Regulation of insulin exocytosis by calcium-dependent protein kinase C in beta cells |
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Affiliation: | 1. Department of Pharmacology, Brehm Diabetes Research Center, University of Michigan Medical School, Ann Arbor, MI 48105, USA;2. Department of Medicine, David Geffen School of Medicine, UCLA, Los Angeles, CA 90095-7073, USA;3. Laboratory of Biological Modeling, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA |
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Abstract: | The control of insulin release from pancreatic beta cells helps ensure proper blood glucose level, which is critical for human health. Protein kinase C has been shown to be one key control mechanism for this process. After glucose stimulation, calcium influx into beta cells triggers exocytosis of insulin-containing dense-core granules and activates protein kinase C via calcium-dependent phospholipase C-mediated generation of diacylglycerol. Activated protein kinase C potentiates insulin release by enhancing the calcium sensitivity of exocytosis, likely by affecting two main pathways that could be linked: (1) the reorganization of the cortical actin network, and (2) the direct phosphorylation of critical exocytotic proteins such as munc18, SNAP25, and synaptotagmin. Here, we review what is currently known about the molecular mechanisms of protein kinase C action on each of these pathways and how these effects relate to the control of insulin release by exocytosis. We identify remaining challenges in the field and suggest how these challenges might be addressed to advance our understanding of the regulation of insulin release in health and disease. |
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Keywords: | Protein kinase C Insulin Exocytosis Beta cell PKC" },{" #name" :" keyword" ," $" :{" id" :" kw0030" }," $$" :[{" #name" :" text" ," _" :" protein kinase C DAG" },{" #name" :" keyword" ," $" :{" id" :" kw0040" }," $$" :[{" #name" :" text" ," _" :" diacylglycerol PIP2" },{" #name" :" keyword" ," $" :{" id" :" kw0050" }," $$" :[{" #name" :" text" ," _" :" phosphatidylinositol-4,5-bisphosphate GSIS" },{" #name" :" keyword" ," $" :{" id" :" kw0060" }," $$" :[{" #name" :" text" ," _" :" glucose stimulated insulin secretion PLC" },{" #name" :" keyword" ," $" :{" id" :" kw0070" }," $$" :[{" #name" :" text" ," _" :" phospholipase C IP3" },{" #name" :" keyword" ," $" :{" id" :" kw0080" }," $$" :[{" #name" :" text" ," _" :" inositol triphosphate PMA" },{" #name" :" keyword" ," $" :{" id" :" kw0090" }," $$" :[{" #name" :" text" ," _" :" phorbol 12-myristate 13-acetate TPA" },{" #name" :" keyword" ," $" :{" id" :" kw0100" }," $$" :[{" #name" :" text" ," _" :" tetradecanoylphorbol acetate (synonym of PMA) RRP" },{" #name" :" keyword" ," $" :{" id" :" kw0110" }," $$" :[{" #name" :" text" ," _" :" readily-releaseable pool MARCKS" },{" #name" :" keyword" ," $" :{" id" :" kw0120" }," $$" :[{" #name" :" text" ," _" :" myristoylated alanine-rich C-kinase substrate MLCK" },{" #name" :" keyword" ," $" :{" id" :" kw0130" }," $$" :[{" #name" :" text" ," _" :" myosin light chain kinase DCV" },{" #name" :" keyword" ," $" :{" id" :" kw0140" }," $$" :[{" #name" :" text" ," _" :" dense-core vesicle |
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