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.
Gregersen
S
S
Department of Endocrinology and Metabolism C, Aarhus University Hospital, Denmark.
Langel
U
U
Bartfai
T
T
Ahrén
B
B
D000818:Animals; D001665:Binding Sites; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D019004:Galanin; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D007328:Insulin; D010446:Peptide Fragments; D010455:Peptides; D044088:Receptors, Galanin; D011964:Receptors, Gastrointestinal Hormone; C074069:galanin-(1-13)-bradykinin-(2-9)-amide; D019004:Galanin; D005947:Glucose; D001920:Bradykinin