Extracellularly regulated kinases 1/2 (p44/42 mitogen-activated protein kinases) phosphorylate synapsin I and regulate insulin secretion in the MIN6 beta-cell line and islets of Langerhans
Autor: | Stéphane Dalle, Safia Costes, Christine Longuet, Dominique Bataille, Christophe Broca, El Habib Hani |
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Přispěvatelé: | Institut de Génomique Fonctionnelle (IGF), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS) |
Jazyk: | angličtina |
Rok vydání: | 2005 |
Předmět: |
Male
Cytoplasm medicine.medical_specialty Synapsin I medicine.medical_treatment 030209 endocrinology & metabolism Islets of Langerhans 03 medical and health sciences 0302 clinical medicine Endocrinology Cell Line Tumor Internal medicine Insulin Secretion medicine Animals Insulin Secretion Phosphorylation RNA Small Interfering Rats Wistar 030304 developmental biology Cell Nucleus Mitogen-Activated Protein Kinase 1 0303 health sciences Mitogen-Activated Protein Kinase 3 biology Kinase 1. No poverty Synapsin [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Synapsins Rats Pancreatic Neoplasms Glucose Mitogen-activated protein kinase biology.protein Beta cell |
Zdroj: | Endocrinology Endocrinology, Endocrine Society, 2005, 146, pp.643-654. ⟨10.1210/en.2004-0841⟩ |
ISSN: | 0013-7227 |
Popis: | The p44/p42 MAPKs (ERK1/2) cascade regulates beta-cell nuclear events, which modulates cell differentiation and gene transcription, whereas its implication in processes occurring in the cytoplasm, such as activation of the exocytotic machinery, is still unclear. Using the MIN6 beta-cell line and isolated rat islets of Langerhans, we investigated whether glucose, by activating the ERK1/2 cascade, induces phosphorylation of cytoplasmic proteins implicated in exocytosis of insulin granules such as synapsin I. We observed that the majority of ERK1/2 activity induced by glucose remains in the cytoplasm and physically interacts with synapsin I, allowing phosphorylation of the substrate. Therefore, we reexamined the potential requirement of ERK1/2 for insulin secretion. Blocking activation of ERK1/2 using MEK1/2, the MAPK kinase inhibitor PD98059 or using small interfering RNA-mediated silencing of ERK1 and ERK2 expressions resulted in partial inhibition of glucose-induced insulin release, indicating that ERK1/2 pathway participates also in the regulation of insulin secretion. Moreover, using the pancreatic islet perifusion model, we found that the ERK1/2 activity participates in the first and second phases of insulin release induced by glucose. Taken together, our results demonstrate new aspects of the glucose-dependent actions of ERK1/2 in beta-cells exerted on cytoplasmic proteins, including synapsin I, and participating in the overall glucose-induced insulin secretion. |
Databáze: | OpenAIRE |
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