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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Mir-375 Maintains Normal Pancreatic α- And β-cell Mass
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Mir-375 Maintains Normal Pancreatic α- And β-cell Mass

机译：Mir-375维持正常的胰腺α细胞和β细胞质量

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摘要

Altered growth and development of the endocrine pancreas is a frequent cause of the hyperglycemia associated with diabetes. Here we show that microRNA-375 (miR-375), which is highly expressed in pancreatic islets, is required for normal glucose homeostasis. Mice lacking miR-375 (375KO) are hyperglycemic, exhibit increased total pancreatic α-cell numbers, fasting and fed plasma glucagon levels, and increased gluconeogenesis and hepatic glucose output. Furthermore, pancreatic β-cell mass is decreased in 375KO mice as a result of impaired proliferation. In contrast, pancreatic islets of obese mice (ob/ob), a model of increased β-cell mass, exhibit increased expression of miR-375. Genetic deletion of miR-375 from these animals (375/ob) profoundly diminished the proliferative capacity of the endocrine pancreas and resulted in a severely diabetic state. Bioinformatic analysis of transcript data from 375KO islets revealed that miR-375 regulates a cluster of genes controlling cellular growth and proliferation. These data provide evidence that miR-375 is essential for normal glucose homeostasis, α-and β-cell turnover, and adaptive β-cell expansion in response to increasing insulin demand in insulin resistance.rndiabetes; glucagon; microRNA; islet; proliferation
机译：内分泌胰腺生长和发育的改变是与糖尿病有关的高血糖症的常见原因。在这里，我们显示正常胰岛葡萄糖稳态需要在胰岛中高度表达的microRNA-375（miR-375）。缺乏miR-375（375KO）的小鼠血糖过多，表现出增加的总胰岛α细胞数量，空腹和进食血浆胰高血糖素水平，以及糖原异生和肝葡萄糖输出增加。此外，由于增殖受损，375KO小鼠的胰腺β细胞量减少。相反，肥胖小鼠（ob / ob）的胰岛（β细胞质量增加的模型）表现出miR-375的表达增加。从这些动物中遗传删除miR-375（375 / ob）大大降低了内分泌胰腺的增殖能力，并导致了严重的糖尿病状态。对来自375KO胰岛的转录数据的生物信息学分析表明，miR-375调节着控制细胞生长和增殖的基因簇。这些数据提供了证据，表明miR-375对于正常的葡萄糖稳态，α和β细胞更新，以及适应性增加的β细胞扩增（对胰岛素抵抗中胰岛素需求的增加）是必不可少的。胰高血糖素微小RNA;胰岛增殖

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    Matthew N. Poy; Jean Hausser; Mirko Trajkovski; Matthias Braun; Stephan Collins; Patrik Rorsman; Mihaela Zavoian; Markus Stoffel;

  • 作者单位

    Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland;

    Swiss Institute of Bioinformatics, Biozentrum, University of Basel, 4056 Basel, Switzerland;

    Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland;

    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, United Kingdom;

    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, United Kingdom;

    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford OX3 7LJ, United Kingdom;

    Swiss Institute of Bioinformatics, Biozentrum, University of Basel, 4056 Basel, Switzerland;

    Institute of Molecular Systems Biology, Swiss Federal Institute of Technology, ETH Zurich, CH-8093 Zurich, Switzerland;

  • 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);
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