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

Abstract

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.

• Authors: Jun Liu, Xue Wang, Yu-Peng Chen, Li-Fei Mao, Jing Shang, Hong-Bin Sun, Lu-Yong Zhang
• Journal: Chinese journal of natural medicines (Chin J Nat Med) Vol. 12 Issue 4 Pg. 259-65 (Apr 2014) ISSN: 1875-5364 [Electronic] China
• PMID: 24863350 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• Enzyme Inhibitors
• Insulin
• Triterpenes
• Glycogen
• maslinic acid
• Glycogen Phosphorylase

Topics

• Animals
• Diabetes Mellitus (drug therapy, enzymology, genetics, metabolism)
• Drugs, Chinese Herbal (administration & dosage)
• Enzyme Inhibitors (administration & dosage)
• Glycogen (metabolism)
• Glycogen Phosphorylase (antagonists & inhibitors, genetics, metabolism)
• Hep G2 Cells
• Humans
• Insulin (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Signal Transduction (drug effects)
• Triterpenes (administration & dosage)