The existence of an optimal range of cytosolic free calcium for insulin-stimulated glucose transport in rat adipocytes.
We have examined the effects of extracellular and intracellular Ca2+ concentrations upon basal and insulin-stimulated 2-deoxyglucose uptake in isolated rat adipocytes. In the absence of extracellular Ca2+, both basal and insulin-stimulated glucose uptake were significantly reduced. Insulin-stimulated glucose transport was optimal at 1 and 2 mM Ca2+. Further increases in extracellular Ca2+ concentration (3 mM) significantly diminished insulin-stimulated glucose uptake. When intracellular Ca2+ concentrations were augmented by ionomycin (1 microM), insulin-stimulated glucose uptake was significantly reduced at extracellular Ca2+ concentrations of 2 and 3 mM. The levels of intracellular free Ca2+ concentrations were then measured with Ca2+ indicator fura-2. The correlation between the levels of intracellular free Ca2+ and the magnitude of insulin-stimulated glucose uptake revealed that the optimal effect of insulin is observed at Ca2+ levels between 140 and 370 nM. At both extremes outside of this window, both low and high levels of intracellular Ca2+ result in diminished cellular responsiveness to insulin. These data suggest that intracellular calcium concentrations may exert a dual role in the regulation of cellular sensitivity to insulin. First, there must exist a minimal concentration of intracellular calcium to promote insulin action. Second, increased levels of intracellular calcium may provide a critical signal for diminution of insulin action.
Draznin
B
B
Medical Research Service, Veterans Administration Medical Center, Denver, Colorado 80220.
Sussman
K
K
Kao
M
M
Lewis
D
D
Sherman
N
N
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000032:analysis* / Q000378:metabolism; D003600:Cytosol / Q000032:analysis*; D004987:Ethers / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D015759:Ionomycin; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014700:Verapamil / Q000494:pharmacology
D004987:Ethers; D007328:Insulin; D015759:Ionomycin; D014700:Verapamil; D005947:Glucose; D002118:Calcium