Ca21-induced loss of Ca21/calmodulin-dependent protein kinase II activity in pancreatic b-cells

Jones, Peter M., and Shanta J. Persaud. Ca21-induced loss of Ca21/calmodulin-dependent protein kinase II activity in pancreatic b-cells. Am. J. Physiol. 274 (Endocrinol. Metab. 37): E708–E715, 1998.—Elevations in intracellular Ca21 in electrically permeabilized islets of Langerhans produced rapid insulin secretory responses from b-cells, but the Ca21induced secretion was not maintained and was irrespective of the pattern of administration of elevated Ca21. Ca21insensitive b-cells responded normally to activators of protein kinase C or cAMP-dependent kinase with increased insulin secretion. The loss of secretory responsiveness to Ca21 was paralleled by a reduction in Ca21-induced protein phosphorylation. This was caused by a reduction in Ca21/calmodulindependent protein kinase II (CaMK II) activity in the desensitized cells, as assessed by measuring the phosphorylation of a CaMK II-specific exogenous substrate, autocamtide-2. The Ca21-induced reductions in kinase activity and protein phosphorylation were not dependent on the activation of Ca21dependent protein kinases and were not caused by the activation of phosphoprotein phosphatases or of Ca21activated proteases. The concomitant reductions in CaMK II activity and Ca21-induced insulin secretion suggest that the activation of CaMK II is required for normal insulin secretory responses to increased intracellular Ca21 concentrations.