Corosolic acid stimulates glucose uptake via enhancing insulin receptor phosphorylation

Eur J Pharmacol. 2008 Apr 14;584(1):21-9. doi: 10.1016/j.ejphar.2008.01.020. Epub 2008 Jan 31.

Abstract

Corosolic acid, a triterpenoid compound widely existing in many traditional Chinese medicinal herbs, has been proved to have antidiabetic effects on animal experiments and clinical trials. However, the underlying mechanisms remain unknown. Here, we investigate its cellular effects and related signaling pathway. We demonstrate that it enhances glucose uptake in L6 myotubes and facilitates glucose transporter isoform 4 translocation in CHO/hIR cells. These actions are mediated by insulin pathway activation and can be blocked by phosphatidylinositol 3-kinase (PI(3) Kinase) inhibitor wortmannin. Furthermore, Corosolic acid inhibits the enzymatic activities of several diabetes-related non-receptor protein tyrosine phosphatases (PTPs) in vitro, such as PTP1B, T-cell-PTP, src homology phosphatase-1 and src homology phosphatase-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases
  • Androstadienes / pharmacology
  • Animals
  • Biological Transport
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology*
  • Glucose / metabolism*
  • Glucose Transporter Type 4 / drug effects
  • Glucose Transporter Type 4 / genetics
  • Glucose Transporter Type 4 / metabolism
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin / metabolism
  • Multienzyme Complexes / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Phosphorylation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Transport
  • Protein Tyrosine Phosphatases, Non-Receptor / antagonists & inhibitors
  • Protein Tyrosine Phosphatases, Non-Receptor / metabolism
  • Protein-Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Receptor, Insulin / drug effects*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Signal Transduction / drug effects*
  • Triterpenes / pharmacology*
  • Wortmannin

Substances

  • Androstadienes
  • Enzyme Inhibitors
  • Glucose Transporter Type 4
  • Hypoglycemic Agents
  • Insulin
  • Multienzyme Complexes
  • Phosphoinositide-3 Kinase Inhibitors
  • Protein Kinase Inhibitors
  • SLC2A4 protein, human
  • Triterpenes
  • corosolic acid
  • Receptor, Insulin
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • AMP-Activated Protein Kinases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • Glucose
  • Wortmannin