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Инсулиновый рецептор в мозге: новая мишень в лечении центральной инсулиновой резистентности

Аннотация

Настоящий обзор посвящен сигнальной системе инсулинового рецептора в мозге, которая имеет ряд существенных отличий от периферической системы. В клетках мозга преобладает, а в нейронах - экспрессируется исключительно высокоафинная короткая изоформа А рецептора (IR-A), которая способна связывать не только инсулин, но и инсулиноподобный фактор 2 (IGF-2). IR-A участвует в регуляции синаптической пластичности, росте дендритов и аксонов, в регуляции взрослого нейрогенеза. Инсулиновая система в мозге играет роль в процессах формирования памяти и регуляции пищевого поведения. Нарушения инсулиновой сигнализации приводят к развитию центральной инсулиновой резистентности, наиболее известным проявлением которой является болезнь Альцгеймера. Разработка средств лечения центральной инсулиновой резистентности с учетом специфики инсулиновой сигнализации в мозге является новым многообещающим подходом в терапии заболеваний центральной нервной системы.

Об авторах

И. А. Помыткин
ФГАОУ ВО Первый Московский государственный медицинский университет им. И.М. Сеченова Минздрава России (Сеченовский Университет)
Россия


И. А. Красильникова
ФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России
Россия


В. Г. Пинелис
ФГАУ «Национальный медицинский исследовательский центр здоровья детей» Минздрава России
Россия


Н. Н. Каркищенко
ФГБУН «Научный центр биомедицинских технологий ФМБА России»
Россия


Список литературы

1. Abbott M.A., Wells D.G., Fallon J.R. The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses // J. Neurosci. 1999. V. 19. Pp. 7300-7308.

2. Aime P., Hegoburu C., Jaillard T., Degletagne C., Garcia S., Messaoudi B., Thevenet M., Lorsignol A., Duchamp C., Mouly A.M., Julliard A.K. A physiological increase of insulin in the olfactory bulb decreases detection of a learned aversive odor and abolishes food odor-induced sniffing behavior in rats // PLoS One. 2012. V. 7. P. e51227.

3. Aimé P., Palouzier-Paulignan B., Salem R., Al Koborssy D., Garcia S., Duchamp C., Romestaing C., Julliard A.K. Modulation of olfactory sensitivity and glucose-sensing by the feeding state in obese Zucker rats // Front. Behav. Neurosci. 2014. V. 8. P. 326.

4. Banks W.A. The source of cerebral insulin // Eur. J. Pharmacol. 2004. V. 490. No. 1-3. Pp. 5-12.

5. Banks W.A., Kastin A.J., Pan W. Uptake and degradation of blood-borne insulin by the olfactory bulb // Peptides. 1999. V. 20. Pp. 373-378.

6. Banks W.A., Owen J.B., Erickson M.A. Insulin in the brain: there and back again // Pharmacol. Ther. 2012. V. 136. Pp. 82-93.

7. Baskin D.G., Porte D.Jr., Guest K., Dorsa D.M. Regional concentrations of insulin in the rat brain // Endocrinology. 1983. V. 112. Pp. 898-903.

8. Baskin D.G., Stein L.J., Ikeda H., Woods S.C., Figlewicz D.P., Porte D.Jr., Greenwood M.R., Dorsa D.M. Genetically obese Zucker rats have abnormally low brain insulin content // Life. Sci. 1985. V. 36. No. 7. Pp. 627-633.

9. Begg D.P., Mul J.D., Liu M., Reedy B.M., D'Alessio D.A., Seeley R.J., Woods S.C. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats // Endocrinology. 2013. V. 154. No. 3. Pp. 1047-1054.

10. Benedict C., Hallschmid M., Hatke A., Schultes B., Fehm H.L., Born J., Kern W. Intranasal insulin improves memory in humans // Psychoneuroendocrinology. 2004. V. 29. Pp. 1326-1334.

11. Benedict C., Hallschmid M., Schmitz K., Schultes B., Ratter F., Fehm H.L., Born J., Kern W. Intranasal insulin improves memory in humans: superiority of insulin aspart // Neuropsychopharmacology. 2007. V. 32. No. 1. Pp. 239-243.

12. Benedict C., Kern W., Schultes B., Born J., Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin // J. Clin. Endocrinol. Metab. 2008. V. 93. No. 4. Pp. 1339-1344.

13. Benoit S.C., Air E.L., Coolen L.M., Strauss R., Jackman A., Clegg D.J., Seeley R.J., Woods S.C. The catabolic action of insulin in the brain is mediated by melanocortins // J. Neurosci. 2002. V. 22. Pp. 9048-52.

14. Brunner Y.F., Benedict C., Freiherr J. Intranasal insulin reduces olfactory sensitivity in normosmic humans // J. Clin. Endocrinol. Metab. 2013. V. 98. Pp. E1626-30.

15. Cheng C.M., Mervis R.F., Niu S.L., Salem N.Jr., Witters L.A., Tseng V., Reinhardt R., Bondy C.A. Insulin-like growth factor 1 is essential for normal dendritic growth // J. Neurosci. Res. 2003. V. 73. No. 1. Pp. 1-9.

16. Chiu S.L., Cline H.T. Insulin receptor signaling in the development of neuronal structure and function // Neural. Dev. 2010. No. 5. P. 7.

17. Choi J., Ko J., Racz B., Burette A., Lee J.R., Kim S., Na M., Lee H.W., Kim K., Weinberg R.J., Kim E. Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases // J. Neurosci. 2005. V. 25. Pp. 869-879.

18. Clarke D.W., Mudd L., Boyd F.T.Jr., Fields M., Raizada M.K. Insulin is released from rat brain neuronal cells in culture // J. Neurochem. 1986. V. 47. Pp. 831-836.

19. Cline B.H., Costa-Nunes J.P., Cespuglio R., Markova N., Santos A.I., Bukhman Y.V., Kubatiev A., Steinbusch H.W., Lesch K.P., Strekalova T. Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression // Front. Behav. Neurosci. 2015. V. 9. P. 37.

20. Cline B.H., Steinbusch H.W., Malin D., Revishchin A.V., Pavlova G.V., Cespuglio R., Strekalova T. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2 // BMC Neurosci. 2012. V. 13. P. 110.

21. Costa-Nunes J.P., Cline B.H., Araújo-Correia M., Valença A., Markova N., Dolgov O., Kubatiev A., Yeritsyan N., Steinbusch H.W., Strekalova T. Animal models of depression and drug delivery with food as an effective dosing method: evidences from studies with celecoxib and dicholine succinate // Biomed. res. int. 2015. V. 2015. P. 596126.

22. Denley A., Bonython E.R., Booker G.W., Cosgrove L.J., Forbes B.E., Ward C.W., Wallace J.C. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR // Mol. Endocrinol. 2004. V. 18. Pp. 2502-2512.

23. Dorn A., Bernstein H.G., Rinne A., Ziegler M., Hahn H.J., Ansorge S. Insulin- and glucagonlike peptides in the brain // Anat. Rec. 1983. V. 207. No. 1. Pp. 69-77.

24. Dorn A., Rinne A., Bernstein H.G., Hahn H.J., Ziegler M. Insulin and C-peptide in human brain neurons (insulin / C-peptide / brain peptides / immunohistochemistry / radioimmunoassay) // J. Hirnforsch. 1983. V. 24. No. 5. Pp. 495-499.

25. Fadool D.A., Tucker K., Pedarzani P. Mitral cells of the olfactory bulb perform metabolic sensing and are disrupted by obesity at the level of the Kv1.3 ion channel // PLoS One. 2011. V. 6. No. 9. P. e24921.

26. Fadool D.A., Tucker K., Phillips J.J., Simmen J.A. Brain insulin receptor causes activity-dependent current suppression in the olfactory bulb through multiple phosphorylation of Kv1.3 // J. Neurophysiol. 2000. V. 83. Pp. 2332-2348.

27. Frölich L., Blum-Degen D., Bernstein H.G., Engelsberger S., Humrich J., Laufer S., Muschner D., Thalheimer A., Türk A., Hoyer S., Zöchling R., Boissl K.W., Jellinger K., Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease // J. Neural. Transm. 1998. V. 105. No. 4-5. Pp. 423-438.

28. Gammeltoft S., Fehlmann M., Van Obberghen E. Insulin receptors in the mammalian central nervous system: binding characteristics and subunit structure // Biochimie. 1985. V. 67. No. 10-11. Pp. 1147-1153.

29. Garwood C.J., Ratcliffe L.E., Morgan S.V., Simpson J.E., Owens H., Vazquez-Villaseñor I., Heath P.R., Romero I.A., Ince P.G., Wharton S.B. Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors // Mol. Brain. 2015. No. 8. P. 51.

30. Geldmacher D.S., Fritsch T., McClendon M.J., Landreth G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease // Arch. Neurol. 2011. V. 68. No. 1. Pp. 45-50.

31. Gerozissis K., Rouch C., Lemierre S., Nicolaidis S., Orosco M. A potential role of central insulin in learning and memory related to feeding. A potential role of central insulin in learning and memory related to feeding // Cell. Mol. Neurobiol. 2001. V. 21. No. 4. Pp. 389-401.

32. Gold M., Alderton C., Zvartau-Hind M., Egginton S., Saunders A.M., Irizarry M., Craft S., Landreth G., Linnamagi U., Sawchak S. Rosiglitazone monotherapy in mild-to-moderate alzheimer's disease: Results from a randomized, double-blind, placebo-controlled phase III study // Dement. Geriatr. Cogn. Disord. 2010. V. 30. Pp. 131-146.

33. Hallschmid M., Benedict C., Schultes B., Born J., Kern W. Obese men respond to cognitive but not to catabolic brain insulin signaling // Int. J. Obes. 2008. V. 32. No. 2. Pp. 275-282.

34. Hallschmid M., Higgs S., Thienel M., Ott V., Lehnert H. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women // Diabetes. 2012. V. 61. Pp. 782-789.

35. Havrankova J., Roth J., Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat // Nature. 1978. V. 272. Pp. 827-829.

36. Heidenreich K.A., Zahniser N.R., Berhanu P., Brandenburg D., Olefsky J.M. Structural differences between insulin receptors in the brain and peripheral target tissues // J. Biol. Chem. 1983. V. 258. No. 14. Pp. 8527-8530.

37. Heni M., Hennige A.M., Peter A., Siegel-Axel D., Ordelheide A.M., Krebs N., et al. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes // PLoS One. 2011. V. 6. No. 6. P. e21594.

38. Hill J.M., Lesniak M.A., Pert C.B., Roth J. Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas // Neuroscience. 1986. V. 17. No. 4. Pp. 1127-1138.

39. Julliard A.K., Chaput M.A., Apelbaum A., Aime P., Mahfouz M., Duchamp-Viret P. Changes in rat olfactory detection performance induced by orexin and leptin mimicking fasting and satiation // Behav. Brain. Res. 2007. V. 183. Pp. 123-129.

40. Kaiyala K.J., Prigeon R.L., Kahn S.E., Woods S.C., Schwartz M.W. Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs // Diabetes. 2000. V. 49. No. 9. Pp. 1525-1533.

41. Kang J., Park H., Kim E. IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders // Neuropharmacology. 2016. V. 100. Pp. 27-39.

42. Kern W., Benedict C., Schultes B., Plohr F., Moser A., Born J., Fehm H.L., Hallschmid M. Low cerebrospinal fluid insulin levels in obese humans // Diabetologia. 2006. V. 49. No. 11. Pp. 2790-2792.

43. Ketterer C., Heni M., Thamer C., Herzberg-Schafer S.A., Haring H.U., Fritsche A. Acute, short-term hyperinsulinemia increases olfactory threshold in healthy subjects // Int. J. Obes. 2011. V. 35. Pp. 1135-1138.

44. Krug R., Benedict C., Born J., Hallschmid M. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory // J. Clin. Endocrinol. Metab. 2010. V. 95. No. 12. Pp. E468-472.

45. Kuczewski N., Fourcaud-Trocmé N., Savigner A., Thevenet M., Aimé P., Garcia S., Duchamp-Viret P., Palouzier-Paulignan B. Insulin modulates network activity in olfactory bulb slices: impact on odour processing // J. Physiol. 2014. V. 592. No. 13. Pp. 2751-69.

46. Kuwabara T., Kagalwala M.N., Onuma Y., et al. Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb // EMBO Mol. Med. 2011. V. 3. Pp. 742-754.

47. Lacroix M.C., Badonnel K., Meunier N., Tan F., Schlegel-Le Poupon C., Durieux D., Monnerie R., Baly C., Congar P., Salesse R., Caillol M. Expression of insulin system in the olfactory epithelium: first approaches to its role and regulation // J. Neuroendocrinol. 2008. V. 20. No. 10. Pp. 1176-1190.

48. Lacroix M.C., Caillol M., Durieux D., Monnerie R., Grebert D., Pellerin L., Repond C., Tolle V., Zizzari P., Baly C. Long-lasting metabolic imbalance related to obesity alters olfactory tissue homeostasis and impairs olfactory-driven behaviors // Chem. Senses. 2015. V. 40. No. 8. Pp. 537-556.

49. Li Z., Okamoto K., Hayashi Y., Sheng M. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses // Cell. 2004. V. 119. Pp. 873-887.

50. Luchsinger J.A., Perez T., Chang H., Mehta P., Steffener J., Pradabhan G., Ichise M., Manly J., Devanand D.P., Bagiella E. Metformin in amnestic mild cognitive impairment: results of a pilot randomized placebo controlled clinical trial // J. Alzheimers. Dis. 2016. V. 51. No. 2. Pp. 501-514.

51. Marks D.R., Tucker K., Cavallin M.A., Mast T.G., Fadool D.A. Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors // J. Neurosci. 2009. V. 29. No. 20. Pp. 6734-6751.

52. McNay E.C., Recknagel A.K. Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes // Neurobiol. Learn. Mem. 2011. V. 96. No. 3. Pp. 432-442.

53. Mielke J.G., Taghibiglou C., Wang Y.T. Endogenous insulin signaling protects cultured neurons from oxygen-glucose deprivation-induced cell death // Neuroscience. 2006. V. 143. No. 1. Pp. 165-173.

54. Morton G.J., Cummings D.E., Baskin D.G., Barsh G.S., Schwartz M.W. Central nervous system control of food intake and body weight // Nature. 2006. V. 443. Pp. 289-295.

55. Mosthaf L., Grako K., Dull T.J., Coussens L., Ullrich A., McClain D.A. Functionally distinct insulin receptors generated by tissue-specific alternative splicing // EMBO J. 1990. V. 9. No. 8. Pp. 2409-2413.

56. Paulesco N.C. Recherche sur le rôle du pancréas dans l'assimilation nutritive // Archives Internationales de Physiologie. 1921. V. 17. Pp. 85-103.

57. Pearson-Leary J., Jahagirdar V., Sage J., McNay E.C. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4 // Behav. Brain. Res. 2018. V. 338. Pp. 32-39.

58. Pearson-Leary J., McNay E.C. Novel roles for the insulin-regulated glucose transporter-4 in hippocampally dependent memory // J. Neurosci. 2016. V. 36. No. 47. Pp. 11851-64.

59. Persiyantseva N.A., Storozhevykh T.P., Senilova Y.E., Gorbacheva L.R., Pinelis V.G., Pomytkin I.A. Mitochondrial H2O2 as an enable signal for triggering autophosphorylation of insulin receptor in neurons // J. Mol. Signal. 2013. V. 8. No. 1. P. 11.

60. Pitt J., Wilcox K.C., Tortelli V., Diniz L.P., Oliveira M.S., Dobbins C., Yu X.W., Nandamuri S., Gomes F.C.A., DiNunno N., Viola K.L., De Felice F.G., Ferreira S.T., Klein W.L. Neuroprotective astrocyte-derived insulin/IGF-1 stimulate endocytic processing and extracellular release of neuron-bound Aβ oligomers // Mol. Biol. Cell. 2017. pii: mbc.E17-06-0416.

61. Plum L., Schubert M., Bruning J.C. The role of insulin receptor signaling in the brain // Trends. Endrocrinol. Metab. 2005. V. 16. Pp. 59-65.

62. Pomytkin I.A. H2O2 signalling pathway: A possible bridge between insulin receptor and mitochondria // Curr. Neuropharmacol. 2012. V. 10. No. 4. Pp. 311-320.

63. Pomytkin I.A., Semenova N.A. Study of the effect of preconditioning with succinic acid salt of choline (1:2) on the disturbances of energy metabolism in the brain during ischemia by 31P NMR in vivo // Dokl. Biochem. Biophys. 2005. V. 403. Pp. 289-292.

64. Qiu J., Wagner E.J., Rønnekleiv O.K., Kelly M.J. Insulin and leptin excite anorexigenic proopiomelanocortin neurons via activation of TRPC5 channels // J. Neuroendocrinol. 2018. V. 30. No. 2.

65. Qiu J., Zhang C., Borgquist A., Nestor C.C., Smith A.W., Bosch M.A., Ku S., Wagner E.J., Rønnekleiv O.K., Kelly M.J. Insulin excites anorexigenic proopiomelanocortin neurons via activation of canonical transient receptor potential channels // Cell. Metab. 2014. V. 19. Pp. 682-693.

66. Sato T., Hanyu H., Hirao K., Kanetaka H., Sakurai H., Iwamoto T. Efficacy of ppar-gamma agonist pioglitazone in mild alzheimer disease // Neurobiol. Aging. 2011. V. 32. Pp. 1626-1633.

67. Schwartz M.W., Marks J.L., Sipols A.J., Baskin D.G., Woods S.C., Kahn S.E., Porte D.Jr. Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats // Endocrinology. 1991. V. 128. Pp. 2645-47.

68. Steen E., Terry B.M., Rivera E.J., et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease - Is this type 3 diabetes? // J. Alzheimers. Dis. 2005. V. 7. Pp. 63-80.

69. Storozheva Z.I., Proshin A.T., Sherstnev V.V., Storozhevykh T.P., Senilova Y.E., Persiyantseva N.A., Pinelis V.G., Semenova N.A., Zakharova E.I., Pomytkin I.A. Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-induced amnesia // BMC Pharmacol. 2008. V. 8. P. 1.

70. Storozhevykh T.P., Senilova Y.E., Persiyantseva N.A., Pinelis V.G., Pomytkin I.A. Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons // BMC Neurosci. 2007. V. 8. P. 84.

71. Strekalova T., Costa-Nunes J.P., Veniaminova E., Kubatiev A., Lesch K.P., Chekhonin V.P., Evans M.C., Steinbusch H.W. Insulin receptor sensitizer, dicholine succinate, prevents both Toll-like receptor 4 (TLR4) upregulation and affective changes induced by a high-cholesterol diet in mice // J. Affect. Disord. 2016. V. 196. Pp. 109-116.

72. Sun X., Yao H., Douglas R.M., Gu X.Q., Wang J., Haddad G.G. Insulin/PI3K signaling protects dentate neurons from oxygen-glucose deprivation in organotypic slice cultures // J. Neurochem. 2010. V. 112. No. 2. Pp. 377-388.

73. Takano K., Koarashi K., Kawabe K., Itakura M., Nakajima H., Moriyama M., Nakamura Y. Insulin expression in cultured astrocytes and the decrease by amyloid β // Neurochem. Int. 2017. pii: S0197-0186(17)30253-X.

74. Talbot K., Wang H.Y. The nature, significance, and glucagon-like peptide-1 analog treatment of brain insulin resistance in Alzheimer's disease // Alzheimers. Dement. 2014. V.10 (1 Suppl). Pp. S12-25.

75. Talbot K., Wang H.Y., Kazi H., Han L.Y., Bakshi K.P., Stucky A., Fuino R.L., Kawaguchi K.R., Samoyedny A.J., Wilson R.S., Arvanitakis Z., Schneider J.A., Wolf B.A., Bennett D.A., Trojanowski J.Q, Arnold S.E. 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. No. 4. Pp. 1316-38.

76. Timper K., Brüning J.C. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity // Dis. Model. Mech. 2017. V. 10. No. 6. Pp. 679-689.

77. Unger J., McNeill T.H., Moxley R.T. 3rd., White M., Moss A., Livingston J.N. Distribution of insulin receptor-like immunoreactivity in the rat forebrain // Neuroscience. 1989. V. 31. No. 1. Pp. 143-157.

78. Urayama A., Banks W.A. Starvation and triglycerides reverse the obesity-induced impairment of insulin transport at the blood-brain barrier // Endocrinology. 2008. V. 149. No.7. Pp. 3592-3597.

79. van der Heide L.P., Ramakers G.M., Smidt M.P. Insulin signaling in the central nervous system: learning to survive // Prog. Neurobiol. 2006. V. 79. Pp. 205-221.

80. Watson G.S., Cholerton B.A., Reger M.A., Baker L.D., Plymate S.R., Asthana S., Fishel M.A., Kulstad J.J., Green P.S., Cook D.G., Kahn S.E., Keeling M.L., Craft S. Preserved cognition in patients with early alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: A preliminary study // Am. J. Geriatr. Psychiatry. 2005. V. 13. Pp. 950-958.

81. Wei L.T., Matsumoto H., Rhoads D.E. Release of immunoreactive insulin from rat brain synaptosomes under depolarizing conditions // J. Neurochem. 1990. V. 54. Pp. 1661-65.

82. White M.F., Kahn C.R. The insulin signaling system // J. Biol. Chem. 1994. V. 269. No. 1. Pp. 1-4.

83. Wilden P.A., Kahn C.R., Siddle K., White M.F. Insulin receptor kinase domain autophosphorylation regulates receptor enzymatic function // J. Biol. Chem. 1992. V. 267. No. 23. Pp. 16660-68.

84. Xu A.W., Kaelin C.B., Takeda K., Akira S., Schwartz M.W., Barsh G.S. PI3K integrates the action of insulin and leptin on hypothalamic neurons // J. Clin. Invest. 2005. V. 115. Pp. 951-958.

85. Yamaguchi Y., Flier J.S., Yokota A., Benecke H., Backer J.M., Moller D.E. Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells // Endocrinology. 1991. V. 129. Pp. 2058-66.

86. Yamaguchi Y., Flier J.S., Benecke H., Ransil B.J., Moller D.E. Ligand-binding properties of the two isoforms of the human insulin receptor // Endocrinology. 1993. V. 132. Pp. 1132-38.

87. Ye F., Luo Y.J., Xiao J., Yu N.W., Yi G. Impact of insulin sensitizers on the incidence of dementia: A meta-analysis // Dement. Geriatr. Cogn. Disord. 2016. V. 41. No. 5-6. Pp. 251-260.

88. Yeh T.C., Ogawa W., Danielsen A.G., Roth R.A. Characterization and cloning of a 58/53-kDa substrate of the insulin receptor tyrosine kinase // J. Biol. Chem. 1996. V. 271. Pp. 2921-28.

89. Ziegler A.N., Chidambaram S., Forbes B.E., Wood T.L., Levison S.W. Insulin-like growth factor-II (IGF-II) and IGF-II analogs with enhanced insulin receptor-a binding affinity promote neural stem cell expansion // J. Biol. Chem. 2014. V. 289. Pp. 4626-33.

90. Ziegler A.N., et al. IGF-II promotes stemness of neural restricted precursors // Stem. Cells. 2012. V. 30. Pp. 1265-76.

91. Abbott M.A., Wells D.G., Fallon J.R. The insulin receptor tyrosine kinase substrate p58/53 and the insulin receptor are components of CNS synapses. J. Neurosci. 1999. V. 19. Pp. 7300-7308.

92. Aime P., Hegoburu C., Jaillard T., Degletagne C., Garcia S., Messaoudi B., Thevenet M., Lorsignol A., Duchamp C., Mouly A.M., Julliard A.K. A physiological increase of insulin in the olfactory bulb decreases detection of a learned aversive odor and abolishes food odor-induced sniffing behavior in rats. PLoS One. 2012. V. 7. P. e51227.

93. Aimé P., Palouzier-Paulignan B., Salem R., Al Koborssy D., Garcia S., Duchamp C., Romestaing C., Julliard A.K. Modulation of olfactory sensitivity and glucose-sensing by the feeding state in obese Zucker rats. Front. Behav. Neurosci. 2014. V. 8. P. 326.

94. Banks W.A. The source of cerebral insulin. Eur. J. Pharmacol. 2004. V. 490. No. 1-3. Pp. 5-12.

95. Banks W.A., Kastin A.J., Pan W. Uptake and degradation of blood-borne insulin by the olfactory bulb. Peptides. 1999. V. 20. Pp. 373-378.

96. Banks W.A., Owen J.B., Erickson M.A. Insulin in the brain: there and back again. Pharmacol. Ther. 2012. V. 136. Pp. 82-93.

97. Baskin D.G., Porte D.Jr., Guest K., Dorsa D.M. Regional concentrations of insulin in the rat brain. Endocrinology. 1983. V. 112. Pp. 898-903.

98. Baskin D.G., Stein L.J., Ikeda H., Woods S.C., Figlewicz D.P., Porte D.Jr., Greenwood M.R., Dorsa D.M. Genetically obese Zucker rats have abnormally low brain insulin content. Life. Sci. 1985. V. 36. No. 7. Pp. 627-633.

99. Begg D.P., Mul J.D., Liu M., Reedy B.M., D'Alessio D.A., Seeley R.J., Woods S.C. Reversal of diet-induced obesity increases insulin transport into cerebrospinal fluid and restores sensitivity to the anorexic action of central insulin in male rats. Endocrinology. 2013. V. 154. No. 3. Pp. 1047-1054.

100. Benedict C., Hallschmid M., Hatke A., Schultes B., Fehm H.L., Born J., Kern W. Intranasal insulin improves memory in humans. Psychoneuroendocrinology. 2004. V. 29. Pp. 1326-1334.

101. Benedict C., Hallschmid M., Schmitz K., Schultes B., Ratter F., Fehm H.L., Born J., Kern W. Intranasal insulin improves memory in humans: superiority of insulin aspart. Neuropsychopharmacology. 2007. V. 32. No. 1. Pp. 239-243.

102. Benedict C., Kern W., Schultes B., Born J., Hallschmid M. Differential sensitivity of men and women to anorexigenic and memory-improving effects of intranasal insulin. J. Clin. Endocrinol. Metab. 2008. V. 93. No. 4. Pp. 1339-1344.

103. Benoit S.C., Air E.L., Coolen L.M., Strauss R., Jackman A., Clegg D.J., Seeley R.J., Woods S.C. The catabolic action of insulin in the brain is mediated by melanocortins. J. Neurosci. 2002. V. 22. Pp. 9048-52.

104. Brunner Y.F., Benedict C., Freiherr J. Intranasal insulin reduces olfactory sensitivity in normosmic humans. J. Clin. Endocrinol. Metab. 2013. V. 98. Pp. E1626-30.

105. Cheng C.M., Mervis R.F., Niu S.L., Salem N.Jr., Witters L.A., Tseng V., Reinhardt R., Bondy C.A. Insulin-like growth factor 1 is essential for normal dendritic growth. J. Neurosci. Res. 2003. V. 73. No. 1. Pp. 1-9.

106. Chiu S.L., Cline H.T. Insulin receptor signaling in the development of neuronal structure and function. Neural. Dev. 2010. No. 5. P. 7.

107. Choi J., Ko J., Racz B., Burette A., Lee J.R., Kim S., Na M., Lee H.W., Kim K., Weinberg R.J., Kim E. Regulation of dendritic spine morphogenesis by insulin receptor substrate 53, a downstream effector of Rac1 and Cdc42 small GTPases. J. Neurosci. 2005. V. 25. Pp. 869-879.

108. Clarke D.W., Mudd L., Boyd F.T.Jr., Fields M., Raizada M.K. Insulin is released from rat brain neuronal cells in culture. J. Neurochem. 1986. V. 47. Pp. 831-836.

109. Cline B.H., Costa-Nunes J.P., Cespuglio R., Markova N., Santos A.I., Bukhman Y.V., Kubatiev A., Steinbusch H.W., Lesch K.P., Strekalova T. Dicholine succinate, the neuronal insulin sensitizer, normalizes behavior, REM sleep, hippocampal pGSK3 beta and mRNAs of NMDA receptor subunits in mouse models of depression. Front. Behav. Neurosci. 2015. V. 9. P. 37.

110. Cline B.H., Steinbusch H.W., Malin D., Revishchin A.V., Pavlova G.V., Cespuglio R., Strekalova T. The neuronal insulin sensitizer dicholine succinate reduces stress-induced depressive traits and memory deficit: possible role of insulin-like growth factor 2. BMC Neurosci. 2012. V. 13. P. 110.

111. Costa-Nunes J.P., Cline B.H., Araújo-Correia M., Valença A., Markova N., Dolgov O., Kubatiev A., Yeritsyan N., Steinbusch H.W., Strekalova T. Animal models of depression and drug delivery with food as an effective dosing method: evidences from studies with celecoxib and dicholine succinate. Biomed. res. int. 2015. V. 2015. P. 596126.

112. Denley A., Bonython E.R., Booker G.W., Cosgrove L.J., Forbes B.E., Ward C.W., Wallace J.C. Structural determinants for high-affinity binding of insulin-like growth factor II to insulin receptor (IR)-A, the exon 11 minus isoform of the IR. Mol. Endocrinol. 2004. V. 18. Pp. 2502-2512.

113. Dorn A., Bernstein H.G., Rinne A., Ziegler M., Hahn H.J., Ansorge S. Insulin- and glucagonlike peptides in the brain. Anat. Rec. 1983. V. 207. No. 1. Pp. 69-77.

114. Dorn A., Rinne A., Bernstein H.G., Hahn H.J., Ziegler M. Insulin and C-peptide in human brain neurons (insulin / C-peptide / brain peptides / immunohistochemistry / radioimmunoassay). J. Hirnforsch. 1983. V. 24. No. 5. Pp. 495-499.

115. Fadool D.A., Tucker K., Pedarzani P. Mitral cells of the olfactory bulb perform metabolic sensing and are disrupted by obesity at the level of the Kv1.3 ion channel. PLoS One. 2011. V. 6. No. 9. P. e24921.

116. Fadool D.A., Tucker K., Phillips J.J., Simmen J.A. Brain insulin receptor causes activity-dependent current suppression in the olfactory bulb through multiple phosphorylation of Kv1.3. J. Neurophysiol. 2000. V. 83. Pp. 2332-2348.

117. Frölich L., Blum-Degen D., Bernstein H.G., Engelsberger S., Humrich J., Laufer S., Muschner D., Thalheimer A., Türk A., Hoyer S., Zöchling R., Boissl K.W., Jellinger K., Riederer P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J. Neural. Transm. 1998. V. 105. No. 4-5. Pp. 423-438.

118. Gammeltoft S., Fehlmann M., Van Obberghen E. Insulin receptors in the mammalian central nervous system: binding characteristics and subunit structure. Biochimie. 1985. V. 67. No. 10-11. Pp. 1147-1153.

119. Garwood C.J., Ratcliffe L.E., Morgan S.V., Simpson J.E., Owens H., Vazquez-Villaseñor I., Heath P.R., Romero I.A., Ince P.G., Wharton S.B. Insulin and IGF1 signalling pathways in human astrocytes in vitro and in vivo; characterisation, subcellular localisation and modulation of the receptors. Mol. Brain. 2015. No. 8. P. 51.

120. Geldmacher D.S., Fritsch T., McClendon M.J., Landreth G. A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease. Arch. Neurol. 2011. V. 68. No. 1. Pp. 45-50.

121. Gerozissis K., Rouch C., Lemierre S., Nicolaidis S., Orosco M. A potential role of central insulin in learning and memory related to feeding. A potential role of central insulin in learning and memory related to feeding. Cell. Mol. Neurobiol. 2001. V. 21. No. 4. Pp. 389-401.

122. Gold M., Alderton C., Zvartau-Hind M., Egginton S., Saunders A.M., Irizarry M., Craft S., Landreth G., Linnamagi U., Sawchak S. Rosiglitazone monotherapy in mild-to-moderate alzheimer's disease: Results from a randomized, double-blind, placebo-controlled phase III study. Dement. Geriatr. Cogn. Disord. 2010. V. 30. Pp. 131-146.

123. Hallschmid M., Benedict C., Schultes B., Born J., Kern W. Obese men respond to cognitive but not to catabolic brain insulin signaling. Int. J. Obes. 2008. V. 32. No. 2. Pp. 275-282.

124. Hallschmid M., Higgs S., Thienel M., Ott V., Lehnert H. Postprandial administration of intranasal insulin intensifies satiety and reduces intake of palatable snacks in women. Diabetes. 2012. V. 61. Pp. 782-789.

125. Havrankova J., Roth J., Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978. V. 272. Pp. 827-829.

126. Heidenreich K.A., Zahniser N.R., Berhanu P., Brandenburg D., Olefsky J.M. Structural differences between insulin receptors in the brain and peripheral target tissues. J. Biol. Chem. 1983. V. 258. No. 14. Pp. 8527-8530.

127. Heni M., Hennige A.M., Peter A., Siegel-Axel D., Ordelheide A.M., Krebs N., et al. Insulin promotes glycogen storage and cell proliferation in primary human astrocytes. PLoS One. 2011. V. 6. No. 6. P. e21594.

128. Hill J.M., Lesniak M.A., Pert C.B., Roth J. Autoradiographic localization of insulin receptors in rat brain: prominence in olfactory and limbic areas. Neuroscience. 1986. V. 17. No. 4. Pp. 1127-1138.

129. Julliard A.K., Chaput M.A., Apelbaum A., Aime P., Mahfouz M., Duchamp-Viret P. Changes in rat olfactory detection performance induced by orexin and leptin mimicking fasting and satiation. Behav. Brain. Res. 2007. V. 183. Pp. 123-129.

130. Kaiyala K.J., Prigeon R.L., Kahn S.E., Woods S.C., Schwartz M.W. Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes. 2000. V. 49. No. 9. Pp. 1525-1533.

131. Kang J., Park H., Kim E. IRSp53/BAIAP2 in dendritic spine development, NMDA receptor regulation, and psychiatric disorders. Neuropharmacology. 2016. V. 100. Pp. 27-39.

132. Kern W., Benedict C., Schultes B., Plohr F., Moser A., Born J., Fehm H.L., Hallschmid M. Low cerebrospinal fluid insulin levels in obese humans. Diabetologia. 2006. V. 49. No. 11. Pp. 2790-2792.

133. Ketterer C., Heni M., Thamer C., Herzberg-Schafer S.A., Haring H.U., Fritsche A. Acute, short-term hyperinsulinemia increases olfactory threshold in healthy subjects. Int. J. Obes. 2011. V. 35. Pp. 1135-1138.

134. Krug R., Benedict C., Born J., Hallschmid M. Comparable sensitivity of postmenopausal and young women to the effects of intranasal insulin on food intake and working memory. J. Clin. Endocrinol. Metab. 2010. V. 95. No. 12. Pp. E468-472.

135. Kuczewski N., Fourcaud-Trocmé N., Savigner A., Thevenet M., Aimé P., Garcia S., Duchamp-Viret P., Palouzier-Paulignan B. Insulin modulates network activity in olfactory bulb slices: impact on odour processing. J. Physiol. 2014. V. 592. No. 13. Pp. 2751-69.

136. Kuwabara T., Kagalwala M.N., Onuma Y., et al. Insulin biosynthesis in neuronal progenitors derived from adult hippocampus and the olfactory bulb. EMBO Mol. Med. 2011. V. 3. Pp. 742-754.

137. Lacroix M.C., Badonnel K., Meunier N., Tan F., Schlegel-Le Poupon C., Durieux D., Monnerie R., Baly C., Congar P., Salesse R., Caillol M. Expression of insulin system in the olfactory epithelium: first approaches to its role and regulation. J. Neuroendocrinol. 2008. V. 20. No. 10. Pp. 1176-1190.

138. Lacroix M.C., Caillol M., Durieux D., Monnerie R., Grebert D., Pellerin L., Repond C., Tolle V., Zizzari P., Baly C. Long-lasting metabolic imbalance related to obesity alters olfactory tissue homeostasis and impairs olfactory-driven behaviors. Chem. Senses. 2015. V. 40. No. 8. Pp. 537-556.

139. Li Z., Okamoto K., Hayashi Y., Sheng M. The importance of dendritic mitochondria in the morphogenesis and plasticity of spines and synapses. Cell. 2004. V. 119. Pp. 873-887.

140. Luchsinger J.A., Perez T., Chang H., Mehta P., Steffener J., Pradabhan G., Ichise M., Manly J., Devanand D.P., Bagiella E. Metformin in amnestic mild cognitive impairment: results of a pilot randomized placebo controlled clinical trial. J. Alzheimers. Dis. 2016. V. 51. No. 2. Pp. 501-514.

141. Marks D.R., Tucker K., Cavallin M.A., Mast T.G., Fadool D.A. Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. J. Neurosci. 2009. V. 29. No. 20. Pp. 6734-6751.

142. McNay E.C., Recknagel A.K. Brain insulin signaling: a key component of cognitive processes and a potential basis for cognitive impairment in type 2 diabetes. Neurobiol. Learn. Mem. 2011. V. 96. No. 3. Pp. 432-442.

143. Mielke J.G., Taghibiglou C., Wang Y.T. Endogenous insulin signaling protects cultured neurons from oxygen-glucose deprivation-induced cell death. Neuroscience. 2006. V. 143. No. 1. Pp. 165-173.

144. Morton G.J., Cummings D.E., Baskin D.G., Barsh G.S., Schwartz M.W. Central nervous system control of food intake and body weight. Nature. 2006. V. 443. Pp. 289-295.

145. Mosthaf L., Grako K., Dull T.J., Coussens L., Ullrich A., McClain D.A. Functionally distinct insulin receptors generated by tissue-specific alternative splicing. EMBO J. 1990. V. 9. No. 8. Pp. 2409-2413.

146. Paulesco N.C. Recherche sur le rôle du pancréas dans l'assimilation nutritive. Archives Internationales de Physiologie. 1921. V. 17. Pp. 85-103.

147. Pearson-Leary J., Jahagirdar V., Sage J., McNay E.C. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4. Behav. Brain. Res. 2018. V. 338. Pp. 32-39.

148. Pearson-Leary J., McNay E.C. Novel roles for the insulin-regulated glucose transporter-4 in hippocampally dependent memory. J. Neurosci. 2016. V. 36. No. 47. Pp. 11851-64.

149. Persiyantseva N.A., Storozhevykh T.P., Senilova Y.E., Gorbacheva L.R., Pinelis V.G., Pomytkin I.A. Mitochondrial H2O2 as an enable signal for triggering autophosphorylation of insulin receptor in neurons. J. Mol. Signal. 2013. V. 8. No. 1. P. 11.

150. Pitt J., Wilcox K.C., Tortelli V., Diniz L.P., Oliveira M.S., Dobbins C., Yu X.W., Nandamuri S., Gomes F.C.A., DiNunno N., Viola K.L., De Felice F.G., Ferreira S.T., Klein W.L. Neuroprotective astrocyte-derived insulin/IGF-1 stimulate endocytic processing and extracellular release of neuron-bound Aβ oligomers. Mol. Biol. Cell. 2017. pii: mbc.E17-06-0416.

151. Plum L., Schubert M., Bruning J.C. The role of insulin receptor signaling in the brain. Trends. Endrocrinol. Metab. 2005. V. 16. Pp. 59-65.

152. Pomytkin I.A. H2O2 signalling pathway: A possible bridge between insulin receptor and mitochondria. Curr. Neuropharmacol. 2012. V. 10. No. 4. Pp. 311-320.

153. Pomytkin I.A., Semenova N.A. Study of the effect of preconditioning with succinic acid salt of choline (1:2) on the disturbances of energy metabolism in the brain during ischemia by 31P NMR in vivo. Dokl. Biochem. Biophys. 2005. V. 403. Pp. 289-292.

154. Qiu J., Wagner E.J., Rønnekleiv O.K., Kelly M.J. Insulin and leptin excite anorexigenic proopiomelanocortin neurons via activation of TRPC5 channels. J. Neuroendocrinol. 2018. V. 30. No. 2.

155. Qiu J., Zhang C., Borgquist A., Nestor C.C., Smith A.W., Bosch M.A., Ku S., Wagner E.J., Rønnekleiv O.K., Kelly M.J. Insulin excites anorexigenic proopiomelanocortin neurons via activation of canonical transient receptor potential channels. Cell. Metab. 2014. V. 19. Pp. 682-693.

156. Sato T., Hanyu H., Hirao K., Kanetaka H., Sakurai H., Iwamoto T. Efficacy of ppar-gamma agonist pioglitazone in mild alzheimer disease. Neurobiol. Aging. 2011. V. 32. Pp. 1626-1633.

157. Schwartz M.W., Marks J.L., Sipols A.J., Baskin D.G., Woods S.C., Kahn S.E., Porte D.Jr. Central insulin administration reduces neuropeptide Y mRNA expression in the arcuate nucleus of food-deprived lean (Fa/Fa) but not obese (fa/fa) Zucker rats. Endocrinology. 1991. V. 128. Pp. 2645-47.

158. Steen E., Terry B.M., Rivera E.J., et al. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer’s disease - Is this type 3 diabetes? J. Alzheimers. Dis. 2005. V. 7. Pp. 63-80.

159. Storozheva Z.I., Proshin A.T., Sherstnev V.V., Storozhevykh T.P., Senilova Y.E., Persiyantseva N.A., Pinelis V.G., Semenova N.A., Zakharova E.I., Pomytkin I.A. Dicholine salt of succinic acid, a neuronal insulin sensitizer, ameliorates cognitive deficits in rodent models of normal aging, chronic cerebral hypoperfusion, and beta-amyloid peptide-(25-35)-induced amnesia. BMC Pharmacol. 2008. V. 8. P. 1.

160. Storozhevykh T.P., Senilova Y.E., Persiyantseva N.A., Pinelis V.G., Pomytkin I.A. Mitochondrial respiratory chain is involved in insulin-stimulated hydrogen peroxide production and plays an integral role in insulin receptor autophosphorylation in neurons. BMC Neurosci. 2007. V. 8. P. 84.

161. Strekalova T., Costa-Nunes J.P., Veniaminova E., Kubatiev A., Lesch K.P., Chekhonin V.P., Evans M.C., Steinbusch H.W. Insulin receptor sensitizer, dicholine succinate, prevents both Toll-like receptor 4 (TLR4) upregulation and affective changes induced by a high-cholesterol diet in mice. J. Affect. Disord. 2016. V. 196. Pp. 109-116.

162. Sun X., Yao H., Douglas R.M., Gu X.Q., Wang J., Haddad G.G. Insulin/PI3K signaling protects dentate neurons from oxygen-glucose deprivation in organotypic slice cultures. J. Neurochem. 2010. V. 112. No. 2. Pp. 377-388.

163. Takano K., Koarashi K., Kawabe K., Itakura M., Nakajima H., Moriyama M., Nakamura Y. Insulin expression in cultured astrocytes and the decrease by amyloid β. Neurochem. Int. 2017. pii: S0197-0186(17)30253-X.

164. Talbot K., Wang H.Y. The nature, significance, and glucagon-like peptide-1 analog treatment of brain insulin resistance in Alzheimer's disease. Alzheimers. Dement. 2014. V.10 (1 Suppl). Pp. S12-25.

165. Talbot K., Wang H.Y., Kazi H., Han L.Y., Bakshi K.P., Stucky A., Fuino R.L., Kawaguchi K.R., Samoyedny A.J., Wilson R.S., Arvanitakis Z., Schneider J.A., Wolf B.A., Bennett D.A., Trojanowski J.Q, Arnold S.E. 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. No. 4. Pp. 1316-38.

166. Timper K., Brüning J.C. Hypothalamic circuits regulating appetite and energy homeostasis: pathways to obesity. Dis. Model. Mech. 2017. V. 10. No. 6. Pp. 679-689.

167. Unger J., McNeill T.H., Moxley R.T. 3rd., White M., Moss A., Livingston J.N. Distribution of insulin receptor-like immunoreactivity in the rat forebrain. Neuroscience. 1989. V. 31. No. 1. Pp. 143-157.

168. Urayama A., Banks W.A. Starvation and triglycerides reverse the obesity-induced impairment of insulin transport at the blood-brain barrier. Endocrinology. 2008. V. 149. No.7. Pp. 3592-3597.

169. van der Heide L.P., Ramakers G.M., Smidt M.P. Insulin signaling in the central nervous system: learning to survive. Prog. Neurobiol. 2006. V. 79. Pp. 205-221.

170. Watson G.S., Cholerton B.A., Reger M.A., Baker L.D., Plymate S.R., Asthana S., Fishel M.A., Kulstad J.J., Green P.S., Cook D.G., Kahn S.E., Keeling M.L., Craft S. Preserved cognition in patients with early alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: A preliminary study. Am. J. Geriatr. Psychiatry. 2005. V. 13. Pp. 950-958.

171. Wei L.T., Matsumoto H., Rhoads D.E. Release of immunoreactive insulin from rat brain synaptosomes under depolarizing conditions. J. Neurochem. 1990. V. 54. Pp. 1661-65.

172. White M.F., Kahn C.R. The insulin signaling system. J. Biol. Chem. 1994. V. 269. No. 1. Pp. 1-4.

173. Wilden P.A., Kahn C.R., Siddle K., White M.F. Insulin receptor kinase domain autophosphorylation regulates receptor enzymatic function. J. Biol. Chem. 1992. V. 267. No. 23. Pp. 16660-68.

174. Xu A.W., Kaelin C.B., Takeda K., Akira S., Schwartz M.W., Barsh G.S. PI3K integrates the action of insulin and leptin on hypothalamic neurons. J. Clin. Invest. 2005. V. 115. Pp. 951-958.

175. Yamaguchi Y., Flier J.S., Yokota A., Benecke H., Backer J.M., Moller D.E. Functional properties of two naturally occurring isoforms of the human insulin receptor in Chinese hamster ovary cells. Endocrinology. 1991. V. 129. Pp. 2058-66.

176. Yamaguchi Y., Flier J.S., Benecke H., Ransil B.J., Moller D.E. Ligand-binding properties of the two isoforms of the human insulin receptor. Endocrinology. 1993. V. 132. Pp. 1132-38.

177. Ye F., Luo Y.J., Xiao J., Yu N.W., Yi G. Impact of insulin sensitizers on the incidence of dementia: A meta-analysis. Dement. Geriatr. Cogn. Disord. 2016. V. 41. No. 5-6. Pp. 251-260.

178. Yeh T.C., Ogawa W., Danielsen A.G., Roth R.A. Characterization and cloning of a 58/53-kDa substrate of the insulin receptor tyrosine kinase. J. Biol. Chem. 1996. V. 271. Pp. 2921-28.

179. Ziegler A.N., Chidambaram S., Forbes B.E., Wood T.L., Levison S.W. Insulin-like growth factor-II (IGF-II) and IGF-II analogs with enhanced insulin receptor-a binding affinity promote neural stem cell expansion. J. Biol. Chem. 2014. V. 289. Pp. 4626-33.

180. Ziegler A.N., et al. IGF-II promotes stemness of neural restricted precursors. Stem. Cells. 2012. V. 30. Pp. 1265-76.


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Помыткин И.А., Красильникова И.А., Пинелис В.Г., Каркищенко Н.Н. Инсулиновый рецептор в мозге: новая мишень в лечении центральной инсулиновой резистентности. БИОМЕДИЦИНА. 2018;(3):17-34.

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Pomytkin I.A., Krasil’Nikova I.A., Pinelis V.G., Karkischenko N.N. Insulin signaling system in the brain: new target in the treatment of central insulin resistance. Journal Biomed. 2018;(3):17-34. (In Russ.)

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