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Insulin receptor mutation results in insulin resistance and hyperinsulinemia but does not exacerbate Alzheimer’s-like phenotypes in mice

2011; Elsevier BV; Volume: 409; Issue: 1 Linguagem: Inglês

10.1016/j.bbrc.2011.04.101

1090-2104

Kazuma Murakami, Shinichi Yokoyama, Nakaba Murata, Yusuke Ozawa, Kazuhiro Irie, Takuji Shirasawa, Takahiko Shimizu,

Biochemical effects in animals

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.