Berberine-induced activation of 5'-adenosine monophosphate-activated protein kinase and glucose transport in rat skeletal muscles

Metabolism. 2010 Nov;59(11):1619-27. doi: 10.1016/j.metabol.2010.03.009. Epub 2010 Apr 27.


Berberine (BBR) is the main alkaloid of Coptis chinensis, which has been used as a folk medicine to treat diabetes mellitus in Asian countries. We explored the possibility that 5'-adenosine monophosphate-activated protein kinase (AMPK) is involved in metabolic enhancement by BBR in skeletal muscle, the important tissue for glucose metabolism. Isolated rat epitrochlearis and soleus muscles were incubated in a buffer containing BBR, and activation of AMPK and related events were examined. In response to BBR treatment, the Thr(172) phosphorylation of the catalytic α-subunit of AMPK, an essential step for full kinase activation, increased in a dose- and time-dependent manner. Ser(79) phosphorylation of acetyl-coenzyme A carboxylase, an intracellular substrate of AMPK, increased correspondingly. Analysis of isoform-specific AMPK activity revealed that BBR activated both the α1 and α2 isoforms of the catalytic subunit. This increase in enzyme activity was associated with an increased rate of 3-O-methyl-d-glucose transport in the absence of insulin and with phosphorylation of AS160, a signaling intermediary leading to glucose transporter 4 translocation. The intracellular energy status estimated from the phosphocreatine concentration was decreased by BBR. These results suggest that BBR acutely stimulates both AMPKα1 and AMPKα2 and insulin-independent glucose transport in skeletal muscle with a reduction of the intracellular energy status.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / drug effects
  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Berberine / pharmacology*
  • Biological Transport / drug effects
  • Energy Metabolism / drug effects
  • Glucose / metabolism*
  • Hypoglycemic Agents
  • Insulin / pharmacology
  • Muscle, Skeletal / enzymology*
  • Rats


  • Hypoglycemic Agents
  • Insulin
  • Berberine
  • Prkaa2 protein, rat
  • AMP-Activated Protein Kinases
  • Glucose