降低载脂蛋白 CIII 可延迟 1 型糖尿病的发病。
Lowering apolipoprotein CIII delays onset of type 1 diabetes.
机构信息
The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, SE-171 76 Stockholm, Sweden.
出版信息
Proc Natl Acad Sci U S A. 2011 Jun 28;108(26):10685-9. doi: 10.1073/pnas.1019553108. Epub 2011 Jun 13.
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.
摘要
血清载脂蛋白 CIII (apoCIII) 水平在 1 型糖尿病患者中升高，当β细胞暴露于这些糖尿病血清中时，会发生细胞凋亡，而针对 apoCIII 的抗体可消除这种作用。我们研究了 BB 大鼠，这是一种会发展出类似人类 1 型糖尿病的动物模型，并且发现糖尿病前期大鼠的血清中 apoCIII 也增加了。这种 apoCIII 的增加促进了β细胞的死亡。通过用针对这种载脂蛋白的反义寡核苷酸来治疗糖尿病前期动物，可以降低内源性 apoCIII 的水平，从而显著延迟糖尿病的发生。因此，apoCIII 是一种促糖尿病因素，在糖尿病前期对这种载脂蛋白进行干预可以阻止疾病的进展。这些发现表明 apoCIII 是 1 型糖尿病治疗的一个靶点。
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