Galanin-induced inhibition of insulin secretion from rat islets: effects of rat and pig galanin and galanin fragments and analogues

Abstract

The 29-amino acid neuropeptide galanin occurs in intrapancreatic nerves and inhibits insulin secretion. To study the structure-activity relations of galanin, we examined the effects of pig and rat galanin, three galanin fragments (galanin-(1–11), galanin-d-16) and rat galanin-( 17–29) and four galanin analogues ([Ala 2pig galanin, [Ala 2rat galanin, [D-Trp 2]rat galanin and [D-Trp 2]galanin-(1–16)) on glucose-stimulated insulin secretion from isolated rat islets. Pig and rat galanin and galanin-(1–11) equipotently inhibited glucose-stimulated (8.3 mM) insulin secretion at and above 10 −7 M (P < 0.05), whereas galanin-(1–16), inhibited insulin secretion at 10 −6 M (P < 0.01). In contrast, the C-terminal rat galanin-(17–29) and the galanin analogues did not influence insulin secretion. Thus, rat and pig galanin are equipotent in inhibiting glucose-stimulated insulin secretion from rat islets. The active site resides in the N-terminal part of the molecule. Furthermore, the binding of galanin to its receptor depends on structural characteristics governed by the N-terminal position and in particular by the Trp 2 residue.