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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities
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Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

机译:果蝇胰岛素样肽的缺失导致生长缺陷和代谢异常

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摘要

Insulin/Insulin-like growth factor signaling regulates homeostasis and growth in mammals, and is implicated in diseases from diabetes to cancer. In Drosophila melanogaster, as in other invertebrates, multiple Insulin-Like Peptides (DILPs) are encoded by a family of related genes. To assess DILPs' physiological roles, we generated small deficiencies that uncover single or multiple dilps, generating genetic loss-of-function mutations. Deletion of dilps 1-5 generated homozygotes that are small, severely growth-delayed, and poorly viable and fertile. These animals display reduced metabolic activity, decreased triglyceride levels and prematurely activate autophagy, indicative of "starvation in the midst of plenty," a hallmark of Type I diabetes. Furthermore, circulating sugar levels are elevated in Df [dilp1-5] homozygotes during eating and fasting. In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies.
机译:胰岛素/类胰岛素生长因子信号传导调节哺乳动物体内的稳态和生长,并涉及从糖尿病到癌症的疾病。与其他无脊椎动物一样,在果蝇中,多个类似胰岛素的肽(DILP)由一系列相关基因编码。为了评估DILP的生理作用,我们产生了一些缺陷,这些缺陷可以揭示单个或多个Dilp,从而产生遗传功能丧失突变。谷粒1-5的缺失产生了纯合子,它们是小的,严重的生长延迟,以及较差的生存能力和繁殖力。这些动物表现出降低的代谢活性,降低的甘油三酸酯水平并过早激活自噬,这表明“大量食物中的饥饿”是I型糖尿病的标志。此外,进食和禁食期间Df [dilp1-5]纯合子的循环糖水平升高。相反,Df [dilp6]或Df [dilp7]动物没有显示出主要的代谢缺陷。我们讨论了哺乳动物和昆虫之间的生理差异,这可能解释了瘦弱的“糖尿病”蝇的意外存活。

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