Rdzak Grzegorz M, Abdelghany Osama
Pharmacy Department, Yale-New Haven Hospital, New Haven, Connecticut.
Pharmacotherapy. 2014 Dec;34(12):1317-23. doi: 10.1002/phar.1494. Epub 2014 Oct 3.
Alzheimer's disease is the most common cause of dementia in the United States. A better understanding of the disease's underlying pathways may provide novel treatment and/or prevention strategies for this progressive chronic neurodegenerative disorder. In recent years, there has been a growing interest in the possible links between insulin and Alzheimer's disease. Insulin-induced hypoglycemia causes adaptive changes in the brain, including an improved ability to use alternative fuels. Insulin has been shown to facilitate reduction of intracellular amyloid plaque and downregulation of amyloid-β-derived diffusible ligand-binding sites. Insulin also promotes tau hypophosphorylation, which stabilizes microtubules and promotes tubulin polymerization. Excess exogenous insulin may also play a role in overcoming the decreased utilization and transport of glucose in patients with Alzheimer's disease. Intranasal insulin therapy may have beneficial effects on cognition and function in patients with Alzheimer's disease, as well as having only minor adverse effects, and this route of administration been the focus in clinical trials. These data support the mechanistic pathways that might link excess exogenous insulin administered to patients with type 1 diabetes mellitus to possible protection from Alzheimer's disease and provide a rationale for using insulin to prevent the disease in high-risk patients.
阿尔茨海默病是美国痴呆症最常见的病因。更好地了解该疾病的潜在发病机制，可能为这种进行性慢性神经退行性疾病提供新的治疗和/或预防策略。近年来，人们对胰岛素与阿尔茨海默病之间可能存在的联系越来越感兴趣。胰岛素诱导的低血糖会引起大脑的适应性变化，包括使用替代燃料能力的提高。胰岛素已被证明有助于减少细胞内淀粉样斑块，并下调淀粉样β衍生的可扩散配体结合位点。胰岛素还能促进tau蛋白去磷酸化，从而稳定微管并促进微管蛋白聚合。过量的外源性胰岛素也可能在克服阿尔茨海默病患者葡萄糖利用和转运减少方面发挥作用。鼻内胰岛素治疗可能对阿尔茨海默病患者的认知和功能有有益影响，且副作用较小，这种给药途径已成为临床试验的重点。这些数据支持了可能将1型糖尿病患者过量使用外源性胰岛素与预防阿尔茨海默病联系起来的机制途径，并为在高危患者中使用胰岛素预防该疾病提供了理论依据。
