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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Lowering apolipoprotein CIII delays onset of type 1 diabetes
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Lowering apolipoprotein CIII delays onset of type 1 diabetes

机译：降低载脂蛋白CIII可延缓1型糖尿病的发作

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摘要

Serum levels of apolipoprotein CHI (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.
机译：在1型糖尿病患者中，血清载脂蛋白CHI（apoCIII）的水平增加，并且当β细胞暴露于这些糖尿病血清时，发生凋亡，抗apoCIII抗体消除了这种作用。我们研究了BB大鼠，它是一种发展为类人1型糖尿病的动物模型，发现糖尿病前期大鼠血清中的apoCIII也升高。 apoCIII的这种增加促进了β细胞死亡。通过对这种载脂蛋白进行反义治疗来治疗糖尿病前期动物，可降低apoCIII的内源性水平，从而显着延迟糖尿病的发作。因此，ApoCIII可以作为致糖尿病的因子，在糖尿病前状态下用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是治疗1型糖尿病的靶标。

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    Rebecka Holmberg; Essam Refai; Anders Hoeoeg; Rosanne M. Crooke; Mark Graham; Gunilla Olivecrona; Per-Olof Berggren; Lisa Juntti-Berggren;

  • 作者单位

    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Instituted SE-171 76 Stockholm, Sweden;

    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Instituted SE-171 76 Stockholm, Sweden,Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden;

    Department of Oncology and Pathology, Karolinska Institutet and Karolinska University Hospital, SE-171 76 Stockholm, Sweden;

    Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, CA 92008;

    Antisense Drug Discovery, Isis Pharmaceuticals, Carlsbad, CA 92008;

    Department of Medical Biosciences and Physiological Chemistry, Umea University, SE-901 87 Umea, Sweden;

    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Instituted SE-171 76 Stockholm, Sweden;

    The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Instituted SE-171 76 Stockholm, Sweden;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    BB rat model; cytoplasmic free Ca~(2+) concentration; insulin release; p-cell destruction; diabetes onset;

    机译：BB大鼠模型;细胞质游离Ca〜（2+）浓度;胰岛素释放;p细胞破坏;糖尿病发作;

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