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大脑胰岛素不仅可调节血糖,而且可改善记忆和认知,而大脑胰岛素缺乏常导致Alzheimer病(Alzheimer’s disease,AD)的发生.本研究检测了正常及2型糖尿病(type 2 diabetes,T2D)大鼠外周及大脑胰岛素信号传导途径,以探讨T2D时由于大脑胰岛素异常导致AD发病的可能性.以同龄正常SD大鼠为对照(CTL组),高糖、高脂、高蛋白饮食加链脲佐菌素(streptozotocin,STZ)腹腔注射建造T2D大鼠模型(T2D组).葡萄糖氧化酶法检测血浆血糖,放免法检测脑脊液及血浆胰岛素,免疫印迹技术检测大脑海马tau蛋白上部分位点磷酸化水平,大脑及肝脏、肌肉组织胰岛素信号传导途径中磷脂酰肌醇3激酶(phosphatidylinositol 3 kinase,PI3K)/蛋白激酶B(protein kinaseB,Akt)、糖原合成激酶3β(glycogen synthase kinase-3β,GSK-3β)活性.结果显示:和对照组相比,T2D大鼠血浆葡萄糖水平及胰岛素水平显著升高,脑脊液胰岛素水平显著降低,大脑海马组织tau蛋白上所检测位点均呈过度磷酸化改变,海马及外周组织(肝脏、肌肉)胰岛素信号传导途径PI3K/Akt活性均显著下降,GSK-3β活性升高.研究结果表明:2型糖尿病大鼠大脑胰岛素缺乏及其信号传导途径下调可能是导致阿尔茨海默病发病的重要原因.
Brain insulin not only regulates blood sugar, but also improves memory and cognition, whereas lack of brain insulin often leads to the development of Alzheimer’s disease (AD) .This study examined the effects of type 2 diabetes (T2D) rats Peripheral and brain insulin signaling pathways to explore the possible pathogenesis of AD due to abnormal brain insulin in T2D.At the same age normal SD rats as control (CTL group), high glucose, high fat, high protein diet plus streptozotocin T2D rat model was established by intraperitoneal injection of streptozotocin (STZ) .Glucose-oxidase method was used to detect plasma glucose, cerebrospinal fluid (CSF) and plasma insulin were detected by radioimmunoassay. Phosphorylation of tau in hippocampus was detected by Western blotting, The phosphorylation of phosphokinase 3 kinase (PI3K) / protein kinase B (Akt), glycogen synthase kinase-3β (GSK-3β) in the brain and liver and muscle and insulin signaling pathways, ) Activity.The results showed that compared with the control group, the plasma glucose and insulin levels were significantly increased in T2D rats, the cerebrospinal fluid insulin levels were significantly decreased, the brain The levels of PI3K / Akt in the hippocampus and peripheral tissues (liver, muscle) were significantly decreased and the activity of GSK-3β was increased in the tau protein of the horses tissues. The results showed that the type 2 Insulin deficiency in the brain of diabetic rats and the down-regulation of their signal transduction pathways may be the important reason for the pathogenesis of Alzheimer’s disease.