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 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.
| Original language | English |
|---|---|
| Journal | American Journal of Physiology (Consolidated) |
| Volume | 250 |
| Issue number | 2 Pt 1 |
| Pages (from-to) | E107-13 |
| ISSN | 0002-9513 |
| Publication status | Published - Feb 1986 |
Keywords
- Animals
- Chemical Phenomena
- Chemistry
- Drug Synergism
- Glucose
- Glutamate Dehydrogenase
- Glutamine
- Insulin
- Islets of Langerhans
- Male
- Mice
- Mice, Inbred Strains
- Peptides
- Secretin
- Structure-Activity Relationship
- Swine