Ca2+-induced loss of ca2+/calmodulin-dependent protein kinase ii
activity in pancreatic [beta]-cells.
Jones, Peter M., and Shanta J. Persaud.
Cellular and Molecular Endocrinology Group, Biomedical Sciences
Division, King's College London, London W8 7AH, England.
APStracts 4:0286E, 1997.
Elevations in intracellular Ca2+ in electrically permeabilized islets
of Langerhans produced rapid insulin secretory responses from [beta]
-cells, but the Ca2+-induced secretion was not maintained, and was
irrespective of the pattern of administration of elevated Ca2+. Ca2+
-insensitive _[beta]_-cells responded normally to activators of
protein kinase C or cyclic AMP-dependent kinase with increased
insulin secretion. The loss of secretory responsiveness to Ca2+ was
paralleled by a reduction in Ca2+-induced protein phosphorylation.
This was caused by a reduction in Ca2+/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 Ca2+-induced reductions in kinase
activity and protein phosphorylation were not dependent upon the
activation of Ca2+-dependent protein kinases, and were not caused by
the activation of phosphoprotein phosphatases or of Ca2+-activated
proteases. The concomitant reductions in CaMK II activity and Ca2+
-induced insulin secretion suggest that the activation of CaMK II is
required for normal insulin secretory responses to increased
intracellular Ca2+ concentrations.
Received 11 June 1997; accepted in final form 18 December 1997.
APS Manuscript Number E271-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998