皮下胰岛素注射减轻2型糖尿病大鼠大脑AD样改变.docVIP

  皮下胰岛素注射减轻 2 型糖尿病大鼠大脑 AD 样改变# 杨雁，马德琳，胡蜀红，余学锋** 5 10 15 20 （华中科技大学同济医学院附属同济医院内分泌科 武汉 430030） 摘要：目的：大脑胰岛素不仅可调节血糖，而且可改善记忆和认知。大脑胰岛素缺乏常导致 Alzheimer 病（Alzheimer’s disease, AD）的发生。以胰岛素抵抗及高胰岛素血症为特征的 2 型糖尿病（type 2 diabetes, T2D）常伴有 AD 的发生，但机制不明。本研究选取 2 型糖尿病 大鼠，检测大脑胰岛素水平，探讨大脑胰岛素异常导致 AD 发病的可能性。 方法：高糖、高脂、高蛋白饮食三月后链脲佐菌素 STZ 腹腔注射建 T2D 大鼠模型（T2D）。 皮下注射胰岛素 2 周干预（T2D+SI）。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，免疫印记技术及免疫组化技术检测大脑海马总 tau 蛋白、tau 蛋白上部分位 点磷酸化状态及糖原合成激酶 3β（Glycogen syntheses kinase 3β, GSK-3β）。 结果：T2D 大鼠血浆葡萄糖水平及胰岛素水平显著升高，胰岛素抵抗程度显著高于对照组， 脑脊液胰岛素水平显著降低，大脑 tau 蛋白呈过度磷酸化状态。运用皮下胰岛素注射 2 周后， 外周血糖水平下降，胰岛素抵抗程度减轻，但 T2D 大鼠大脑胰岛素水平无显著改变，大脑 tau 蛋白过度磷酸化状态得到逆转。大脑 GSK-3β在 T2D 组中活性显著上升，但运用胰岛素后 其活性无显著改变。 结论：2 型糖尿病大鼠大脑外周胰岛素抵抗导致的大脑胰岛素缺乏这可能是导致 AD 发病的 重要风险因素。运用外周注射胰岛素可通过降低外周胰岛素抵抗及降低血糖改善 T2D 时 AD 的发病风险，而对大脑胰岛素缺乏状态无影响。 关键词：内科学；糖尿病；阿尔茨海默病；tau 蛋白；胰岛素 中图分类号：R587.1 25 Insulin subcutaneous injection ameliorates tau hyperphosphorylation in brain of type 2 diabetic rat YANG Yan, MA Deling, HU Shuhong, YU Xuefeng (Department of Endocrinology, Tongji Hospital, Tongji Medical College,Huazhong University of 30 35 40 45 Science and Technology, Wuhan, 430030) Abstract: Aims: Brain insulin could regulate brain glucose metabolism, and accelerate the memory and cognition.The lack of brain insulin is one of the mechanisms of Alzheimers disease (AD), the most common form of dementia.It has been proved that type 2 diabetes (T2D), the characteristics of which is insulin resistance/hyperinsulinmia, has been proved that it has the potiential to increase the risk of AD. However, the underlying mechanism is obscured. Methods: We evaluted the effects of abnormal brain insulin on pathophysiological changes in the brain with streptozocin (STZ) induced T2D rat model with a high protein, high glucose and high fat diet. and then insulin subcutaneous injected for 2 weeks (T2D+SI). Plasma insulin level was measured by RIA method, as well as plasma glucose was measured by glucose-oxidase method. Total tau level, the phosphorylation leve