Distribution and stimulation by gastrin-releasing peptide of protein kinase C subfamilies in insulin-secreting cells.
The role of the different isoforms of protein kinase C (PKC) in modulating insulin secretion is still widely unknown. The aim of our studies was to investigate which isoforms are influenced by gastrin-releasing peptide (GRP), a neuropeptide which has been shown to modulate insulin secretion by activating PKC. Presence of PKC isoforms alpha, beta, gamma, delta, epsilon and zeta was tested by immunoblot analysis in whole pancreatic islets of mouse and rat and in the insulinoma cell line RINm5F. Effects of GRP, the truncated peptide GRP1-16 and KCl were also measured on translocation of PKC isoforms. In pancreatic islets of mouse and rat, the PKC isoforms alpha, beta, gamma, delta, epsilon and zeta could be detected. No PKCgamma activity was present in the pancreatic tumor cell line RINm5F. Incubation of mouse or rat islets or of RINm5F cells with GRP induced translocation of the PKC isoforms alpha, beta and zeta. The N-terminal portion of the peptide GRP1-16 induced partial translocation only of the PKC isoforms alpha, beta and zeta in mouse and rat islets in 4 out of 10 cases, but failed to show any effect on PKC isoforms in RINm5F cells. Depolarization of the islets by KCl did not translocate any tested PKC isoform. However, incubation with GRP followed by depolarization with KCl led to translocation of the PKC isoforms alpha, beta and zeta. It is suggested that PKC alpha, beta and/or zeta may play a role in the modulation of insulin secretion by GRP.
Bihlmayer
A
A
Department of Pharmacology, Institute of Pharmaceutical Sciences, Eberhard-Karls University, Tübingen, Germany.
Ammon
H P
HP
Wahl
M A
MA
D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000494:pharmacology*; D015151:Immunoblotting; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007340:Insulinoma; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D010190:Pancreatic Neoplasms; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D007328:Insulin; D007527:Isoenzymes; D011189:Potassium Chloride; D019886:Gastrin-Releasing Peptide; D011493:Protein Kinase C