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

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 Thr172 phosphorylation of the catalytic α-subunit of AMPK, an essential step for full kinase activation, increased in a dose- and time-dependent manner. Ser79 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.