Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways

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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Correspondence to R. U. Ostrovskaya.

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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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Key Words

  • diabetes
  • C57Bl/6 mice
  • streptozotocin
  • low-molecular-weight BDNF mimetics