IR (insulin resistance) in diabetic brain gave rise to the generation of toxic factor Aβ42 and axon collapse which were the marker of AD (Alzheimer's disease)-like lesions in the circumstance of diabetes mellitus. But the underling molecular mechanism was not clear. Chronic HGHI (high glucose and high insulin) exposure accelerates IR has been reported in type II diabetes models. Berberine has been shown to promising effect for IR in vitro and in vivo. This study demonstrates the protective effect and the underlying mechanism of berberine on HGHI-induced IR. HGHI-induced cells were used to mimic the hyperinsulinemia resulting in IR. Berberine was used to uncover the mechanisms for the treatment of hyperinsulinemia in IR model. Morris water maze (MWM), PET imaging, CCK8 assay, ELISA assay, glucose kits, microscopy, and western blot analysis were performed to evaluate the protective effects of berberine. Berberine-improved HGHI-induced IR was correlated with the increase of glucose application in neurons. Meanwhile, the expressions of Pi3K, as well as GLUT3, PKCε, and APP were downregulated in the model, while p-IRS Ser307 was upregulated compared with Normal group. Fortunately, these scenes were reversed by berberine administration. Furthermore, berberine decreased GSK3β Y216 expressions, inhibited the production of oligomer Aβ42 and extended neuronal axon. The monomeric berberine treatment improves IR that may be involved in glucose effective application, rectifying the related proteins of the aberrant insulin pathway. Additionally, it suppressed the generation of Aβ42 and ameliorated neuron axon damage. Finally, berberine improves DM (diabetes mellitus)-induced cognitive impairment.

中文翻译：

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小檗碱通过激活 Pi3k/PGCε 通路改善神经元 AD 样变化


糖尿病脑中的IR（胰岛素抵抗）引起毒性因子Aβ42的产生和轴突塌陷，这是糖尿病环境下AD（阿尔茨海默病）样病变的标志。但其基本分子机制尚不清楚。据报道，在 II 型糖尿病模型中，慢性 HGHI（高葡萄糖和高胰岛素）暴露会加速 IR。小檗碱已被证明对体外和体内 IR 具有良好的效果。本研究证明了小檗碱对 HGHI 诱导的 IR 的保护作用及其潜在机制。 HGHI 诱导的细胞被用来模拟导致 IR 的高胰岛素血症。小檗碱被用来揭示治疗 IR 模型中高胰岛素血症的机制。采用 Morris 水迷宫 (MWM)、PET 成像、CCK8 测定、ELISA 测定、葡萄糖试剂盒、显微镜检查和蛋白质印迹分析来评估小檗碱的保护作用。小檗碱改善的 HGHI 诱导的 IR 与神经元中葡萄糖应用的增加相关。同时，与正常组相比，模型中Pi3K、GLUT3、PKCε、APP的表达下调，而p-IRS Ser307的表达上调。幸运的是，小檗碱的服用扭转了这些局面。此外，小檗碱降低 GSK3β Y216 的表达，抑制寡聚物 Aβ42 的产生和神经元轴突的延伸。单体小檗碱治疗可改善胰岛素抵抗，这可能与葡萄糖的有效应用有关，纠正异常胰岛素途径的相关蛋白质。此外，它还能抑制 Aβ42 的生成并改善神经元轴突损伤。最后，小檗碱可改善 DM（糖尿病）引起的认知障碍。