title: The role of Ca2+ influx for insulin-mediated glucose uptake in skeletal muscle.
abstract: The involvement of Ca(2+) in insulin-mediated glucose uptake is uncertain. We measured Ca(2+) influx (as Mn(2+) quenching or Ba(2+) influx) and 2-deoxyglucose (2-DG) uptake in single muscle fibers isolated from limbs of adult mice; 2-DG uptake was also measured in isolated whole muscles. Exposure to insulin increased the Ca(2+) influx in single muscle cells. Ca(2+) influx in the presence of insulin was decreased by 2-aminoethoxydiphenyl borate (2-APB) and increased by the membrane-permeable diacylglycerol analog 1-oleyl-2-acetyl-sn-glycerol (OAG), agents frequently used to block and activate, respectively, nonselective cation channels. Maneuvers that decreased Ca(2+) influx in the presence of insulin also decreased 2-DG uptake, whereas increased Ca(2+) influx was associated with increased insulin-mediated glucose uptake in isolated single cells and whole muscles from both normal and insulin-resistant obese ob/ob mice. 2-APB and OAG affected neither basal nor hypoxia- or contraction-mediated 2-DG uptake. 2-APB did not inhibit the insulin-mediated activation of protein kinase B or extracellular signal-related kinase 1/2 in whole muscles. In conclusion, alterations in Ca(2+) influx specifically modulate insulin-mediated glucose uptake in both normal and insulin-resistant skeletal muscle. Moreover, the present results indicate that Ca(2+) acts late in the insulin signaling pathway, for instance, in the GLUT4 translocation to the plasma membrane.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
authors.forename: Johanna T
authors.initials: JT
authors.lastname: Lanner
authors.forename: Abram
authors.initials: A
authors.lastname: Katz
authors.forename: Pasi
authors.initials: P
authors.lastname: Tavi
authors.forename: Marie E
authors.initials: ME
authors.lastname: Sandström
authors.forename: Shi-Jin
authors.initials: SJ
authors.lastname: Zhang
authors.forename: Charlott
authors.initials: C
authors.lastname: Wretman
authors.forename: Stephen
authors.initials: S
authors.lastname: James
authors.forename: Jérémy
authors.initials: J
authors.lastname: Fauconnier
authors.forename: Jan
authors.initials: J
authors.lastname: Lännergren
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Bruton
authors.forename: Håkan
authors.initials: H
authors.lastname: Westerblad
mesh_terms: D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D003847:Deoxyglucose / Q000493:pharmacokinetics; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D018482:Muscle, Skeletal / Q000502:physiology*
chemical_list: D007328:Insulin; D003847:Deoxyglucose; D005947:Glucose; D002118:Calcium