胰岛素信号转导、昆虫发育与老化

胰岛素及其信号转导的探讨为当代生物学一大热点,研究显示:从线虫到果蝇、小鼠及其人类其胰岛素信号转导路径十分类似。昆虫胰岛素的研究开始于家蚕,在20世纪80年代,日本学者在分离家蚕促前胸腺激素(prothoracictropic hormone,简称PTTH)时,发现所纯化的为一称为家蚕素的神经激素,该激素之氨基酸排列顺序与高等动物体内的胰岛素部分相似,但是家蚕素的生理功能至今仍不是很清楚。而果蝇的分子遗传学研究则显示,胰岛素及其信号转导调控果蝇的生长、发育、寿命等许许多多的生理现象。专一性地改变果蝇前胸腺之胰岛素信号转导,会严重影响幼虫的蜕皮与变态。而作者利用家蚕所进行的研究更显示,将牛的胰岛素注射于家蚕幼虫体内可显着提高其蜕皮激素的分泌,离体培养前胸腺时加入牛胰岛素也可直接增加其激素的分泌,牛胰岛素可直接活化家蚕前胸腺细胞之胰岛素受体及信号分子Akt的磷酸化。另外,从线虫、果蝇到小鼠胰岛素及其信号转导突变体的研究结果显示了胰岛素信号转导调控寿命的重要性。利用猴子及人所进行的研究结果显示,低卡路里摄取之所以会延长寿命是因为卡路里的摄取与胰岛素信号转导的变化有关。因此,不同物种利用相同的胰岛素信号转导通路调控发育及老化机制,该发现大大鼓舞了科学家们利用低等的生物来研究复杂的生命现象。

Insulin signaling, Insect development and ageing

The investigation of insulin and its signaling is one of the hot topics in modern biology. It has become apparent that there exists a evolutionary conservation of insulin signaling mechanism from worms, flies, mice and human. The study of insect insulin began in Bombyx mori. Japanese researchers discovered the bombyxin, an insulin -like peptide which showed high similarity with human insulin in amino acid when they investigated the prothoracictropic hormone （PITH） in 1980. However, the exact role of bombyxin is still not very clear. In Drosophila melanogaster, molecular genetic study showed that insulin signaling plays an important role in regulating insect growth, development, and ageing. The studies on D. melanogaster during recent years showed that alternation in insulin signaling through molecular genetic engineering, specifically in the prothoracic glands leads to altered insect molting and metamorphosis. Our study on B. mori showed that bovine insulin stimulates prothoracic gland＇ s ecdysteroidogenesis both in vivo and in vitro. Insulin/Akt signaling is involved in the action of insulin. Reduced insulin signaling extends the life span of worms, flies, and mice. In addition, caloric restriction is the only known non - genetic intervention that robustly extends lifespan in mammals. Results showed that reduced insulin signaling and caloric restriction promote longevity by the same mechanism. Using the similar insulin signaling, different organisms from worms, flies, mice and human regulate their growth, development, and ageing. These results prompted scientists to investigate complex regulatory mechanism using simple animals