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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene
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Reversal of preexisting hyperglycemia in diabetic mice by acute deletion of the Men1 gene

机译：通过急性删除Men1基因来逆转糖尿病小鼠中先前存在的高血糖

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摘要

A hallmark of diabetes is an absolute or relative reduction in the number of functional β cells. Therapies that could increase the number of endogenous p cells under diabetic conditions would be desirable. Prevalent gene targeting mouse models for assessing β-cell proliferation and diabetes pathogenesis only address whether deletion of a gene prevents the development of diabetes. Models testing whether acute excision of a single gene can ameliorate or reverse preexisting hyperglycemia in established diabetes remain to be explored, which could directly validate the effect of gene excision on treating diabetes. Here, we report that acute and temporally controlled excision of the Men 1 gene, which encodes menin, ameliorated preexisting hyperglycemia in streptozotocin-treated mice. Moreover, Men1 excision also improved the preexisting hyperglycemia and glucose intolerance in genetic db/db diabetic mice. Furthermore, acute Men1 excision reversed preexisting glucose intolerance in high-fat diet-fed mice. Men1 excision improved glucose metabolism at least partly through increasing proliferation of endogenous p cells and islet size. Acute Men 1 excision up-regulated a group of proproliferative genes in pancreatic islets. Together, these findings demonstrate that established hyperglycemia can be reversed through repression of a single gene, Men1, in diabetic conditions, and suggest that menin is a vital regulator in pathogenesis of diabetes.
机译：糖尿病的标志是功能性β细胞数量的绝对或相对减少。可能需要在糖尿病条件下增加内源性p细胞数量的疗法。用于评估β细胞增殖和糖尿病发病机理的流行的基因靶向小鼠模型只能解决基因缺失是否会阻止糖尿病的发展。测试单个基因的急性切除是否可以缓解或逆转已建立的糖尿病中高血糖的模型仍有待探索，这可以直接验证基因切除对糖尿病的治疗作用。在这里，我们报告说Men1基因的急性和时间控制切除，该基因编码menin，改善了链脲佐菌素治疗的小鼠中先前存在的高血糖。此外，Men1切除还改善了遗传性db / db糖尿病小鼠中先前存在的高血糖和葡萄糖耐受不良。此外，急性Men1切除逆转了高脂饮食喂养小鼠中先前存在的葡萄糖不耐症。 Men1切除术至少部分地通过增加内源性p细胞的增殖和胰岛大小来改善葡萄糖代谢。急性男子1切除术上调了胰岛中的一组增生性基因。总之，这些发现表明，在糖尿病患者中，可以通过抑制单个基因Men1逆转既定的高血糖症，并表明Menin是糖尿病发病机理中的重要调节剂。

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  • 作者

    Yuqing Yang; Buddha Gurung; Ting Wu; Haoren Wang; Doris A. Staffers; Xianxin Hua;

  • 作者单位

    Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center;

    Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center;

    Department of Basic Medical Sciences, Medical College, Xiamen University,Xiamen 361005, China;

    Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center;

    Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104,lnstitute for Diabetes,Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104;

    Abramson Family Cancer Research Institute, Department of Cancer Biology, Abramson Cancer Center,lnstitute for Diabetes,Obesity, and Metabolism, University of Pennsylvania, Philadelphia, PA 19104;

  • 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
  • 中图分类
  • 关键词

    cell proliferation; dbldb; high-fat diet; type 2 diabetes;

    机译：细胞增殖;dbldb;高脂饮食2型糖尿病;

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