Abstract
We showed previously that ERK1/2 were activated by glucose and amino acids in pancreatic beta cells. Here we examine and compare signaling events that are necessary for ERK1/2 activation by glucose and other stimuli in beta cells. We find that agents that interrupt Ca2+ signaling by a variety of mechanisms interfere with glucose- and glucagon-like peptide (GLP-1)-stimulated ERK1/2 activity. In particular, calmodulin antagonists, FK506, and cyclosporin, immunosuppressants that inhibit the calcium-dependent phosphatase calcineurin, suppress ERK1/2 activation by both glucose and GLP-1. Ca2+ signaling from intracellular stores is also essential for ERK1/2 activation, because thapsigargin blocks ERK1/2 activation by glucose or GLP-1. The glucose-sensitive mechanism is distinct from that used by phorbol ester or insulin to stimulate ERK1/2 but shares common features with that used by GLP-1.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenoviridae / genetics
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Androstadienes / pharmacology
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Animals
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Calcineurin / metabolism
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Calcium / metabolism
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Calmodulin / metabolism
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Cyclosporine / pharmacology
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Dose-Response Relationship, Drug
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Enzyme Activation
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Gene Expression Regulation, Enzymologic*
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Glucose / metabolism*
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Immunosuppressive Agents / pharmacology
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Insulin / metabolism
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Islets of Langerhans / metabolism*
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Mitogen-Activated Protein Kinase 1 / metabolism*
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / metabolism*
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Models, Biological
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Peptide Hormones / metabolism*
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Rats
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Signal Transduction
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Tacrolimus / pharmacology
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Thapsigargin / pharmacology
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Time Factors
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Wortmannin
Substances
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Androstadienes
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Calmodulin
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Immunosuppressive Agents
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Insulin
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Peptide Hormones
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Thapsigargin
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Cyclosporine
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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Calcineurin
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Glucose
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Calcium
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Tacrolimus
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Wortmannin