Black M A, Fournier L A, Heick H M, Bégin-Heick N
Department of Biochemistry, University of Ottawa, Canada.
Biochem J. 1988 Jan 15;249(2):401-7. doi: 10.1042/bj2490401.
The purpose of these experiments was to determine whether the activity of the voltage-dependent Ca2+ channel was modulated in the same manner in islets of the ob/ob mouse as in islets of homozygous lean mice of the same strain. The effect of agents that are known to alter the concentrations and movements of intracellular Ca2+ were investigated in relation to glucose-stimulated insulin secretion and in relation to the effect of forskolin. In islets of obese mice, verapamil and nifedipine both inhibited glucose-induced insulin release, nifedipine being the more potent inhibitor. Forskolin-stimulated secretion was inhibited either not at all (verapamil) or much less (nifedipine) in islets of the ob/ob mouse compared with those of lean mice. At basal glucose concentrations, verapamil initiated insulin secretion in islets of the ob/ob mouse and acted synergistically with forskolin to evoke a secretory activity that was 3-fold greater than that evoked by 20 mM-glucose. Nifedipine also initiated secretion at basal glucose concentrations and acted synergistically with forskolin, but its effect was considerably smaller than that of verapamil. A comparison of the effect of forskolin in the presence of Ca2+-channel blockers and in the absence of Ca2+ suggests that, in the obese mouse, the operation of the voltage-dependent Ca2+ channel is impaired.
这些实验的目的是确定在ob/ob小鼠胰岛中，电压依赖性Ca2+通道的活性是否与同品系纯合瘦小鼠胰岛中的调节方式相同。研究了已知能改变细胞内Ca2+浓度和移动的药物对葡萄糖刺激的胰岛素分泌以及对福斯高林作用的影响。在肥胖小鼠的胰岛中，维拉帕米和硝苯地平均抑制葡萄糖诱导的胰岛素释放，硝苯地平是更有效的抑制剂。与瘦小鼠胰岛相比，在ob/ob小鼠胰岛中，福斯高林刺激的分泌要么完全不受抑制（维拉帕米），要么抑制程度小得多（硝苯地平）。在基础葡萄糖浓度下，维拉帕米在ob/ob小鼠胰岛中引发胰岛素分泌，并与福斯高林协同作用，引发的分泌活性比20 mM葡萄糖引发的分泌活性高3倍。硝苯地平在基础葡萄糖浓度下也引发分泌，并与福斯高林协同作用，但其作用比维拉帕米小得多。比较福斯高林在存在Ca2+通道阻滞剂和不存在Ca2+时的作用表明，在肥胖小鼠中，电压依赖性Ca2+通道的功能受损。
