小檗碱
莫里斯水上航行任务
化学
药理学
高胰岛素血症
PI3K/AKT/mTOR通路
下调和上调
糖尿病
胰岛素抵抗
内科学
内分泌学
信号转导
生物化学
医学
海马体
基因
作者
Ning‐hua Wu,Wu Liu,Jiawen Wang,Yanqi Han,Ye Yu,Xiufen Liu,Yuandong Yu,Qingjie Chen,Yongfen Bao,Chao Liu
出处
期刊:Biofactors
[Wiley]
日期:2021-03-19
卷期号:47 (4): 587-599
被引量:9
摘要
Abstract 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.
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