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Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets

Kofod, H. ; Hansen, B. LU ; Lernmark, A. LU and Hedeskov, C. J. (1986) In American Journal of Physiology - Endocrinology and Metabolism 250(2).
Abstract

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 μg/ml; the maximal effect was obtained with 1 μg/ml secretin. This effect was mimicked by 50-500 μg/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... (More)

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 μg/ml; the maximal effect was obtained with 1 μg/ml secretin. This effect was mimicked by 50-500 μg/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.

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author
publishing date
type
Contribution to journal
publication status
published
in
American Journal of Physiology - Endocrinology and Metabolism
volume
250
issue
2
publisher
American Physiological Society
external identifiers
  • scopus:0022552553
  • pmid:3513606
ISSN
0193-1849
language
English
LU publication?
no
id
28c8e476-357e-43c8-a312-afd1ef129f83
date added to LUP
2019-09-16 12:34:26
date last changed
2019-10-24 16:38:52
@article{28c8e476-357e-43c8-a312-afd1ef129f83,
  abstract     = {<p>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 μg/ml; the maximal effect was obtained with 1 μg/ml secretin. This effect was mimicked by 50-500 μg/ml NH<sub>2</sub>-Leu-Leu-Gln-Gly-Leu-Val-NH<sub>2</sub>, [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-NH<sub>2</sub>, 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-NH<sub>2</sub> 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.</p>},
  author       = {Kofod, H. and Hansen, B. and Lernmark, A. and Hedeskov, C. J.},
  issn         = {0193-1849},
  language     = {eng},
  month        = {01},
  number       = {2},
  publisher    = {American Physiological Society},
  series       = {American Journal of Physiology - Endocrinology and Metabolism},
  title        = {Secretin and its C-terminal hexapeptide potentiates insulin release in mouse islets},
  volume       = {250},
  year         = {1986},
}