Key Laboratory of Medical Cell Biology of Ministry of Education, and Key Laboratory of Endocrine Diseases of Liaoning Province, China Medical University, Shenyang, PR China.
Mol Neurodegener. 2010 Nov 2;5:46. doi: 10.1186/1750-1326-5-46.
Although increasing evidence has indicated that brain insulin dysfunction is a risk factor for Alzheimer disease (AD), the underlying mechanisms by which insulin deficiency may impact the development of AD are still obscure. Using a streptozotocin (STZ)-induced insulin deficient diabetic AD transgenic mouse model, we evaluated the effect of insulin deficiency on AD-like behavior and neuropathology.
Our data showed that administration of STZ increased the level of blood glucose and reduced the level of serum insulin, and further decreased the phosphorylation levels of insulin receptors, and increased the activities of glycogen synthase kinase-3α/β and c-Jun N-terminal kinase in the APP/PS1 mouse brain. We further showed that STZ treatment promoted the processing of amyloid-β (Aβ) precursor protein resulting in increased Aβ generation, neuritic plaque formation, and spatial memory deficits in transgenic mice.
Our present data indicate that there is a close link between insulin deficient diabetes and cerebral amyloidosis in the pathogenesis of AD.
虽然越来越多的证据表明大脑胰岛素功能障碍是阿尔茨海默病（AD）的一个风险因素，但胰岛素缺乏如何影响 AD 的发展的潜在机制仍不清楚。本研究使用链脲佐菌素（STZ）诱导的胰岛素缺乏型糖尿病 AD 转基因小鼠模型，评估了胰岛素缺乏对 AD 样行为和神经病理学的影响。
我们的数据显示，STZ 给药增加了血糖水平，降低了血清胰岛素水平，进一步降低了胰岛素受体的磷酸化水平，并增加了 APP/PS1 小鼠大脑中糖原合成酶激酶-3α/β 和 c-Jun N-末端激酶的活性。我们进一步表明，STZ 处理促进了淀粉样前体蛋白（Aβ）的加工，导致 Aβ生成增加、神经突斑块形成和转基因小鼠空间记忆缺陷。
本研究数据表明，胰岛素缺乏型糖尿病与 AD 发病机制中的脑淀粉样变性密切相关。
