AJP - Endocrinology and Metabolism, Vol 250, Issue 2 107-E113, Copyright © 1986 by American Physiological Society
Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets
H. Kofod, B. Hansen, A. Lernmark and C. J. Hedeskov
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.
