The role of Ca2+ influx for insulin-mediated glucose uptake in skeletal muscle.
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.
Lanner
Johanna T
JT
Department of Physiology and Pharmacology, Karolinska Institutet, SE-171 77, Stockholm, Sweden.
Katz
Abram
A
Tavi
Pasi
P
Sandström
Marie E
ME
Zhang
Shi-Jin
SJ
Wretman
Charlott
C
James
Stephen
S
Fauconnier
Jérémy
J
Lännergren
Jan
J
Bruton
Joseph D
JD
Westerblad
Håkan
H
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*
D007328:Insulin; D003847:Deoxyglucose; D005947:Glucose; D002118:Calcium