Ostrovskaya R U, Yagubova S S, Gudasheva T A, Seredenin S B
V. V. Zakusov Research Institute of Pharmacology, Moscow, Russia.
Bull Exp Biol Med. 2018 Apr;164(6):734-737. doi: 10.1007/s10517-018-4069-y. Epub 2018 Apr 16.
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.
糖尿病中β细胞增殖减少和凋亡增加与脑源性神经营养因子（BDNF）缺乏有关。在V. V. 扎库索夫药理研究所合成了与不同BDNF环相似的低分子量化合物。它们对TrkB磷酸化产生增强作用，但对受体后信号通路的激活方式不同。我们比较了它们对链脲佐菌素诱导的C57Bl/6小鼠糖尿病严重程度的影响。抗糖尿病作用（根据高血糖程度和体重动态评估）是选择性激活PI3K/Akt的GSB - 214化合物所特有的。在MAPK/Erk的选择性激活剂GTS - 201中未发现这种活性。激活两种信号通路的GSB - 106化合物表现出较弱的抗糖尿病活性。我们的结果表明，抗糖尿病作用主要与PI3K/Akt信号通路的激活有关。
