N-terminally elongated fragments of galanin(1-16) inhibit insulin secretion from isolated mouse islets.

The neuropeptide galanin inhibits insulin secretion and has been suggested to be an adrenergic co-transmitter in the endocrine pancreas. Recently, N-terminally elongated forms of galanin have been identified in both porcine brain and adrenals. Whether these elongated peptides show galanin-like biological effects is not known. We therefore synthesized two N-terminally elongated fragments of galanin(1-16), which contains the active site of galanin. The synthesized peptides were galanin(-9-16) and galanin(-7-16), which correspond to amino acids 24-61 and 26-61 in the galanin precursor molecule. Both these peptides were found to potently inhibit glucose-(11.1 mM)-stimulated insulin secretion from isolated mouse islets of Langerhans in all concentrations studied (1-1000 nM) (P < 0.0001). The potency of the peptides was not different from that of synthetic rat galanin. Thus, at 100 nM, insulin secretion was inhibited by galanin(-7-16) by 83 +/- 7% and by galanin(-9-16) by 71 +/- 17% and by rat galanin by 93 +/- 4% (not statistically different). Furthermore, the galanin receptor antagonist, M35 (10 nM), prevented the inhibitory action of the two N-terminally galanin fragments. This study thus shows that N-terminally elongated galanin-fragments as entire galanin inhibits insulin and thus indicates that the effect of galanin on insulin secretion is not dependent on a free amino-terminus.