Lowering apolipoprotein CIII delays onset of type 1 diabetes

Rebecka Holmberg, Essam Refai, Anders Höög, Rosanne M. Crooke, Mark Graham, Gunilla Olivecrona, Per Olof Berggren, Lisa Juntti-Berggren

Research output: Contribution to journalArticle

41 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)10685-10689
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume108
Issue number26
DOIs
StatePublished - Jun 28 2011

Keywords

  • β-cell destruction
  • BB rat model
  • Cytoplasmic free Ca concentration
  • Diabetes onset
  • Insulin release

ASJC Scopus subject areas

  • General

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    Holmberg, R., Refai, E., Höög, A., Crooke, R. M., Graham, M., Olivecrona, G., Berggren, P. O., & Juntti-Berggren, L. (2011). Lowering apolipoprotein CIII delays onset of type 1 diabetes. Proceedings of the National Academy of Sciences of the United States of America, 108(26), 10685-10689. https://doi.org/10.1073/pnas.1019553108