Effects Of Electro-acupuncture On Hepatic Insulin Signaling Pathway In The Neuron Specific Stat5 Knockout Insulin Resistant Mice

Objective:To observe effect of Electro-acupuncture(EA)on hepatic insulin signaling pathway in the central nueron conditional knockout Stat5(signal transduction and activator of transcription 5 conditional-knockout,Stat5NKO)mice and explore the underlying mechanism of EA treatment in insulin resistance.Methods:Twelve week-old male Stat5fl/fl and Stat5NKO mice were randomly divided into four groups:Stat5fl/fl group(n=12),Stat5fl/fl+EA group(n=12),Stat5NKO group(n=12),and Stat5NKO+EA group(n=12).All mice were fed with ordinary forage.EA group received 2Hz/15Hz,0.8?1.0mA,dilatational wave treatment at "housanli"(ST36)and "Neiting"(ST44)for 20 min everyday,6 times a week for 4 weeks.Fasting plasma glucose(FPG)content and fasting insulin(FINS)content were measured by glucometer and ELISA,and insulin sensitivity index(ISI)was calculated by the formula of 1/(FINSxFPG).We also applied glucose tolerance test(GTT)and insulin tolerance test(ITT)in mice for glucose and insulin tolerance at the same time.Insulin receptor substrate 1(IRS1),insulin receptor ?(InsR(3)and protein kinases B(Akt)protein phosphorylation levels in the liver were detected by western blotting.Results:1.Compared with the Stat5fl/fl mice,the Stat5NKO mice appeared pronounced insulin intolerance and glucose intolerance(P<0.05,P<0.001),and significantly increased FPG(P<0.O1),accompanied with reduced ISI(P<0.05).These changes might suggest that insulin resistant exists in the Stat5NKO mice.Compared withtheStat5NKO mice,both insulin tolerance and glucose tolerance in the EA group were obviously improved(P<0.001,P<0.01).FPG was decreased(P<0.05),and ISI was increased(P<0.05)in the Stat5fl/fl+EA group compared to the Stat5NKOmice.There was no significant difference in FINS among the three groups(P>0.05).2.Compared with the Stat5fl/fl mice,phosphorylated InsR? and IRS1 expression were increased(P<0.01),while phosphorylated Akt expression was obviously decreased in the Stat5NKO mice(P<0.01)but increased evidently in the Stat5fl/fl+EA mice(P<0.O1);compared with the Stat5NKO mice,EA group showed decreased phosphorylated InsRP and IRS1 expression(P<0.05),accompanied with increased phosphorylated Akt expression(P<0.05).Conclusion:EA intervention was able to improve the insulin sensitivity in the Stat5 knockout induced insulin resistant mice,at least partially via activating hepatic IRS/Akt signaling pathway.