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

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Abstract
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 < 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 < 0.001), whereas the insulin response to glucose (8.3 mmol 1‐l) 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 < 0.01), but was without effect on cholecysto‐kinin‐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 (lo‐8— 10‐6 mol l‐1, P < 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.

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