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 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.
Lindskog
S
S
Department of Pharmacology, Lund University, Sweden.
Ahrén
B
B
D000818:Animals; D003994:Bucladesine / Q000037:antagonists & inhibitors; D002132:Calcium Radioisotopes; D005576:Colforsin / Q000037:antagonists & inhibitors; D003981:Diazoxide / Q000494:pharmacology; D019004:Galanin; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D009479:Neuropeptides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D012414:Rubidium Radioisotopes; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D002132:Calcium Radioisotopes; D007328:Insulin; D009479:Neuropeptides; D010455:Peptides; D012414:Rubidium Radioisotopes; D005576:Colforsin; D003994:Bucladesine; D019004:Galanin; D005947:Glucose; D013755:Tetradecanoylphorbol Acetate; D003981:Diazoxide