The Effect Of Ang-(1-7) On PI3K/Akt Signaling Pathway In Hepatic Tissus Of Type 2 Diabetic Rats

Objective:To study the changes of insulin signal key molecules in hepatic tissus by upregulating the activity of ACE2-Ang-(1-7)-Mas pathway in type 2 diabetic rats. With the understanding of the mechanism of protection effect of Ang-(1-7) on insulin resistance, we hope to provide a new method and target to improve insulin sensitivity of type 2 diabetes mellitus.Methods:A total of 34 healthy male Wistar rats were randomly divided into normal control(NC)group fed standard diet, diabetic control(D0)group fed high-fat diet plus injection of a low dose of STZ, and Ang-(1-7)intervention(D1)group receiving injection of streptozotocin followed by Ang-(1-7) intervention(300?g· kg–1·d–1). The levels of body weight, fasting blood glucose(FBG), fasting insulin(Fins), angiotensin ?(Ang ?)were determined. HOMA-IR and HOMA-ISI were measured to detect insulin sensitivity. The protein and m RNA expression levels of IRS-2, PI3 K, Akt-2, GSK-3? in hepatic tissus were examined by Real-time PCR and immunohistochemistry.Result:D0 group compared to NC group, it showed a significantly increase in FBG, Ang II levels and HOMA-IR values and decrease in weight, Fins levels and HOMA-ISI values(P<0.05). The PI3 K, Akt-2 protein and m RNA expression in hepatic tissus were downregulated while the GSK-3? were upregulated(P<0.05). There was a obviousdecreasing in the level of IRS-2 m RNA(P<0.05). In contrast, after Ang-(1-7) intervention,FBG, Ang II levels and HOMA-IR values were decreased significantly while the Fins levels and HOMA-ISI values were increase significantly in D1 group(P<0.05). Ang-(1-7)treatment potently increased PI3 K, Akt-2 protein and gene expression in hepatic tissus while decreased the GSK-3?(P<0.05). There was a obvious increasing in the level of IRS-2 m RNA(P<0.05).Conclusions:The results of the present study show that Ang-(1-7) treatment might decrease the level of blood glucose, suggesting an improvement of insulin resistance, which might associate with the upregulation of the PI3K/Akt signaling pathway in type 2 diabetic rats.