AMP-activated protein kinase, AMPK, is responsible for regulation of exercise-induced GLUT4 gene expression in skeletal muscle. But the molecular mechanisms for this regulation and key protein in this signaling pathway are obscure. There has been growing recognition that histone acetylation probably represents a central mechanism for regulation of gene transcription, and recent studies showed that numerous gene expressions are regulated by nucleosomal histone acetylation, which is modulated through histone acetyltransferases (HATs) and histone deacetylases (HDACs). So we have a hypothesis that the AMPK regulates GLUT4 gene through recruiting HDACs. Skeletal muscle cells cultured with normal (5 mmol/L) and high (20 mmol/L) glucose concentration were incubated with AICAR, and then total and nuclear AMPKalpha2, HDAC5 protein and GLUT4 mRNA were measured. The results show that the AICAR activated AMPKalpha2, reduced nuclear HDAC5,and increased GLUT4 mRNA in skeletal muscle cells; in contrast, the effect evoked by AICAR was blunted in cultured skeletal muscle cells with high glucose. Therefore, the changes of GLUT4 gene expression under different glucose concentration are closely related to the changes of AMPKalpha2 and HDAC5 protein in skeletal muscle cells. This result demonstrates that HDAC5 plays an important role in regulating GLUT4 gene transcription by AMPK signaling pathway skeletal muscle cells.
AMP-Activated Protein Kinases ; metabolism ; Cells, Cultured ; Glucose Transporter Type 4 ; biosynthesis ; genetics ; Histone Deacetylases ; metabolism ; Humans ; Muscle, Skeletal ; cytology ; enzymology ; metabolism ; RNA, Messenger ; biosynthesis ; genetics ; Signal Transduction ; Transcription, Genetic