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Acta Physiol (Oxf). 2011 Feb;201(2):227-38. doi: 10.1111/j.1748-1716.2010.02169.x.

Caffeine activates preferentially α1-isoform of 5'AMP-activated protein kinase in rat skeletal muscle.

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1
Laboratory of Sports and Exercise Medicine, Graduate School of Human and Environmental Studies, Kyoto University, Kyoto, Japan.

Abstract

AIM:

Caffeine activates 5'AMP-activated protein kinase (AMPK), a signalling intermediary implicated in the regulation of glucose, lipid and energy metabolism in skeletal muscle. Skeletal muscle expresses two catalytic α subunits of AMPK, α1 and α2, but the isoform specificity of caffeine-induced AMPK activation is unclear. The aim of this study was to determine which α isoform is preferentially activated by caffeine in vitro and in vivo using rat skeletal muscle.

METHODS:

Rat epitrochlearis muscle was isolated and incubated in vitro in the absence or presence of caffeine. In another experiment, the muscle was dissected after intravenous injection of caffeine. Isoform-specific AMPK activity, the phosphorylation status of AMPKα Thr(172) and acetyl-CoA carboxylase (ACC) Ser(79) , the concentrations of ATP, phosphocreatine (PCr) and glycogen, and 3-O-methyl-d-glucose (3MG) transport activity were estimated.

RESULTS:

Incubation of isolated epitrochlearis muscle with 1 mm of caffeine for 15 min increased AMPKα1 activity, but not AMPKα2 activity; concentrations of ATP, PCr and glycogen were not affected. Incubation with 3 mm of caffeine activated AMPKα2 and reduced PCr and glycogen concentrations. Incubation with 1 mm of caffeine increased the phosphorylation of AMPK and ACC and enhanced 3MG transport. Intravenous injection of caffeine (5 mg kg(-1) ) predominantly activated AMPKα1 and increased 3MG transport without affecting energy status.

CONCLUSION:

Our results suggest that of the two α isoforms of AMPK, AMPKα1 is predominantly activated by caffeine via an energy-independent mechanism and that the activation of AMPKα1 increases glucose transport and ACC phosphorylation in skeletal muscle.

[Indexed for MEDLINE]

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