title: Is contraction-stimulated glucose transport feedforward regulated by Ca2+?
abstract: In many cell types, Ca(2+) signals to increase the movement and surface membrane insertion of vesicles. In skeletal muscle, Ca(2+) is predominantly released from the sarcoplasmic reticulum (SR) to initiate contraction. Sarcoplasmic reticulum Ca(2+) release is widely believed to be a direct feedforward regulator of the translocation of glucose transporter 4 to the cell surface to facilitate transmembrane glucose transport. This review summarizes the evidence supporting the Ca(2+) feedforward model and its proposed signalling links to regulation of glucose transport in skeletal muscle and other cell types. The literature is contrasted against our recent findings suggesting that SR Ca(2+) release is neither essential nor adequate to stimulate glucose transport in muscle. Instead, feedback signals through AMPK and mechanical stress are likely to account for most of contraction-stimulated glucose transport. A revised working model is proposed, in which muscle glucose transport during contraction is not directly regulated by SR Ca(2+) release but rather responds exclusively to feedback signals activated secondary to cross-bridge cycling and tension development.
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark tejensen@nexs.ku.dk.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Jensen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.
authors.forename: Yeliz
authors.initials: Y
authors.lastname: Angin
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.
authors.forename: Lykke
authors.initials: L
authors.lastname: Sylow
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, University of Copenhagen, Denmark.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Richter
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D009119:Muscle Contraction / Q000502:physiology*; D018482:Muscle, Skeletal / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
chemical_list: D005947:Glucose; D002118:Calcium