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 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.
Ma
Xiao
X
Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
Egawa
Tatsuro
T
Kimura
Hajime
H
Karaike
Kouhei
K
Masuda
Shinya
S
Iwanaka
Nobumasa
N
Hayashi
Tatsuya
T
D055372:AMP-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D007004:Hypoglycemic Agents; D007328:Insulin / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000201:enzymology*; D051381:Rats
D007004:Hypoglycemic Agents; D007328:Insulin; D001599:Berberine; C543928:Prkaa2 protein, rat; D055372:AMP-Activated Protein Kinases; D005947:Glucose