Regulation of ERK1 and ERK2 by glucose and peptide hormones in pancreatic beta cells.
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.
Arnette
Don
D
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
Gibson
Tara Beers
TB
Lawrence
Michael C
MC
January
Bridgette
B
Khoo
Shih
S
McGlynn
Kathleen
K
Vanderbilt
Colleen A
CA
Cobb
Melanie H
MH
D000256:Adenoviridae / Q000235:genetics; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002147:Calmodulin / Q000378:metabolism; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008954:Models, Biological; D036361:Peptide Hormones / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction; D016559:Tacrolimus / Q000494:pharmacology; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D000077191:Wortmannin
D000730:Androstadienes; D002147:Calmodulin; D007166:Immunosuppressive Agents; D007328:Insulin; D036361:Peptide Hormones; D019284:Thapsigargin; D016572:Cyclosporine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin; D005947:Glucose; D002118:Calcium; D016559:Tacrolimus; D000077191:Wortmannin