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Retinoic Acid Regulates Glucose Uptake Through AMPK-38 MAPK in Skeletal Muscle Cells

Prof SH Park, Ms YM Lee, Ms ES Lee, Dr KO Uhm, Prof HS Kim
Korea University College Of Medicine

Retinoic acid (RA) is one of the major components of Vitamin A. The differentiation function of RA has been fairly well established in the skeletal muscles. However, its metabolic role and molecular mechanism within the muscles remain largely unclear. In the present study, we found that retinoic acid activates AMP-activated protein kinase (AMPK) and also stimulated glucose uptake in differentiated C2C12 myoblast cells. In addition, RA activated p38 mitogen-activated protein kinase (MAPK). Moreover, the inhibition of AMPK and p38 MAPK blocked retinoic acid-induced glucose uptake. Mechanistically, RA induced Rac1-GTP formation and phosphorylation of its downstream target, p21-activated kinase (PAK), while the inhibition of AMPK blocked RA-induced Rac1 activation. In summary, our results demonstrate that retinoic acid has a beneficial role in glucose metabolism via stimulation of the AMPK-Rac1-PAK pathway and also suggest that RA can be a molecular target of the treatment development for diabetes.

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