Possible involvement of diacylglycerol-activated, Ca2+-dependent protein kinase in glucose memory of the rat pancreatic B-cell

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Abstract
Exposure to high concentrations of glucose potentiates insulin release from the pancreatic B-cell stimulated by various secretagogues after an interval under basal condition. We studied the role of diacyglycerol-activated, Ca2+-dependent protein kinase (protein kinase C) in this priming effect of glucose in rat pancreatic islets, using 12-O-tetradecanoyl phorbol-13-acetate (TPA). 1-(5-isoquionolinesulfonyl)-2-methylpiperazine (H-7), N-(2-guanidinoethyl)-5-isoquinolinesulfonamide (HA-1004) and forskolin. The priming effect of glucose was mimiced by 10 nmol/l of TPA, an activator of protein kinase, C, but not by 5 .mu.mol/l of forskolin, which increases cAMP via activating adenylate cyclase. When pancreatic islets were exposed to glucose (10 mmol/l) together with 50 .mu.mol/l of H-7 an inhibitor of protein kinase C, the secretory response to glucose (10 mmol/l) after a 30-min interval was significantly reduced compared with that in the islets previously exposed to 10 mmol/l glucose alone. In contrast, this was not the case for HA-1004, its inhibitory activity against protein kinase C being less potent than H-7. These findings suggest that protein kinase C may play an important role in the priming effect of glucose on the pancreatic B-cell.