CYCLOSPORIN-INDUCED INHIBITION OF INSULIN RELEASE - POSSIBLE ROLE OF VOLTAGE-DEPENDENT CALCIUM-TRANSPORT CHANNELS
CYCLOSPORIN-INDUCED INHIBITION OF INSULIN RELEASE - POSSIBLE ROLE OF VOLTAGE-DEPENDENT CALCIUM-TRANSPORT CHANNELS
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DOI：
10.1016/0006-2952(88)90077-9
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发表时间：
1988-10-15
影响因子：
5.8
通讯作者：
LEITNER, JW
中科院分区：
文献类型：
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作者：
DRAZNIN, B;METZ, SA;LEITNER, JW
正常胰岛暴露于环孢素A(1微克/毫升)24小时后，可显著抑制葡萄糖诱导的(16.7 mM)胰岛素的释放。14U/10个胰岛/15分钟(对照)至103.+-。14微U/10个胰岛/15分钟(Cy-A处理的胰岛；P<；0.001)。在非刺激性(1.7 nM)或亚最大有效葡萄糖浓度(9.2 mM)存在下，CY-A不改变胰岛素的释放。在平行实验中，Cy-A降低了葡萄糖刺激的胞浆游离钙浓度的增加，[Ca~(2+)]i(217.+-.15海里和137海里。+-。在16.7 mM葡萄糖存在下，Cy-A与Nm混合，P<；0.01)。为了更好地确定Cy-A的作用部位，我们研究了Cy-A对胰岛素释放和[Ca~(2+)]i增加的影响，K~+(50 MM)通过电压依赖的Ca~(2+)通道促进Ca~(2+)内流，或者Forskolin(20微米)、二丁基环AMP(1微米)或花生四烯酸(49微米)诱导胰岛素释放和[Ca~(2+)]i增加，所有这些都刺激细胞内钙储备库的动员。CY-A显著抑制K+诱导的改变(203。+-。无海里13海里和77海里+。6 nM+Cy-A，P<；0.001)，而Forskolin、二丁酰环磷腺苷或花生四烯酸不诱导。这些观察结果表明，Cy-A通过干扰电压依赖性钙通道的钙内流来抑制胰岛素的释放。
The exposure of normal pancreatic islets to cyclosporin-A (1 .mu.g/ml) for 24 hr resulted in significant inhibition of glucose-induced (16.7 mM) insulin release from 197 .+-. 14 .mu.U/10 islets/15 min (control) to 103 .+-. 14 .mu.U/10 islets/15 min (Cy-A-treated islets; P < 0.001). Cy-A did not alter insulin release in the presence of non-stimulatory (1.7 nM) or submaximally effective glucose concentrations (9.2 mM). In parallel experiments, Cy-A reduced glucose-stimulated increases in cytosolic free calcium concentrations, [Ca2+]i (217 .+-. 15 nM without and 137 .+-. nM with Cy-A in the presence of 16.7 mM glucose, P < 0.01). To better define the site of Cy-A action, we studied its effect on insulin release and increases in [Ca2+]i induced by either K+ (50 mM), which promotes Ca2+ influx via the voltage-dependent Ca2+ channels, or by forskolin (20 .mu.M),dibutyryl cyclic AMP (1 mM) or arachidonic acid (49 .mu.M), all of which stimulate mobilization of intracellular Ca2+ stores. Cy-A significantly inhibited K+-induced changes (203 .+-. 13 nM without and 77 .+-. 6 nM with Cy-A, respectively, P < 0.001), but not those induced by forskolin, dibutyryl cyclic AMP or arachidonic acid. These observations suggest that Cy-A inhibits insulin release by interfering with Ca2+ influx via voltage-dependent calcium channels.