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 › peer-review

43 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

Keywords

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

ASJC Scopus subject areas

General

Access to Document

10.1073/pnas.1019553108

Fingerprint Dive into the research topics of 'Lowering apolipoprotein CIII delays onset of type 1 diabetes'. Together they form a unique fingerprint.

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 › peer-review

@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",

publisher = "National Academy of Sciences",

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 -