Department of Zoology, Stockholm University, Stockholm, Sweden.
PLoS One. 2011 May 10;6(5):e19866. doi: 10.1371/journal.pone.0019866.
The insulin-signaling pathway is evolutionarily conserved in animals and regulates growth, reproduction, metabolic homeostasis, stress resistance and life span. In Drosophila seven insulin-like peptides (DILP1-7) are known, some of which are produced in the brain, others in fat body or intestine. Here we show that DILP5 is expressed in principal cells of the renal tubules of Drosophila and affects survival at stress. Renal (Malpighian) tubules regulate water and ion homeostasis, but also play roles in immune responses and oxidative stress. We investigated the control of DILP5 signaling in the renal tubules by Drosophila tachykinin peptide (DTK) and its receptor DTKR during desiccative, nutritional and oxidative stress. The DILP5 levels in principal cells of the tubules are affected by stress and manipulations of DTKR expression in the same cells. Targeted knockdown of DTKR, DILP5 and the insulin receptor dInR in principal cells or mutation of Dilp5 resulted in increased survival at either stress, whereas over-expression of these components produced the opposite phenotype. Thus, stress seems to induce hormonal release of DTK that acts on the renal tubules to regulate DILP5 signaling. Manipulations of S6 kinase and superoxide dismutase (SOD2) in principal cells also affect survival at stress, suggesting that DILP5 acts locally on tubules, possibly in oxidative stress regulation. Our findings are the first to demonstrate DILP signaling originating in the renal tubules and that this signaling is under control of stress-induced release of peptide hormone.
胰岛素信号通路在动物中是进化保守的，调节生长、繁殖、代谢稳态、应激抗性和寿命。在果蝇中，已知有七种胰岛素样肽（DILP1-7），其中一些在大脑中产生，另一些在脂肪体或肠道中产生。在这里，我们表明 DILP5 在果蝇的肾小管主细胞中表达，并影响应激时的存活。肾脏（马氏管）小管调节水和离子稳态，但也在免疫反应和氧化应激中发挥作用。我们研究了在干燥、营养和氧化应激期间，果蝇速激肽肽（DTK）及其受体 DTKR 对 DILP5 信号在肾小管中的控制。管主细胞中 DILP5 的水平受应激和同一细胞中 DTKR 表达的操纵影响。靶向敲低主细胞中的 DTKR、DILP5 和胰岛素受体 dInR 或突变 Dilp5 导致在任一种应激下的存活率增加，而这些成分的过表达则产生相反的表型。因此，应激似乎诱导 DTK 的激素释放，作用于肾小管以调节 DILP5 信号。主细胞中 S6 激酶和超氧化物歧化酶（SOD2）的操纵也影响应激时的存活，表明 DILP5 可能在局部作用于肾小管，可能在氧化应激调节中发挥作用。我们的发现首次证明了 DILP 信号源自肾小管，并且这种信号受应激诱导的肽激素释放的控制。
