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

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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
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
Externally publishedYes

Fingerprint

Apolipoprotein C-III
Type 1 Diabetes Mellitus
Apolipoproteins
Serum
Inbred BB Rats
Prediabetic State
Disease Progression
Cell Death
Animal Models
Apoptosis
Antibodies

Keywords

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

ASJC Scopus subject areas

  • General

Cite this

Holmberg, R., Refai, E., Höög, A., Crooke, R. M., Graham, M., Olivecrona, G., ... 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

Lowering apolipoprotein CIII delays onset of type 1 diabetes. / Holmberg, Rebecka; Refai, Essam; Höög, Anders; Crooke, Rosanne M.; Graham, Mark; Olivecrona, Gunilla; Berggren, Per Olof; Juntti-Berggren, Lisa.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 108, No. 26, 28.06.2011, p. 10685-10689.

Research output: Contribution to journalArticle

Holmberg, R, Refai, E, Höög, A, Crooke, RM, Graham, M, Olivecrona, G, Berggren, PO & 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, vol. 108, no. 26, pp. 10685-10689. https://doi.org/10.1073/pnas.1019553108
Holmberg, Rebecka ; Refai, Essam ; Höög, Anders ; Crooke, Rosanne M. ; Graham, Mark ; Olivecrona, Gunilla ; Berggren, Per Olof ; Juntti-Berggren, Lisa. / Lowering apolipoprotein CIII delays onset of type 1 diabetes. In: Proceedings of the National Academy of Sciences of the United States of America. 2011 ; Vol. 108, No. 26. pp. 10685-10689.
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