Irisin通过AMPK和PI3K/Akt信号通路调控鲤糖代谢的机制研究

Irisin, named after the Greek messenger goddess Iris, is a novel hormone first identified in 2012. In mammals, Irisin is mainly secreted from muscle, which promotes the uptake and utilization of glucose and lipids, reduces insulin resistance and improves diabetes, etc. Therefore, based on our previous study , this project will systematically study the following points from the molecular level: 1) The expression and secretion of irisin in common carp (Cyprinus carpio); 2) The regulation of insulin, glucagon and blood glucose homeostasis by irisin in carp; 3)The regulation and signaling pathways of glucose metabolism mediated by irisin in the muscle, liver and adipose tissue of carp; 4) The regulation and signaling pathways of intestinal glucose uptake mediated by irisin in carp. The results of the study will clarify the regulatory mechanism of irisin on glucose metabolism in carp, supplement and perfect the endocrine regulation network of glucose metabolism in fish. In addition, this study is conducive to further reveal the causes s of low glucose tolerance in fish, enrich the theory of fish nutritional physiology, and lay a theoretical foundation for increasing the utilization of carbohydrate in the fish diet.

Irisin是2012年首次发现的新型激素，以希腊信使女神Iris命名。在哺乳动物中，Irisin主要由肌肉分泌产生，具有促进糖类和脂质的摄取与利用、降低胰岛素抵抗和改善糖尿病等生理功能。本项目拟以Irisin为切入点，在前期研究工作基础上，从分子水平系统研究：①鲤Irisin的表达与分泌；②Irisin对鲤胰岛素、胰高血糖素及血糖稳态的调控；③Irisin对鲤肌肉、肝脏和脂肪糖代谢的调控及其信号通路；④Irisin对鲤肠道葡萄糖吸收转运的调控及其信号通路。研究成果可阐明Irisin对鲤糖代谢的调控机制，完善鱼类糖代谢的内分泌调控网络，有利于进一步揭示鱼类糖耐量低下的原因，丰富鱼类营养生理学理论，并为提高糖类在鱼类饲料中的利用率奠定理论基础。

鱼类属“先天性糖尿病体质”，摄入糖类后高血糖状态持续的时间长。内分泌调节是葡萄糖稳态的重要调控方式。irisin是2012年在哺乳动物中首次发现的新型激素，但它在鱼类糖代谢和血糖稳态中的作用及机制尚不清楚。本项目研究了irisin的表达特性，制备了鲤irisin重组蛋白及抗体，建立了鲤血浆irisin含量的检测方法。通过在体和离体实验，在分子水平上系统研究了irisin对鲤胰岛素、胰高血糖素及血糖稳态的调控，以及irisin对鲤肝胰脏和肌肉糖代谢、肠道葡萄糖吸收转运的调控机制。主要结果如下：（1）irisin前体基因在鲤脑区表达丰富，并可感知食物供给、日粮糖脂水平、葡萄糖负荷以及胰岛素或胰高血糖素的刺激；（2）irisin可以调节胰岛素、胰高血糖素的合成，维持血糖稳态；（3）irisin能够通过促进肠道葡萄糖吸收，促进肝胰脏和肌肉中葡萄糖的转运、糖原合成和糖酵解，抑制糖原分解和糖异生，从而促进葡萄糖的吸收、转运和利用，进而促进鲤对葡萄糖的利用；（4）αVβ3/αVβ5受体以及AMPK、PI3K/Akt信号通路参与了上述调控过程。本项目阐明了irisin对鲤糖代谢的调控机制，补充和完善了鱼类糖代谢的内分泌调控网络，丰富了鱼类营养学和生理学理论，并为提高糖类在鱼类饲料中的利用奠定了理论基础。