Draznin B, Sussman K E, Leitner J W, Metz S A
Medical Research Service, Veterans Administration Medical Center, Denver, CO 80220.
Metabolism. 1988 Jul;37(7):660-3. doi: 10.1016/0026-0495(88)90086-8.
We have attempted to delineate the effect of glyburide on the regulation of cytosolic-free calcium concentrations, [Ca2+]i, in normal rat pancreatic islet cells. In the presence of extracellular calcium (1 mmol/L), glyburide increased [Ca2+]i from 70 nmol/L to 260 nmol/L in a dose-dependent manner. The maximal effect was seen at a concentration of 2 mumol/L with half-maximal stimulation observed at .25 mumol/L. The effect of glyburide (.25 mumol/L) was inhibited 90% by the calcium channel blocker, verapamil (30 mumol/L). At a maximally effective concentration of glyburide (2 mumol/L), the inhibitory effect of verapamil was only 17%. In the absence of extracellular calcium, glyburide increased [Ca2+]i from 55 nmol/L to 107 nmol/L, indicating its ability to mobilize intracellular calcium stores. These results correlated well with the ability of glyburide (2 mumol/L) to stimulate insulin secretion both in the presence (from 38 +/- 5 mumol/L/10 islets to 131 +/- 28 microU/10 islets) and in the absence (from 49 +/- 4 microU/10 islets to 93 +/- 7 microU/10 islets) of extracellular Ca2+. The present observations suggest that glyburide promotes calcium influx via voltage-dependent calcium channels and may mobilize intracellular calcium stores.
我们试图描述格列本脲对正常大鼠胰岛细胞胞质游离钙浓度（[Ca2+]i）调节的影响。在细胞外钙（1 mmol/L）存在的情况下，格列本脲以剂量依赖的方式将[Ca2+]i从70 nmol/L增加到260 nmol/L。在2 μmol/L的浓度下观察到最大效应，在0.25 μmol/L时观察到半数最大刺激效应。钙通道阻滞剂维拉帕米（30 μmol/L）可使格列本脲（0.25 μmol/L）的效应抑制90%。在格列本脲的最大有效浓度（2 μmol/L）下，维拉帕米的抑制作用仅为17%。在无细胞外钙的情况下，格列本脲将[Ca2+]i从55 nmol/L增加到107 nmol/L，表明其具有动员细胞内钙储存的能力。这些结果与格列本脲（2 μmol/L）在有（从38±5 μmol/L/10个胰岛增加到131±28 μU/10个胰岛）和无（从49±4 μU/10个胰岛增加到93±7 μU/10个胰岛）细胞外Ca2+时刺激胰岛素分泌的能力密切相关。目前的观察结果表明，格列本脲通过电压依赖性钙通道促进钙内流，并可能动员细胞内钙储存。
