Lowering apolipoprotein CIII delays onset of type 1 diabetes

被引：54

作者：

Holmberg, Rebecka ^{[1
]}

Refai, Essam ^{[1
,2
]}

Hoog, Anders ^{[3
,4
]}

Crooke, Rosanne M. ^{[5
]}

Graham, Mark ^{[5
]}

Olivecrona, Gunilla ^{[6
]}

Berggren, Per-Olof ^{[1
]}

Juntti-Berggren, Lisa ^{[1
]}

机构：

[1] Karolinska Inst, Rolf Luft Res Ctr Diabet & Endocrinol, SE-17176 Stockholm, Sweden

[2] Karolinska Inst, Dept Med Biochem & Biophys, SE-17177 Stockholm, Sweden

[3] Karolinska Inst, Dept Pathol & Oncol, SE-17176 Stockholm, Sweden

[4] Karolinska Univ Hosp, SE-17176 Stockholm, Sweden

[5] ISIS Pharmaceut, Antisense Drug Discovery, Carlsbad, CA 92008 USA

[6] Umea Univ, Dept Med Biosci & Physiol Chem, SE-90187 Umea, Sweden

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2011年 / 108卷 / 26期

基金：

瑞典研究理事会;

关键词：

BB rat model; cytoplasmic free Ca2+ concentration; insulin release; beta-cell destruction; diabetes onset; INSULIN RELEASE; CELL; RAT; PROLIFERATION; AUTOIMMUNITY; MOUSE; SERUM; CA2+;

D O I：

10.1073/pnas.1019553108

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

Serum levels of apolipoprotein CIII (apoCIII) are increased in type 1 diabetic patients, and when beta 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 beta-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.

引用

页码：10685 / 10689

页数：5

共 19 条

[1]

Autoimmunity and β cell regeneration in mouse and human type 1 diabetes -: The peace is not enough [J].