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dc.contributor.authorSelway, J.-
dc.contributor.authorRigatti, R.-
dc.contributor.authorStorey, N.-
dc.contributor.authorLu, J.-
dc.contributor.authorWillars, G. B.-
dc.contributor.authorHerbert, T. P.-
dc.identifier.citationPLOS ONE, 2012, 7 (3), p. e33004-
dc.description.abstractGlucagon like peptide-1 (GLP-1) is released from intestinal L-cells in response to nutrient ingestion and acts upon pancreatic β-cells potentiating glucose-stimulated insulin secretion and stimulating β-cell proliferation, differentiation, survival and gene transcription. These effects are mediated through the activation of multiple signal transduction pathways including the extracellular regulated kinase (ERK) pathway. We have previously reported that GLP-1 activates ERK through a mechanism dependent upon the influx of extracellular Ca(2+) through L-type voltage gated Ca(2+) channels (VGCC). However, the mechanism by which L-type VGCCs couple to the ERK signalling pathway in pancreatic β-cells is poorly understood. In this report, we characterise the relationship between L-type VGCC mediated changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) and the activation of ERK, and demonstrate that the sustained activation of ERK (up to 30 min) in response to GLP-1 requires the continual activation of the L-type VGCC yet does not require a sustained increase in global [Ca(2+)](i) or Ca(2+) efflux from the endoplasmic reticulum. Moreover, sustained elevation of [Ca(2+)](i) induced by ionomycin is insufficient to stimulate the prolonged activation of ERK. Using the cell permeant Ca(2+) chelators, EGTA-AM and BAPTA-AM, to determine the spatial dynamics of L-type VGCC-dependent Ca(2+) signalling to ERK, we provide evidence that a sustained increase in Ca(2+) within the microdomain of the L-type VGCC is sufficient for signalling to ERK and that this plays an important role in GLP-1- stimulated ERK activation.-
dc.publisherPublic Library of Science-
dc.rightsCopyright © 2012 Selway et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.-
dc.subjectCalcium Channels-
dc.subjectCell Line-
dc.subjectEnzyme Activation-
dc.subjectExtracellular Signal-Regulated MAP Kinases-
dc.subjectGlucagon-Like Peptide 1-
dc.subjectSignal Transduction-
dc.titleEvidence That Ca2+ within the Microdomain of the L-Type Voltage Gated Ca2+ Channel Activates ERK in MIN6 Cells in Response to Glucagon-Like Peptide-1-
dc.typeJournal Article-
dc.description.versionPublisher Version-
Appears in Collections:Published Articles, Dept. of Cell Physiology and Pharmacology

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