro-Inositol on Glucose Metabolism in db/db Mice and the Associated Underlying Mechanisms. Front Pharmacol 2020; 11: 354. DOI: 10.3389/fphar.2020.00354
22. Ostlund RE Jr, McGill JB, Herskowitz I et al. D-chiro-inositol metabolism in diabetes mellitus. Proc Natl Acad Sci USA 1993; 90 (21): 9988–92. DOI: 10.1073/pnas.90.21.9988
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Авторы
О.А. Громова*1,2, И.Ю. Торшин1,2, Е.В. Уварова3,4, Н.И. Тапильская5,6, А.Г. Калачева7
1 ФИЦ «Информатика и управление» РАН, Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия;
3 ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии
имени академика В.И. Кулакова» Минздрава России, Москва, Россия;
4 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
5 ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта», Санкт-Петербург, Россия;
6 ФГБОУ ВО «Санкт-Петербургский государственный педиатрический университет» Минздрава России, Санкт-Петербург, Россия;
7 ФГБОУ ВО «Ивановская государственная медицинская академия» Минздрава России, Иваново, Россия
*unesco.gromova@gmail.com
1 Federal Research Center "Computer Science and Management", Moscow, Russia;
2 Lomonosov Moscow State University, Moscow, Russia;
3 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia;
4 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
5 Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia;
6 Saint Petersburg State Paediatric Medical University, Saint Petersburg, Russia;
7 Ivanovo State Medical Academy, Ivanovo, Russia
*unesco.gromova@gmail.com
1 ФИЦ «Информатика и управление» РАН, Москва, Россия;
2 ФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова», Москва, Россия;
3 ФГБУ «Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии
имени академика В.И. Кулакова» Минздрава России, Москва, Россия;
4 ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия;
5 ФГБНУ «Научно-исследовательский институт акушерства, гинекологии и репродуктологии им. Д.О. Отта», Санкт-Петербург, Россия;
6 ФГБОУ ВО «Санкт-Петербургский государственный педиатрический университет» Минздрава России, Санкт-Петербург, Россия;
7 ФГБОУ ВО «Ивановская государственная медицинская академия» Минздрава России, Иваново, Россия
*unesco.gromova@gmail.com
________________________________________________
1 Federal Research Center "Computer Science and Management", Moscow, Russia;
2 Lomonosov Moscow State University, Moscow, Russia;
3 Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia;
4 Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia;
5 Ott Research Institute of Obstetrics, Gynecology and Reproductology, Saint Petersburg, Russia;
6 Saint Petersburg State Paediatric Medical University, Saint Petersburg, Russia;
7 Ivanovo State Medical Academy, Ivanovo, Russia
*unesco.gromova@gmail.com
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