Galanin fragments and analogues: effects on glucose-stimulated insulin secretion from isolated rat islets.
Galanin occurs in intrapancreatic nerves and inhibits insulin secretion both in vivo and in vitro. To investigate which part of the galanin molecule accounts for this inhibition, we studied the effect of porcine galanin, four galanin fragments and three galanin analogues with substitutions of the 2nd amino acid in galanin, on glucose-stimulated insulin secretion from isolated rat islets cultured overnight. The islets were incubated for 1 h at 8.3 mM glucose. Porcine galanin1-29 inhibited insulin secretion at dose levels from 10(-8) M to 10(-6) M (p less than 0.001). Also, the galanin fragments GAL1-15, GAL2-29, and GAL3-29 significantly inhibited insulin secretion at and above concentrations of 10(-7) M (p less than 0.001), 10(-8) M (p less than 0.001), and 10(-7) M (p less than 0.001), respectively. Galanin analogues where the 2nd N-terminal amino acid had been changed from tryptophan to tyrosine (GAL-TYR2) or isoleucine (GAL-ILE2) inhibited insulin secretion, as did porcine galanin1-29, whereas after substitution with phenylalanine (GAL-PHE2) no effect was observed. Furthermore, the C-terminal fragment GAL10-29 did not influence insulin secretion. We conclude that the inhibitory action by galanin on glucose-stimulated insulin secretion from normal islets resides in the N-terminal part of the molecule. In contrast, the C-terminal part of galanin apparently does not influence insulin secretion.
Gregersen
S
S
Second University Clinic of Internal Medicine, Aarhus Kommunehospital, Denmark.
Hermansen
K
K
Yanaihara
N
N
Ahrén
B
B
D000818:Animals; D005260:Female; 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*; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D009479:Neuropeptides; D010446:Peptide Fragments; D010455:Peptides; D019004:Galanin; D005947:Glucose