钙通道拮抗剂对大鼠胰岛细胞胰岛素分泌的影响

目的　研究钙通道拮抗剂对大鼠胰岛细胞分泌胰岛素的影响和机制。方法　用放免和荧光方法分别检测不同治疗血浓度的硝苯地平 (NIF)、维拉帕米 (VER)、地尔硫 (DIL)等药物对低糖和高糖刺激状态下胰岛细胞Ca2 含量和胰岛素分泌量的影响。结果　低糖状态组 :NIF、VER、DIL在 2 5、50、10 0 μg/L药物浓度下未对胰岛细胞内Ca2 含量和胰岛素分泌量产生影响 ,其结果与对照组相比差异无统计学意义 (P >0 0 5)。在高糖状态组 ,NIF、VER、DIL在 2 5μg/L药物浓度下不抑制胰岛素分泌 ,NIF在 50、10 0 μg/L浓度时 ,胰岛细胞内Ca2 浓度和胰岛素分泌量明显减少 ,与对照组相比差异有显著性 (P <0 0 5)并呈剂量相关 (P <0 0 1)。VER在 50 μg/L时胰岛素分泌有减少趋势 ,10 0 μg/L时明显减少 (P <0 0 5)。DIL在 10 0 μg/L时胰岛素分泌量减少与对照组相比差异具有显著性 (P <0 0 5)。结论　高浓度药理治疗量的NIF、VER、DIL具有抑制高糖作用下的胰岛细胞外钙内流和使胰岛素分泌减少的作用

The effect of Ca2+ channel blocker on insulin secretion in rat pancreatic islet cells

OBJECTIVE: To study the effect and mechanism of Ca2+ channel blocker on the insulin secretion in islet beta cells of rats. METHODS: The cells were divided into two groups: the low sugar concentration and high sugar concentration groups. These cells were examined with radioimmunoassay and fluorescence method and the effects of nifedipine (NIF), verapamil (VER), and diltiazem (DIL) on the contents of Ca2+ in the islet cells and the secretion volume of insulin at different concentrations were observed. RESULTS: In the low sugar concentration group, NIF, VER and DIL at concentration of 25, 50 and 100 microg/L respectively showed no effect on the contents of Ca2+ in islet cells and the insulin secretion (no statistical significance, P > 0.05). In the high sugar concentration group, these drugs had no inhibitory effect on insulin secretion at concentration of 25 microg/L. However, there was remarkable reduction in Ca2+ contents and insulin secretion when NIF was at the concentration of 50 and 100 microg/L, showing a relationship with dosage (P > 0.05, P > 0.01). VER, when given at 50 microg/L, showed a tendency of reduction in insulin secretion and there was a remarkable reduction at a dosage of 100 microg/L as compared with the control group (P > 0.05). When DIL was given at 100 microg/L, there was a noticeable difference in reduction of insulin secretion as compared with the control group (P > 0.05). CONCLUSION: High dosage of NIF, VER and DIL has an inhibitory effect on the entrance of extracellular Ca2+ into islet cells and thus reduces insulin secretion.