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

doi:10.1073/pnas.1019553108

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

Surgery

Research output: Contribution to journal › Article

40 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 language	English (US)
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	https://doi.org/10.1073/pnas.1019553108
State	Published - Jun 28 2011

Fingerprint

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., 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

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

@article{38f69fc9b5214318876c3c3208525438,

title = "Lowering apolipoprotein CIII delays onset of type 1 diabetes",

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.",

keywords = "β-cell destruction, BB rat model, Cytoplasmic free Ca concentration, Diabetes onset, Insulin release",

author = "Rebecka Holmberg and Essam Refai and Anders H{\"o}{\"o}g and Crooke, {Rosanne M.} and Mark Graham and Gunilla Olivecrona and Berggren, {Per Olof} and Lisa Juntti-Berggren",

year = "2011",

month = jun

day = "28",

doi = "10.1073/pnas.1019553108",

language = "English (US)",

volume = "108",

pages = "10685--10689",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "26",

}

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

UR - http://www.scopus.com/inward/record.url?scp=79960602485&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960602485&partnerID=8YFLogxK

U2 - 10.1073/pnas.1019553108

DO - 10.1073/pnas.1019553108

M3 - Article

C2 - 21670290

AN - SCOPUS:79960602485

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 -

Access to Document

10.1073/pnas.1019553108