Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets.
Peptides representing the C-terminal end of secretin were synthetized and their effects tested along with secretin on column-perifused isolated mouse pancreatic islets. Insulin release induced by 10 mmol/l D-glucose was potentiated by secretin tested in a concentration range of 0.01-10 micrograms/ml; the maximal effect was obtained with 1 microgram/ml secretin. This effect was mimicked by 50-500 micrograms/ml NH2-Leu-Leu-Gln-Gly-Leu-Val-NH2, [S-(22-27)], which represents an amidated C-terminal sequence of the secretin molecule. The consecutive smaller secretin C-terminal peptides had either no effects [Val-NH2, S-(24-27)] or only marginally [S-(26-27), S-(23-27)] potentiating effects on insulin release in the presence of 10 mmol/l D-glucose. The effects of secretin and S-(22-27) were not influenced by 2 mmol/l glutamine. The intact hormone and the five synthetic peptides as well as Val-NH2 had no stimulatory effect on islet glutamate dehydrogenase activity. In fact, S-(23-27), S-(24-27), and S-(25-27) inhibited the islet glutamate dehydrogenase activity, the activation by which amino acids and amino acid derivatives are known to elicit a potentiation of insulin release. Our results suggest that the C-terminal part is important to the marked potentiation of glucose-induced insulin release in vitro by secretin.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004357:Drug Synergism; D005947:Glucose / Q000494:pharmacology; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D007515:Islets of Langerhans / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010455:Peptides / Q000494:pharmacology*; D012633:Secretin / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013552:Swine
D007328:Insulin; D010455:Peptides; D005973:Glutamine; D012633:Secretin; D005969:Glutamate Dehydrogenase; D005947:Glucose