The Regulation Effect Of Bone Morphogenetic Protein 7 On Insulin Signaling Pathway And The Preliminary Study Of Mechanism

Objective To analyze the effect of BMP 7 on downstream protein expression related to insulin signaling pathway,JNK in relevant members of MAPK family and the downstream proteins.To study BMP7 and JNK regulation function in the insulin signaling transduction,and explore its potential mechanism.Insulin signaling pathway is thought to be the most important role in diabetes development.If we could find factors that influence its signal transduction and explore its molecular mechanisms,we will have a better understanding of the pathogenesis of diabetes.Besides,it is very likely leading to the discovery of new therapeutic targets and methods of early diagnosis.Methods1.Dispose skeletal muscle cells C2C12 and HepG2 of liver parenchyma cells with different concentrations of BMP7,major proteins in insulin signaling pathway and the JNK signaling pathway were detected using Western blot assay.2.The effect of BMP7 on gene expression of insulin effector was detected by quantitative PCR after extraction of total RNA of C2C12 and HepG2 cells.3.The expression of BMP7 in mouse liver was raised with the intravenous injection of adenovirus expressing BMP7.4.The impact of BMP7 overexpression on glucose metabolism was tested by glucose tolerance test and insulin resistance test.5.The proteins of the insulin signaling pathway and the JNK signaling pathway were tested,which were included in the liver,skeletal muscle and adipose tissue.Results1.In the differentiated C2C12 and HepG2 cells,insulin treatment significantly increased the expression of phosphorylation insulin receptor(p-IR),phosphorylation Akt(p-Akt)and phosphorylated glycogen synthase 3 beta(p-Gsk3?).It also promoted glucose transport into cells.However,the BMP7 treatment markedly reduced insulin response to these phosphorylated proteins and inhibited insulin induced glucose transfer in cells.2.After BMP7 disposal,the gene expression of Akt1,insulin-like growth factor receptor(Igf1r),insulin receptor(Insr)and insulin receptor substrate(Irs1)had no significant effect.3.In HepG2 cells,the phosphorylation JNK signaling proteins were improved at 5 minuts after BMP7 processing.while the effect of this promotion had diminished,as the duration of the action extended.4.After overexpressing BMP7 in the mouse liver,blood glucose levels elevated,glucose tolerance and insulin tolerance gone down.5.BMP7 activated JNK sinaling pathway,and inhibited insulin signal transmission in the liver and epididymal white adipose tissue.Conclusions1.BMP7 reduced insulin signaling in HepG2 and C2C12 cells.2.In mice,BMP7 elevated blood sugar and decreased glucose and insulin tolerance.3.BMP7 inhibited the insulin signaling pathway in the liver and epididymal white adipose tissue.This inhibitory effect on the insulin signaling pathway was likely to achieve by activating the JNK signaling pathway.