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 language | English |
|---|---|
| Pages (from-to) | 10685-10689 |
| Number of pages | 5 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Volume | 108 |
| Issue number | 26 |
| DOIs | |
| State | Published - Jun 28 2011 |
| Externally published | Yes |
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Keywords
- β-cell destruction
- BB rat model
- Cytoplasmic free Ca concentration
- Diabetes onset
- Insulin release
ASJC Scopus subject areas
- General
Cite this
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 journal › Article
}
TY - JOUR
T1 - Lowering apolipoprotein CIII delays onset of type 1 diabetes
AU - Holmberg, Rebecka
AU - Refai, Essam
AU - Höög, Anders
AU - Crooke, Rosanne M.
AU - Graham, Mark
AU - Olivecrona, Gunilla
AU - Berggren, Per Olof
AU - Juntti-Berggren, Lisa
PY - 2011/6/28
Y1 - 2011/6/28
N2 - 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.
AB - 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.
KW - β-cell destruction
KW - BB rat model
KW - Cytoplasmic free Ca concentration
KW - Diabetes onset
KW - Insulin release
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U2 - 10.1073/pnas.1019553108
DO - 10.1073/pnas.1019553108
M3 - Article
VL - 108
SP - 10685
EP - 10689
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
SN - 0027-8424
IS - 26
ER -