STUDIES ON THE MECHANISM BY WHICH GALANIN INHIBITS INSULIN-SECRETION IN ISLETS

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-mu-M). In rat islets prelabelled with Rb-86+ or Ca-45(2+), galanin inhibited glucose-induced insulin secretion at the same time as increasing Rb-86+ efflux and reducing Ca-45(2+) efflux. The diazoxide-induced Rb-86+ efflux was not affected by galanin, indicating that galanin activates ATP-regulated K+ channels in rat islets. In mouse islets prelabelled with Rb-86+, galanin (10(-6) M) decreased Rb-86+ 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-mu-M), dibutyryl cyclic AMP (1 mM), or TPA (12-O-tetradecanoylphorbol-13-acetate; 0.1-mu-M). 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.