Cholecystokinin-stimulated insulin secretion and protein kinase C in rat pancreatic islets

Acta Physiol Scand. 1991 Jul;142(3):397-403. doi: 10.1111/j.1748-1716.1991.tb09173.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology
  • Animals
  • Cholecystokinin / pharmacology*
  • Down-Regulation
  • In Vitro Techniques
  • Insulin / blood
  • Insulin / metabolism*
  • Insulin Secretion
  • Islets of Langerhans / drug effects
  • Islets of Langerhans / enzymology
  • Islets of Langerhans / metabolism*
  • Male
  • Protein Kinase C / antagonists & inhibitors
  • Protein Kinase C / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Staurosporine
  • Stimulation, Chemical
  • Tetradecanoylphorbol Acetate / pharmacology


  • Alkaloids
  • Insulin
  • Cholecystokinin
  • Protein Kinase C
  • Staurosporine
  • Tetradecanoylphorbol Acetate