Diabetes
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Diabetes Publish Ahead of Print published online ahead of print April 24, 2007
DOI: 10.2337/db07-0171
This Article
Right arrow Full Text (PDF)
Right arrow Erratum (v56,p2650)
Right arrow All Versions of this Article:
db07-0171v1
56/7/1817    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, Z.-g.
Right arrow Articles by Sima, A. A.F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, Z.-g.
Right arrow Articles by Sima, A. A.F.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Original Research

Alzheimer-like Changes in Rat Models of Spontaneous Diabetes

Zhen-guo Li, MD, PhD1, Weixian Zhang, MD1, and Anders A.F. Sima, MD, PhD1,,2

1Departments of Pathology and
2Neurology, Wayne State University, School of Medicine, Detroit, MI

Correspondence: asima{at}med.wayne.edu

Objective:To examine if changes characteristic of Alzheimer's disease (AD) occur in two rat models with spontaneous onset of type 1 and type 2 diabetes.

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), ß-secretase, beta-amyloid (Aß), C-terminal fragment (CTF), insulin receptor (IR), insulin-like growth factor 1 receptor (IGF-1R), glycogen synthase kinase 3-beta (GSK-3ß), 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 BBZDR/Wor-rats compared to type 1 BB/Wor-rats and was associated with a 9-fold increase of dystrophic neurites. APP, ß-secretase, Aß and CTF were significantly increased in type 2 diabetic rats as was phospho-tau. The IR expression was decreased in type 1, whereas IGF-1R was decreased in both models as were Akt and GSK-3ß expression.

Interpretation:The data show that Aß and phospho-tau accumulation occurs 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 AD.


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2007 by the American Diabetes Association.