title: Insulin receptor mutation results in insulin resistance and hyperinsulinemia but does not exacerbate Alzheimer's-like phenotypes in mice.
abstract: 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.
authors.affiliation: Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Murakami
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Nakaba
authors.initials: N
authors.lastname: Murata
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ozawa
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Irie
authors.forename: Takuji
authors.initials: T
authors.lastname: Shirasawa
authors.forename: Takahiko
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000544:Alzheimer Disease / Q000150:complications / Q000235:genetics / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D006946:Hyperinsulinism / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D008569:Memory Disorders / Q000209:etiology / Q000235:genetics / Q000473:pathology; D051379:Mice; D011972:Receptor, Insulin / Q000235:genetics*
chemical_list: D011972:Receptor, Insulin