Draznin B, Sussman K, Kao M, Lewis D, Sherman N
Medical Research Service, Veterans Administration Medical Center, Denver, Colorado 80220.
J Biol Chem. 1987 Oct 25;262(30):14385-8.
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.
我们研究了细胞外和细胞内钙离子浓度对分离的大鼠脂肪细胞基础及胰岛素刺激的2-脱氧葡萄糖摄取的影响。在无细胞外钙离子的情况下，基础及胰岛素刺激的葡萄糖摄取均显著降低。胰岛素刺激的葡萄糖转运在钙离子浓度为1 mM和2 mM时达到最佳。细胞外钙离子浓度进一步升高（3 mM）会显著降低胰岛素刺激的葡萄糖摄取。当用离子霉素（1 microM）提高细胞内钙离子浓度时，在细胞外钙离子浓度为2 mM和3 mM时，胰岛素刺激的葡萄糖摄取显著降低。然后用钙离子指示剂fura-2测量细胞内游离钙离子浓度水平。细胞内游离钙离子水平与胰岛素刺激的葡萄糖摄取幅度之间的相关性表明，在钙离子水平为140至370 nM之间观察到胰岛素的最佳作用。在此范围两端，细胞内钙离子水平过低或过高都会导致细胞对胰岛素的反应性降低。这些数据表明，细胞内钙离子浓度可能在调节细胞对胰岛素的敏感性中发挥双重作用。首先，必须存在最低浓度的细胞内钙离子以促进胰岛素作用。其次，细胞内钙离子水平升高可能为胰岛素作用减弱提供关键信号。
