Pseudosubstrate Inhibition of Cyclic AMP-Dependent Protein Kinase in Intact Pancreatic Islets: Effects on Cyclic AMP-Dependent and Glucose-Dependent Insulin Secretion

1997 ◽  
Vol 232 (3) ◽  
pp. 648-651 ◽  
Author(s):  
Tracey E. Harris ◽  
Shanta J. Persaud ◽  
Peter M. Jones
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Pancreatic Islets ◽  
Dependent Protein Kinase ◽  
Dependent Protein

scholarly journals Muscarinic activation of Ca2+/calmodulin-dependent protein kinase II in pancreatic islets. Temporal dissociation of kinase activation and insulin secretion

1996 ◽  
Vol 317 (1) ◽  
pp. 167-172 ◽  
Author(s):  
Eric L. BABB ◽  
Jim TARPLEY ◽  
Michael LANDT ◽  
Richard A. EASOM
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Pancreatic Islets ◽  
Cam Kinase Ii ◽  
Muscarinic Agonist ◽  
Cam Kinase ◽  
Dependent Protein Kinase ◽  
Kinase Activation ◽  
Protein Kinase Ii ◽  
Dependent Protein

We have demonstrated previously that glucose activates the multifunctional Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) in isolated rat pancreatic islets in a manner consistent with a role of this enzyme in the regulation of insulin secretion [Wenham, Landt and Easom (1994) J. Biol. Chem. 269, 4947–4952]. In the current study, the muscarinic agonist, carbachol, has been shown to induce the conversion of CaM kinase II into a Ca2+-independent, autonomous form indicative of its activation. Maximal activation (2-fold) was achieved by 15 s, followed by a rapid return to basal levels by 1 min. This response was primarily the result of the mobilization of Ca2+ from intracellular stores since it was not affected by a concentration (20 μM) of verapamil that completely prevented the activation of CaM kinase II by glucose. Surprisingly, carbachol added prior to, or simultaneously with, glucose attenuated nutrient activation of CaM kinase II. This effect was mimicked by cholecystokinin-8 (CCK-8) and thapsigargin, suggesting its mediation by phospholipase C and the mobilization of intracellular Ca2+. In contrast, carbachol, CCK-8 and thapsigargin markedly potentiated glucose (12 mM)-induced insulin secretion. These results suggest that CaM kinase II activation can be temporally dissociated from insulin secretion but do not exclude the potential dependence of insulin exocytosis on CaM kinase II-mediated protein phosphorylation.

scholarly journals Effects of dehydrouramil on protein phosphorylation and insulin secretion in rat islets of Langerhans

1986 ◽  
Vol 237 (1) ◽  
pp. 191-196 ◽  
Author(s):  
D E Harrison ◽  
M Poje ◽  
B Rocic ◽  
S J H Ashcroft
Keyword(s):  
Insulin Secretion ◽  
Protein Kinase ◽  
Cyclic Amp ◽  
Protein Phosphorylation ◽  
Islets Of Langerhans ◽  
Dependent Protein Kinase ◽  
Tetradecanoylphorbol Acetate ◽  
Endogenous Protein ◽  
Dependent Protein ◽  
Rat Islets Of Langerhans

Dehydrouramil hydrate hydrochloride (DHU), a stable analogue of alloxan, inhibited the phosphorylation of an endogenous protein of Mr 53,000 catalysed by a Ca2+-calmodulin-dependent protein kinase in extracts of islets of Langerhans. The concentration of DHU required for 50% inhibition was 0.09 mM. DHU did not inhibit islet cyclic AMP-dependent protein kinase and caused only slight inhibition of Ca2+-phospholipid-dependent protein kinase. Inhibition of Ca2+-calmodulin-dependent protein kinase was neither prevented nor reversed by dithiothreitol. DHU did not affect the ability of calmodulin to activate cyclic AMP phosphodiesterase. In intact islets, pre-exposure to DHU impaired the insulin-secretory response to glucose and blocked the potentiatory effect on insulin secretion of forskolin, an activator of adenylate cyclase, and of tetradecanoylphorbol acetate (TPA), an activator of Ca2+-phospholipid-dependent protein kinase. The increase in islet cyclic AMP elicited by forskolin was not affected by DHU. The data are consistent with the hypothesis that protein phosphorylation catalysed by a Ca2+-calmodulin-dependent protein kinase may play a central role in the regulation of insulin secretion.

scholarly journals A cytosolic cyclic AMP-dependent protein kinase in Dictyostelium discoideum. I. Properties.

1984 ◽  
Vol 259 (1) ◽  
pp. 654-661 ◽  
Author(s):  
I H Majerfeld ◽  
B H Leichtling ◽  
J A Meligeni ◽  
E Spitz ◽  
H V Rickenberg
Keyword(s):  
Protein Kinase ◽  
Cyclic Amp ◽  
Dictyostelium Discoideum ◽  
Dependent Protein Kinase ◽  
Dependent Protein
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