Maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase

AIM:To investigate the molecular signaling mechanism by which the plant-derived,pentacyclic triterpene maslinic acid(MA) exerts anti-diabetic effects.METHOD:HepG2 cells were stimulated with various concentrations of MA.The effects of MA on glycogen phosphorylase a(GPa) activity and the cellular glycogen content were measured.Western blot analyses were performed with anti-insulin receptor (IR),protein kinase B(also known as Akt),and glycogen synthase kinase-3(GSK3) antibodies.Activation status of the insulin pathway was investigated using phospho-IR,as well as phospho-Akt,and phospho-GSK3 antibodies.The specific PI3-kinase inhibitor wortmannin was added to the cells to analyze the Akt expression.Enzyme-linked immunosorbent assay(ELISA) was used to measure the effect of MA on IR auto-phosphorylation.Furthermore,the effect of MA on glycogen metabolism was investigated in C57BL/6J mice fed with a high-fat diet(HFD).RESULTS:The results showed that MA exerts anti-diabetic effects by increasing glycogen content and inhibiting glycogen phosphorylase activity in HepG2 cells.Furthermore,MA was shown to induce the phosphorylation level of IR-subunit,Akt,and GSK3.The MA-induced activation of Akt appeared to be specific,since it could be blocked by wortmannin.Finally,MA treatment of mice fed with a high-fat diet reduced the model-associated adiposity and insulin resistance,and increased the accumulated hepatic glycogen content.CONCLUSION:The results suggested that maslinic acid modulates glycogen metabolism by enhancing the insulin signaling pathway and inhibiting glycogen phosphorylase.