Otsuki M, Okabayashi Y, Ohki A, Suehiro I, Oka T, Baba S
Endocrinology. 1986 Jul;119(1):244-9. doi: 10.1210/endo-119-1-244.
(Bu)2cGMP is known to act as a specific competitive inhibitor for gastrin and cholecystokinin (CCK) peptides. We have examined the effects of (Bu)2cGMP on CCK octapeptide (CCK-8) stimulation of insulin release in the isolated perfused pancreas and compared them with those on protein output. Addition of (Bu)2cGMP after a 20-min perfusion with 100 pM CCK-8 resulted in two distinctly different phases of insulin suppression. There was a sharp initial decline in insulin release for 3 min, followed by transient recovery toward the control level for 5 min, and then a small decline until termination of (Bu)2cGMP infusion. (Bu)2cGMP produced a concentration-dependent inhibition of both phases of insulin decrement. (Bu)2cGMP also produced a concentration-dependent inhibition of protein output. Addition of 1 mM (Bu)2cGMP rapidly and completely abolished CCK-8-stimulated protein output. Since CCK is released by meal intake and exogenous CCK stimulates insulin release and augments glucose-induced insulin release, it is possible that endogenous CCK plays an important role in the enteroinsular axis. The present findings of blockade of CCK-8-induced insulin release by selective antagonist of the action of CCK provide evidence for CCK as a mediator in the enteroinsular axis.
已知（丁酰）2 - 环鸟苷酸可作为胃泌素和胆囊收缩素（CCK）肽的特异性竞争性抑制剂。我们研究了（丁酰）2 - 环鸟苷酸对离体灌注胰腺中CCK八肽（CCK - 8）刺激胰岛素释放的影响，并将其与对蛋白质输出的影响进行了比较。在用100 pM CCK - 8灌注20分钟后添加（丁酰）2 - 环鸟苷酸，导致胰岛素抑制出现两个明显不同的阶段。胰岛素释放最初急剧下降3分钟，随后短暂恢复至对照水平5分钟，然后在（丁酰）2 - 环鸟苷酸输注终止前略有下降。（丁酰）2 - 环鸟苷酸对胰岛素下降的两个阶段均产生浓度依赖性抑制。（丁酰）2 - 环鸟苷酸还对蛋白质输出产生浓度依赖性抑制。添加1 mM（丁酰）2 - 环鸟苷酸可迅速且完全消除CCK - 8刺激的蛋白质输出。由于CCK由进食释放，外源性CCK刺激胰岛素释放并增强葡萄糖诱导的胰岛素释放，因此内源性CCK可能在肠胰岛轴中起重要作用。目前通过CCK作用的选择性拮抗剂阻断CCK - 8诱导的胰岛素释放的研究结果为CCK作为肠胰岛轴中的介质提供了证据。
