Reduced proliferation and enhanced apoptosis of β cells in diabetes mellitus are associated with a deficiency of brain-derived neurotrophic factor (BDNF). Low-molecular weight compounds similar to different BDNF loops were synthesized at the V. V. Zakusov Research Institute of Pharmacology. They produce a potentiating effect on TrkB phosphorylation, but differently activate post-receptor signaling pathways. We compared their effects on the severity of streptozotocin-induced diabetes mellitus in C57Bl/6 mice. The antidiabetic effect (estimated from the degree of hyperglycemia and dynamics of body weight) was typical of GSB-214 compound that selectively activates PI3K/Akt. This activity was not revealed in GTS-201, selective activator of MAPK/Erk. GSB-106 compound activating both signaling pathways exhibited weak antidiabetic activity. Our results indicate that the antidiabetic effect is mainly related to activation of the PI3K/Akt signaling pathway.
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Gudasheva TA, Antipova TA, Konstantinopolsky MA, Povarnina PY, Seredenin SB. Nerve growth factor novel dipeptide mimetic GK-2 selectively activates TrkA postreceptor signaling pathways and does not cause adverse effects of native neurotrophin. Dokl. Biochem. Biophysics. 2014;456(1):88-91.
Gudasheva TA, Antipova TA, Seredenin SB. Novel low-molecular-weight mimetics of the nerve growth factor. Dokl. Biochem. Biophysics. 2010;434(1):262-265.
Gudasheva TA, Tarasyuk AB, Pomogaibo SV, Logvinov IO, Povarnina PYu, Antipova TA, Seredenin SB. Design and synthesis of dipeptide mimetics of the brain neurotrophic factor. Bioorgan. Khimiya. 2012;38(3):280-290.
Gudasheva TA, Tarasiuk AV, Sazonova NM, Povarnina PYu, Antipova TA, Seredenin SB. A Novel Dimeric Dipeptide Mimetic of the BDNF Selectively Activates the MAPK-Erk Signaling Pathway. Dokl. Biochem. Biophysics. 2017;476(1):291-295.
Ostrovskaya RU, Yagubova SS, Gudasheva TA, Seredenin SB. Low-molecular-weight ngf mimetic corrects the cognitive deficit and depression-like behavior in experimental diabetes. Acta Naturae. 2017;9(2):94-102.
Patent RU No. 2613314. Small molecules with ngf-like activity and antidiabetic properties. Bull. No. 8. Published March 15, 2017.
Bathina S, Das UN. Brain-derived neurotrophic factor and its clinical implications. Arch. Med. Sci. 2015;11(6):1164-1178.
Gudasheva TA, Povarnina P, Logvinov IO, Antipova TA, Seredenin S.B. Mimetics of brain-derived neurotrophic factor loops 1 and 4 are active in a model of ischemic stroke in rats. Drug Des. Devel. Ther. 2016;10:3545-3553.
Gudasheva TA, Povarnina PYu, Seredenin SB. Dipeptide mimetic of the brain-derived neurotrophic factor prevents impairments of neurogenesis in stressed mice. Bull. Exp. Biol. Med. 2017;162(4):454-457.
Hayashi K, Kojima R, Ito M. Strain differences in the diabetogenic activity of streptozotocin in mice. Biol. Pharm. Bull. 2006;29(6):1110-1119.
Kaplan DR, Miller FD. Neurotrophin signal transduction in the nervous system. Curr. Opin. Neurobiol. 2000;10(3):381-391.
Krabbe KS, Nielsen AR, Krogh-Madsen R, Plomgaard P, Rasmussen P, Erikstrup C, Fischer CP, Lindegaard B, Petersen AM, Taudorf S, Secher NH, Pilegaard H, Bruunsgaard H, Pedersen BK. Brain-derived neurotrophic factor (BDNF) and type 2 diabetes. Diabetologia. 2007;50(2):431-438.
Nakagawa T, Tsuchida A, Itakura Y, Nonomura T, Ono M, Hirota F, Inoue T, Nakayama C, Taiji M, Noguchi H. Brainderived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice. Diabetes. 2000;49(3):436-444.
Yamanaka M, Itakura Y, Ono-Kishino M, Tsuchida A, Nakagawa T, Taiji M. Intermittent administration of brain-derived neurotrophic factor (BDNF) ameliorates glucose metabolism and prevents pancreatic exhaustion in diabetic mice. J. Biosci. Bioeng. 2008;105(4):395-402.
Yanev S, Aloe L, Fiore M, Chaldakov GN. Neurotrophic and metabotrophic potential of nerve growth factor and brain-derived neurotrophic factor: Linking cardiometabolic and neuropsychiatric diseases. World J. Pharmacol. 2013;2(4):92-99.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 164, No. 12, pp. 701-705, December, 2017
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Ostrovskaya, R.U., Yagubova, S.S., Gudasheva, T.A. et al. Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways. Bull Exp Biol Med 164, 734–737 (2018). https://doi.org/10.1007/s10517-018-4069-y
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DOI: https://doi.org/10.1007/s10517-018-4069-y