[Hepatic IRβ/IRS 1/Akt Signaling May Contribute to the Effectiveness of Electroacupuncture in Improving Insulin Resistance in Central Stat 5 Knockout Mice]

Abstract

Objective: To observe the effect of electroacupuncture (EA) on insulin signaling pathway in liver tissues of central neuronal specific signal transduction and activator of transcription 5 conditional-knockout (Stat 5 NKO) mice, so as to explore its mechanism underlying improvement of insulin resistance (IR)．.

Methods: Twenty-four male Stat 5 NKO mice were randomly divided into model and EA groups (n＝12 mice/group), and 12 Stat 5 fl/fl mice were used as the normal control group. EA (2 Hz/15 Hz, 0.8－1.0 mA) was alternatively applied to ipsilateral "Zusanli" (ST 36) and "Neiting" (ST 44) for 20 min, once a day, 6 times a week for 4 weeks. The glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the values of fasting plasma glucose (FPG) and fasting insulin (FINS) were measured by glucometer and ELISA, separately. The insulin sensitivity index (ISI) was calculated. The phosphorylation protein expressions of insulin receptor substrate 1 (IRS 1), insulin receptor β (IRβ) and protein kinases B (Akt) in the liver tissues were detected by Western blot.

Results: In Stat 5 NKO mice (model group), FPG level and glucose area under the curve (GAUC) of ITT and GTT were significantly increased (P<0.01, P<0.05, P<0.001), while the ISI was notably down-regulated in comparison with the Stat 5 fl/fl mice (normal group, P<0.01), suggesting an impairment of both glucose tolerance (GT) and insulin tolerance (IT) in mice of the model group. After the EA treatment, the increased FPG and GAUC levels and the decreased ISI were reversed markedly (P<0.05, P<0.01, P<0.001). No significant differences were found in FINS among the three groups (P>0.05). Compared with the normal group, the protein expression levels of liver p-IRS 1 and p-IRβ were significantly up-regulated (P<0.001), and the p-Akt expression was significantly down-regulated (P<0.01) in the model group. Following EA treatment, the increased p-IRS 1 and p-IRβ protein expression and the decreased p-Akt expression were apparently reversed in the EA group relevant to the model group (P<0.001, P<0.01)．.

Conclusion: EA can improve the IR induced by central neuronal Stat 5-knockout in mice, which may contribute to its effectiveness in regulating hepatic IRβ/IRS 1/Akt signaling pathway.

Keywords: Electroacupuncture; Insulin receptor substrate 1; Insulin receptor β; Insulin resistance; Protein kinases B.