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Inhibition of insulin secretion by KN-62, a specific inhibition of the multifunctional calcium/calmodulin-dependent protein kinase II



Inhibition of insulin secretion by KN-62, a specific inhibition of the multifunctional calcium/calmodulin-dependent protein kinase II



Biochemical & Biophysical Research Communications 189(1): 128-133



The effects of KN-62, a specific inhibitor of Ca-2+/calmodulin-dependent protein kinase II (CamPKII), on insulin secretion and protein phosphorylation were studied in rat pancreatic islets and RINm5F cells. KN-62 was found to dose-dependently inhibit autophosphorylation of CamPKII in subcellular preparations of RINm5F cells (K-0.5 = 3.1 +- 0.3 mu-M), but had no effect on protein kinase C or myosin light chain kinase activity. KN-62, but not the inactive analogue KN-04, dose-dependently inhibited glucose-induced insulin release (K-0.5 = 1.5 +- 0.5 mu-M) in a manner similar to the inhibition of CamPKII autophosphorylation. KN-62 (10 mu-M) inhibited carbachol (in the presence of 8 mM glucose) and potassium-stimulated insulin secretion from islets by 53% and 59%, respectively. These results support a role of CamPKII in glucose-sensitive insulin secretion.

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