...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Making insulin-deficient type 1 diabetic rodents thrive without insulin
【24h】

Making insulin-deficient type 1 diabetic rodents thrive without insulin

机译：使胰岛素缺乏型1型糖尿病啮齿动物在没有胰岛素的情况下壮成长

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Terminally ill insulin-deficient rodents with uncontrolled diabetes due to autoimmune or chemical destruction of β-cells were made hyper-leptinemic by adenoviral transfer of the leptin gene. Within 10 days their severe hyperglycemia and ketosis were corrected. Despite the lack of insulin, moribund animals resumed linear growth and appeared normal. Normoglycemia persisted 10-80 days without other treatment; normal physiological conditions lasted for ≈175 days despite reappearance of moderate hyperglycemia. Inhibition of glu-coneogenesis by suppression of hyperglucagonemia and reduction of hepatic cAMP response element-binding protein, phoshoenolpyru-vate carboxykinase, and peroxisome proliferator-activated receptor-γ-coactivator-1α may explain the anticatabolic effect. Up-regulation of insulin-like growth factor 1 (IGF-1) expression and plasma levels and increasing IGF-1 receptor phosphorylation in muscle may explain the increased insulin receptor substrate 1, PI3K, and ERK phosphorylation in skeletal muscle. These findings suggest that leptin reverses the catabolic consequences of total lack of insulin, potentially by suppressing glucagon action on liver and enhancing the insulinomi-metic actions of IGF-1 on skeletal muscle, and suggest strategies for making type 1 diabetes insulin-independent.
机译：通过瘦素基因的腺病毒转移，使由于自身免疫或β细胞化学破坏而无法控制的糖尿病的绝症胰岛素缺乏型啮齿动物变得高脂血症。在10天内纠正了他们的严重高血糖症和酮症。尽管缺乏胰岛素，垂死的动物仍恢复了线性生长并看起来正常。未经其他治疗，血糖正常持续10-80天。尽管再次出现中度高血糖，正常的生理状况仍持续约175天。通过抑制高血糖症和减少肝cAMP反应元件结合蛋白，磷酸烯醇式丙酮酸羧化激酶和过氧化物酶体增殖物激活的受体-γ-coactivator-1α来抑制glu-coneogenesis可能解释了抗催化作用。胰岛素样生长因子1（IGF-1）表达和血浆水平的上调以及肌肉中IGF-1受体磷酸化的增加可能解释了骨骼肌中胰岛素受体底物1，PI3K和ERK磷酸化的增加。这些发现表明，瘦素可能通过抑制胰高血糖素对肝脏的作用并增强IGF-1对骨骼肌的类似胰岛素的作用来逆转完全缺乏胰岛素的分解代谢的后果，并提出了使1型糖尿病不依赖胰岛素​​的策略。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号