Contraction- and hypoxia-stimulated glucose transport is mediated by a Ca -dependent mechanism in slow-twitch rat soleus muscle

Wright, David C., Paige C. Geiger, John O. Holloszy, and Dong-Ho Han. Contractionand hypoxia-stimulated glucose transport is mediated by a Ca -dependent mechanism in slow-twitch rat soleus muscle. Am J Physiol Endocrinol Metab 288: E1062–E1066, 2005. First published January 18, 2005; doi:10.1152/ajpendo.00561.2004.—Increases in contraction-stimulated glucose transport in fast-twitch rat epitrochlearis muscle are mediated by AMPKand Ca /calmodulindependent protein kinase (CAMK)-dependent signaling pathways. However, recent studies provide evidence suggesting that contraction-stimulated glucose transport in slow-twitch skeletal muscle is mediated through an AMPK-independent pathway. The purpose of the present study was to test the hypothesis that contraction-stimulated glucose transport in rat slow-twitch soleus muscle is mediated by an AMPK-independent/Ca dependent pathway. Caffeine, a sarcoplasmic reticulum (SR) Ca releasing agent, at a concentration that does not cause muscle contractions or decreases in high-energy phosphates, led to an 2-fold increase in 2-deoxyglucose (2-DG) uptake in isolated split soleus muscles. This increase in glucose transport was prevented by the SR calcium channel blocker dantrolene and the CAMK inhibitor KN93. Conversely, 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR), an AMPK activator, had no effect on 2-DG uptake in isolated split soleus muscles yet resulted in an 2-fold increase in the phosphorylation of AMPK and its downstream substrate acetyl-CoA carboxylase. The hypoxia-induced increase in 2-DG uptake was prevented by dantrolene and KN93, whereas hypoxia-stimulated phosphorylation of AMPK was unaltered by these agents. Tetanic muscle contractions resulted in an 3.5-fold increase in 2-DG uptake that was prevented by KN93, which did not prevent AMPK phosphorylation. Taken in concert, our results provide evidence that hypoxiaand contraction-stimulated glucose transport is mediated entirely through a Ca -dependent mechanism in rat slowtwitch muscle.