Cholecystokinin‐stimulated insulin secretion and protein kinase C in rat pancreatic islets
- 1 July 1991
- journal article
- Published by Wiley in Acta Physiologica Scandinavica
- Vol. 142 (3), 397-403
- https://doi.org/10.1111/j.1748-1716.1991.tb09173.x
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 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.Keywords
This publication has 31 references indexed in Scilit:
- Protein kinase C in insulin releasing cellsFEBS Letters, 1990
- Activation of protein kinase C assists insulin producing cells in recovery from raised cytoplasmic Ca2+ by stimulating Ca2+ effluxBiochemical and Biophysical Research Communications, 1989
- Glucose and carbachol generate 1,2-diacylglycerols by different mechanisms in pancreatic islets.JCI Insight, 1988
- Selective α2‐adrenoceptor activation by clonidine: effects on 45Ca2 efflux and insulin secretion from isolated rat isletsActa Physiologica Scandinavica, 1988
- Stimulation of insulin release by the phorbol ester 12-O-tetradecanoylphorbol 13-acetate in the clonal cell line RINm5F despite a lowering of the free cytoplasmic Ca2+ concentrationBiochimica et Biophysica Acta (BBA) - Molecular Cell Research, 1986
- Localization of saturable CCK binding sites in rat pancreatic islets by light and electron microscope autoradiographyDiabetes, 1985
- Phosphatidylinositol and phosphatidic acid metabolism in rat pancreatic islets in response to neurotransmitter and hormonal stimuliBiochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism, 1983
- Calcium‐activated, phospholipid‐dependent protein kinase in rat pancreas islets of langerhansFEBS Letters, 1982
- Effects of two cholecystokinin variants, CCK-39 and CCK-8, on basal and stimulated insulin secretionActa Diabetologica, 1981
- Neural regulation of pancreatic hormone secretion by the C-terminal tetrapeptide of CCKNature, 1980