Gymnemic Acid Ameliorates Hyperglycemia through PI3K/AKT- and AMPK-Mediated Signaling Pathways in Type 2 Diabetes Mellitus Rats

Gymnemic acid (GA) isolated from Gymnema sylvestre (Retz.) Schult. has been shown to have antihyperglycemic activity; however, the molecular mechanisms governing these effects are unclear. In this study, GA (40 and 80 mg kg(-1) day(-1)) 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(-1) day(-1) for 6 weeks in T2DM rats. Our data showed that real-time polymerase chain reaction and western blot indicated that GA upregulated the level of phosphatidylinositol-3-kinase (PI3K) and glycogen synthesis (GS) and promoted the phosphorylation of protein kinase B (Akt) while downregulated the expression of glycogen synthesis kinase-3 beta (GSK-3 beta) in T2DM rats. In addition, key proteins involved in adenosine monophosphate (AMP)-activated protein kinase (AMPK)-mediated gluconeogenesis [such as phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphatase (G6Pase)] were downregulated 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 pathways in T2DM rats.