Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Diabetes. 2007 Jul;56(7):1817-24. Epub 2007 Apr 24.

Alzheimer-like changes in rat models of spontaneous diabetes.

Author information

  • 1Department of Pathology, Wayne State University, School of Medicine, 540 E. Canfield Ave., Detroit, MI 48201, USA.

Erratum in

  • Diabetes. 2007 Oct;56(10):2650.

Abstract

OBJECTIVE:

To examine whether changes characteristic of Alzheimer's disease occur in two rat models with spontaneous onset of type 1 and type 2 diabetes.

RESEARCH DESIGN AND METHODS:

The frontal cortices of 8-month-diabetic rats were examined with respect to neuronal densities, neurite degeneration, expression, and/or immunolocalization of amyloid precursor protein (APP), beta-secretase, beta-amyloid, COOH-terminal fragment (CTF), insulin receptor, IGF-1 receptor, glycogen synthase kinase 3-beta (GSK-3beta), protein kinase B (Akt), phosphorylated tau (phospho-tau), synaptophysin, and phosphorylated neurofilaments (SMI-31).

RESULTS:

Neuronal loss occurred in both models, significantly more so in type 2 diabetic BBZDR/Wor rats compared with type 1 diabetic BB/Wor rats and was associated with a ninefold increase of dystrophic neurites. APP, beta-secretase, beta-amyloid, and CTF were significantly increased in type 2 diabetic rats, as was phospho-tau. The insulin receptor expression was decreased in type 1 diabetes, whereas IGF-1 receptor was decreased in both models, as were Akt and GSK-3beta expression.

CONCLUSIONS:

The data show that beta-amyloid and phospho-tau accumulation occur in experimental diabetes and that this is associated with neurite degeneration and neuronal loss. The changes were more severe in the type 2 diabetic model and appear to be associated with insulin resistance and possibly hypercholesterolemia. The two models will provide useful tools to unravel further mechanistic associations between diabetes and Alzheimer's disease.

PMID:
17456849
[PubMed - indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Icon for HighWire
    Loading ...
    Write to the Help Desk