Berberine modulates insulin signaling transduction in insulin-resistant cells

Mol Cell Endocrinol. 2010 Apr 12;317(1-2):148-53. doi: 10.1016/j.mce.2009.12.027. Epub 2009 Dec 29.


Berberine has been shown to have insulin-sensitizing effect, but the molecular mechanism underlying remains elusive. In this work, we investigated the effect of berberine on insulin-induced signal transduction and glucose uptake in both insulin-sensitive and insulin-resistant rat skeletal muscle cells. Berberine increased the activity of AMPK and PKCzeta and AS160 phosphorylation in normal cells, but had little effect on PKB activation. In insulin-resistant state, berberine exhibited synergistic effect on insulin-induced glucose uptake and GLUT4 translocation. Berberine improved insulin-induced tyrosine-phosphorylation of IRS-1 and the recruitment of p85 to IRS-1. These changes were accompanied by enhancement in insulin-induced PKCzeta and PKB activity and actin remodeling. The ameliorated insulin signal transduction was related to the inhibition of mTOR by berberine, which attenuated serine-phosphorylation of IRS-1. These results suggest that berberine may overcome insulin resistance via modulating key molecules in insulin signaling pathway, leading to increased glucose uptake in insulin-resistant cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins
  • Animals
  • Berberine / pharmacology*
  • Glucose / metabolism
  • Glucose Transporter Type 4 / metabolism
  • Insulin / metabolism*
  • Insulin Resistance*
  • Mice
  • Muscle Cells / drug effects*
  • Muscle Cells / enzymology
  • Muscle Cells / metabolism*
  • Protein Transport / drug effects
  • Protein-Tyrosine Kinases / metabolism
  • Rats
  • Signal Transduction / drug effects*


  • Actins
  • Glucose Transporter Type 4
  • Insulin
  • Berberine
  • insulin receptor tyrosine kinase
  • Protein-Tyrosine Kinases
  • Glucose