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Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells

dc.relation.isnodouble66858f25-2364-4afc-81b3-e7b4d71b457c*
dc.relation.isnodouble42c1c468-44d8-4fac-af8e-8836e8d7e2ca*
dc.relation.isnodouble00f003ca-a279-4ddc-91a2-85b889507c5d*
dc.contributor.authorDOU, H.
dc.contributor.authorWANG, C.
dc.contributor.authorWU, X.
dc.contributor.authorYAO, L.
dc.contributor.authorZHANG, X.
dc.contributor.authorTENG, S.
dc.contributor.authorXU, H.
dc.contributor.authorLIU, B.
dc.contributor.authorWU, Q.
dc.contributor.authorZHANG, Q.
dc.contributor.authorHU, M.
dc.contributor.authorWANG, Y.
dc.contributor.authorWANG, L.
dc.contributor.authorWU, Y.
dc.contributor.authorSHANG, S.
dc.contributor.authorKANG, X.
dc.contributor.authorZHENG, L.
dc.contributor.authorZHANG, J.
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorRAOUX, Matthieu
hal.structure.identifierChimie et Biologie des Membranes et des Nanoobjets [CBMN]
dc.contributor.authorLANG, Jochen
IDREF: 085209600
dc.contributor.authorLI, Q.
dc.contributor.authorSU, J.
dc.contributor.authorYU, X.
dc.contributor.authorCHEN, L.
dc.contributor.authorZHOU, Z.
dc.date.accessioned2020-09-03T08:02:13Z
dc.date.available2020-09-03T08:02:13Z
dc.date.issued2015
dc.identifier.issn0012-186x
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/10989
dc.description.abstractEnAIMS/HYPOTHESIS: Insulin is a key metabolic regulator in health and diabetes. In pancreatic beta cells, insulin release is regulated by the major second messengers Ca(2+) and cAMP: exocytosis is triggered by Ca(2+) and mediated by the cAMP/protein kinase A (PKA) signalling pathway. However, the causal link between these two processes in primary beta cells remains undefined. METHODS: Time-resolved confocal imaging of fluorescence resonance energy transfer signals was performed to visualise PKA activity, and combined membrane capacitance recordings were used to monitor insulin secretion from patch-clamped rat beta cells. RESULTS: Membrane depolarisation-induced Ca(2+) influx caused an increase in cytosolic PKA activity via activating a Ca(2+)-sensitive adenylyl cyclase 8 (ADCY8) subpool. Glucose stimulation triggered coupled Ca(2+) oscillations and PKA activation. ADCY8 knockdown significantly reduced the level of depolarisation-evoked PKA activation and impaired replenishment of the readily releasable vesicle pool. Pharmacological inhibition of PKA by two inhibitors reduced depolarisation-induced PKA activation to a similar extent and reduced the capacity for sustained vesicle exocytosis and insulin release. CONCLUSIONS/INTERPRETATION: Our findings suggest that depolarisation-induced Ca(2+) influx plays dual roles in regulating exocytosis in rat pancreatic beta cells by triggering vesicle fusion and replenishing the vesicle pool to support sustained insulin release. Therefore, Ca(2+) influx may be important for glucose-stimulated insulin secretion.
dc.language.isoen
dc.title.enCalcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells
dc.title.alternativeDiabetologia
dc.typeArticle de revue
dc.identifier.doi10.1007/s00125-014-3437-z
dc.subject.halChimie/Matériaux
bordeaux.journalDiabetologia
bordeaux.page324-33
bordeaux.volume58
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN) - UMR 5248*
bordeaux.hal.laboratoriesInstitut de Chimie & de Biologie des Membranes & des Nano-objets (CBMN, UMR 5248)
bordeaux.issue2
bordeaux.institutionUniversité de Bordeaux
bordeaux.institutionBordeaux INP
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