Antidiabetic Properties of Low-Molecular-Weight BDNF Mimetics Depend on the Type of Activation of Post-Receptor Signaling Pathways
- Authors: Ostrovskaya R.U.1, Yagubova S.S.1, Gudasheva T.A.1, Seredenin S.B.1
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Affiliations:
- V. V. Zakusov Research Institute of Pharmacology
- Issue: Vol 164, No 6 (2018)
- Pages: 734-737
- Section: Pharmacology and Toxicology
- URL: https://journals.rcsi.science/0007-4888/article/view/239886
- DOI: https://doi.org/10.1007/s10517-018-4069-y
- ID: 239886
Cite item
Abstract
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.
About the authors
R. U. Ostrovskaya
V. V. Zakusov Research Institute of Pharmacology
Author for correspondence.
Email: rita.ostrovskaya@gmail.com
Russian Federation, Moscow
S. S. Yagubova
V. V. Zakusov Research Institute of Pharmacology
Email: rita.ostrovskaya@gmail.com
Russian Federation, Moscow
T. A. Gudasheva
V. V. Zakusov Research Institute of Pharmacology
Email: rita.ostrovskaya@gmail.com
Russian Federation, Moscow
S. B. Seredenin
V. V. Zakusov Research Institute of Pharmacology
Email: rita.ostrovskaya@gmail.com
Russian Federation, Moscow