Lee Kyu-Sun, Kwon O-Yu, Lee Joon H, Kwon Kisang, Min Kyung-Jin, Jung Sun-Ah, Kim Ae-Kyeong, You Kwan-Hee, Tatar Marc, Yu Kweon
Centre for Regenerative Medicine, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-333, Korea.
Nat Cell Biol. 2008 Apr;10(4):468-75. doi: 10.1038/ncb1710. Epub 2008 Mar 16.
Insulin and insulin growth factor have central roles in growth, metabolism and ageing of animals, including Drosophila melanogaster. In Drosophila, insulin-like peptides (Dilps) are produced by specialized neurons in the brain. Here we show that Drosophila short neuropeptide F (sNPF), an orthologue of mammalian neuropeptide Y (NPY), and sNPF receptor sNPFR1 regulate expression of Dilps. Body size was increased by overexpression of sNPF or sNPFR1. The fat body of sNPF mutant Drosophila had downregulated Akt, nuclear localized FOXO, upregulated translational inhibitor 4E-BP and reduced cell size. Circulating levels of glucose were elevated and lifespan was also extended in sNPF mutants. We show that these effects are mediated through activation of extracellular signal-related kinases (ERK) in insulin-producing cells of larvae and adults. Insulin expression was also increased in an ERK-dependent manner in cultured Drosophila central nervous system (CNS) cells and in rat pancreatic cells treated with sNPF or NPY peptide, respectively. Drosophila sNPF and the evolutionarily conserved mammalian NPY seem to regulate ERK-mediated insulin expression and thus to systemically modulate growth, metabolism and lifespan.
胰岛素和胰岛素样生长因子在包括黑腹果蝇在内的动物生长、代谢及衰老过程中发挥着核心作用。在果蝇中，胰岛素样肽（Dilps）由大脑中的特定神经元产生。在此我们表明，果蝇短神经肽F（sNPF），即哺乳动物神经肽Y（NPY）的同源物，以及sNPF受体sNPFR1可调节Dilps的表达。过表达sNPF或sNPFR1可使体型增大。sNPF突变果蝇的脂肪体中Akt表达下调，FOXO定位于细胞核，翻译抑制剂4E - BP表达上调，细胞大小减小。sNPF突变体中循环葡萄糖水平升高，寿命也延长。我们表明，这些效应是通过激活幼虫和成虫胰岛素产生细胞中的细胞外信号相关激酶（ERK）介导的。在培养的果蝇中枢神经系统（CNS）细胞以及分别用sNPF或NPY肽处理的大鼠胰腺细胞中，胰岛素表达也以ERK依赖的方式增加。果蝇sNPF和进化上保守的哺乳动物NPY似乎调节ERK介导的胰岛素表达，从而系统性地调节生长、代谢和寿命。
