Pancreastatin: characterization of biological activity.
Pancreastatin (PST) (1-49) was first isolated from the porcine pancreas and can inhibit glucose-induced insulin release. PST (33-49), a PST C-terminal fragment, can also inhibit insulin release. The purpose of this study was to determine the shortest C-terminal biologically active fragment of PST, in terms of inhibition of insulin release from the isolated perfused rat pancreas. Porcine PST (1-49) and C-terminal fragments, PST (33-49), PST (35-49), PST (37-49) and PST (39-49) were synthesized by solid-phase methodology. PST (1-49), PST (33-49) and PST (35-49), at 10 nM, significantly (p less than 0.05) inhibited insulin release from isolated perfused rat pancreas: the first phase was inhibited by 15.6 +/- 2.4, 24.4 +/- 6.5 and 12.5 +/- 1.9% and the second phase, 18.9 +/- 2.7, 25.7 +/- 4.8 and 20.1 +/- 1.9% by PST (1-49), PST (33-49) and PST (35-49), respectively. PST (35-49) shows a dose-dependent inhibition of insulin release. PST (37-49) and PST (39-49) were, however, inactive. Our results indicate that the shortest C-terminal biologically active fragment is PST (35-49). These data further indicate that the C-terminal portion of PST is primarily responsible for the biological activity of PST.
Zhang
T
T
Department of Surgery, University of Texas Medical Branch, Galveston 77550.
Mochizuki
T
T
Kogire
M
M
Ishizuka
J
J
Yanaihara
N
N
Thompson
J C
JC
Greeley
G H
GH
D000818:Animals; D053379:Chromogranin A; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010187:Pancreatic Hormones / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D053379:Chromogranin A; D007328:Insulin; D010187:Pancreatic Hormones; C050836:pancreastatin; D005947:Glucose