Lowering apolipoprotein CIII delays onset of type 1 diabetes

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 diabe...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2011-06, Vol.108 (26), p.10685-10689
Main Authors: Holmberg, Rebecka, Refai, Essam, Höög, Anders, Crooke, Rosanne M, Graham, Mark, Olivecrona, Gunilla, Berggren, Per-Olof, Juntti-Berggren, Lisa
Format: Article
Language:English
Subjects:
Age of Onset
Animal models
Animals
Antibodies
Apolipoprotein C-III - blood
Apoptosis
Base Sequence
Biological Sciences
blood serum
Culture Media
death
Diabetes
Diabetes complications
Diabetes Mellitus, Type 1 - blood
disease course
Disease models
Disease Models, Animal
DNA Primers
Immunohistochemistry
Insulin
Insulin - metabolism
Insulin Secretion
insulin-dependent diabetes mellitus
Islet cells
islets of Langerhans
Islets of Langerhans - cytology
Islets of Langerhans - metabolism
Medical treatment
Medicin och hälsovetenskap
patients
Prediabetic state
Rats
Rats, Inbred BB
Rodents
Type 1 diabetes mellitus
Viability
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Summary: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.
ISSN:0027-8424
1091-6490
1091-6490
DOI:10.1073/pnas.1019553108