Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Japan.
Biochem Biophys Res Commun. 2011 May 27;409(1):34-9. doi: 10.1016/j.bbrc.2011.04.101. Epub 2011 Apr 28.
Obesity is a risk factor for Alzheimer's disease (AD), which is characterized by amyloid β depositions and cognitive dysfunction. Although insulin resistance is one of the phenotypes of obesity, its deleterious effects on AD progression remain to be fully elucidated. We previously reported that the suppression of insulin signaling in a mouse with a heterozygous mutation (P1195L) in the gene for the insulin receptor showed insulin resistance and hyperinsulinemia but did not develop diabetes mellitus [15]. Here, we generated a novel AD mouse model carrying the same insulin receptor mutation and showed that the combination of insulin resistance and hyperinsulinemia did not accelerate plaque formation or memory abnormalities in these mice. Interestingly, the insulin receptor mutation reduced oxidative damage in the brains of the AD mice. These findings suggest that insulin resistance is not always involved in the pathogenesis of AD.
肥胖是阿尔茨海默病（AD）的一个风险因素，其特征是淀粉样β沉积和认知功能障碍。尽管胰岛素抵抗是肥胖的表型之一，但它对 AD 进展的有害影响仍有待充分阐明。我们之前曾报道过，胰岛素受体基因杂合突变（P1195L）的小鼠中胰岛素信号的抑制表现出胰岛素抵抗和高胰岛素血症，但并未发展为糖尿病[15]。在这里，我们生成了一种携带相同胰岛素受体突变的新型 AD 小鼠模型，并表明胰岛素抵抗和高胰岛素血症的组合并未加速这些小鼠的斑块形成或记忆异常。有趣的是，胰岛素受体突变减轻了 AD 小鼠大脑中的氧化损伤。这些发现表明，胰岛素抵抗并不总是参与 AD 的发病机制。
