Mechanistic Study Of GBP5 And HULC In Inflammation Induced Insulin Resistance

Diabetes is an endocrine and metabolic disease,which is featured withhyperglycemia.At present,diabetes is a serious threat to human health.In 2016,the World Health Organization survey shows that the current incidence of type 2 diabetes in adults ofChinese has been reached to 10%.It is well recognized that insulin resistance(IR)is leading cause of type 2 diabetes.In insulin resistant individuals,the normal amount of insulin can not efficiently stimulate fat,skeletal muscle and liver to uptakeglucose from the blood,leading to hyperglycemia.Sustained insulin resistance damages islet beta cell function and finally leads to type 2 diabetes.In this project,we investigated whether GBP5 and HULC are involved in inflammatory factor-induced insulin resistance.GBP5 belongs to the guanine acid binding protein GBPs family,and can be induced by bacterial lipopolysaccharide(LPS).In addition,GBP5 also promotes the assembly and immunization of mammalian NLRP3 inflammatory body.HULC is a kind of long noncoding RNAs(lncRNAs),which has been shown to regulate a wide range of biological processes includingdevelopment,cell differentiation,tissue,regeneration,and metabolism.However,it is unclear whether GBP5 and HULC expression is regulated by inflammatory factors,and whether GBP5 and HULC regulate cytokine-induced insulin resistance.The aim of this project is to investigate whether GBP5 and HULC expression is regulated byinflammatory factors,and whether GBP5 and HULC are involved in chronicinflammation-induced insulin resistance.The results are as follows:In the first part,treatment of Hepa1 cells with inflammatory factors(TNF-?,IFN-?)promotes GBP5 expression.GBP5 mRNA level is increased by2200 folds in TNF-? and IFN-?treated Hepa1 cells.TNF-? treatment aloneincreases GBP5 mRNA level by1.7 folds while IFN-? treatment increases GBP5 mRNA levelby 700 folds comparing with the control group.Consistently,TNF-?and IFN-? also dose-dependently promote GBP5 expression in primary hepatocytes.These experiments demonstrates that inflammatory factorsdirectlystimulate GBP5 expression.Furthermore,adenovirus-mediated overexpression of GBP5 decreases insulin-stimulated Akt proteinphosphorylation levels in hepatocytes.The Akt protein levels are also decreased.Therefore,weconclude that GBP5 is involved in inflammation-induced insulin resistance.In the second part,we treated HepG2 cells with TNF-?,and found that the expression of HULC levels in TNF-? treated group were increased by2.5folds than that in the control group.However,adenovirus mediated overexpression of HULC does not change Akt protein expressionlevels and insulin-stimulated Akt protein phosphorylation levels in HepG2 cells.Therefore,we conclude that HULC is not involved in inflammation-induced insulin resistance.