中国病理生理杂志Issue(1)：56-61,6.DOI:10.3969/j.issn.1000-4718.2013.01.009
鼻腔滴入胰岛素改善2型糖尿病大鼠海马阿尔茨海默病样改变
Intranasal insulin treatment ameliorates Alzheimer disease-like changes in hippocampus in a rat model of type 2 diabetes
摘要
Abstract
AIM: To investigate Alzheimer disease (AD)-like changes and 2 key components of the insulin signaling pathway in the brain of a rat model of type 2 diabetes (T2D) after insulin treatment. METHODS: The rat model of T2D was established by feeding a high-protein, high-glucose and high-fat diet followed by intrasubcutaneous injection of streptozocin. Intranasal insulin treatment (T2D + I-I) and subcutaneous insulin injection (T2D +S-I) were applied to elevate the insulin level in the brain. The insulin levels in plasma and cerebrospinal fluid as well as the concentration of plasma glucose were measured. Total tau level, the phosphorylation level of tau at some phosphorylation sites, and the activation of GSK-3β and Akt in subcutaneous of the rats were also analyzed by Western blotting. RESULTS: AD-like changes, decreased Akt activation and over-activation of GSK-3β in the hippocampus of the T2D rats were observed. Intranasal insulin treatment for 4 weeks normalized the levels of Akt and GSK-3β, as well as reduced the AD-like changes in the hippocampus of the T2D rats, whereas the treatment with insulin by subcutaneous injection for 4 weeks had minimal effects on the levels of GSK-3β and tau phosphorylation in the hippocampus. CONCLUSION: Intranasal insulin treatment, but not subcutaneous insulin treatment, might decrease the risk of AD in T2D rats by reducing AD-like changes and up-regulating the impaired insulin signaling pathway in the hippocampus, indicating the potential use of intranasal insulin delivery for treatment of AD.关键词
阿尔茨海默病/2型糖尿病/胰岛素/Tau蛋白过度磷酸化/胰岛素信号途径Key words
Alzheimer disease/ Type 2 diabetes/ Insulin/ Tau hyperphosphorylation/ Insulin signaling pathway分类
医药卫生引用本文复制引用
杨雁,马德琳,王玉萍,姜腾,胡蜀红,余学锋..鼻腔滴入胰岛素改善2型糖尿病大鼠海马阿尔茨海默病样改变[J].中国病理生理杂志,2013,(1):56-61,6.基金项目
国家自然科学基金青年基金资助项目(No.81100582) （No.81100582）
教育部博士点新教师基金资助项目(No.200804871047) （No.200804871047）
湖北省卫生厅一般项目(No.JX5B04) （No.JX5B04）
