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J. Biol. Chem., Vol. 262, Issue 30, 14385-14388, Oct, 1987
B Draznin, K Sussman, M Kao, D Lewis and N Sherman
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.
The existence of an optimal range of cytosolic free calcium for insulin- stimulated glucose transport in rat adipocytes
Medical Research Service, Veterans Administration Medical Center, Denver, Colorado 80220.
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