Caffeine acutely activates 5'adenosine monophosphate-activated protein kinase and increases insulin-independent glucose transport in rat skeletal muscles.
Caffeine (1,3,7-trimethylxanthine) has been implicated in the regulation of glucose and lipid metabolism including actions such as insulin-independent glucose transport, glucose transporter 4 expression, and fatty acid utilization in skeletal muscle. These effects are similar to the exercise-induced and 5'adenosine monophosphate-activated protein kinase (AMPK)-mediated metabolic changes in skeletal muscle, suggesting that caffeine is involved in the regulation of muscle metabolism through AMPK activation. We explored whether caffeine acts on skeletal muscle to stimulate AMPK. Incubation of rat epitrochlearis and soleus muscles with Krebs buffer containing caffeine (> or =3 mmol/L, > or =15 minutes) increased the phosphorylation of AMPKalpha Thr(172), an essential step for full kinase activation, and acetyl-coenzyme A carboxylase Ser(79), a downstream target of AMPK, in dose- and time-dependent manners. Analysis of isoform-specific AMPK activity revealed that both AMPKalpha1 and alpha2 activities increased significantly. This enzyme activation was associated with a reduction in phosphocreatine content and an increased rate of 3-O-methyl-d-glucose transport activity in the absence of insulin. These results suggest that caffeine has similar actions to exercise by acutely stimulating skeletal muscle AMPK activity and insulin-independent glucose transport with a reduction of the intracellular energy status.
Egawa
Tatsuro
T
Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, Japan.
Hamada
Taku
T
Kameda
Naoko
N
Karaike
Kouhei
K
Ma
Xiao
X
Masuda
Shinya
S
Iwanaka
Nobumasa
N
Hayashi
Tatsuya
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D015153:Blotting, Western; D002110:Caffeine / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D051275:Glucose Transporter Type 4 / Q000378:metabolism; D006003:Glycogen / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D051275:Glucose Transporter Type 4; D007004:Hypoglycemic Agents; D007328:Insulin; D007527:Isoenzymes; D010726:Phosphodiesterase Inhibitors; C495694:Slc2a4 protein, rat; D010725:Phosphocreatine; D002110:Caffeine; D000255:Adenosine Triphosphate; D006003:Glycogen; D017868:Cyclic AMP-Dependent Protein Kinases; D005947:Glucose