Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro.
Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5.6 mmol glucose/l. 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16.7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2.8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11.1 mmol/l. At 5.6 mmol glucose/l, GRP (100 pmol/1-100 nmol/l) increased (by 50-70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 mumol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores.
Wilkes
L C
LC
Department of Pharmaceutical Sciences, Aston University, Birmingham.
Bailey
C J
CJ
Thompson
M G
MG
Conlon
J M
JM
Buchanan
K D
KD
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D019886:Gastrin-Releasing Peptide; D005755:Gastrins / Q000494:pharmacology*; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010187:Pancreatic Hormones / Q000378:metabolism*; D010455:Peptides / Q000494:pharmacology*
D005755:Gastrins; D007328:Insulin; D010187:Pancreatic Hormones; D010455:Peptides; D019886:Gastrin-Releasing Peptide; D005934:Glucagon; D002118:Calcium