Cholecystokinin-stimulated insulin secretion and protein kinase C in rat pancreatic islets.
In isolated rat pancreatic islets, the possible involvement of protein kinase C in cholecystokinin-8-stimulated insulin secretion was investigated. In islets exposed for 24 hours to the phorbol ester 12-O-tetradecanoyl phorbol 13-acetate (500 nmol l-1), a procedure known to down-regulate islet protein kinase C-activity, the insulinotropic effect of cholecystokinin-8 (10(-7) mol l-1) was partially reduced (by 34 +/- 8%, P less than 0.001). In contrast the insulinotropic response to acute exposure to 12-O-tetradecanoyl phorbol 13-acetate (10(-6) mol l-1) was totally abolished (P less than 0.001), whereas the insulin response to glucose (8.3 mmol l-1) was not affected. In normal islets, the protein kinase C-inhibitor, staurosporine, inhibited 12-O-tetradecanoyl phorbol 13-acetate- and glucose-stimulated insulin secretion (P less than 0.01), but was without effect on cholecystokinin-8-stimulated insulin release. Furthermore, in normal islets, cholecystokinin-8 had no effect on insulin release at a low glucose level (3.3 mmol l-1). However, at this low glucose level, cholecystokinin-8 clearly potentiated insulin release induced by acute exposure to 12-O-tetradecanoyl phorbol 13-acetate (10(-8) -10(-6) mol l-1, P less than 0.001). This potentiating effect was abolished by the removal of extracellular Ca2+. It is concluded that the insulinotropic effect of cholecystokinin-8 in rat islets is partially mediated by the protein kinase C pathway. Furthermore, the lack of effect of cholecystokinin-8 on insulin secretion at a low glucose level might be explained by an insufficient activation of protein kinase C under these conditions.
Department of Pharmacology, Lund University, Sweden.
S
S
Karlsson
B
B
Ahrén
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D015536:Down-Regulation; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D019311:Staurosporine; D013268:Stimulation, Chemical; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D000470:Alkaloids; D007328:Insulin; D002766:Cholecystokinin; D011493:Protein Kinase C; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate