TY - JOUR
T1 - Galparan
T2 - A powerful insulin-releasing chimeric peptide acting at a novel site
AU - Östenson, Claes Göran
AU - Zaitsev, Sergei
AU - Berggren, Per Olof
AU - Efendic, Suad
AU - Langel, Ülo
AU - Bartfai, Tamas
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 1997
Y1 - 1997
N2 - Galparan is a 27-amino acid long chimeric peptide, GWTLN-SAGYLLGP- INLKALAALAKKIL amide, consisting of galanin-(1-13) linked to mastoparan amide via a peptide bond to provide the mastoparan and galanin effector parts of the molecules. Galparan (10 μM) powerfully stimulates insulin secretion from isolated rat pancreatic islets in a reversible and dose-dependent manner; the stimulation is 26-fold at 3.3 mM glucose and 6-fold at 16.7 mM glucose. Galparan also enhances insulin secretion to a similar extent from islets of diabetic GK rats. The stimulatory effect of galparan on insulin release is not directly dependent on extracellular Ca2+, nor can it be explained only by changes in free cytosolic Ca2+ concentrations. Furthermore, galparan is effective in evoking insulin release in B cells depolarized by 25 mM KCI when ATP-sensitive K+ channels are kept open by diazoxide. Thus, galparan, like mastoparan, stimulates exocytosis of insulin at a distal site in the stimulus-secretion coupling of the B cell. This distal site is not identical to that used by mastoparan, as pertussle toxin pretreatment does not influence the insulinogenic effect of galparan. In conclusion, galparan evokes a large and reversible insulin secretion, acting at a yet unknown distal site and also promoting exocytosis in depolarized B cells from normal rats as well as diabetic GK rats.
AB - Galparan is a 27-amino acid long chimeric peptide, GWTLN-SAGYLLGP- INLKALAALAKKIL amide, consisting of galanin-(1-13) linked to mastoparan amide via a peptide bond to provide the mastoparan and galanin effector parts of the molecules. Galparan (10 μM) powerfully stimulates insulin secretion from isolated rat pancreatic islets in a reversible and dose-dependent manner; the stimulation is 26-fold at 3.3 mM glucose and 6-fold at 16.7 mM glucose. Galparan also enhances insulin secretion to a similar extent from islets of diabetic GK rats. The stimulatory effect of galparan on insulin release is not directly dependent on extracellular Ca2+, nor can it be explained only by changes in free cytosolic Ca2+ concentrations. Furthermore, galparan is effective in evoking insulin release in B cells depolarized by 25 mM KCI when ATP-sensitive K+ channels are kept open by diazoxide. Thus, galparan, like mastoparan, stimulates exocytosis of insulin at a distal site in the stimulus-secretion coupling of the B cell. This distal site is not identical to that used by mastoparan, as pertussle toxin pretreatment does not influence the insulinogenic effect of galparan. In conclusion, galparan evokes a large and reversible insulin secretion, acting at a yet unknown distal site and also promoting exocytosis in depolarized B cells from normal rats as well as diabetic GK rats.
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U2 - 10.1210/endo.138.8.5307
DO - 10.1210/endo.138.8.5307
M3 - Article
C2 - 9231782
AN - SCOPUS:0030741027
VL - 138
SP - 3308
EP - 3313
JO - Endocrinology
JF - Endocrinology
SN - 0013-7227
IS - 8
ER -