Lindskog S, Ahrén B
Department of Pharmacology, Lund University, Sweden.
Eur J Pharmacol. 1991 Nov 19;205(1):21-7. doi: 10.1016/0014-2999(91)90765-i.
The mechanism by which the neuropeptide galanin inhibits insulin secretion in normal islets is not yet fully elucidated. Isolated rat or mouse islets were perifused in a medium containing glucose (8.3 mM) and galanin (10(-6) M) or the sulphonamide diazoxide (400 microM). In rat islets prelabelled with 86Rb+ or 45Ca2+, galanin inhibited glucose-induced insulin secretion at the same time as increasing 86Rb+ efflux and reducing 45Ca2+ efflux. The diazoxide-induced 86Rb+ efflux was not affected by galanin, indicating that galanin activates ATP-regulated K+ channels in rat islets. In mouse islets prelabelled with 86Rb+, galanin (10(-6) M) decreased 86Rb+ efflux. These results suggest that galanin inhibits insulin release in isolated islets by increasing K+ and decreasing Ca2+ permeability. The increased K+ permeability, which is probably regulated differently in rat and mouse islets, is followed by a reduced Ca2+ influx, possibly through voltage-dependent Ca2+ channels. In addition, during a 60-min incubation with isolated islets, galanin inhibited insulin secretion induced by forskolin (1 microM), dibutyryl cyclic AMP (1 mM), or TPA (12-O-tetradecanoylphorbol-13-acetate; 0.1 microM). Galanin also reduced the content of cyclic AMP in islets stimulated by 16.7 mM glucose. We therefore conclude that the inhibitory action of galanin on insulin secretion in normal islets includes increasing K+ permeability as well as interference with the activation of adenylate cyclase and the activity of protein kinase C and cyclic AMP.
神经肽甘丙肽抑制正常胰岛胰岛素分泌的机制尚未完全阐明。将分离的大鼠或小鼠胰岛在含有葡萄糖（8.3 mM）和甘丙肽（10^(-6) M）或磺胺类药物二氮嗪（400 μM）的培养基中进行灌流。在用86Rb+或45Ca2+预标记的大鼠胰岛中，甘丙肽在抑制葡萄糖诱导的胰岛素分泌的同时增加了86Rb+外流并减少了45Ca2+外流。二氮嗪诱导的86Rb+外流不受甘丙肽影响，这表明甘丙肽激活了大鼠胰岛中的ATP调节钾通道。在用86Rb+预标记的小鼠胰岛中，甘丙肽（10^(-6) M）减少了86Rb+外流。这些结果表明，甘丙肽通过增加钾通透性和降低钙通透性来抑制分离胰岛中的胰岛素释放。钾通透性的增加在大鼠和小鼠胰岛中可能受到不同调节，随后钙内流减少，可能是通过电压依赖性钙通道。此外，在与分离胰岛孵育60分钟期间，甘丙肽抑制了福斯可林（1 μM）、二丁酰环磷酸腺苷（1 mM）或佛波酯（12-O-十四烷酰佛波醇-13-乙酸酯；0.1 μM）诱导的胰岛素分泌。甘丙肽还降低了由16.7 mM葡萄糖刺激的胰岛中环磷酸腺苷的含量。因此，我们得出结论，甘丙肽对正常胰岛胰岛素分泌的抑制作用包括增加钾通透性以及干扰腺苷酸环化酶的激活、蛋白激酶C的活性和环磷酸腺苷。
