Ca2+-induced loss of Ca2+/calmodulin-dependent protein kinase II activity in pancreatic beta -cells

• Published in: American journal of physiology: endocrinology and metabolism 1998-04, Vol.274 (4), p.E708
• Main Authors: Jones, Peter M, Persaud, Shanta J
• Format: Article
• Language: English
• ISSN: 0193-1849; 1522-1555
• DOI: 10.1152/ajpendo.1998.274.4.E708

Cellular and Molecular Endocrinology Group, Biomedical Sciences Division, King's College London, London W8 7AH, United Kingdom Elevations in intracellular Ca 2+ in electrically permeabilized islets of Langerhans produced rapid insulin secretory responses from -cells, but the Ca 2+ -induced secretion was not maintained and was irrespective of the pattern of administration of elevated Ca 2+ . Ca 2+ -insensitive -cells responded normally to activators of protein kinase C or cAMP-dependent kinase with increased insulin secretion. The loss of secretory responsiveness to Ca 2+ was paralleled by a reduction in Ca 2+ -induced protein phosphorylation. This was caused by a reduction in Ca 2+ /calmodulin-dependent 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 Ca 2+ -induced reductions in kinase activity and protein phosphorylation were not dependent on the activation of Ca 2+ -dependent protein kinases and were not caused by the activation of phosphoprotein phosphatases or of Ca 2+ -activated proteases. The concomitant reductions in CaMK II activity and Ca 2+ -induced insulin secretion suggest that the activation of CaMK II is required for normal insulin secretory responses to increased intracellular Ca 2+ concentrations. islets of Langerhans; protein phosphorylation; calcium ion