Calcium stimulates glucose transport in skeletal muscle by a pathway independent of contraction.
In this study we investigated the possibility that an increase in cytoplasmic Ca2+ concentration that is too low to cause muscle contraction can induce an increase in glucose transport activity in skeletal muscle. The compound N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7), which induces Ca2+ release from the sarcoplasmic reticulum (SR), caused a dose-dependent increase in tension in rat epitrochlearis muscles at concentrations more than approximately 200 microM. Although 100 microM W-7 did not increase muscle tension, it accelerated loss of preloaded 45Ca2+. Glucose transport activity, measured with the nonmetabolizable glucose analogue 3-O-methylglucose, increased sixfold in muscles treated for 100 min with 50 microM W-7 (P less than 0.001) and eightfold in response to 100 microM W-7 (P less than 0.001). The increase in glucose transport activity was completely blocked with 25 microM cytochalasin B. There was no decrease in ATP or creatine phosphate concentrations ([approximately P]) in muscles incubated with 50 microM W-7. Dantrolene (25 microM), which blocks Ca2+ release from the SR, blocked the effects of W-7 both on 45Ca2+ release and on glucose transport activity. 9-Aminoacridine, another inhibitor of Ca2+ release from the SR, also blocked the stimulation of hexose transport by W-7. Caffeine, a compound structurally unrelated to W-7 that also releases Ca2+ from the SR, also increased glucose transport activity. Incubation of muscles with 3 mM caffeine for 30 min, which did not cause contraction or lower [approximately P], induced a threefold increase in 3-O-methylglucose transport (P less than 0.001). These results provide evidence suggesting that an increase in cytoplasmic Ca2+ too low to cause contraction or [approximately P] depletion can bring about an increase in glucose transport activity in skeletal muscle.
Youn
J H
JH
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Gulve
E A
EA
Holloszy
J O
JO
D019325:3-O-Methylglucose; D000255:Adenosine Triphosphate / Q000378:metabolism; D000585:Aminacrine / Q000494:pharmacology; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D003571:Cytochalasin B / Q000494:pharmacology; D003620:Dantrolene / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008757:Methylglucosides / Q000378:metabolism*; D009119:Muscle Contraction; D009132:Muscles / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010725:Phosphocreatine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology
D008757:Methylglucosides; D013449:Sulfonamides; D010725:Phosphocreatine; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D002110:Caffeine; C017967:W 7; D000585:Aminacrine; D000255:Adenosine Triphosphate; D003620:Dantrolene; D002118:Calcium