Lowering apolipoprotein CIII delays onset of type 1 diabetes
Lowering apolipoprotein CIII delays onset of type 1 diabetes
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DOI：
10.1073/pnas.1019553108
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发表时间：
2011-06-28
影响因子：
11.1
通讯作者：
Juntti-Berggren, Lisa
中科院分区：
文献类型：
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作者：
Holmberg, Rebecka;Refai, Essam;Juntti-Berggren, Lisa
载脂蛋白CIII（apoCIII）的血清水平在1型糖尿病患者中增加，并且当β细胞暴露于这些糖尿病血清时，发生细胞凋亡，抗apoCIII的抗体消除了这种作用。我们研究了BB大鼠（一种患上类似人类1型糖尿病的动物模型），发现糖尿病前期大鼠血清中的apoCIII也增加。apoCIII的这种增加促进了β细胞死亡。内源性水平的apoCIII降低治疗糖尿病前期动物与反义对这种载脂蛋白，导致糖尿病的发病显着延迟。因此，ApoCIII作为一种致糖尿病因子，在糖尿病前期状态下使用这种载脂蛋白进行干预可以阻止疾病进展。这些发现表明apoCIII是治疗1型糖尿病的靶点。
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.