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


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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 Thr172 and acetyl-CoA carboxylase (ACC) Ser79, 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.

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