Ostrovskaya R U, Ivanov S V, Gudasheva T A, Seredenin S B
V. V. Zakusov Research Institute of Pharmacology, Baltiyskaya Str. 8, 125315, Moscow, Russia.
Acta Naturae. 2019 Jan-Mar;11(1):48-57.
We investigated the cytoprotective effect of a novel low-molecular-weight NGF mimetic, GK-2 (hexamethylenediamide bis-N-monosuccinyl-L-glutamyl-L-lysine), on pancreatic β-cells. The neuroprotective effect of GK-2 had been previously shown to be associated with selective activation of the PI3K/Akt signaling pathway. In this study, rats with streptozotocin (STZ)-induced type 2 diabetes mellitus were used. Metformin was used as a reference drug. STZ was immunohistochemically demonstrated to reduce the number of β-cells and affect their morphological structure. Treatment of diabetic animals with GK-2 (at a dose of 0.5 mg/kg intraperitoneally or 5 mg/kg orally) or metformin (300 mg/kg orally) for 28 days reduced the damaging effect of STZ. The effect of GK-2 on manifestations of STZ-induced diabetes, such as hyperglycemia, weight loss, polyphagia, and polydipsia, was comparable to that of metformin, while the cytoprotective activity of GK-2 was slightly stronger than that of metformin. A strong positive correlation between morphometric parameters and the blood glucose level was revealed. The GK-2 cytoprotective effect on β-cells is supposed to manifest through the PI3K/Akt signaling pathway.
我们研究了一种新型低分子量神经生长因子模拟物GK-2（六亚甲基二胺双-N-单琥珀酰-L-谷氨酰-L-赖氨酸）对胰腺β细胞的细胞保护作用。先前已证明GK-2的神经保护作用与PI3K/Akt信号通路的选择性激活有关。在本研究中，使用链脲佐菌素（STZ）诱导的2型糖尿病大鼠。二甲双胍用作参比药物。免疫组织化学证明STZ可减少β细胞数量并影响其形态结构。用GK-2（腹腔注射剂量为0.5mg/kg或口服剂量为5mg/kg）或二甲双胍（口服300mg/kg）治疗糖尿病动物28天可降低STZ的损伤作用。GK-2对STZ诱导的糖尿病表现（如高血糖、体重减轻、多食和多饮）的作用与二甲双胍相当，而GK-2的细胞保护活性略强于二甲双胍。形态学参数与血糖水平之间存在强正相关。推测GK-2对β细胞的细胞保护作用是通过PI3K/Akt信号通路实现的。
