Lowering apolipoprotein CIII delays onset of type 1 diabetes
- 13 June 2011
- journal article
- research article
- Published by National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 108 (26) , 10685-10689
Abstract
Serum levels of apolipoprotein CIII (apoCIII) are increased in type 1 diabetic patients, and when β 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 β-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.Keywords
This publication has 19 references indexed in Scilit:
- Blood Glucose Levels Regulate Pancreatic β-Cell Proliferation during Experimentally-Induced and Spontaneous Autoimmune Diabetes in MicePLOS ONE, 2009
- A Null Mutation in Human APOC3 Confers a Favorable Plasma Lipid Profile and Apparent CardioprotectionScience, 2008
- Type 1 Diabetic Serum Interferes with Pancreatic β-cell Ca2+ -HandlingBioscience Reports, 2007
- Autoimmunity and β Cell Regeneration in Mouse and Human Type 1 DiabetesAnnals of the New York Academy of Sciences, 2007
- Effects of Autoimmunity and Immune Therapy on β-Cell Turnover in Type 1 DiabetesDiabetes, 2006
- Lipoprotein Genotype and Conserved Pathway for Exceptional Longevity in HumansPLOS Biology, 2006
- Protein kinase C activity affects glucose‐induced oscillations in cytoplasmic free Ca2+ in the pancreatic B‐cellFEBS Letters, 1992
- The BB ratDiabetes/Metabolism Research and Reviews, 1987
- Rapid colorimetric assay for cellular growth and survival: Application to proliferation and cytotoxicity assaysJournal of Immunological Methods, 1983
- The preparation of, and studies on, free cell suspensions from mouse pancreatic isletsDiabetologia, 1974