ArticleDiabetologia2015
Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells.
Article in Diabetologia, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 52 citations in OpenAlex.
- Spatiotemporal orchestration of calcium-cAMP oscillations on AKAP/AC nanodomains is governed by an incoherent feedforward loop.PLoS computational biology · 2024Article
- Galectin-3 impairs calcium transients and β-cell function.Nature communications · 2024Article
- Polymorphism in ovineAnimal biotechnology · 2023Article
- Noncanonical Regulation of cAMP-Dependent Insulin Secretion and Its Implications in Type 2 Diabetes.Comprehensive Physiology · 2023Article
- The effect of forskolin and the role of Epac2A during activation, activity, and deactivation of beta cell networks.Frontiers in endocrinology · 2023Article
- Therapeutic potentials of agonist and antagonist of adenosine receptors in type 2 diabetes.Reviews in endocrine & metabolic disorders · 2021Review
- Identification of dysregulated pathways underlying HTLV-1-associated myelopathy/tropical spastic paraparesis through co-expression network analysis.Journal of neurovirology · 2021Article
- Thiazolidinediones (TZDs) enhance insulin secretory response via GPR40 and adenylate cyclase (AC).Journal of cellular physiology · 2021Article
- Biochemical Activity Architectures Visualized-Using Genetically Encoded Fluorescent Biosensors to Map the Spatial Boundaries of Signaling Compartments.Accounts of chemical research · 2021Review
- Glucose-induced cAMP elevation in β-cells involves amplification of constitutive and glucagon-activated GLP-1 receptor signalling.Acta physiologica (Oxford, England) · 2021Article
- Article
- Role of Phosphodiesterase in the Biology and Pathology of Diabetes.International journal of molecular sciences · 2020Review
- In vitro expansion of pancreatic islet clusters facilitated by hormones and chemicals.Cell discovery · 2020Article
- Deletion of pancreatic β-cell adenosine kinase improves glucose homeostasis in young mice and ameliorates streptozotocin-induced hyperglycaemia.Journal of cellular and molecular medicine · 2019Article
- FXR Mediates Adenylyl Cyclase 8 Expression in PancreaticJournal of diabetes research · 2019Article
- Regulation of cAMP accumulation and activity by distinct phosphodiesterase subtypes in INS-1 cells and human pancreatic β-cells.PloS one · 2019Article
- β-arrestin-1: Bridging GPCRs to active TRP channels.Channels (Austin, Tex.) · 2017Article
- A Role for Calcium-Activated Adenylate Cyclase and Protein Kinase A in the Lens Src Family Kinase and Na,K-ATPase Response to Hyposmotic Stress.Investigative ophthalmology & visual science · 2017Article
- A cullin 4B-RING E3 ligase complex fine-tunes pancreatic δ cell paracrine interactions.The Journal of clinical investigation · 2017Article
- Arrestin-biased AT1R agonism induces acute catecholamine secretion through TRPC3 coupling.Nature communications · 2017Article
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisInsulin 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.
methodsTime-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.
resultsMembrane 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/
interpretationOur 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.