Differential effects of secretin-fragments imply a dual mechanism of action for secretin.
The effects of synthetic peptides, representing different parts of the secretin molecule in isolated mouse pancreatic islets have been investigated in perifusion studies. In the presence of 10 mM D-glucose the C-terminal nonapeptide Leu-Gln-Arg-Leu-Leu-Gln-Gly-Leu-Val-NH2 (S19-27) showed a 2-fold higher activity than that earlier shown for S22-27 and had the same effect on the dynamic pattern of insulin release as secretin, while the elongating sequence Leu-Gln-Arg (S19-21) had no effect on the insulin release. The nonapeptide Leu-Ser-Arg-Leu-Arg-Asp-Ser-Ala-Arg (S10-18) had no influence on the insulin release. Glucagon release seen after intact secretin could not be shown for any of the smaller fragments. Accumulation of cAMP in the islets as seen with secretin, could at 10 mmol/L D-glucose only be demonstrated with S22-27 or S19-27 but not with S10-18 or S1-6. Our results indicate that full size secretin has to be present to stimulate glucagon release while insulin-releasing activity can be confined to the C-terminal part of the hormone.
Kofod
H
H
Hagedorn Research Laboratory, Gentoft, Denmark.
Thams
P
P
Holst
J J
JJ
D000595:Amino Acid Sequence; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000494:pharmacology*; D012633:Secretin / Q000494:pharmacology*
D007328:Insulin; D010446:Peptide Fragments; D012633:Secretin; D005934:Glucagon; D000242:Cyclic AMP; D005947:Glucose