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 β (IRβ), protein kinase B (also known as Akt), and glycogen synthase kinase-3β (GSK3β) antibodies. Activation status of the insulin pathway was investigated using phospho-IRβ, as well as phospho-Akt, and phospho-GSK3β 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 IRβ 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 IRβ-subunit, Akt, and GSK3β. 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.
['Liu|Jun|J|', 'Wang|Xue|X|', 'Chen|Yu-Peng|YP|', 'Mao|Li-Fei|LF|', 'Shang|Jing|J|', 'Sun|Hong-Bin|HB|', 'Zhang|Lu-Yong|LY|']
D000818:Animals D003920:Diabetes Mellitus D004365:Drugs, Chinese Herbal D004791:Enzyme Inhibitors D006003:Glycogen D024981:Glycogen Phosphorylase D056945:Hep G2 Cells D006801:Humans D007328:Insulin D008297:Male D051379:Mice D008810:Mice, Inbred C57BL D015398:Signal Transduction D014315:Triterpenes
Maslinic acid Glycogen metabolism Glycogen phosphorylation a Insulin signal transduction