Roe M W, Lancaster M E, Mertz R J, Worley J F, Dukes I D
Department of Cell Physiology and Immunology, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
J Biol Chem. 1993 May 15;268(14):9953-6.
Glucose-activated beta-cell insulin secretion depends upon elevation of intracellular calcium concentration, [Ca2+]i, which is thought to arise from Ca2+ influx through voltage-dependent calcium channels. Using fura-2-loaded mouse islets, we demonstrate, in fact, that the major component of the glucose-activated [Ca2+]i rise represents voltage-dependent intracellular Ca2+ release. Furthermore, the Ca2+ release pool possesses a novel pharmacology in that it is caffeine-sensitive but ryanodine-insensitive. In the absence of external Ca2+, glucose still caused intracellular Ca2+ release, an effect blockable by tetrodotoxin. However, depolarization of the islet with KCl in low Ca(2+)-containing solutions induced intracellular Ca2+ release, which was resistant to tetrodotoxin. We conclude that glucose release of intracellular Ca2+ is dependent upon depolarization alone, possibly through increasing inositol 1,4,5-trisphosphate production.
葡萄糖激活的β细胞胰岛素分泌依赖于细胞内钙浓度[Ca2+]i的升高，一般认为这是由钙通过电压依赖性钙通道内流引起的。实际上，使用负载fura-2的小鼠胰岛，我们证明葡萄糖激活的[Ca2+]i升高的主要成分是电压依赖性细胞内钙释放。此外，钙释放池具有一种新的药理学特性，即它对咖啡因敏感但对ryanodine不敏感。在没有细胞外钙的情况下，葡萄糖仍能引起细胞内钙释放，这种效应可被河豚毒素阻断。然而，在含低钙的溶液中用氯化钾使胰岛去极化会诱导细胞内钙释放，这种释放对河豚毒素有抗性。我们得出结论，细胞内钙的葡萄糖释放仅依赖于去极化，可能是通过增加肌醇1,4,5-三磷酸的产生来实现的。
