Gymnemic Acid Ameliorate Hyperglycemia Through PI3K/AKT and AMPK Mediated Signaling Pathway in T2DM Rats.

Gymnemic acid (GA) isolated from gymnema sylvestre (Retz.) Schult has been shown to display anti-diabetic activity, however the molecular mechanisms governing these effects are unclear. In this study, GA (40, 80 mg/kg/day) was evaluated by type 2 diabetes mellitus (T2DM) rats to explore its hypoglycemic activity and underlying mechanisms of action. The results indicated that GA decreased fasting blood glucose (FBG) concentrations by 26.7 %, and lowered insulin concentrations by 16.1 % after oral administration of GA at a dose of 80 mg/kg/day for 6 weeks in T2DM rats. Our data showed that RT-PCR and Western blot analysis indicated that GA up-regulated the expression of phosphatidylinositol-3-kinase (PI3K) and glycogen synthesis (GS), promoted the phosphorylation of protein kinase B (Akt), while down-regulated the expression of glycogen synthesis kinase-3β (GSK-3β) in T2DM rats. In addition, key proteins involved in AMPK-mediated gluconeogenesis (such as phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase)) were down-regulated in GA-treated T2DM rats. In summary, the hypoglycemic mechanisms of GA may be related to promoting insulin signal transduction and activating PI3K/Akt and AMPK-mediated signaling pathway in T2DM rats.