Morus alba leaf extract stimulates 5'-AMP-activated protein kinase in isolated rat skeletal muscle.
OBJECTIVE
Morus alba (mulberry) leaf is a natural therapeutic agent that has been shown to have an antidiabetic effect. We explored the possibility that 5'-AMP-activated protein kinase (AMPK) is involved in metabolic enhancement by the Morus alba leaf.


METHODS
Isolated rat epitrochlearis muscle was incubated in a buffer containing Morus alba leaf hot water extract (MLE) and the AMPK activation and related events were examined.


RESULTS
In response to MLE treatment, the Thr(172) phosphorylation of the catalytic alpha subunit of AMPK, an essential step for full kinase activation increased in a dose- and time-dependent manner. Ser(79) phosphorylation of acetyl CoA carboxylase, an intracellular substrate of AMPK, increased similarly. Analysis of isoform-specific AMPK activity revealed that MLE activated both the alpha1 and alpha2 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 ATP and phosphocreatine concentrations, was not affected by MLE.


CONCLUSIONS
MLE stimulates skeletal muscle AMPK activity acutely without changing the intracellular energy status.
Ma
Xiao
X
Kyoto University Graduate School of Human and Environmental Studies, Yoshida-Nihonmatsu-Cho, Sakyo-ku, Kyoto 606-8501, Japan.
Iwanaka
Nobumasa
N
Masuda
Shinya
S
Karaike
Kouhei
K
Egawa
Tatsuro
T
Hamada
Taku
T
Toyoda
Taro
T
Miyamoto
Licht
L
Nakao
Kazuwa
K
Hayashi
Tatsuya
T
D019325:3-O-Methylglucose / Q000378:metabolism; D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D020690:GTPase-Activating Proteins / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D008297:Male; D031625:Morus / Q000737:chemistry; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000201:enzymology; D009994:Osmolar Concentration; D010725:Phosphocreatine / Q000378:metabolism; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves; D020033:Protein Isoforms; D051381:Rats; D017208:Rats, Wistar
D020690:GTPase-Activating Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D010936:Plant Extracts; D020033:Protein Isoforms; C533101:TBC1D4 protein, rat; D010725:Phosphocreatine; D019325:3-O-Methylglucose; D000255:Adenosine Triphosphate; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase