Retinoic acid stimulates glucose transporter expression in L6 muscle cells

Factors that regulate the tissue specific and developmental expression of the GLUT4 gene, whose transcribed protein is primarily responsible for mediating insulin stimulated glucose transport, are poorly defined. In this study we examined the effects of retinoic acid, a circulating factor that can promote cellular differentiation, on glucose uptake and glucose transporter expression in cultured L6 muscle cells. At the myoblast stage, treatment with 1 microM retinoic acid for 24 h increased both 1 h and 8 h insulin stimulated uptake of 2-deoxyglucose by more than twofold. A dose and time dependent effect of retinoic acid on 8 h insulin stimulated 2-deoxyglucose uptake was observed at both the myoblast and myocyte stage. Comparatively little effect from retinoic acid treatment was found on basal uptake at either stage. In myoblast cells, retinoic acid increased the content of GLUT4 mRNA in a dose and time dependent manner, an effect that was partially attenuated by insulin. In myocytes retinoic acid increased GLUT4 mRNA levels to 2.3 times basal. Nuclear run-on studies indicate that the increased GLUT4 mRNA represents enhanced transcriptional activity. The results suggest a role for retinoic acid in regulation of expression of the GLUT 4 gene in muscle cells.