果蝇胰岛素样肽8(Dilp8)的功能及作用机制

果蝇Drosophila作为一种模式生物，具有生长周期短、繁殖能力强和研究成本低等优点。而且果蝇有65%的基因与人类同源，特别是其遗传背景简单的特点，使其在生物生长发育研究、病理机制研究和基因表达调控等研究中发挥重要作用。目前在果蝇中已发现8种胰岛素样肽，即果蝇胰岛素样肽1-8(Drosophila insulin-like peptide 1-8, Dilp1-8),而对于果蝇胰岛素信号通路的研究主要集中在其调控机体生长发育和能量代谢的方面，这些功能主要通过Dilp1-7来发挥作用。对于Dilp8的功能及其发挥作用的分子机制知之甚少。本文总结了自Dilp8被发现以来，人们对于其功能的研究结果。Dilp8主要在幼虫成虫盘和成年雌果蝇的卵巢中表达，其主要作用是调节果蝇的组织生长和发育时间，使果蝇生长为具有相对固定体型和一定对称性的个体。当果蝇幼虫在生长过程中受到损伤时，Dilp8会通过延缓发育时间来缓解异常生长。Dilp8被激活后，在中枢神经系统与其受体富含亮氨酸重复序列的G蛋白偶联受体3(leucine-rich repeat-containing G protein-coupled ...

Function and mechanism of action ofDrosophilainsulin-like peptide 8 (Dilp8)

As a model organism, Drosophila has the advantages of short growth cycle, high reproductive capacity, and low research cost. Moreover, 65% of genes in Drosophila are homologous with those in human, especially the simple genetic background of Drosophila makes Drosophila play an important role in the study of biological growth and development, pathological mechanism and gene expression regulation. So far, eight insulins, Drosophila insulin-like peptides 1-8 (Dilp1-8), have been identified in Drosophila, and studies of the Drosophila insulin signaling pathway have focused on its regulation of growth and development and energy metabolism, which is mainly mediated through Dilp1-7. Little is known about the function of Dilp8 and the molecular mechanism of its action. In this article, we summarized the results of studies on Dilp8 since its discovery. Dilp8 was mainly expressed in imaginal discs and ovaries of adult female Drosophila. Dilp8 allows Drosophila to grow into individuals with a normal-sized and symmetrical body by regulating tissue growth and developmental timing. Dilp8 in damaged larvae mitigates abnormal growth by delaying developmental time. After being activated, Dilp8 enters the central nervous system and specifically binds to its receptor leucine-rich repeat-containing G protein-coupled receptor 3 (Lgr3), thereby inhibiting the synthesis of ecdysone to control the growth and development of Drosophila. It has been suggested that Lgr3 is associated with sex regulation in Drosophila. Dilp8 regulates the ovulatory capacity of adult female Drosophila. In addition, tumour-derived Dilp8 is associated with anorexia of Drosophila. Dilp8/Lgr3 is highly homologous with human INSL3/RXFP2. The molecular mechanism of action of Dilp8 needs further exploration.