Calcium stimulates glucose transport in skeletal muscle by a pathway independent of contraction

Am J Physiol. 1991 Mar;260(3 Pt 1):C555-61. doi: 10.1152/ajpcell.1991.260.3.C555.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3-O-Methylglucose
  • Adenosine Triphosphate / metabolism
  • Aminacrine / pharmacology
  • Animals
  • Biological Transport, Active / drug effects
  • Caffeine / pharmacology
  • Calcium / metabolism*
  • Cytochalasin B / pharmacology
  • Dantrolene / pharmacology
  • In Vitro Techniques
  • Kinetics
  • Male
  • Methylglucosides / metabolism*
  • Muscle Contraction*
  • Muscles / drug effects
  • Muscles / metabolism
  • Muscles / physiology*
  • Phosphocreatine / metabolism
  • Rats
  • Rats, Inbred Strains
  • Sarcoplasmic Reticulum / drug effects
  • Sarcoplasmic Reticulum / metabolism
  • Sulfonamides / pharmacology


  • Methylglucosides
  • Sulfonamides
  • Phosphocreatine
  • 3-O-Methylglucose
  • Cytochalasin B
  • Caffeine
  • W 7
  • Aminacrine
  • Adenosine Triphosphate
  • Dantrolene
  • Calcium