DISSOCIATION BETWEEN CHANGES IN CYTOPLASMIC FREE CA2-SECRETION AS EVIDENCED FROM MEASUREMENTS IN MOUSE SINGLE PANCREATIC-ISLETS( CONCENTRATION AND INSULIN)

Simultaneous measurements of cytosolic free Ca2+ concentration and ins ulin release. in mouse single pancreatic islets, revealed a direct cor relation only initially after stimulation with glucose or K+. Later, t here is an apparent dissociation between these two parameters, with tr anslocation of alpha and epsilon isoenzymes of protein kinase C to mem branes and simultaneous desensitization of insulin release in response to glucose. Recovery of insulin release, without any concomitant chan ges in cytosolic free Ca2+ concentration, after addition of phorbol 12 -myristate 13-acetate, okadaic acid, and forskolin supports the notion that the desensitization process is accounted for by dephosphorylatio n of key regulatory sites of the insulin exocytotic machinery.