家蚕类胰岛素肽的结构及信号传导与作用

Structure,Signal Transduction and Function of Insulin-like Peptides (Bombyxins) in the Silkworm,Bombyx mori

胰岛素(insulin)及其信号传导途径具有多种生物学效应,在调节生物的生长、代谢、生殖以及衰老等过程中起到非常重要的作用。国内外学者的研究表明:家蚕素(bombyxin)是无脊椎动物中首个被鉴定的类胰岛素肽,分子质量5kD,为异二聚体分子,与人胰岛素的氨基酸组成约有40%的同源性,家蚕素基因为基因组多拷贝基因,已发现的32个家蚕类胰岛素肽家族基因都无内含子,分成7个亚族,集中在基因组的3个片段,并以3种特有的基因排列模式排列;家蚕素基因主要在脑组织表达,在其他组织的表达量较低;家蚕素由脑中央背部的4对大型神经分泌细胞合成,通过神经轴突运送至对侧的咽侧体,然后释放到血淋巴液中,是一种由超日振荡放电节律所控制的分泌模式;家蚕素参与了糖代谢调控,有促进翅芽和造血器官细胞增殖,调控前胸腺分泌活性等作用。家蚕素信号通路的Pi3k60、Pdk、InR和Akt同源基因已相继被克隆,其中Akt编码的蛋白保守性最强,并能被商业化供应的抗哺乳动物丝氨酸-苏氨酸激酶(AKT)和磷酸化AKT抗体识别,为家蚕素信号系统研究提供了便利。鉴于家蚕变态和能量代谢等诸多特点,以家蚕作为模式生物研究胰岛素及其信号传导途径具有独特优势。

Insulin and its signal transduction pathways have various biological effects which play very important roles in the regulation of organismal growth, metabolism, reproduction and aging. Studies from both at home and abroad indicate that Bombyxin is the first insulin-like peptide having been identified in invertebrates. It has a molecular mass of 5 kD and exists in a heterodimer form. Its amino acid composition is about 40% identical with human insulin. The bombyxin gene is a multiple copy gene. So far, 32 bombyxin genes have been identified in Bombyx mori. All these genes are intronless and have been classified into 7 families. These genes cluster on three genomic DNA segments, each of which has its own unique distribution pattern. Bombyxin gene is expressed predominantly in brain of the Bombyx mori larvae. Its expressions in other larval tissues are relatively low. Bombyxin is produced by four pairs of large neurosecretory cells in the dorsomedial region of the brain and is axonally transported to the contral ateral corpus allatum （CA） via the corpus cardiacum （CC）, and then released into the haemolymph. The secretion pattern of bombyxin is related to the ultradian oscillation firing activity of a population of bombyxin-producing cells. It has been demonstrated that bombyxin participates regulation of sugar metabolism, promotes cell proliferation of insect wingbuds and hematopoietic organ, and regulates the secretory function of prothoracic gland. The homologous genes Pi3k60, Pdk,InR and Akt which are involved in bombyxin signal transduction pathways have been cloned successively. The protein encoded by Akt is the most conservative. It can be recognized by two commercially available antibodies, namely antimammalian AKT and anti-phosphorylated AKT, which can facilitate further researches on signal transduction of bombyxin. Owing to the favorable characteristics of Bombyx mori in metamorphosis and energy metabolism, it has unique advantages to use Bombyx mori as the model animal for studies on insulin and its signal transduction pathways.