Coordinate Regulation of Contraction Signal-Induced GLUT4 Transcription by CaMK and AMPK Signaling Pathways in Cultured Skeletal Muscle Cells / 生物化学与生物物理进展

ABSTRACT

Glucose transporter 4 (GLUT4), a major contributor to glucose transport in skeletal muscle, is closely related to diabetic treatment. Exercise regulates apparently GLUT4 gene expression which produces many beneficial metabolic adaptations for diabetic patients. Study has shown that both AMPK (AMP-activated protein kinase) and CaMK (calcium-calmodulin dependent protein kinase) signaling pathways are involved in regulation of exercise-induced GLUT4 gene expression in skeletal muscles, but the relationship between these two signaling pathways in regulating the GLUT4 gene is unclear. The purpose of the following study was to investigate the relationship of these two pathways in Caffeine- and AICAR-stimulated skeletal muscle cells GLUT4 gene expression. Muscle contractile activity results in increases in both cytosolic Ca2+ and AMPK activity. To mimic this response, primary cultured rat skeletal muscle cells were treated with Caffeine to raise cytosolic Ca2+ and with AICAR to activate AMPK. The muscle cells were divided into different groups (Control, AICAR, Caffeine, AICAR/Caffeine, Caffeine +Compound C, AICAR/Caffeine +Compound C, AICAR +KN93, AICAR/Caffeine + KN93), which were used for experiments of stimulation by AICAR and Caffeine, inhibition by AMPK inhibitor, Compound C and CaMK inhibitor, KN93 respectively. The results showed that both AICAR and Caffeine induced about 2- and 3-fold increases respectively (P