Unknown

Dataset Information

0

Contribution of genetic and dietary insulin resistance to Alzheimer phenotype in APP/PS1 transgenic mice.


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 ?-amyloid burden in the brain. In male mice, IGF-2 increased ?-amyloid 42/40 ratio, which correlated with poor spatial learning. In contrast, inhibitory phosphorylation of glycogen synthase kinase 3?, 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 ? isoform expression and increased phosphorylation of ? 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.

SUBMITTER: Hiltunen M 

PROVIDER: S-EPMC3823075 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications


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. Howeve  ...[more]

Similar Datasets

| S-EPMC6421685 | biostudies-literature
| S-EPMC7719723 | biostudies-literature
| S-EPMC4128532 | biostudies-literature
| S-EPMC5996202 | biostudies-literature
| S-EPMC5376028 | biostudies-literature
| S-EPMC7471266 | biostudies-literature
| S-EPMC4791593 | biostudies-literature
2022-06-16 | PXD034613 |
2019-10-04 | GSE138382 | GEO
| S-EPMC6682662 | biostudies-literature