Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 108, Issue 26, Pages 10685-10689Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1019553108
Keywords
BB rat model; cytoplasmic free Ca2+ concentration; insulin release; beta-cell destruction; diabetes onset
Categories
Funding
- Barndiabetesfonden
- Swedish Diabetes Association
- Karolinska Institutet
- Swedish Research Council
- Swedish Society for Medical Research
- Novo Nordisk Foundation
- Erling-Persson Family Foundation
- Knut and Alice Wallenberg Foundation
- Skandia Insurance Company, Ltd.
- TONECA
- Eurodia [FP6-518153]
- VIBRANT [FP7-228933-2]
- Juvenile Diabetes Research Foundation International
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Serum levels of apolipoprotein CIII (apoCIII) are increased in type 1 diabetic patients, and when beta cells are exposed to these diabetic sera, apoptosis occurs, an effect abolished by an antibody against apoCIII. We have investigated the BB rat, an animal model that develops a human-like type 1 diabetes, and found that apoCIII was also increased in sera from prediabetic rats. This increase in apoCIII promoted beta-cell death. The endogenous levels of apoCIII were reduced by treating prediabetic animals with an antisense against this apolipoprotein, resulting in a significantly delayed onset of diabetes. ApoCIII thus serves as a diabetogenic factor, and intervention with this apolipoprotein in the prediabetic state can arrest disease progression. These findings suggest apoCIII as a target for the treatment of type 1 diabetes.
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