Abstract | AIMS/HYPOTHESIS: METHODS: Transgenic mice expressing the human form of IAPP ( hIAPP (+/0)) were crossbred with apoE deficient ( apoE (-/-)) mice and followed for 12 months, at which time the prevalence and severity of islet amyloid, as well as plasma glucose, hIAPP, immunoreactive insulin (IRI) and lipid concentrations were measured. RESULTS: The prevalence and severity of islet amyloid after one year of follow up were comparable among hIAPP (+/0) mice that were apoE (+/+), apoE (+/-) or apoE (-/-). Differences in glucose tolerance, lipid abnormalities or changes in pancreatic content or plasma concentrations of hIAPP and/or IRI did not account for these findings. CONCLUSION/INTERPRETATION: Our data shows that, unlike in the localized amyloidosis in the brain characteristic of Alzheimer's disease, apoE is not critical for islet amyloid formation in a transgenic mouse model of Type 2 diabetes mellitus. These results indicate that the mechanisms of localised amyloid formation probably vary among different amyloid-associated disorders. Therefore, therapeutic strategies targeting apoE might not apply equally to patients with different amyloid associated diseases.
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Authors | J Vidal, C Bruce Verchere, S Andrikopoulos, F Wang, R L Hull, M Cnop, K L Olin, R C LeBoeuf, K D O'Brien, A Chait, S E Kahn |
Journal | Diabetologia
(Diabetologia)
Vol. 46
Issue 1
Pg. 71-9
(Jan 2003)
ISSN: 0012-186X [Print] Germany |
PMID | 12637985
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Amyloid
- Apolipoproteins E
- Islet Amyloid Polypeptide
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Topics |
- Amyloid
(genetics, metabolism)
- Animals
- Apolipoproteins E
(deficiency, genetics)
- Chimera
- Genotype
- Glucose Intolerance
- Humans
- Islet Amyloid Polypeptide
- Islets of Langerhans
(metabolism)
- Lipid Metabolism
- Mice
- Mice, Inbred Strains
- Mice, Knockout
(genetics)
- Mice, Transgenic
(genetics)
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