CORRELATION OF THE ACTIVATION OF CA2+ CALMODULIN-DEPENDENT PROTEIN-KINASE-II WITH THE INITIATION OF INSULIN-SECRETION FROM PERIFUSED PANCREATIC-ISLETS/

An experimental procedure has been designed to permit the simultaneous assessment of the activation status of the multifunctional Ca2+/calmo dulin-dependent protein kinase II (CaM kinase II) with insulin secreti on in perifused islets. By this procedure, the activation of CaM kinas e II by glucose correlated closely with the initial and sustained phas es of insulin secretion within a 30-min test period. By contrast, isle ts (160-200/tube) in static incubations neither supported second-phase insulin secretion nor CaM kinase II activation beyond 10-15 min. This was not the result of the accumulation of insulin, because the introd uction of insulin (40-160 ng/ml) into the perifusion medium failed to mimic the suppression of glucose-induced insulin secretion or CaM kina se II activation. A similar addition of SRIF (0.01-1 mu M) or epinephr ine (1 mu M) profoundly suppressed insulin secretion although failing to significantly influence CaM kinase II activation. Finally, on withd rawal of glucose from perifused islets, insulin secretion rapidly retu rned to basal rates, but CaM kinase II deactivation was significantly delayed. The correlation of kinase activation with the initiation of i nsulin secretion suggests that CaM kinase II may be important in the r egulation of glucose-induced insulin secretion. The observed dissociat ion of these parameters in the presence of inhibitory hormones or afte r the withdrawal of a glucose stimulus, however, suggests that the kin ase is not directly involved in the final steps of insulin exocytosis.