Evidence 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

Glucagon 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 Ca2+ through L-type voltage gated Ca2+ 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 Ca2+ concentration ([Ca2+]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 [Ca2+]i or Ca2+ efflux from the endoplasmic reticulum. Moreover, sustained elevation of [Ca2+]i induced by ionomycin is insufficient to stimulate the prolonged activation of ERK. Using the cell permeant Ca2+ chelators, EGTA-AM and BAPTA-AM, to determine the spatial dynamics of L-type VGCC-dependent Ca2+ signalling to ERK, we provide evidence that a sustained increase in Ca2+ 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

Un nouveau système d’imagerie gamma portable dédié à la détection et à la visualisation des points chauds dans les centrales nucléaires

International audienceA new portable gamma imaging system dedicated to the detection and the direct visualisation of hot spots in nuclear power plants. In a nuclear power plant (NPP), the localization of radioactive hot spots is a major issue, as they are responsible for a significant part of the doses received by the workers, especially during maintenance operations. Since 2010, EDF and CEA havebeen adapting a new generation caméra gamma, GAMPIX, to have a dedicated portable tool available for this use. This system enables to superimpose a gamma image with a visible image, in order to locate radioactive sources in a given area. Onsitemeasurements at the Tricastin EDF NPP, combined with specific developments at CEA, have been carried out in order to meet the particular environmental and radiological conditions experienced in such industrial facilities: the relatively high energy of cobalt-60 (1.17 and 1.33 MeV) and the existence of an ubiquitous background. This article will present the specifications required, the corresponding improvements and the main results obtained during the on-site measurements campaigns. Even if they were dedicated to the qualification of the camera, the tests carried out showed useful results like the leakage lines along a lead protection and the displacement of a hot spot in a pipe (compared to its identified position). At the end, further developments are presented.Dans une centrale nucléaire (CNPE), la localisation des points chauds est une préoccupation importante, car ils participent à la dose que reçoivent les intervenants, en particulier lors des opérations de maintenance. Depuis 2010, EDF et le CEA ont entrepris d’adapter une nouvelle génération de caméra gamma, GAMPIX, pour disposer d’un instrument portable dédié à cet usage. Ce système permet de superposer une image gamma à une image visible, afin de localiser les sources radioactives pré-sentes dans un environnement. Des essais sur site au CNPE de Tricastin ont été associés aux développements spécifiques réalisés par le CEA, afin d’appréhender les conditions particulières rencontrées en CNPE, à la fois environnementales et radiologiques : l’énergie relativement élevée des gamma du cobalt 60 (1,17 et 1,33 MeV) et la présence d’un bruit de fond ambiant permanent. Cet article présente les principaux axes du cahier des charges initial, les développements réalisés pour y répondre, et les résultats obtenus lors des campagnes d’essais. Même s’ils étaient uniquement dédiés à la qualification de la caméra gamma, les tests réalisés ont montré des résultats très prometteurs, par exemple la mise en évidence de lignes de fuite le long d’une protection biologique ou le mouvement d’un point chaud dans une tuyauterie (par rapport à sa position identifiée). En dernier lieu, les développements futurs sont évoqués