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, and Lisa Juntti-Berggren
PNAS June 28, 2011 108 (26) 10685-10689; https://doi.org/10.1073/pnas.1019553108

  1. Edited* by Solomon H. Snyder, The Johns Hopkins University School of Medicine, Baltimore, MD, and approved May 19, 2011 (received for review December 29, 2010)

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.

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: lisa.juntti-berggren{at}ki.se.

  • Author contributions: R.H., P.-O.B., and L.J.-B. designed research; R.H., E.R., and L.J.-B. performed research; R.M.C., M.G., and G.O. contributed new reagents/analytic tools; R.H., E.R., A.H., and L.J.-B. analyzed data; and P.-O.B. L.J.-B. wrote the paper.

  • Conflict of interest statement: P.-O.B. is a co-founder of Biocrine, a company that is developing apoCIII as a target for the treatment of type 1 diabetes and its complications. R.M.C. and M.G. are affiliated with ISIS, a company whose main focus is to develop antisense treatment strategies for various diseases.

  • ↵*This Direct Submission article had a prearranged editor.

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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
Proceedings of the National Academy of Sciences Jun 2011, 108 (26) 10685-10689; DOI: 10.1073/pnas.1019553108
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