Investigation of PI3K/PKB/mTOR/S6K1 signaling pathway in relationship of type 2 diabetes and Alzheimer's disease.

The aim of this study was to investigate the roles of PI3K/PKB/mTOR/S6K1 signaling pathway in the risk-increasing mechanisms of type 2 diabetes mellitus (T2DM) towards the Alzheimer's disease (AD). Based on the high-sugar high-fat diet, the single intraperitoneal injection of streptozotocin was performed to induce the T2DM rat model; the immunohistochemistry and RT-PCR technique were then performed to detect the expression levels of mTOR, PI3K, PKB, S6K1 and phosphorylated Tau protein in the hippocampal tissues of each group. The related metabolic indicators of the T2DM group and the T2DM + AD group were significantly higher than the normal control group and the AD group (P<0.01); the Morris water maze test of the AD group and the learning and memory of the T2DM + AD group were than significantly decreased than the T2DM group (P<0.01); the T2DM + AD group exhibited significantly increased expression levels of mTOR, S6K1 and Tau protein in the hippocampal tissues than the AD group and the T2DM group (P<0.05), and while the expression levels of PI3K and PKB were decreased (P<0.05). Among the possible mechanisms through which T2DM increased the risk of AD, the dystransduction of insulin signaling pathway (PI3K/PKB/mTOR/S6K1) was the important cause of hyperphosphorylation of Tau protein, thus it prompted the AD occurrence.