The Preliminary Study On The Regulation Of Musclin And Fndc5 Gene Expression And Its Mechanism By Glucosamine

The hexose biosynthesis pathway(HBP)plays an important role in the energy metabolism disorders of glucose and fatty acids.In particular,there is a close relationship between insulin resistance and beta cell damage in the pathophysiology of type 2 diabetes mellitus.Glucosamine,as a product of glucose metabolism in the hexose biosynthetic pathway(HBP),is involved in the regulation of related gene expression.Musclin and FNDC5 are novel myogenic cytokines that are involved in insulin resistance related metabolic diseases such as diabetes,obesity.The purpose of this study was to investigate the effect and its mechanism of glucosamine on gene expression of myogenic cytokines Musclin and Fndc5.First,we selected different concentrations of glucosamine treatment of C2C12 myotubes,found that glucosamine can increase the expression of Musclin gene and down regulate the expression of Fndc5 gene.At the same time,the expression of ER stress marker gene GRP78 is up-regulated and activates the PERK and IRE1 pathways in the three unfolded protein response(UPR)pathway,but has no significant effect on the ATF6 pathway.It is hypothesized that endoplasmic reticulum stress activated PERK and IRE1 pathways are involved in glucosamine regulates the expression of Musclin and Fndc5.Secondly,interference and inhibition of PERK and IRE1 pathways were induced by transfection of interference fragments and pathway inhibitors respectively,q RT-PCR and western blot methods were used to determine the inhibition of the two pathways.On this basis,the expression of Musclin and Fndc5 genes was detected,The results showed that,when the PERK and IRE1 pathways were inhibited,The up-regulated effect of glucosamine on Musclin gene expression was attenuated,but the downregulation of Fndc5 gene was not significantly affected.Based on the above data,this study confirmed that PERK and IRE1 pathway participate in the regulation of Musclin gene expression by glucosamine,but not involved in the expression of Fndc5 gene.The results provide a new reference for the study of the mechanism of insulin resistance induced by the biosynthesis of hexose amine.