Galanin-induced inhibition of insulin secretion from rat islets: effects of rat and pig galanin and galanin fragments and analogues.
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-(1-16) and rat galanin-(17-29) and four galanin analogues ([Ala2]pig galanin, [Ala2]rat galanin, [D-Trp2]rat galanin and [D-Trp2]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 less than 0.05), whereas galanin-(1-16), inhibited insulin secretion at 10(-6) M (P less than 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 Trp2 residue.
Gregersen
S
S
Department of Medicine, Aarhus Kommunehospital, Denmark.
Hermansen
K
K
Langel
U
U
Fisone
G
G
Bartfai
T
T
Ahrén
B
B
D000595:Amino Acid Sequence; D000818:Animals; D005260:Female; D019004:Galanin; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013552:Swine
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D019004:Galanin