Visfatin Improve Glucose Metabolism Via PI3K/AKT/GSK Signaling Pathway In Skeletal Musclescle Of KKAy Mice

Objective: To observe the influences of visfatin on protein kinase B(AKT), glycogen synthase kinase-3β(GSK-3β), glucose transporter 4(GLUT-4) in skeletal muscle of KKAy mice, Investigate the role of visfatin in PI3K/Akt GSK/GLUT-4 signaling pathway and its mechanism in improving glucose metabolism.Methods: C57 BL / 6J mice were randomly divided into control group(CON), high-fat diet group(HFD);KKAy mice with the high-fat diet were divided into four groups:diabetic group(DM), visfatin treatment group(v), visfatin + LY294002 combined group(v + LY), LY294002 group(LY).The diabetes mellitus model was considered as success when fasting blood glucose(FBG) were higher than 13.9mmol/L twice.After two weeks,visfatin group intraperitoneal injection of recombinant protein visfatin, visfatin + LY294002 combined group intraperitoneal injection of visfatin and LY294002, LY294002 group were injected with LY294002, The blood samples were measured for fasting blood glucose(FBG), fasting insulin(FINS), triglyceride(TG), total cholesterol(TC),high density lipoprotein-C(HDL-C) and low density lipoprotein-C(LDL-C). The homeostasis model assessment(HOMA-IR) and insulin sensitivity index(ISI) were calculated. The expression of PI3 K AKT and GLUT-4 m RNA in skeletal muscle tissue were detected by RT-PCR,and the expression of PI3K、AKT、GLUT-4 and GSK-3β protein were determined by western blot.Results:Compared with the control group, Levels of FINS, TC, LDL-C and HOMA-IR were Significantly increased in the high-fat diet group;Levels of FBG, FINS, TG, TC,LDL-C and HOMA-IR were significantly higher in KKAy mice than those in the high-fat diet group;Levels of FBG, TC, Ins were significantly lower in the Visfatin group than those in the model group.Compared with the control group, the expression of AKT m RNA was reduced in the high-fat diet group;Compared with the high-fat group, theexpression of PI3 K, AKT,GLUT-4 mRNA were reduced in diabetes group(P< 0.05); Compared with the model group the m RNA level of PI3 K, AKT,GLUT-4 were increased in the visfatin group(P < 0.01);Compared with the visfatin group, the expression of AKT,GLUT-4, PI3 K m RNA were increased in the combined group significantly;Compared with the combined group, the m RNA expressi of PI3 K, AKT, GLUT-4 were significantly lower in the inhibitor group.Protein:Compared with the control group, the expression of GLUT-4 was reduced in the high-fat diet group;The content of PI3 K,GLUT-4,AKT were decreased,AKT phosphorylation level was decreased,content of GSK-3β was increased,and GSK-3β phosphorylation level was decreased in the model group compared with the high-fat group(P < 0.05).content of PI3 K, GLUT-4,AKT phosphorylation level were increased,content of GSK-3β was decreased,and GSK-3β phosphorylation level was increased in visfatin group compared with the model group(P< 0.05);The protein expression of PI3 K, GLUT4,the phosphorylation of Akt and GSK-3 beta were significantly lower in the combined and the inhibitor group than those in the visfatin group,but the protein expression of GSK-3 beta was increased obviously;Compared with the combined group, the protein expression of GLUT-4 was significantly reduced in the inhibitor group(P< 0.01).Conclusion: Visfatin can lower blood sugar, which may be related to the PI3K/Akt/GSK-3β/ GLUT-4 signaling pathway.