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。
