Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.
J Cell Mol Med
; 16(6): 1206-22, 2012 Jun.
Article
em En
| MEDLINE
| ID: mdl-21762376
ABSTRACT
According to epidemiological studies, type-2 diabetes increases the risk of Alzheimer's disease. Here, we induced hyperglycaemia in mice overexpressing mutant amyloid precursor protein and presenilin-1 (APdE9) either by cross-breeding them with pancreatic insulin-like growth factor 2 (IGF-2) overexpressing mice or by feeding them with high-fat diet. Glucose and insulin tolerance tests revealed significant hyperglycaemia in mice overexpressing IGF-2, which was exacerbated by high-fat diet. However, sustained hyperinsulinaemia and insulin resistance were observed only in mice co-expressing IGF-2 and APdE9 without correlation to insulin levels in brain. In behavioural tests in aged mice, APdE9 was associated with poor spatial learning and the combination of IGF-2 and high-fat diet further impaired learning. Neither high-fat diet nor IGF-2 increased ß-amyloid burden in the brain. In male mice, IGF-2 increased ß-amyloid 42/40 ratio, which correlated with poor spatial learning. In contrast, inhibitory phosphorylation of glycogen synthase kinase 3ß, which correlated with good spatial learning, was increased in APdE9 and IGF-2 female mice on standard diet, but not on high-fat diet. Interestingly, high-fat diet altered τ isoform expression and increased phosphorylation of τ at Ser202 site in female mice regardless of genotype. These findings provide evidence for new regulatory mechanisms that link type-2 diabetes and Alzheimer pathology.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
/
Presenilina-1
/
Doença de Alzheimer
/
Dieta Hiperlipídica
Limite:
Animals
Idioma:
En
Revista:
J Cell Mol Med
Assunto da revista:
BIOLOGIA MOLECULAR
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Finlândia