ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2013-5-104-118ssmu-268Research ArticleОБЗОР ЛИТЕРАТУРЫLITERATURE REVIEWИНСУЛИН И ИНСУЛИНОРЕЗИСТЕНТНОСТЬ: НОВЫЕ МОЛЕКУЛЫ-МАРКЕРЫ И МОЛЕКУЛЫ-МИШЕНИ ДЛЯ ДИАГНОСТИКИ И ТЕРАПИИ ЗАБОЛЕВАНИЙ ЦЕНТРАЛЬНОЙ НЕРВНОЙ СИСТЕМЫINSULIN AND INSULIN RESISTANCE: NEW MOLECULE MARKERS AND TARGET MOLECULE FOR THE DIAGNOSIS AND THERAPY OF DISEASES OF THE CENTRAL NERVOUS SYSTEMСалминаА. Б.SalminaA. B.

Салмина Алла Борисовна – доктор медицинских наук, профессор

allasalmina@mail.ruЯузинаН. А.YauzinaN. A.

Яузина Нина Анатольевна – аспирант

allasalmina@mail.ruКувачеваН. В.KuvachevaN. V.

Кувачева Наталья Валерьевна – кандидат фармацевтических наук, доцент

allasalmina@mail.ruПетроваМ. М.PetrovaM. M.

Петрова Марина Михайловна – доктор медицинских наук, профессор

allasalmina@mail.ruТаранушенкоТ. Е.TaranushenkoT. Ye.

Таранушенко Татьяна Евгеньевна – доктор медицинских наук, профессор

allasalmina@mail.ruМалиновскаяН. А.MalinovskayaN. A.

Малиновская Наталия Александровна – кандидат медицинских наук, доцент

allasalmina@mail.ruЛопатинаО. Л.LopatinaO. L.

Лопатина Ольга Леонидовна – старший преподаватель

allasalmina@mail.ruМоргунА. В.MorgunA. V.

Моргун Андрей Васильевич – кандидат медицинских наук, ассистент

allasalmina@mail.ruПожиленковаЕ. А.PozhilenkovaYe. A.

Пожиленкова Елена Анатольевна – кандидат биологических наук, доцент

allasalmina@mail.ruОкуневаО. С.OkunevaO. S.

Окунева Олеся Сергеевна – кандидат медицинских наук, старший преподаватель

allasalmina@mail.ruМорозоваГ. А.MorozovaG. A.

Морозова Галина Александровна – кандидат медицинских наук, научный сотрудник

allasalmina@mail.ruПрокопенкоС. В.ProkopenkoS. V.

Прокопенко Семен Владимирович – доктор медицинских наук, профессор

allasalmina@mail.ruКрасноярский государственный медицинский университет им. проф. В.Ф. Войно-Ясенецкого, КрасноярскРоссияV.F. Voino-Yasenetsky Krasnoyarsk State Medical University, KrasnoyarskRussian Federation201328102013125104118Copyright © Салмина А.Б., Яузина Н.А., Кувачева Н.В., Петрова М.М., Таранушенко Т.Е., Малиновская Н.А., Лопатина О.Л., Моргун А.В., Пожиленкова Е.А., Окунева О.С., Морозова Г.А., Прокопенко С.В., 20132013Салмина А.Б., Яузина Н.А., Кувачева Н.В., Петрова М.М., Таранушенко Т.Е., Малиновская Н.А., Лопатина О.Л., Моргун А.В., Пожиленкова Е.А., Окунева О.С., Морозова Г.А., Прокопенко С.В.Salmina A.B., Yauzina N.A., Kuvacheva N.V., Petrova M.M., Taranushenko T.Y., Malinovskaya N.A., Lopatina O.L., Morgun A.V., Pozhilenkova Y.A., Okuneva O.S., Morozova G.A., Prokopenko S.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/268

В статье рассматриваются вопросы, связанные с ролью инсулина в обмене глюкозы в центральной нервной системе в физиологических условиях и при развитии нейродегенеративных заболеваний и инсулинорезистентности. Долгие годы головной мозг считался инсулиннезависимым органом, способным утилизировать глюкозу без участия инсулина. В настоящее время инсулину принадлежит не только роль регулятора транспорта глюкозы и ее метаболизма, но и модулятора таких процессов, как электровозбудимость нейронов, пролиферация и дифференцировка прогениторных клеток, синаптическая пластичность, формирование памяти, секреция нейротрансмиттеров, апоптоз. В настоящем обзоре критически проанализирована современная литература, с учетом собственных данных, о роли инсулина и инсулинорезистентности в регуляции нейрон-глиального метаболического сопряжения, поддержании гомеостаза НАД+ и регуляции активности НАД+ -зависимых ферментов, нейрогенеза и развития мозга в (пато)физиологических условиях. Раскрываются причинно-следственные связи между нарушением гомеостаза глюкозы, развитием инсулинорезистентности и нейродегенеративными заболеваниями (болезнь Альцгеймера и Паркинсона), аутизмом, острым нарушением мозгового кровообращения, депрессией. Обсуждается применение новых молекул-маркеров инсулинорезистентности (адипокины, α-гидроксибутират, BDNF, инсулинрегулируемая аминопептидаза, провазопрессин) и молекул-мишеней для диагностики и терапии заболеваний головного мозга, ассоциированных с развитием инсулинорезистентности. 

The review summarizes current data on the role of insulin in the regulation of t glucose metabolism in the central nervous system at physiologic and pathologic conditions. For many years, the brain has been considered as an insulin-independent organ which utilizes glucose without insulin activity. However, it is become clear now that insulin not only regulates glucose transport and metabolism, but also has modulatory efftects in impact on excitability, proliferation and differentiation of brain progenitor cells, synaptic plasticity and memory formation, secretion of neurotransmitters, apoptosis. We have critically reviewed literature information and our own data on the role of insulin and insulin resistance in neuron-glia metabolic coupling, regulation of NAD+ metabolism and action of NAdependent enzymes, neurogenesis, brain development in (patho)physiological conditions. The paper clarifies interrelations between alterations in glucose homeostasis, development of insulin resistance and development of neurodegeneration (Alzheimer's disease and Parkinson's disease), autism, stroke, and depression. We discuss the application of novel molecular markers of insulin resistance (adipokines, α-hydroxybutyrate, BDNF, insulin-regulated aminopeptidase, provasopressin) and molecular targets for diagnostics and treatment of brain disorders associated with insulin resistance.

инсулининсулинорезистентностьмаркерголовной мозгнейрогенезнейропротекцияinsulininsulin resistancemarkerneurogenesisneuroprotectionReferencesKahn C.R., Suzuki R. Insulin action in the brain and the pathogenesis of Alzheimers disease // Diabetes, insulin and Alzheimer`s disease / Ed. S. Craft. Hardcover: Springer, 2010, XIV, 218 p.Kahn C.R., Suzuki R. Insulin action in the brain and the pathogenesis of Alzheimers disease. Diabetes, insulin and Alzheimer`s disease. Ed. S. Craft. Springer, 2010, XIV, 218 p., Hardcover.Chiu S.L., Cline H.T. Insulin receptor signaling in the development of neuronal structure and function // Neural Dev. 2010. V. 15. P. 5–7.Chiu S.L., Cline H.T. Insulin receptor signaling in the development of neuronal structure and function. Neural Dev., 2010, vol. 15, pp. 5–7.Schwartz M.W., Figlewicz D.P., Baskin D.G. et al. Insulin in the brain: a hormonal regulator of energy balance // Endocr. Rev. 1992. V. 13, № 3. Р. 387–414.Schwartz M.W., Figlewicz D.P., Baskin D.G. et al. Insulin in the brain: a hormonal regulator of energy balance. Endocr. Rev., 1992, vol. 13, no. 3, pp. 387–414.Heidenreich K.A., Zahniser N.R., Berhanu P. et al. Structural differences between insulin receptors in the brain and peripheral target tissues // J. Biol. Chem. 1983. V. 258, № 14. P. 8527–8530.Heidenreich K.A., Zahniser N.R., Berhanu P. et al. Structural differences between insulin receptors in the brain and peripheral target tissues. J. Biol. Chem., 1983, vol. 258, no. 14. P. 8527–8530.Pagotto U. Where does insulin resistance start? The brain // Diabetes Care. 2009. V. 32, № 2. Р. 174–177.Pagotto U. Where does insulin resistance start? The brain. Diabetes Care, 2009, vol. 32, no.2. Р. 174–177.Banks W.A. The source of cerebral insulin // Eur. J. Pharmacol. 2004. V. 490, № 1–3. Р. 5–12.Banks W.A. The source of cerebral insulin. Eur. J. Pharmacol., 2004, vol. 490, no. 1–3. Р. 5–12.Wada A., Yokoo H., Yanagita T., Kobayashi H. New twist on neuronal insulin receptor signaling in health, disease, and therapeutics // J. Pharmacol. Sci. 2005. V. 99, № 2. Р. 128–143.Wada A., Yokoo H., Yanagita T., Kobayashi H. New twist on neuronal insulin receptor signaling in health, disease, and therapeutics. J. Pharmacol Sci., 2005, vol. 99, no. 2. Р 128–143.Devaskar S.U., Giddings S.J., Rajakumar P.A. et al. Insulin gene expression and insulin synthesis in mammalian neu-ronal cells // J. Biol. Chem. 1994. V. 269, № 11. Р. 845–854.Devaskar S.U., Giddings S.J., Rajakumar P.A., et al. Insulin gene expression and insulin synthesis in mammalian n neuronal cells. J. Biol. Chem., 1994, vol. 269, no. 11., pp. 8445– 854.Monte S.M. de la, Wands J.R. Review of insulin and insulinlike growth factor expression, signaling, and malfunction in the central nervous system: Relevance to Alzheimer’s disease // J. of Alzheimer’s Disease. 2005. V. 7. P. 45–61.Monte S.M. de la, Wands J.R. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: Relevance to Alzheimer’s disease. Journal of Alzheimer’s Disease, 2005, vol. 7, pp. 45–61.Clarke D.W., Mudd L., Boyd F.T. J. et al.r, Insulin is released from rat brain neuronal cells in culture. J. Neurochem., 1986, vol. 47, no. 3, pp. 831–836.Clarke D.W., Mudd L., Boyd F.T. J. et al. Insulin is released from rat brain neuronal cells in culture // J. Neurochem. 1986. V. 47, № 3. Р. 831–836.Zhao W., Chen H., Xu H. et al. Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J. Biol. Chem., 1999, vol. 274, no. 49, pp. 34893–34902.Zhao W., Chen H., Xu H. et al. Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats // J. Biol. Chem. 1999. V. 274, № 49. Р. 34893–34902.Havrankova J., Schmechel D., Roth J., Brownstein M. Identification of insulin in rat brain. PNAS USA, 1978, vol. 75, no. 11, pp. 5737–5741.Havrankova J., Schmechel D., Roth J., Brownstein M. Identification of insulin in rat brain // PNAS USA. 1978. V. 75. № 11. Р. 5737–5741.Woods S.C., Seeley R.J., Baskin D.G., Schwartz M.W. Insulin and the blood-brain barrier. Curr. Pharm. Des., 2003, vol. 9, no. 10, pp. 795–800.Woods S.C., Seeley R.J., Baskin D.G., Schwartz M.W. Insulin and the blood-brain barrier // Curr. Pharm. Des. 2003. V. 9, №. 10. P. 795–800.Duarte A.I., Moreira P.I., Oliveira C.R. Insulin in Central Nervous System: More than Just a Peripheral Hormone. J., Aging. Res., vol. 2012. Article ID 384017.Duarte A.I., Moreira P.I., Oliveira C.R. Insulin in Central Nervous System: More than Just a Peripheral Hormone // J. Aging. Res. V. 2012. Article ID 384017.Kauffman A.L., Ashraf J.M., Ryan M. et al. Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age. PLoS Biology, 2010, vol. 8, no. 5, e1000372. DOI: 10.1371/journal.pbio.1000372.Kauffman A.L., Ashraf J.M., Ryan M. et al. Insulin signaling and dietary restriction differentially influence the decline of learning and memory with age // PLoS Biology. 2010. V. 8, № 5. e1000372. DOI: 10.1371/journal.pbio.1000372.Yanagita T., Nemoto T., Satoh S. et al. Neuronal insulin receptor signaling: a potential target for the treatment of cognitive and mood disorders. Mood Disorders. Ed. Kocabasoglu N. InTech, 2013, pp. 263–287.Yanagita T., Nemoto T., Satoh S. et al. Neuronal insulin receptor signaling: a potential target for the treatment of cognitive and mood disorders // Mood Disorders / Ed. Kocabasoglu N. InTech, 2013. P. 263–287.Levin B.E., Sherwin R.S. Peripheral glucose homeostasis: does brain insulin matter? J. Clin. Invest., 2011, vol. 121, no. 9, pp. 3392–3395.Levin B.E., Sherwin R.S. Peripheral glucose homeostasis: does brain insulin matter? // J. Clin. Invest. 2011. V. 121, №9. P. 3392–3395.Duelli R., Kuschinsky W. Brain glucose transporters: relationship to local energy demand. News Physiol. Sci., 2001, vol. 16, pp. 71–76.Duelli R., Kuschinsky W. Brain glucose transporters: relationship to local energy demand // News Physiol. Sci. 2001. V. 16. P. 71–76.Simpson I.A., Appel N.M., Hokari M. et al. Blood-brain barrier glucose transporter: effects of hypoand hyperglycemia revisited. J. Neurochem., 1999, vol. 72, no. 1, pp. 238–247.Simpson I.A., Appel N.M., Hokari M. et al. Blood-brain barrier glucose transporter: effects of hypoand hyperglycemia revisited // J. Neurochem. 1999. V. 72, № 1. Р. 238–247.Messari S., Leloup C., Quignon M. et al. Immunocytochemical localization of the insulin-responsive glucose transporter 4 (GLUT4) in the rat central nervous system. J. Comp. Neurol., 1998, vol. 399, no. 4, pp. 492–512.Messari S., Leloup C., Quignon M. et al. Immunocytochemical localization of the insulin-responsive glucose transporter 4 (GLUT4) in the rat central nervous system // J. Comp. Neurol. 1998. V. 399, № 4. Р. 492–512.Rafalski V.A., Brunet A. Energy metabolism in adult neural stem cell fate. Progress in Neurobiology, 2011, vol. 93, pp. 182–203.Rafalski V.A., Brunet A. Energy metabolism in adult neural stem cell fate // Progress in Neurobiology. 2011. V. 93. P. 182–203.Bingham E.M., Hopkins D., Smith D. et al. The role of insulin in human brain glucose metabolism: an 18fluorodeoxyglucose positron emission tomography study. Diabetes, 2002, vol. 51, no. 12, pp. 3384–3390.Bingham E.M., Hopkins D., Smith D. et al. The role of insulin in human brain glucose metabolism: an 18fluorodeoxyglucose positron emission tomography study // Diabetes. 2002. V. 51, № 12. P. 3384–3390.Anthony K., Reed L.J., Dunn J.T. et al. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome? Diabetes, 2006, vol. 55, no. 11, pp. 2986–2992.Anthony K., Reed L.J., Dunn J.T. et al. Attenuation of insulin-evoked responses in brain networks controlling appetite and reward in insulin resistance: the cerebral basis for impaired control of food intake in metabolic syndrome? // Diabetes. 2006. V. 55, №. 11. P. 2986–2992.Sanchez R., Ac L., Hom D. Insulin, Brain Function And Alzheimer’s Disease – Is Insulin Resistance To Blame For Alzheimer’s? URL: http://www.thealzheimerssolution.com/insulin-brain-functionand-alzheimers-disease-is-insulin-resistance-to-blame-foralzheimers/ (accessed: 03 May 2013).Sanchez R., Ac L., Hom D. Insulin, Brain Function And Alzheimer’s Disease – Is Insulin Resistance To Blame For Alzheimer’s? URL: http://www.thealzheimerssolution.com/insulin-brain-functionand-alzheimers-disease-is-insulin-resistance-to-blame-foralzheimers/ (accessed: 03 May 2013).Salmina A.B. Neuron-glia interactions as therapeutic targets in neurodegeneration. J. Alzheimers Dis., 2009, vol. 16, no. 3. Р. 485–502.Salmina A.B. Neuron-glia interactions as therapeutic targets in neurodegeneration // J Alzheimers Dis. 2009. V. 16, № 3. Р. 485–502.Salmina A.B., Inzhutova A.I., Morgun A.V. et al. NAD+ converting enzymes in neuronal and glial cells: CD38 as a novel target for neuroprotection. Bulletin of the Russian Academy of Medical Sciences, 2012, no. 10, pp. 29–37 (in Russian).Салмина А.Б., Инжутова А.И., Моргун А.В. и др. НАД+-конвертирующие ферменты в клетках нейрональной и глиальной природы: СD38 как новая молекула-мишень для нейропротекции // Вестн. РАМН. 2012. № 10. С. 29–37.Bambrick L., Kristian T., Fiskum G. Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection. Neurochemical Res., 2004, vol. 29, no.3. Р. 601–608.Bambrick L., Kristian T., Fiskum G. Astrocyte mitochondrial mechanisms of ischemic brain injury and neuroprotection // Neurochemical Res. 2004. V. 29. № 3. Р. 601–608.Callana M.A., Clementsa N., Ahrendt N. et al. Fragile X Protein is required for inhibition of insulin signaling and regulates glial-dependent neuroblast reactivation in the developing brain. Brain Res., 2012, vol. 1462, pp. 151– 161.Callana M.A., Clementsa N., Ahrendt N. et al. Fragile X Protein is required for inhibition of insulin signaling and regulates glial-dependent neuroblast reactivation in the developing brain // Brain Res. 2012. V. 1462. P. 151–161.Ables E.T., Drummond-Barbosa D. Food for thought: neural stem cells on a diet. Cell Stem. Cell., 2011, vol. 8, pp. 352– 354.Ables E.T., Drummond-Barbosa D. Food for thought: neural stem cells on a diet // Cell. Stem. Cell. 2011. V. 8. P. 352–354.Fanne R.A., Nassar T., Heyman S.N. et al. Insulin and glucagon share the same mechanism of neuroprotection in diabetic rats: role of glutamate. Am. J. Physiol. Regul. Integr. Comp. Physiol., 2011, vol. 301, no. 3, pp. 668–673.Fanne R.A., Nassar T., Heyman S.N. et al. Insulin and glucagon share the same mechanism of neuroprotection in diabetic rats: role of glutamate // Am. J. Physiol. Regul. Integr. Comp. Physiol. 2011. V. 301. № 3. Р. 668–673.Duarte A.I., Santos M.S., Oliveira C.R., Rego A.C. Insulin neuroprotection against oxidative stress in cortical neurons-involvement of uric acid and glutathione antioxidant defenses. Free Radic. Biol. Med., 2005, vol. 39, no. 7, pp. 876–889.Duarte A.I., Santos M.S., Oliveira C.R., Rego A.C. Insulin neuroprotection against oxidative stress in cortical neurons--involvement of uric acid and glutathione antioxidant defenses // Free Radic Biol Med. 2005. V. 39. № 7. Р. 876–889.Duarte A.I., Santos P., Oliveira C.R. et al. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression. Biochim. Biophys. Acta, 2008, vol. 1783, no. 6, pp. 994–1002.Duarte A.I., Santos P., Oliveira C.R. et al. Insulin neuroprotection against oxidative stress is mediated by Akt and GSK-3beta signaling pathways and changes in protein expression // Biochim Biophys Acta. 2008. V. 1783, № 6. Р. 994–1002.Leibowitz A., Boyko M., Shapira Y., Zlotnik А. Blood glutamate scavenging: insight into neuroprotection. Int. J. Mol. Sci., 2012, vol. 13, pp. 10041–10066.Leibowitz A., Boyko M., Shapira Y., Zlotnik А. Blood glutamate scavenging: insight into neuroprotection // Int. J. Mol. Sci. 2012. V. 13. P. 10041–10066.Tang B.L., Chua C.E.L. SIRT1 and neuronal diseases. Molecular Aspects of Medicine, 2008, vol. 29, pp. 187–200.Tang B.L., Chua C.E.L. SIRT1 and neuronal diseases // Molecular Aspects of Medicine. 2008. V. 29. P. 187–200.Cohem D.E., Supinski A.M., Bonkowski M.S. et al. Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction. Genes Develop., 2009, vol. 23, pp. 2812– 2817.Cohem D.E., Supinski A.M., Bonkowski M.S. et al. Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction // Genes Develop. 2009. V. 23. P. 2812–2817.Michan S., Li Y., Chou M.M-H. et al. SIRT1 is essential for normal cognitive function and synaptic plasticity. J. Neuroscience, 2010, vol. 30. №. 29, pp. 9695–9707.Michan S., Li Y., Chou M.M-H. et al. SIRT1 is essential for normal cognitive function and synaptic plasticity // J. Neuroscience. 2010. V. 30, № 29. P. 9695–9707.Liang F., Kume S., Koya D. SIRT1 and insulin resistance. Nat. Rev .Endocrinol., 2009, vol. 5, no. 7, pp. 367–373.Liang F., Kume S., Koya D. SIRT1 and insulin resistance //Nat. Rev. Endocrinol. 2009. V. 5, № 7. Р. 367–373.Pfister J.A., Ma C., Morrison B.E., D'Mello S.R. Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity. PLoS One, 2008, vol. 3, no. 12, pp. 1–8.Pfister J.A., Ma C., Morrison B.E., D'Mello S.R. Opposing effects of sirtuins on neuronal survival: SIRT1-mediated neuroprotection is independent of its deacetylase activity // PLoS One. 2008. V. 3, № 12. Р. 1–8.Wang S., Chong Z.Z., Shang Y.C., Maiese K. WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1. Curr. Neurovasc. Res., 2013, vol. 10, no. 1, pp. 54–69.Wang S., Chong Z.Z., Shang Y.C., Maiese K. WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1 // Curr. Neurovasc. Res. 2013. V. 10, № 1. Р. 54–69.Song E.K., Lee Y.R., Kim Y.R. et al. NAADP mediates insulin-stimulated glucose uptake and insulin sensitization by PPARγ in adipocytes. Cell, Rep., 2012, vol. 2, no. 6, pp. 1607–1619.Song E.K., Lee Y.R., Kim Y.R. et al. NAADP mediates insulin-stimulated glucose uptake and insulin sensitization by PPARγ in adipocytes // Cell Rep. 2012. V. 2, № 6. Р. 1607–1619.Salmina A.B., Malinovskaja N.A., Okuneva O.S. et al. Modulation of CD38 expression in brain cells by retinoic acid. Siberian medical review, 2009, no. 1, pp. 22–26 (in Russian).Салмина А.Б., Малиновская Н.А., Окунева О.С. и др. Модуляция экспрессии CD38 в клетках головного мозга ретиноевой кислотой // Сиб. мед. обозрение. 2009. № 1. С. 22–26.Higashida H., Salmina A.B., Olovyannikova R.Y. et al. Cyclic ADP-ribose as a universal calcium signal molecule in the nervous system. Neurochem. Int., 2007, vol. 51, no. 2–4, pp. 192–199.Higashida H., Salmina A.B., Olovyannikova R.Y. et al. Cyclic ADP-ribose as a universal calcium signal molecule in the nervous system // Neurochem. Int. 2007. V. 51, № 2–4. Р. 192–199.Lu M., Sarruf D.A., Li P. et al. Neuronal sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues. J. Biol. Chem., 2013, vol. 288, no. 15, pp. 10722– 10735.Lu M., Sarruf D.A., Li P. et al. Neuronal sirt1 deficiency increases insulin sensitivity in both brain and peripheral tissues // J. Biol. Chem. 2013. V. 288, № 15. Р. 10722–10735.Muniyappa R., Lee S., Chen H., Quon M.J. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage. Am. J. Physiol. Endocrinol. Metab., 2008, vol. 294, no. 1, pp. 15– 26.Muniyappa R., Lee S., Chen H., Quon M.J. Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage // Am. J. Physiol. Endocrinol. Metab. 2008. V. 294, № 1. Р. 15–26.Balabolkin M.I. Diabetologia. М., 2000. 672 p (in Russian).Балаболкин М.И. Диабетология: учебник. М., 2000. 672 с.Granberry M.C., Fonseca V.A. Insulin resistance syndrome: options for treatment. South. Med J., 1999, vol. 92, no. 1, pp. 2–15.Granberry M.C., Fonseca V.A. Insulin resistance syndrome: options for treatment // South. Med. J. 1999. V. 92, № 1. P. 2–15.Rabe K., Lehrke M., Parhofer K.G. et al. Adipokines and insulin resistance. Mol. Med., 2008, vol. 14, no. 11–12, pp. 741–751.Rabe K., Lehrke M., Parhofer K.G. et al. Adipokines and insulin resistance // Mol. Med. 2008. V. 14, № 11–12. P. 741–751.Samuel V.T., Shulman G.I. Mechanisms for insulin resistance: common threads and missing links. Cell., 2012, vol. 148, no. 5, pp. 852–871.Samuel V.T., Shulman G.I. Mechanisms for insulin resistance: common threads and missing links // Cell. 2012. V. 148, № 5. P. 852–871.Kern W., Benedict C., Schultes B. et al. Low cerebrospinal fluid insulin levels in obese humans. Diabetologia, 2006, vol. 49, no. 11, pp. 2790–2792.Kern W., Benedict C., Schultes B. et al. Low cerebrospinal fluid insulin levels in obese humans // Diabetologia. 2006. V. 49, № 11. P. 2790–2792.Hallschmid M., Benedict C., Schultes B. et al. Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders. Regul. Pept., 2008, vol. 149, no. 1–3, pp. 79–83.Hallschmid M., Benedict C., Schultes B. et al. Towards the therapeutic use of intranasal neuropeptide administration in metabolic and cognitive disorders // Regul. Pept. 2008.V. 149, № 1–3. P. 79–83.Williamson R., McNeilly A., Sutherland C. Insulin resistance in the brain: an old-age or new-age problem? Biochem. Pharmacol., 2012, vol. 84, no. 6, pp. 737–745.Williamson R., McNeilly A., Sutherland C. Insulin resistance in the brain: an old-age or new-age problem? // Biochem. Pharmacol. 2012. V. 84, № 6. P. 737–745.Hirvonen J., Virtanen K.A., Nummenmaa L. et al. Effects of insulin on brain glucose metabolism in impaired glucose tolerance. Diabetes., 2011, vol. 60, no. 2, pp. 443–447.Hirvonen J., Virtanen K.A., Nummenmaa L. et al. Effects of insulin on brain glucose metabolism in impaired glucose tolerance // Diabetes. 2011. V. 60, № 2. P. 443–447.van der Heide L.P., Ramakers G.M., Smidt M.P. Insulin signaling in the central nervous system: learning to survive. Prog. Neurobiol., 2006, vol. 79, no. 4, pp. 205–221.Heide L.P. van der, Ramakers G.M., Smidt M.P. Insulin signaling in the central nervous system: learning to survive // Prog. Neurobiol. 2006. V. 79, № 4. P. 205–221.Emmanuel Y., Cochlin L.E., Tyler D.J. et al. Human hippocampal energy metabolism is impaired during cognitive activity in a lipid infusion model of insulin resistance. Brain Behav., 2013, vol. 3, no. 2, pp. 134–144.Emmanuel Y., Cochlin L.E., Tyler D.J. et al. Human hippocampal energy metabolism is impaired during cognitive activity in a lipid infusion model of insulin resistance // Brain Behav. 2013. V. 3, № 2. P. 134–144.McNay E.C., Ong C.T., McCrimmon R.J. et al. Hippocampal memory processes are modulated by insulin and high-fatinduced insulin resistance. Neurobiol. Learn. Mem., 2010, vol. 93, no. 4, pp. 546–553.McNay E.C., Ong C.T., McCrimmon R.J. et al. Hippocampal memory processes are modulated by insulin and high-fatinduced insulin resistance // Neurobiol. Learn Mem. 2010. V. 93, № 4. P. 546–553.Gupta A., Dey C.S. PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance. Mol. Biol. Cell., 2012, vol. 23, no. 19, pp. 3882–3898.Gupta A., Dey C.S. PTEN, a widely known negative regulator of insulin/PI3K signaling, positively regulates neuronal insulin resistance // Mol. Biol. Cell. 2012. V. 23, № 19. P. 3882–3898.Lu Z., Marcelin G., Bauzon F. et al. pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location. EMBO J., 2013, vol. 32, no. 6, pp. 844–857.Lu Z., Marcelin G., Bauzon F. et al. pRb is an obesity suppressor in hypothalamus and high-fat diet inhibits pRb in this location // EMBO J. 2013. V. 32,№ 6. P. 844–857.Cakir I., Perello M., Lansari O. et al. Hypothalamic Sirt1 regulates food intake in a rodent model system. PLoS One, 2009, vol. 4, no. 12, pp. e8322.Cakir I., Perello M., Lansari O. et al. Hypothalamic Sirt1 regulates food intake in a rodent model system // PLoS One.2009. V. 4, № 12. P. e8322.Hirabara S.M., Gorjão R., Vinolo M.A. et al. Molecular targets related to inflammation and insulin resistance and potential interventions. J. Biomed. Biotechnol., 2012, vol. 2012, pp. 379024.Hirabara S.M., Gorjão R., Vinolo M.A. et al. Molecular targets related to inflammation and insulin resistance and potential interventions // J. Biomed. Biotechnol. 2012. V. 2012. P. 379024.Tack C.J., Stienstra R., Joosten L.A. et al. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family. Immunol. Rev., 2012, vol. 249, no. 1, pp. 239– 252.Tack C.J., Stienstra R., Joosten L.A. et al. Inflammation links excess fat to insulin resistance: the role of the interleukin-1 family // Immunol Rev. 2012. V. 249, № 1. P. 239–252.Grant R.W., Dixit V.D. Mechanisms of disease: inflammasome activation and the development of type 2 diabetes. Front. Immunol., 2013, vol. 4, pp. 50.Grant R.W., Dixit V.D. Mechanisms of disease: inflammasome activation and the development of type 2 diabetes // Front Immunol. 2013. V. 4. P. 50.Schenk S., Saberi M., Olefsky J.M. Insulin sensitivity: modulation by nutrients and inflammation. J. Clin. Invest., 2008, vol. 118, no. 9, pp. 2992–3002.Schenk S., Saberi M., Olefsky J.M. Insulin sensitivity: modulation by nutrients and inflammation // J. Clin. Invest. 2008. V. 118, № 9. P. 2992–3002.Koenen T.B., Stienstra R., van Tits L.J. et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue. Diabetes, 2011, vol. 60, no. 2, pp. 517–524.Koenen T.B., Stienstra R., van Tits L.J. et al. Hyperglycemia activates caspase-1 and TXNIP-mediated IL-1beta transcription in human adipose tissue // Diabetes. 2011. V. 60, № 2. P. 517–524.Halle A., Hornung V., Petzold G.C. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta. Nat. Immunol., 2008, vol. 9, no. 8, pp. 857– 865.Halle A., Hornung V., Petzold G.C. et al. The NALP3 inflammasome is involved in the innate immune response to amyloid-beta // Nat. Immunol. 2008. V. 9, № 8. P. 857–865.Liu S.B., Mi W.L., Wang Y.Q. Research progress on the NLRP3 inflammasome and its role in the central nervous system. Neurosci Bull., 2013. [Epub ahead of print]Liu S.B., Mi W.L., Wang Y.Q. Research progress on the NLRP3 inflammasome and its role in the central nervous system // Neurosci. Bull. 2013. [Epub ahead of print]Frisardi V., Solfrizzi V., Seripa D. et al. Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer's disease. Ageing. Res. Rev., 2010, vol. 9, no. 4, pp. 399–417.Frisardi V., Solfrizzi V., Seripa D. et al. Metabolic-cognitive syndrome: a cross-talk between metabolic syndrome and Alzheimer's disease // Ageing. Res. Rev. 2010. V. 9, № 4. P.399–417.Roriz-Filho J.S., Sá-Roriz T.M., Rosset I. et al. Review (Pre)diabetes, brain aging, and cognition. Biochimica et Biophysica Acta, 2009, vol. 1792, no. 5, pp. 432–443.Roriz-Filho J.S., Sá-Roriz T.M., Rosset I. et al. Review (Pre)diabetes, brain aging, and cognition // Biochimica et Biophysica Acta. 2009. V. 1792, № 5. P. 432–443.Kaidanovich-Beilin O., Cha D.S., McIntyre R.S. Crosstalk between metabolic and neuropsychiatric disorders. F1000 Biol Rep., 2012, vol. 4, pp. 14.Kaidanovich-Beilin O., Cha D.S., McIntyre R.S. Crosstalk between metabolic and neuropsychiatric disorders // F1000 Biol. Rep. 2012. V. 4. P. 14.Salmina A.B., Inzhutova A.I., Malinovskaya N.A. et al. Endothelial dysfunction and repair in Alzheimer-type neurodegeneration: neuronal and glial control. J. Alzheimers. Dis., 2010, vol. 22, no. 1, pp. 17–36.Salmina A.B., Inzhutova A.I., Malinovskaya N.A. et al. Endothelial dysfunction and repair in Alzheimer-type neurodegeneration: neuronal and glial control // J. Alzheimers Dis. 2010. V. 22, № 1. P. 17–36.Higashida H., Lopatina O., Yoshihara T. et al. Oxytocin signal and social behaviour: comparison among adult and infant oxytocin, oxytocin receptor and CD38 gene knockout mice. J. Neuroendocrinol., 2010, vol. 22, no. 5, pp. 373–379.Higashida H., Lopatina O., Yoshihara T. et al. Oxytocin signal and social behaviour: comparison among adult and infant oxytocin, oxytocin receptor and CD38 gene knockout mice // J. Neuroendocrinol. 2010. V. 22, № 5. P. 373–379.Lopatina O., Inzhutova A., Salmina A.B. et al. The roles of oxytocin and CD38 in social or parental behaviors. Front Neurosci., 2012, vol. 6, pp. 182.Lopatina O., Inzhutova A., Salmina A.B. et al. The roles of oxytocin and CD38 in social or parental behaviors // Front.Neurosci. 2012. V. 6. P. 182.Camerino C. Low sympathetic tone and obese phenotype in oxytocin-deficient mice. Obesity (Silver Spring), 2009, vol. 17, no. 5, pp. 980–984.Camerino C. Low sympathetic tone and obese phenotype in oxytocin-deficient mice // Obesity (Silver Spring). 2009. V. 17, № 5. P. 980–984.Kaidanovich-Beilin O., Lipina T.V., Takao K. et al. Abnormalities in brain structure and behavior in GSK-3alpha mutant mice. Mol. Brain, 2009, vol. 2, pp. 35.Kaidanovich-Beilin O., Lipina T.V., Takao K. et al. Abnormalities in brain structure and behavior in GSK-3alpha mutant mice // Mol Brain. 2009. V. 2. P. 35.Perello M., Raingo J. Leptin activates oxytocin neurons of the hypothalamic paraventricular nucleus in both control and diet-induced obese rodents. PLoS One, 2013, vol. 8, no. 3, pp. e59625.Perello M., Raingo J. Leptin activates oxytocin neurons of the hypothalamic paraventricular nucleus in both control and diet-induced obese rodents // PLoS One. 2013. V. 8, № 3. P.e59625.Suzuki M., Honda Y., Li M.Z. et al. The localization of oxytocin receptors in the islets of Langerhans in the rat pancreas. Regul. Pept., 2013, vol. 183, pp. 42–45.Suzuki M., Honda Y., Li M.Z. et al. The localization of oxytocin receptors in the islets of Langerhans in the rat pancreas // Regul. Pept. 2013. V. 183. P. 42–45.Goebel-Stengel M., Wang L. Central And Peripheral Expression And Distribution Of NUBC2/Nesfatin-1. Curr. Pharm. Des., 2013. [Epub ahead of print].Goebel-Stengel M., Wang L. Central And Peripheral Expression And Distribution Of NUBC2/Nesfatin-1 // Curr. Pharm. Des. 2013. [Epub ahead of print].Yang M., Zhang Z., Wang C. et al. Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AMPK/TORC2 pathway in diet-induced insulin resistance. Diabetes, 2012, vol. 61, no. 8, pp. 1959–1968.Yang M., Zhang Z., Wang C. et al. Nesfatin-1 action in the brain increases insulin sensitivity through Akt/AMPK/TORC2 pathway in diet-induced insulin resistance // Diabetes. 2012. V. 61, № 8. P. 1959–1968.Nilsen K.A., Ihle K.E., Frederick K. et al. Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology. J. Exp. Biol., 2011, vol. 214. Pt. 9, pp. 1488–1497.Nilsen K.A., Ihle K.E., Frederick K. et al. Insulin-like peptide genes in honey bee fat body respond differently to manipulation of social behavioral physiology // J. Exp. Biol. 2011. V. 214. Pt. 9. P. 1488–1497.Saleem U., Khaleghi M., Morgenthaler N.G. et al. Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome. J. Clin. Endocrinol. Metab., 2009, vol. 94, no. 7, pp. 2558–2564.Saleem U., Khaleghi M., Morgenthaler N.G. et al. Plasma carboxy-terminal provasopressin (copeptin): a novel marker of insulin resistance and metabolic syndrome // J. Clin. Endocrinol. Metab. 2009. V. 94, № 7. P. 2558–2564.Loyens E., De Bundel D., Demaegdt H. et al. Antidepressant-like effects of oxytocin in mice are dependent on the presence of insulin-regulated aminopeptidase. Int. J. Neuropsychopharmacol., 2012, pp. 1–11. [Epub ahead of print].Loyens E., De Bundel D., Demaegdt H. et al. Antidepressant-like effects of oxytocin in mice are dependent on the presence of insulin-regulated aminopeptidase // Int J Neuropsychopharmacol. 2012. P. 1–11. [Epub ahead of print].Keller S.R. Role of the insulin-regulated aminopeptidase IRAP in insulin action and diabetes. Biol. Pharm. Bull., 2004, vol. 27, no. 6, pp. 761–764.Keller S.R. Role of the insulin-regulated aminopeptidase IRAP in insulin action and diabetes // Biol. Pharm. Bull. 2004. V. 27, № 6. P. 761–764.Fernando R.N., Albiston A.L., Chai S.Y. The insulinregulated aminopeptidase IRAP is colocalised with GLUT4 in the mouse hippocampus-potential role in modulation of glucose uptake in neurones? Eur. J. Neurosci., 2008, vol. 28, no. 3, pp. 588–598.Fernando R.N., Albiston A.L., Chai S.Y. The insulinregulated aminopeptidase IRAP is colocalised with GLUT4 in the mouse hippocampus--potential role in modulation of glucose uptake in neurones? // Eur. J. Neurosci. 2008. V. 28, № 3. P. 588–598.Guang C., Phillips R.D., Jiang B. et al. Three key proteasesangiotensin-I-converting enzyme (ACE), ACE2 and reninwithin and beyond the renin-angiotensin system. Arch. Cardiovasc. Dis., 2012, vol. 105, no. 6–7, pp. 373–385.Guang C., Phillips R.D., Jiang B. et al. Three key proteases-angiotensin-I-converting enzyme (ACE), ACE2 and reninwithin and beyond the renin-angiotensin system // Arch. Cardiovasc. Dis. 2012. V. 105, № 6–7. P. 373–385.Wallis M.G., Lankford M.F., Keller S.R. Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP. Am. J. Physiol. Endocrinol. Metab., 2007, vol. 293, no. 4, pp. 1092–1102.Wallis M.G., Lankford M.F., Keller S.R. Vasopressin is a physiological substrate for the insulin-regulated aminopeptidase IRAP // Am. J. Physiol. Endocrinol. Metab. 2007. V. 293, № 4. P. 1092–1102.Han W., Li C. Linking type 2 diabetes and Alzheimer's disease. Proc. Natl. Acad. Sci. USA, 2010, vol. 107, no. 15, pp. 6557–6558.Han W., Li C. Linking type 2 diabetes and Alzheimer's disease // Proc. Natl. Acad. Sci. USA. 2010. V. 107, № 15. P. 6557–6558.Correia S.C., Santos R.X., Perry G. et al. Insulin-resistant brain state: the culprit in sporadic Alzheimer's disease? Ageing. Res. Rev., 2011, vol. 10, no. 2, pp. 264–273.Correia S.C., Santos R.X., Perry G. et al. Insulin-resistant brain state: the culprit in sporadic Alzheimer's disease? // Ageing Res Rev. 2011. V. 10. № 2. P. 264–273.Schiöth H.B., Craft S., Brooks S.J. et al. Brain insulin signaling and Alzheimer's disease: current evidence and future directions. Mol. Neurobiol., 2012, vol. 46, no. 1, pp. 4–10.Schiöth H.B., Craft S., Brooks S.J. et al. Brain insulin signaling and Alzheimer's disease: current evidence and future directions // Mol. Neurobiol. 2012. V. 46. № 1. P. 4–10.Son S.M., Song H., Byun J. et al. Accumulation of autophagosomes contributes to enhanced amyloidogenic APP processing under insulin-resistant conditions. Autophagy, 2012, vol. 8, no. 12, pp. 1842–1844.Son S.M., Song H., Byun J. et al. Accumulation of autophagosomes contributes to enhanced amyloidogenic APP processing under insulin-resistant conditions // Autophagy. 2012. V. 8, № 12. P. 1842–1844.Talbot K., Wang H.Y., Kazi H. et al. Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J. Clin. Invest., 2012, vol. 122, no. 4, pp. 1316– 1338.Talbot K., Wang H.Y., Kazi H. et al. Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline // J. Clin. Invest. 2012. V. 122, № 4. P. 1316–1338.Lee Y.J., Kim J.E., Hwang I.S. et al. Alzheimer's phenotypes induced by overexpression of human presenilin 2 mutant proteins stimulate significant changes in key factors of glucose metabolism. Mol. Med. Rep., 2013, vol. 7, no. 5, pp. 1571–1578.Lee Y.J., Kim J.E., Hwang I.S. et al. Alzheimer's phenotypes induced by overexpression of human presenilin 2 mutant proteins stimulate significant changes in key factors of glucose metabolism // Mol. Med. Rep. 2013. V. 7, № 5. P. 1571–1578.O' Neill С. PI3-kinase/Akt/mTOR signaling: Impaired on/off switches in aging, cognitive decline and Alzheimer's disease. Experimental Gerontology, 2013. [Article in press]O'Neill С. PI3-kinase/Akt/mTOR signaling: Impaired on/off switches in aging, cognitive decline and Alzheimer's disease // Experimental Gerontology. 2013. [Article in press]Bosco D., Plastino M., Cristiano D. et al. Dementia is associated with insulin resistance in patients with Parkinson's disease. J. Neurol. Sci., 2012, vol. 315, no. 1–2, pp. 39–43.Bosco D., Plastino M., Cristiano D. et al. Dementia is associated with insulin resistance in patients with Parkinson's disease // J. Neurol. Sci. 2012. V. 315, № 1–2. P. 39–43.Aviles-Olmos I., Limousin P., Lees A. et al. Parkinson's disease, insulin resistance and novel agents of neuroprotection. Brain, 2013, vol. 136. Pt 2, pp. 374–384.Aviles-Olmos I., Limousin P., Lees A. et al. Parkinson's disease, insulin resistance and novel agents of neuroprotection // Brain. 2013. V. 136. Pt 2. P. 374–384.Stern M. Insulin signaling and autism. Front Endocrinol (Lausanne), 2011, vol. 2, pp. 54.Stern M. Insulin signaling and autism // Front. Endocrinol. (Lausanne). 2011. V. 2. P. 54.Rundek T., Gardener H., Xu Q. et al. Insulin resistance and risk of ischemic stroke among nondiabetic individuals from the northern Manhattan study. Arch. Neurol., 2010, vol. 67, no. 10, pp. 1195–1200.Rundek T., Gardener H., Xu Q. et al. Insulin resistance and risk of ischemic stroke among nondiabetic individuals from the northern Manhattan study // Arch. Neurol. 2010. V. 67, № 10. P. 1195–1200.Lawlor D.A., Smith G.D., Ebrahim S. Association of insulin resistance with depression: cross sectional findings from the British Women's Heart and Health Study. BMJ, 2003, vol. 327, no. 7428, pp. 1383–1384.Lawlor D.A., Smith G.D., Ebrahim S. Association of insulin resistance with depression: cross sectional findings from the British Women's Heart and Health Study // BMJ. 2003. V. 327, № 7428. P. 1383–1384.Lawlor D.A., Ben-Shlomo Y., Ebrahim S. et al. Insulin resistance and depressive symptoms in middle aged men: findings from the Caerphilly prospective cohort study. BMJ, 2005, vol. 330, no. 7493, pp. 705–706.Lawlor D.A., Ben-Shlomo Y., Ebrahim S. et al. Insulin resistance and depressive symptoms in middle aged men: findings from the Caerphilly prospective cohort study // BMJ. 2005. V. 330, № 7493. P. 705–706.Timonen M., Laakso M., Jokelainen J. et al. Insulin resistance and depression: cross sectional study. BMJ, 2005, vol. 330, no. 7481, pp. 17–18.Timonen M., Laakso M., Jokelainen J. et al. Insulin resistance and depression: cross sectional study // BMJ. 2005. V. 330. № 7481. P. 17–18.Pearson S., Schmidt M., Patton G. et al. Depression and insulin resistance: cross-sectional associations in young adults. Diabetes Care, 2010, vol. 33, no. 5, pp. 1128–1133. 1Pearson S., Schmidt M., Patton G. et al. Depression and insulin resistance: cross-sectional associations in young adults // Diabetes Care. 2010. V. 33, № 5. P. 1128–1133.Golomb B.A., Tenkanen L., Alikoski T. et al. Insulin sensitivity markers: predictors of accidents and suicides in Helsinki Heart Study screenees. J. Clin. Epidemiol., 2002, vol. 55, no. 8, pp. 767–773.Golomb B.A., Tenkanen L., Alikoski T. et al. Insulin sensitivity markers: predictors of accidents and suicides in Helsinki Heart Study screenees // J. Clin. Epidemiol. 2002. V. 55, № 8. P. 767–773.Okamura F., Tashiro A., Utumi A. et al. Insulin resistance in patients with depression and its changes during the clinical course of depression: minimal model analysis. Metabolism, 2000, vol. 49, no. 10, pp. 1255–1260.Okamura F., Tashiro A., Utumi A. et al. Insulin resistance in patients with depression and its changes during the clinical course of depression: minimal model analysis // Metabolism. 2000. V. 49, № 10. P. 1255–1260.Yanagita T., Adachi R., Kamioka H. et al. Severe open bite due to traumatic condylar fractures treated nonsurgically with implanted miniscrew anchorage. Am. J. Orthod. Dentofacial. Orthop., 2013, vol. 143, no. 4 Suppl, pp. 137– 147.Yanagita T., Adachi R., Kamioka H. et al. Severe open bite due to traumatic condylar fractures treated nonsurgically with implanted miniscrew anchorage // Am. J. Orthod. Dentofacial Orthop. 2013. V. 143, № 4, Suppl. P. 137–147.Grillo C.A., Piroli G.G., Kaigler K.F. et al. Downregulation of hypothalamic insulin receptor expression elicits depressive-like behaviors in rats. Behav. Brain. Res., 2011, vol. 222, no. 1, pp. 230–235.Grillo C.A., Piroli G.G., Kaigler K.F. et al. Downregulation of hypothalamic insulin receptor expression elicits depressive-like behaviors in rats // Behav. Brain. Res. 2011. V. 222. № 1. P. 230–235.DeFronzo R.A., Tobin J.D., Andres R. Glucose clamp technique: a meth od for quantifying insulin secretion and resistance. Am. J. Physiol., 1979, vol. 237, no. 3, pp. 214–223.DeFronzo R.A., Tobin J.D., Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance // Am. J. Physiol. 1979. V. 237, № 3. P. 214–223.Gall W.E., Beebe K., Lawton K.A. et al. Alphahydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One, 2010, vol. 5, no. 5, pp. e10883.Gall W.E., Beebe K., Lawton K.A. et al. Alphahydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population // PLoS One. 2010. V. 5, № 5. P. e10883.Hertz L. The astrocyte-neuron lactate shuttle: a challenge of a challenge. J. Cereb. Blood Flow Metab., 2004, vol. 24, no. 11, pp. 1241–1248.Hertz L. The astrocyte-neuron lactate shuttle: a challenge of a challenge // J. Cereb. Blood. Flow. Metab. 2004. V. 24. №11. P. 1241–1248.Dean O., Bush A.I., Berk M. et al. Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice. Behav. Brain Res., 2009, vol. 198, no. 1, pp. 258–262.Dean O., Bush A.I., Berk M. et al. Glutathione depletion in the brain disrupts short-term spatial memory in the Y-maze in rats and mice // Behav. Brain Res. 2009. V. 198, № 1. P. 258–262.Castagné V., Rougemont M., Cuenod M. et al. Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat's development induce long-term cognitive deficit: relevance to schizophrenia. Neurobiol. Dis., 2004, vol. 15, no. 1, pp. 93–105.Castagné V., Rougemont M., Cuenod M. et al. Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat's development induce long-term cognitive deficit: relevance to schizophrenia // Neurobiol. Dis. 2004. V. 15, № 1. P. 93–105.Komulainen P., Pedersen M., Hänninen T. et al. BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA Study. Neurobiol. Learn Mem., 2008, vol. 90, no. 4, pp. 596–603.Komulainen P., Pedersen M., Hänninen T. et al. BDNF is a novel marker of cognitive function in ageing women: the DR's EXTRA Study // Neurobiol. Learn. Mem. 2008. V. 90, № 4. P. 596–603.Arentoft A., Sweat V., Starr V. et al. Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: evidence of a compensatory mechanism. Brain Cogn., 2009, vol. 71, no. 2, pp. 147–152.Arentoft A., Sweat V., Starr V. et al. Plasma BDNF is reduced among middle-aged and elderly women with impaired insulin function: evidence of a compensatory mechanism // Brain. Cogn. 2009. V. 71, № 2. P. 147–152.Morgenthaler N.G., Struck J., Jochberger S. et al. Copeptin: clinical use of a new biomarker. Trends Endocrinol. Metab., 2008, vol. 19, no. 2, pp. 43–49.Morgenthaler N.G., Struck J., Jochberger S. et al. Copeptin: clinical use of a new biomarker // Trends Endocrinol. Metab. 2008. V. 19, № 2. P. 43–49.Albiston A.L., Diwakarla S., Fernando R.N. et al. Identification and development of specific inhibitors for insulinregulated aminopeptidase as a new class of cognitive enhancers. Br. J. Pharmacol., 2011, vol. 164, no. 1, pp. 37–47.Albiston A.L., Diwakarla S., Fernando R.N. et al. Identification and development of specific inhibitors for insulin-regulated aminopeptidase as a new class of cognitive enhancers // Br. J. Pharmacol. 2011. V. 164, № 1. P. 37–47.Benedict C., Frey W.H. 2nd, Schiöth H.B. et al. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments. Exp. Gerontol., 2011, vol. 46, no. 2–3, pp. 112–115.Benedict C., Frey W.H. 2nd, Schiöth H.B. et al. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments // Exp. Gerontol. 2011. V. 46, № 2–3. P. 112–115Benedict C., Frey W.H. 2nd, Schiöth H.B. et al. Intranasal insulin as a therapeutic option in the treatment of cognitive impairments // Exp. Gerontol. 2011. V. 46, № 2–3. P. 112–115

The authors declare that there are no conflicts of interest present.