Summary
The central role of reversible protein phosphorylation in regulation of beta-cell function is reviewed and the properties of the protein kinases so far defined in beta cells are summarised. The key effect of Ca2+ to initiate insulin secretion involves activation of a Ca2+/calmodulin-dependent protein kinase. Potentiation of secretion by agents activating protein kinase A or C appears to involve an increase in the sensitivity of the secretory system to intracellular Ca2+. The effects of MgATP on the binding of [3H]-glibenclamide to the beta-cell sulphonylurea receptor suggest that the properties of this receptor, which controls the activity of ATP-sensitive K-channels, are modulated by phosphorylation. The identity of the kinases and phosphatases responsible is not known but the presence in beta-cell membranes of various kinases not dependent on Ca2+ or cyclic AMP, and including tyrosine kinase, is documented, together with the presence of both Ca2+-dependent and Ca2+-independent protein phosphatases. Protein phosphorylation is also involved in regulation of beta-cell Ca2+ fluxes and evidence is presented that protein kinase C activation inhibits Ca2+ signalling by reducing influx of Ca2+ into the beta cell. The identity of the Ca2+/calmodulin-dependent protein kinase activity in beta cells is discussed. Comparison of its properties towards substrates and inhibitors with those of brain Ca2+/calmodulin-dependent protein kinase II suggests that the beta-cell enzyme may be similar or identical to the brain enzyme. Evidence from Northern and Western blotting experiments supports this conclusion. These findings are incorporated in a model for control of insulin secretion.
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Abbreviations
- K-ATP channels:
-
ATP-sensitive potassium channels
- DAG:
-
diacylglycerol
- TPA:
-
12-O-tetradecanoyl phorbol acetate
- CaM kinase:
-
calcium/calmodulin-dependent protein kinase
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Ashcroft, S.J.H. Protein phosphorylation and beta-cell function. Diabetologia 37 (Suppl 2), S21–S29 (1994). https://doi.org/10.1007/BF00400822
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DOI: https://doi.org/10.1007/BF00400822