On the nature of the galanin action on the endocrine pancreas: studies with six galanin fragments in the perfused dog pancreas.
Galanin, a 29 amino acid peptide, inhibits insulin and somatostatin secretion from the isolated, perfused dog pancreas. To assess the nature of the influences of galanin on the endocrine pancreas, we examined the effects of porcine galanin and six different galanin analogues at the equimolar concentration of 1 nmol/l on the hormone release from the isolated, perfused dog pancreas. It was found that galanin2-29 (by 75 +/- 4%), like the native galanin1-29 (by 90 +/- 3%) potently inhibited insulin secretion (p less than 0.001). In contrast, galanin3-29 did not significantly affect insulin secretion. This indicates that removal of the two N-terminal amino acids markedly reduces the potency of galanin. Also, the replacement of the amino acid number 2 (Trp) by Tyr or Phe was followed by a loss of the insulin lowering effect of galanin at this dose level. Likewise, galanin10-29 had no significant effect on insulin secretion. In contrast, the C-terminally deleted galanin1-15 significantly inhibited insulin secretion (by 24 +/- 5%; p less than 0.01), though with a lower potency than did native galanin (p less than 0.05). Consequently, the C-terminal end of galanin is also of importance for the effect. Somatostatin secretion was inhibited by galanin (p less than 0.001), but not by any of the other investigated peptides. Glucagon secretion was not affected by galanin. It is concluded that the two N-terminal amino acids of galanin are essential for the inhibitory action on the insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Hermansen
K
K
Second University Clinic of Internal Medicine, Aarhus Kommunehospital, Denmark.
Yanaihara
N
N
Ahrén
B
B
D000595:Amino Acid Sequence; D000818:Animals; D004285:Dogs; D019004:Galanin; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D015394:Molecular Structure; D010455:Peptides / Q000008:administration & dosage*; D010477:Perfusion; D013004:Somatostatin / Q000378:metabolism
D007328:Insulin; D010455:Peptides; D013004:Somatostatin; D019004:Galanin; D005934:Glucagon