Abstract:
The term type 3 diabetes mellitus (T3DM) has been considered for Alzheimer\'s disease (AD) due to the common molecular and cellular characteristics found between type 2 diabetes mellitus (T2DM) and cognitive deficits. However, the specific mechanism of T3DM remains elusive, especially the neuroprotective effects of dietary components in hyperglycemic individuals. In this study, a peptide, Leu-Val-Arg-Leu (LVRL), found in walnuts significantly improved memory decline in streptozotocin (STZ)- and high-fat-diet (HFD)-stimulated T2DM mouse models (p < 0.05). The LVRL peptide also mitigated hyperglycemia, enhanced synaptic plasticity, and ameliorated mitochondrial dysfunction, as demonstrated by Morris water maze tests, immunoblotting, immunofluorescence, immunohistochemistry, transmission electron microscopy, and cellular staining. A Wnt3a inhibitor, DKK1, was subsequently used to verify the possible role of the Wnt3a/β-Catenin/GSK-3β pathway in glucose-induced insulin resistance in PC12 cells. In vitro LVRL treatment dramatically modulated the protein expression of p-Tau (Ser404), Synapsin-1, and PSD95, elevated the insulin level, increased glucose consumption, and relieved the mitochondrial membrane potential, and MitoSOX (p < 0.05). These data suggested that peptides like LVRL could modulate the relationship between brain insulin and altered cognition status via the Wnt3a/β-Catenin/GSK-3β pathway.
摘要:
由于在2型糖尿病(T2DM)和认知缺陷之间发现的共同分子和细胞特征,术语3型糖尿病(T3DM)被认为是阿尔茨海默病(AD)。然而,T3DM的具体机制仍然难以捉摸,尤其是饮食成分对高血糖个体的神经保护作用。在这项研究中,一种肽,Leu-Val-Arg-Leu(LVRL),在核桃中发现,链脲佐菌素(STZ)和高脂饮食(HFD)刺激的T2DM小鼠模型的记忆力下降显着改善(p<0.05)。LVRL肽还减轻了高血糖症,增强突触可塑性,改善线粒体功能障碍,正如莫里斯水迷宫测试所证明的那样,免疫印迹,免疫荧光,免疫组织化学,透射电子显微镜,和细胞染色。一种Wnt3a抑制剂,DKK1随后用于验证Wnt3a/β-Catenin/GSK-3β途径在PC12细胞中葡萄糖诱导的胰岛素抵抗中的可能作用。体外LVRL处理显着调节p-Tau(Ser404)的蛋白质表达,Synapsin-1和PSD95升高了胰岛素水平,葡萄糖消耗增加,减轻了线粒体膜电位,和MitoSOX(p<0.05)。这些数据表明,LVRL等肽可以通过Wnt3a/β-Catenin/GSK-3β途径调节脑胰岛素与认知状态改变之间的关系。