Preliminary Study On The Mechanism Of Corosolic Acid Reducing Glycogen Production

The elevated blood glucose levels and the declining sensitivity of insulin receptor are the mainly clinical manifestations for the type II diabetes.HepG2 cell,a liver cancer cell line derived from human,retains many of the liver-specific features and can proliferate infinitely in vitro.Zebrafish acts as an ideal model organism.Zebrafish has many characteristics including short growth cycle,large numbers of spawning,long breeding time,high synchronization of zygote and easy of raising.The embryos of zebrafish have been hatched after fertilizing 96h,associated with the organs involving glucose metabolism such as pancreas islet hasing been fully developed.Therefore,we employ HepG2 cells and zebrafish larvae establishing the models that imitate clinical manifestations for the type II diabetes.We used the models to explore the mechanism of corosolic acid(CA)on reducing hepatic glucose output in vitro and in vivo.On the one hand,HepG2 cells were treated with cAMP(100μM)and DEX(1000nM)for 12h.Then a cell model which can reduce glucose consumption in a unit cell and intracellular glycogen content,as well as increase PEPCK gene expression was established.At the same time of modeling,we treated the cell model with different concentrations of corosolic asid.The glucose consumption in a unit cell and the intracellular glycogen content of the model were significantly increased,while the PEPCK gene expression were decreased.The results showed that the cell model treated with corosolic acid(10μM)could enhance glucose consumption in a unit,increase intracellular glycogen content and lower PEPCK gene expression in the cells at a maximum extent.On the other hand,zebrafish larvae treated with 100μM cAMP and 1000nM DEX were incubated for 48h.Therewith,we established a model with PEPCK gene overexpression.The results showed that CA could reduce gene expression of phosphoenolpyruvate carboxykinase(PEPCK),glycogen phosphorylase(GP)and insulina(INSa),with an increase in gene expression of GLUT2,glycogen synthas-el(GYS1),glucose-6-phosphorylase(G6P-ase),phosphofructokinase(PFKFB3),in-sulin receptor(type a and β).In conclusion,both the HepG2 and the zebrafish larvae model for type Ⅱdiabetes show that corosolic acid can effectively lower blood sugar level,and improve the condition in insulin resistance.Corosolic acid plays good role in HepG2 model at larger concentrations than zebrafish larvae.In this case,we should focus on the intracorporal studies for future research due to different effects of corosoic acid on the in vivo and in vitro studies.