Ca2+ and AMPK both mediate stimulation of glucose transport by muscle contractions.
It is now generally accepted that activation of AMP-activated protein kinase (AMPK) is involved in the stimulation of glucose transport by muscle contractions. However, earlier studies provided evidence that increases in cytosolic Ca(2+) mediate the effect of muscle contractions on glucose transport. The purpose of this study was to test the hypothesis that both the increase in cytosolic Ca(2+) and the activation of AMPK are involved in the stimulation of glucose transport by muscle contractions. Caffeine causes release of Ca(2+) from the sarcoplasmic reticulum. Incubation of rat epitrochlearis muscles with a concentration of caffeine that raises cytosolic Ca(2+) to levels too low to cause contraction resulted in an approximate threefold increase in glucose transport. Caffeine treatment also resulted in increased phosphorylation of calmodulin-dependent protein kinase (CAMK)-II in epitrochlearis muscle. The stimulation of glucose transport by caffeine was blocked by the Ca(2+)-CAMK inhibitors KN62 and KN93. Activation of AMPK with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) also resulted in an approximate threefold increase in glucose transport in the epitrochlearis. The increases in glucose transport induced by AICAR and caffeine were additive, and their combined effect was not significantly different from that induced by maximally effective contractile activity. KN62 and KN93 caused an approximately 50% inhibition of the stimulation of glucose transport by contractile activity. Our results provide evidence that both Ca(2+) and AMPK are involved in the stimulation of glucose transport by muscle contractions. They also suggest that the stimulation of glucose transport by Ca(2+) involves activation of CAMK.
Wright
David C
DC
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
Hucker
Kathleen A
KA
Holloszy
John O
JO
Han
Dong Ho
DH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D001596:Benzylamines / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D018482:Muscle, Skeletal / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology
D001596:Benzylamines; D004791:Enzyme Inhibitors; D007328:Insulin; C425780:KN 92; D013449:Sulfonamides; D002110:Caffeine; C063302:KN 62; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000263:Adenylate Kinase; D005947:Glucose; D002118:Calcium